Evidence on procedures that bypass the reproductive system rather than resolve why conception fails, covering outcomes, safety, registries, cost, and how results are reported.
Increasing numbers of children are conceived using infertility treatment; concerns remain about potential effects on child neurodevelopment. To evaluate whether infertility treatment is associated with child neurodevelopment and whether such an association may be attributable to underlying subfecundity. DESIGN, SETTING, This cohort study was conducted among mother-child dyads in the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) Cohort, with infants conceived between 1998 and 2022. Associations of subfecundity and infertility treatment with neurodevelopmental outcomes were assessed among children ages 2 to 10 years. Data were analyzed from May 14, 2025, to March 31, 2026. Subfecundity was defined as prior consultation for, treatment of, or diagnosis of infertility for either partner; at least 2 prior miscarriages; or ever having had unprotected heterosexual intercourse for 12 months without conceiving. Infertility treatment was categorized as in vitro fertilization (IVF) or non-IVF treatment. Harmonized caregiver responses to the Strengths and Difficulties Questionnaire and the Child Behavior Checklist yielded continuous raw scores for externalizing and internalizing problems. The total raw Social Responsiveness Scale (SRS) score quantified autism-like symptoms. Caregivers reported physician diagnosis of autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Among 15 382 mother-infant dyads, there were 14 191 unique maternal participants (mean [SD] age at delivery, 30.9 [5.33] years; 8780 parous participants [57.1%]). ASD and ADHD were diagnosed in 876 offspring (7.6%) and 819 offspring (7.1%), respectively. In generalized linear models, subfecundity was associated with higher externalizing problem and SRS scores among all pregnancies (externalizing problems: b = 0.47 [95% CI, 0.14-0.81]; SRS score: b = 1.08 [95% CI, 0.01-2.14]) and when restricted to natural conceptions (externalizing problems: b = 0.45 [95% CI, 0.07-0.83]; SRS score: b = 1.12 [95% CI, -0.09 to 2.34]). Offspring of parents with subfecundity had higher odds of ASD (overall: odds ratio [OR], 1.27 [95% CI, 1.03-1.57]; natural conceptions: OR, 1.31 [95% CI, 1.04-1.64]). Children conceived via non-IVF treatment had higher odds of ADHD compared with those conceived via natural conception with subfecundity (OR, 1.77 [95% CI, 1.16-2.68]) or without subfecundity (OR, 1.54 [95% CI, 1.05-2.25]). There were no significant associations for IVF treatment. In this large US cohort study, subfecundity was associated with elevated scores for caregiver-reported symptoms of behavioral problems and higher odds of ASD diagnosis, independent of infertility treatment. Non-IVF treatment was associated with ADHD, warranting further research into specific indications for treatment that may increase risk of offspring neurodevelopmental problems.
[OBJECTIVE] The role of intrauterine PRP infusion in managing recurrent implantation failure (RIF) remains controversial despite its emerging clinical use. This systematic review aims to evaluate its therapeutic potential in RIF patients and further to investigate variations in outcomes based on transfer cycle type, embryo developmental stage, RIF diagnostic criteria, and endometrial thickness. [METHODS] We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials (RCTs) investigating PRP treatment for RIF patients from the beginning of the database to May 2025. [RESULTS] This meta-analysis showed that PRP administration significantly improved clinical pregnancy rate (CPR) [OR = 3.18, 95%CI (2.45, 4.14), I2 = 3%], biochemical pregnancy rate (BPR) [OR = 2.84, 95%CI (2.22, 3.63), I2 = 0%], ongoing pregnancy rate (OPR) [OR = 3.41, 95%CI (2.08, 5.60), I2 = 30%] and live birth rate (LBR) [OR=5.10, 95%CI (1.95, 13.37), I2 = 75%] in women with RIF. However, PRP intrauterine infusion did not reduce miscarriage rate (MR). Notably, the preterm birth rate was significantly higher in the PRP group compared to controls [OR = 8.24, 95%CI (2.09, 32.41), I2 = 0%]. Subgroup analysis demonstrated that PRP improved CPR, BPR and LBR in both the fresh and frozen embryo transfer cycles. Additionally, while PRP increased CPR, LBR and reduced MR in blastocyst transfers [CPR OR = 3.84, 95%CI (2.82, 5.23), I2 = 0%; LBR OR = 7.32, 95%CI (3.17, 16.90), I2 = 63%; MR OR = 0.27, 95%CI (0.07, 0.96), I2 = 54%], these effects were not observed in cleavage-stage embryo transfers. Moreover, PRP administration associated with a higher CPR [OR = 3.84, 95%CI (2.82, 5.23), I2 = 0%], OPR[OR = 4.13, 95%CI (1.79, 9.56), I2 = 48%], LBR [OR = 7.32, 95%CI (3.17, 16.90), I2 = 63%] and a lower MR [OR = 0.27, 95%CI (0.07, 0.96), I2 = 54%] in women with ≥3 prior implantation failure, it did not confer the same benefit to those with a history of ≥2 failed cycles. [CONCLUSION] These findings suggest a possible beneficial role for PRP on pregnancy outcomes to some extent in women with RIF, particularly in cases with ≥3 prior failed transfers, and blastocyst transfer may increase LBR and reduce miscarriage risk. However, further investigation is warranted to determine whether this treatment may pose an increased risk of preterm birth. [SYSTEMATIC REVIEW REGISTRATION] https://www.crd.york.ac.uk/prospero/, identifier CRD420251061511.
Does IVF worsen pelvic pain in women with endometriosis? Nearly half of women with endometriosis reported perceived worsening of pelvic pain after IVF. Prior studies generally suggested no IVF-related pain worsening, but few assessed delayed flares or longer-term trajectories. International cross-sectional study based on an online survey conducted between September 2024 and April 2025 including 546 respondents. PARTICIPANTS/MATERIALS Women aged ≥18 years with surgically or imaging-confirmed endometriosis and at least one completed IVF cycle. A 25-item questionnaire captured demographics, reproductive history, comorbidities, and patient-reported pain trajectories before, during, and after IVF. The primary outcome was perceived worsening of pelvic pain after IVF (patient-reported outcome measure; PROM). Secondary outcomes were worsening of dysmenorrhoea and dyspareunia. Group comparisons and exploratory multivariable logistic regressions were performed. Predictor analyses were exploratory. MAIN Among 546 respondents, 48.9% reported worsening pelvic pain after IVF, 49.1% reported worsening dysmenorrhoea, and 35.5% worsening dyspareunia. Current pain scores were significantly higher in women reporting worsening versus no worsening (all P < 0.001). In multivariable analyses, immediate post-cycle pain flare emerged as the strongest and most consistent predictor across all pain outcomes, independently associated with worsening of pelvic pain (adjusted odds ratio [aOR] 5.91, 95% CI 3.88-9.14), dysmenorrhoea (aOR 4.03, 95% CI 2.08-8.05), and dyspareunia (aOR 3.17, 95% CI 2.07-4.90) (all P < 0.001). For the primary outcome, reporting oocyte retrieval as the most painful IVF step (aOR 0.53, 95% CI 0.31-0.88; P = 0.016) and achieving a live birth after IVF (aOR 0.63, 95% CI 0.42-0.92; P = 0.020) were independently associated with lower odds of pelvic pain worsening. In secondary outcome models, live birth was associated with lower odds of dysmenorrhoea worsening, while bladder pain syndrome/interstitial cystitis independently predicted worsening of dyspareunia. A formal response rate could not be calculated due to open online dissemination without a known denominator. LIMITATIONS Self-reported, retrospective data are prone to recall and selection bias, and the cross-sectional design precludes causal inference. Recruitment via associations and social media without a denominator limits generalizability, absence of baseline pain scores impedes assessment of change, and incomplete capture of peri-IVF hormonal regimens may confound results. IVF may not be pain-neutral in endometriosis. Monitoring pain trajectories at key IVF milestones may help identify women at risk of long-term exacerbation. Prospective studies should test whether early monitoring combined with tailored interventions-optimized analgesia, psychological support, or adapted stimulation protocols-can mitigate chronic pain trajectories throughout the IVF journey and ultimately improve quality of life. No specific funding; authors declare no conflicts of interest. N/A.
To examine birth outcomes between children conceived with in vitro fertilization (IVF) or intrauterine insemination (IUI) and sibling births from unassisted conceptions. Retrospective sibling cohort. Live born children conceived via IVF, with or without intracytoplasmic sperm injection, or IUI at the Utah Center for Reproductive Medicine, 1999-2018, and sibling births from unassisted conceptions (born 1985-2018). The main analysis included singleton births (460 IVF, 666 IUI, and 1,579 unassisted siblings). Exposure: In vitro fertilization, with or without intracytoplasmic sperm injection, or IUI. Preterm birth, low birth weight, small for gestational age, large for gestational age (LGA), and major congenital anomalies. Compared with unassisted siblings, singleton children conceived via IVF had gestational ages shorter by nearly half a week (95% confidence interval [CI], -0.6 to -0.3), birth weights of 72.1 g lower (95% CI, -118.8 to -25.4), and higher proportions of preterm birth (IVF, 11.1%; IUI, 8.7%; unassisted siblings, 6.8%), LGA (IVF, 9.1%; IUI, 4.5%; unassisted siblings, 5.9%), and major congenital anomalies (IVF, 3.7%; IUI, 2.0%; unassisted siblings, 1.4%). Models adjusted for maternal age, infant sex, infant birth year, previous pregnancy, and birth order showed that children conceived via IVF were more likely to be preterm (adjusted risk ratio [aRR], 1.6; 95% CI, 1.2-2.2; absolute difference, 4.3%) and LGA (aRR, 1.8; 95% CI, 1.2-2.5; absolute difference, 3.2%). Children conceived via IVF had a higher risk of major congenital anomalies than unassisted siblings adjusted for maternal age, infant sex, and birth order (aRR, 1.9; 95% CI, 1.0-3.8; absolute difference, 2.3%). Children conceived via IUI had birth weights 55.8 g lower (95% CI, -95.6 to -15.9) than unassisted siblings. We observed an increased risk of preterm birth, low birth weight, LGA, and major congenital anomalies among singleton children conceived with IVF compared with that among unassisted siblings; however, absolute differences remain small. For children conceived via IUI, lower birth weights were observed. These results suggest that treatment-related factors in addition to underlying subfertility may contribute to adverse birth outcomes.
Katagiri Y et al., 2026·Reproductive Medicine and Biology·
Open Access
To summarize assisted reproductive technology (ART) data for 2023 collected through the Japan Society of Obstetrics and Gynecology registry. 625 out of 638 registered ART facilities took part in the study, documenting 561 664 treatment cycles and 85 048 newborns (+3.3% and +10.2% increases from 2022). The average age of women undergoing treatment was 37.3 years (standard deviation: 4.8); 205 986 cycles (36.7%) involved women aged ≥ 40 years. Among fresh cycles, oocyte retrieval was performed in 281 665 cycles, including 168 343 freeze-all cycles (59.8%). A total of 2329 pregnancies and 3375 newborns resulted from in vitro fertilization and intracytoplasmic sperm injection cycles, yielding 1772 and 2502 newborns, respectively. The overall rates for single embryo transfer (SET) and singleton delivery were 80.5% and 96.5%. Frozen-thawed embryo transfer accounted for 271 361 cycles, resulting in 109 850 pregnancies and 80 774 newborns, with a SET rate of 84.7% and a singleton delivery rate of 96.3%. In 2023, the second year of insurance coverage, the registry recorded the highest numbers of treatment cycles and newborns. Effective registry systems planned for 2026 will enable comprehensive evaluation of emerging trends in Japanese ART practice.
Zegers-Hochschild F et al., 2026·Reproductive Biomedicine Online
What are the trends and effects of assisted reproductive technology (ART) interventions on the effectiveness and safety of ART carried out in Latin America during 2022. Retrospective collection of cycle-based multinational data obtained from ART procedures carried out by 204 accredited institutions in 16 countries. In total 123,265 initiated cycles resulted in 19,663 deliveries and 22,203 births. Use of ART varied greatly, from 643.3 cycles/million inhabitants in Uruguay to 28.8 in Guatemala. In autologous cycles, the proportion of women aged ≥40 years represents 35.1% of cycles, whereas women <34 years represents only 18.8%. The proportion of single embryo transfers (SET) increased from 42.4% in 2021 to 47.3% in 2022. Out of 22,203 babies born, 77.4% were singletons, 21.7% twins and 0.9% triplets or more. Intracytoplasmic sperm injection represented 85.4% of fertilization techniques, and blastocyst transfer increased from 79.3% in 2021 to 85.3% in 2022. Delivery rate after fresh blastocyst elective single embryo transfer (32.6%) was significantly higher than after the transfer of one frozen embryo transfer (FET) from freeze-all cycle (25.2%) (P = 0.0001). The number of aspirations leading to preimplantation genetic testing increased 2.6 times in 6 years, and significantly increased delivery rates/transfer (P ≤ 0.008) and reduced miscarriage at all ages (P ≤ 0.004) in autologous cycles, but not in oocyte donation cycles. Delivery rates after fresh transfer of embryos from vitrified-warmed donated oocytes, generated similar outcome to FET from fresh oocyte donation cycles (P = 0.5621). Perinatal mortality increased from 7.5‰ in singletons to 22.8‰ in twins. Systematic collection of cycle-based multinational data contributes to cooperative sustained development and helps implement evidence-based reproductive decisions.
Premature ovarian insufficiency (POI) severely limits reproductive options. We report a successful live birth in a patient with POI following a combined approach of intraovarian platelet-rich plasma (PRP) treatment, double ovarian stimulation (DuoStim protocol), and preimplantation genetic testing for aneuploidy (PGT-A). PRP treatment was performed to restore ovarian function, after which DuoStim was used to maximize oocyte yield. An embryo obtained underwent PGT-A, and transfer of a euploid blastocyst resulted in an uncomplicated pregnancy and the birth of a healthy child. This case highlights the potential of personalized and multidisciplinary strategies to overcome the traditional barriers in POI by integrating regenerative medicine (PRP), advanced ovarian stimulation (DuoStim), and genetic embryo selection (PGT-A). While this innovative approach appears promising for women with diminished ovarian reserve, further studies are needed to confirm its efficacy and safety.
Human Fertilisation and Embryology Authority, 2025·
# The fertility sector 2024/25
Annual publication on HFEA licensed clinics (1 April 2024 – 31 March 2025)
Published: November 2025
[Download the underlying dataset as Excel Worksheet](https://www.hfea.gov.uk/media/cpzhqp1p/the-fertility-sector-2024-25-underlying-dataset.xlsx "The fertility sector 2024/25 - underlying dataset")
## Table of contents
- [1\. How we regulate](https://www.hfea.gov.uk/about-us/publications/research-and-data/the-fertility-sector-2024-2025/#how-we-regulate)
- [2\. Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/the-fertility-sector-2024-2025/#main-points)
- [3\. How the HFEA inspects clinics](https://www.hfea.gov.uk/about-us/publications/research-and-data/the-fertility-sector-2024-2025/#how-the-hfea-inspects-clinics)
- [4\. Inspections](https://www.hfea.gov.uk/about-us/publications/research-and-data/the-fertility-sector-2024-2025/#inspections)
- [5\. Non-compliances identified at inspections](https://www.hfea.gov.uk/about-us/publications/research-and-data/the-fertility-sector-2024-2025/#non-compliances-identified-at-inspections)
- [6\. Clinic licences](https://www.hfea.gov.uk/about-us/publications/research-and-data/the-fertility-sector-2024-2025/#clinic-licences)
- [7\. Incidents](https://www.hfea.gov.uk/about-us/publications/research-and-data/the-fertility-sector-2024-2025/#incidents)
- [8\. Ovarian Hyperstimulation Syndrome (OHSS)](https://www.hfea.gov.uk/about-us/publications/research-and-data/the-fertility-sector-2024-2025/#ovarian-hyperstimulation-syndrome-ohss)
- [9\. Patient complaints](https://www.hfea.gov.uk/about-us/publications/research-and-data/the-fertility-sector-2024-2025/#patient-complaints)
- [10\. Patient feedback](https://www.hfea.gov.uk/about-us/publications/research-and-data/the-fertility-sector-2024-2025/#patient-feedback)
- [11\. About our data](https://www.hfea.gov.uk/about-us/publications/research-and-data/the-fertility-sector-2024-2025/#about-our-data)
## 1\. How we regulate
The Human Fe...
**STUDY ** What are the data and trends of ART and IUI cycle numbers and their outcomes, and of fertility preservation (FP) interventions, reported in 2020 as compared to previous years? **SUMMARY ** This 24th ESHRE report highlights the number of ART treatment cycles and children born over the years, showing a decline in the total number of treatment cycles, when comparing 2020 with 2019, alongside a decline in twin deliveries owing to a decrease in transfers of multiple embryos; however, fresh IVF or ICSI cycles and frozen embryo transfers (FET) showed similar pregnancy rates, and the reported IUI cycle numbers decreased while maintaining stable outcomes. **WHAT ** ART aggregated data generated by national registries, clinics, or professional societies have been gathered and analyzed by the European IVF Monitoring (EIM) consortium since 1997 and reported in a total of 23 manuscripts published in *Human Reproduction* and *Human Reproduction Open*. **STUDY DESIGN, SIZE, ** Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE each year. The data on treatment cycles performed between January 1 and December 31, 2020, were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons in the 44 countries that are members of the EIM Consortium. **PARTICIPANTS/MATERIALS, SETTING, ** Overall, 1440 clinics offering ART services in 41 countries reported 923 318 treatment cycles (−14%; in 2019: 1 077 813), including 135 231 with IVF, 356 408 with ICSI, 305 373 with FET, 57 051 with preimplantation genetic testing (PGT), 64 007 with oocyte donation, and 4895 cycles using frozen oocytes. A total of 1288 institutions reported data on IUI cycles using either husband/partner's semen (IUI-H; n = 112 663) or donor semen (IUI-D; n = 38 839) in 30 and 21 countries, respectively. Sixteen countries reported 29 566 interventions in pre-and post-pubertal patients for FP, including oocyte, ovarian tissue, semen, and testicular tissue banking. **MAIN ** In 24 countries (21 in 2019) in which all ART clinics reported to the registry, 356 427 treatment cycles were registered for a total population of approximately 268 million inhabitants in these countries, allowing the best estimate of a mean of 1330 cycles performed per million inhabitants (range: 142–3230). Among the reporting countries, for IVF, the clinical pregnancy rates (PR) per aspiration were similar to that in 2019 (22.1% versus 21.8% in 2019). For ICSI, the corresponding PRs showed similar trends (20.0% in 2020 versus 20.2% in 2019). When freeze-all cycles were excluded from the calculations, the clinical PRs per aspiration were 26.4% (28.5% in 2019) and 25.6% (26.2% in 2019) for IVF and ICSI, respectively. After oocyte donation, the PR per embryo transfer was 51.3% (50.5% in 2019) with freshly donated oocytes and 45.7% (44.8% in 2019) with thawed oocytes. After FET, the PR per thawing was 34.9% (versus 35.1% in 2019). In fresh cycles of both IVF and ICSI, the trend towards the transfer of fewer embryos continued with the transfer of 1, 2, 3, and ≥4 embryos in 57.2%, 37.8%, 4.8%, and 0.2%, of all treatments, respectively (corresponding to 55.4%, 39.9%, 2.6%, and 0.2% in 2019). This resulted in a reduced proportion of twin delivery rates (DRs) of 10.9% (11.9% in 2019) and a similar triplet DR of 0.2%. In FET cycles in 2020, the twin and triplet DRs were 7.9% and 0.1%, respectively (versus 8.9% and 0.1% in 2019). While the number of IUI cycles in 2020 decreased from 2019, the DRs remained stable at 8.8% after IUI-H (8.7% in 2019) and at 12.5% after IUI-D (12.1% in 2019). Twin and triplet DRs after IUI-H were 7.9% and 0.4% (in 2019: 8.7% and 0.4%) and 5.7% and 0.1% after IUI-D (in 2019: 6.2% and 0.2%), respectively. Data on FP were provided by 16 countries (18 in 2019), reporting a total of 29 566 interventions (24 139 in 2019). Cryopreservation of ejaculated sperm (n = 21 864 versus n = 11 592 in 2019) and cryopreservation of oocytes (n = 6077 versus n = 10 784 in 2019) were the most frequently reported forms of FP. **LIMITATIONS, ** Caution with the interpretation of results should remain as data collection systems and completeness of reporting vary among European countries.
Boyle P et al., 2025·J Restorative Reprod Med·
Open Access
Restorative reproductive medicine (RRM) is an emerging approach that can be used to treat infertility. Our goal was to compare RRM to IVF outcomes in 2019.
We conducted a retrospective clinic-based analysis and referenced it against publicly available data from IVF registries, as published by the Centers for Disease Control and Prevention (CDC) or the Society for Assisted Reproductive Technology (SART) in the USA, and the Human Fertilization and Embryology Authority (HFEA), in the UK. Data from 2019 was collected from routine medical records following treatment at one clinic in Dublin, Ireland during 2019. We defined the demographics, diagnoses, and treatments and then calculated the crude percentages of conception, live birth, multiple pregnancy, prematurity, and low birth weight. These results were benchmarked against data reported in IVF databases. 249 couples had at least one RRM consultation, 187 committed to the RRM treatment program and met the inclusion criteria. The average female age for all included patients was 36.4 years and couples were trying to conceive for a mean of 32.2 months. Of the 187 patients/couples who underwent treatment, 28% had a previous live birth, 30% had a previous miscarriage, and 42% had never conceived;19% (35/187) had previously had IVF, 2.3 + 1.6 IVF cycles per couple. Of the 187 couples, 52% (98/187) conceived, 41% (77/187) had a documented live birth. There were 75 singletons and 2 sets of twins, producing 79 babies. Time to conception for live birth patients averaged 12 + 8 months. The average birth weight was 3422g (7lb 9oz) and average weeks’ gestation at delivery was 39 + 1.5 weeks. 4.0% (3/75) of singleton babies were premature (33-37 weeks) and none were very premature (< 32 weeks). 5.3% (4/75) of singleton babies had low birth weight (< 2,500g). When we compared births across age groups, the RRM percentages with live birth were comparable to those in a single cycle of IVF with multiple subsequent embryo transfers, and greater than a single cycle of IVF with a single embryo transfer. Furthermore, RRM babies had fewer multiple pregnancies, and singleton RRM pregnancies had less than half as many premature deliveries compared to IVF, (6.5% RRM all pregnancies or 4.0% RRM, singleton pregnancies vs 14.4% SART, all pregnancies or 11.8% CDC, singleton pregnancies). 74% (26/35) of couples who remained in contact with us and tried for another pregnancy had a repeat successful live birth. In our clinic, a comprehensive RRM assessment and treatment followed by up to 12 optimal cycles of timed intercourse resulted in a 41% live birth rate (crude rate). We propose that using RRM may improve a couple’s chance of having a healthy pregnancy and reduce the demand for IVF. Furthermore, RRM reduces the risk of multiple pregnancy, low birth weight and premature delivery compared to IVF. The majority of couples who sought a second live birth were successful.
Limitations and Future directions: This is a retrospective analysis with a small number of RRM patients, compared to large IVF databases of patients using one cycle of IVF, including all transfers made from the IVF retrieval. While useful for benchmarking, conclusions are limited by sample size, and the lack of relevant prognostic data (other than female age) for the IVF patients. Larger prospective studies with full prognostic data are needed to make a proper comparison of RRM and IVF outcomes.
Kotevski DP et al., 2025·National Perinatal Epidemiology and Statistics Unit, UNSW Sydney
ANZARD annual report on assisted reproductive technology activity, outcomes, and safety across Australia and New Zealand for 2023. Covers fresh-cycle and FET cycle counts, single-embryo transfer rates, clinical pregnancy and live birth rates, ART-conceived births, multiple pregnancy rates, and patient demographics. Published by the National Perinatal Epidemiology and Statistics Unit (NPESU) at UNSW Sydney with data submitted from all RTAC-accredited ART units in Australia and New Zealand.
Add-Ons and Adjuncts · Preimplantation Genetic Testing
Preimplantation genetic testing for polygenic disorders (PGT-P) has been commercially available since 2019. PGT-P makes use of polygenic risk scores for conditions which are multifactorial and are significantly influenced by environmental and lifestyle factors. If current predictions are accurate, then absolute risk reductions range from about 0.02% to 10.1%, meaning that between 10 and 5,000 in vitro fertilization patients would need to be tested with PGT-P to prevent one offspring from becoming affected in the future, depending on the condition and the number of embryos available. Survey and interview data reveal that patients and the public have largely favorable views regarding the use of PGT-P for disease prevention; however, clinicians and professional organizations have many reservations. The use of PGT-P raises multiple social and ethical concerns including the need for adequate counseling, the setting of realistic expectations, the application of distributive justice, the impact of environmental and social determinants of health, and the potential exacerbation of health inequities. Clinicians expressed significant concerns relating to the cost of PGT-P, the potential time-consuming counseling for reproductive endocrinologists and genetic counselors, the intentional creation of supernumerary embryos, and patients' unrealistic expectations regarding "healthiest disease-free" embryos. Furthermore, current evidence lacks long-term outcome data and generalizability. Prior to offering PGT-P to patients, additional clinical validation studies are needed. Also, ethical and social considerations raised by PGT-P should be carefully delineated. Systemic practices to increase equitable access to unbiased genetic counseling and reproductive services would be desirable prior to the ethical implementation of PGT-P.
Human Fertilisation and Embryology Authority, 2025·
# Fertility treatment 2023: trends and figures
Preliminary UK statistics for IVF and DI treatment, storage, and donation
Published: June 2025
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[Download the underlying dataset as Excel Worksheet](https://www.hfea.gov.uk/media/3qip3kon/fertility-treatment-2023-trends-and-figures-underlying-dataset.xlsx "Download the underlying dataset for the ‘Fertility treatment 2023: trends and figures’ report")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#main-points)
- [Note on preliminary data](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#note-on-preliminary-data)
- [Section 1: More babies born from IVF in the UK](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#section-1)
- [Section 2: IVF pregnancy and birth rates using fresh embryo transfers increased over the years, though lower for Black patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#section-2)
- [Section 3: Average pregnancy and birth rates using frozen embryo transfers increased in 2023](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#section-3)
- [Section 4: Multiple births rate from IVF is one of the lowest in the world](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#section-4)
- [Section 5: Most treatment types have increased across the UK since 2019](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertili...
Outcomes and Effectiveness · Outcomes by Diagnosis
Deneer JJM et al., 2025·Reproductive Sciences·
Open Access
For women with idiopathic diminished ovarian reserve (DOR), direct start with IVF has been suggested to potentially shorten the time to pregnancy. Others however prefer intra-uterine insemination with ovarian stimulation (IUI + OS) due to the expected low response in IVF. In this pilot study, we determined the effect of these two strategies in women with DOR < 40 years. From a retrospective cohort, we included 135 women that met the diagnostic criteria of DOR. Patients were randomly referred to two different outpatient clinics in the Netherlands between 2012-2018 because of subfertility. Primary outcome was clinical pregnancy; secondary outcomes included ongoing pregnancies, live births, time to pregnancy and pregnancy-related complications. An instrumental variable analysis was used to assess the average effect of treatment with IUI + OS followed by IVF (protocol A) compared to IVF alone (protocol B) and correct for (unknown) confounders. Treatment protocol A was performed in 72.6% patients in Centre 1 and 30.6% in Centre 2. In Centre 1 61.6% (45/73) women had a clinical pregnancy compared to 41.9% (26/62) in Centre 2 (difference 19.7% (95% CI 3.1%-36.3%), p = 0.02). Early miscarriage occurred in 24% of the women in Centre 1 in comparison to 45% of the women in Centre 2. There were no significant differences in pregnancy-related complications. This pilot study suggests that women < 40 with DOR, if treated with IUI + OS followed by IVF, have higher estimated cumulative clinical pregnancy success, with a trend towards higher ongoing pregnancies and live births, in comparison to women treated with IVF alone.
What were the rates of utilization, effectiveness, and safety for assisted reproductive technology (ART) throughout the world in 2017 and 2018, and what trends were observed? The total reported number of ART fresh and frozen cycles conducted in 83 participating countries was 2 913 498 in 2017 and 3 303 505 in 2018, with 5-year trends including an increasing proportion of cycles utilizing frozen embryo transfer (FET) and an increasing number of cycles utilizing pre-implantation genetic testing (PGT). Prior reports from the International Committee Monitoring ART (ICMART) have reported on the utilization, effectiveness, and safety of ART from participating countries, with an increase in the number of cycles and number of participating countries over time. These reports have described regional differences in the utilization of ART overall, as well as differences in the utilization of specific practices such as ICSI, PGT and single embryo transfer. Past reports demonstrated that rates of delivery per cycle have increased and rates of multiple gestations have decreased over time. STUDY DESIGN, SIZE, This retrospective, cross-sectional survey describes ART procedures performed globally in 2017 and 2018. Data were submitted to ICMART by participating countries from national or regional registries. PARTICIPANTS/MATERIALS, SETTING, There were 83 countries which provided data for cycles performed in 2017 or 2018, with the majority of countries providing data for both years. Aggregate data are reported for each participating country and analysed using methods developed by ICMART to calculate measures of utilization, effectiveness, and safety. MAIN A total of 2 913 498 cycles and 671 012 babies born were reported for treatment performed in 2017, increasing to 3 303 505 cycles and 728 383 babies born for treatment performed in 2018. After imputing data for non-reporting centres in reporting countries, the estimated number of cycles performed in 2017 was 3 107 188 resulting in an estimated 814 588 babies. For 2018, the estimated number of cycles was 3 568 635 resulting in an estimated 870 814 babies. Utilization of ICSI for autologous fresh non-PGT cycles declined slightly compared with 2014 (54.6% in 2017 and 57.3% in 2018 compared with 64.8% in 2014). The percentage of transfers which were of frozen embryos was 55.7 % in 2017 and 57.9% in 2018, up from 38.9% in 2014. Among all countries, including those which reported no 'freeze all' cycles, the percentage of 'freeze all' cycles was 30.5% in 2017 and 32.7% in 2018, up from 13.1% in 2014. In countries reporting at least one retrieval cycle in which all embryos were frozen, the percentage of retrievals with no fresh embryo transfer increased (36.2% in 2017 and 36.8% in 2018, up from 20.1% in 2014). The number of PGT cycles in 2018 (172 247) was nearly 5-fold higher than the number reported in 2014 (36 512) with wide regional variation in utilization of PGT observed. In 2017, the delivery rate for autologous oocytes was 23.5% per oocyte retrieval, with a cumulative delivery rate of 36.4% per retrieval (excluding cycles which utilized PGT). The delivery rates per embryo transfer were 31.8% per autologous fresh transfer, 32.5% per autologous frozen transfer, and 47.3% per transfer after PGT. The delivery rate for transfers utilizing donor oocytes was 33.1% (combined fresh transfer and frozen transfers). In 2018, the delivery rate for autologous oocytes was 23.8% per oocyte retrieval, with a cumulative delivery rate of 37.3% per retrieval (excluding cycles which utilized PGT). The delivery rates per embryo transfer were 31.3% per autologous fresh transfer, 31.9% per autologous frozen transfer, and 48.4% per transfer after PGT. The delivery rate for transfers utilizing donor oocytes was 34.3%. The multiple delivery rate with autologous fresh transfer was 19.7% in 2017, and 18.3% in 2018. For autologous FET, the multiple delivery rate was 16.2% in 2017, and 14.9% in 2018. With oocyte donation (combined fresh and frozen embryo transfers), the multiple delivery rate was 15.9% in 2017, and 13.4% in 2018. Finally, the multiple delivery rate for cycles utilizing PGT was 6.9% in 2017 and 5.5% in 2018. LIMITATIONS, The data and analysis presented are dependent on the quality and completeness of the data submitted to ICMART, which varies globally. There is little data from the Middle East and some countries in Asia. It is important to note that delivery rates per transfer after PGT required the availability of embryos suitable for transfer, and therefore should not be interpreted as suggesting that PGT increases the overall success of ART per oocyte retrieval. Because of an updated methodology in the calculation of delivery rates and number of babies born, direct comparisons with past reports for these metrics cannot be made. Data are observational and it
DIR Jahrbuch 2024 des Deutschen IVF-Registers. 2024 Annual Report of the German IVF Registry (Deutsches IVF-Register, DIR). Reports German ART cycle counts, treatment indications, embryo-transfer outcomes, pregnancy and live-birth rates by treatment type, age strata, and cycle counts. The DIR is the largest German ART registry covering nearly all licensed reproductive medicine centers under voluntary professional-society registration.
Nulianti R et al., 2025·International medical case reports journal
Premature ovarian insufficiency (POI) leads to the early loss of ovarian function before age 40, resulting in infertility and hormonal imbalance. Despite the use of assisted reproductive technologies (ART), success rates remain low in this population. Platelet-rich plasma (PRP) therapy is emerging as a potential adjunct to enhance ovarian reserve. CASE ILLUSTRATIONCASE 1: A 25-year-old nulliparous woman with a history of ectopic pregnancy and an anti-Müllerian hormone (AMH) level below 1 ng/mL received two PRP injections scheduled between days 7 to 12 of her cycle. After the first injection, her AMH level remained <0.5 ng/mL. Following the second PRP injection, her AMH level increased to >0.5 ng/mL. A frozen embryo transfer resulted in a successful term pregnancy and healthy newborn. CASE 2: A 36-year-old nulliparous woman, married for seven years, also presented POI and AMH levels <1 ng/mL followed the same PRP and IVF protocol. After two PRP sessions, her AMH levels improved similarly to Case 1. Despite an initial pregnancy, the patient experienced pregnancy loss. These findings suggest that PRP may improve ovarian response in women with POI undergoing IVF. Further studies are warranted.
Solmonovich R et al., 2025·Fertility and sterility
To determine whether an association exists between in vitro fertilization (IVF) and severe maternal morbidity among low-risk pregnant patients. Retrospective cohort study. Low-risk pregnant patients who delivered between January 2019 and December 2022. Low-risk was defined as having an obstetric comorbidity index score of 0. In vitro fertilization. MAIN OUTCOME MEASURE(S): The primary outcome (dependent variable) was any severe maternal morbidity. The secondary outcome was the need for a cesarean delivery. A modified Poisson regression with robust error variance was used to model the probability of severe maternal morbidity as a function of IVF. Risk ratios and their associated 95% confidence intervals (CIs) were computed. An α value of 0.05 was considered statistically significant. RESULT(S): A total of 39,668 pregnancies were included for analysis, and 454 (1.1%) were conceived by IVF. The overall severe maternal morbidity rate was 2.4% (n = 949), with the most common indicator being blood transfusion. The overall cesarean delivery rate was 18.8% (n = 7,459). On modified Poisson regression, IVF-conceived pregnancies were associated with 2.56 times the risk of severe maternal morbidity (95% CI, 1.73-3.79) and 1.54 times the risk of having a cesarean delivery (95% CI, 1.37-1.74) compared with non-IVF pregnancies. CONCLUSION(S): In vitro fertilization is associated with higher rates of severe maternal morbidity, primarily the need for a blood transfusion, and cesarean delivery in low-risk pregnancies without major comorbidities. Recognizing this association allows healthcare providers to implement proactive measures for better monitoring and tailored postpartum care.
Nationwide survey of JSOG-registered ART facilities on perceptions of disclosing institutional success rates for IVF. Provides context for the JSOG registry's reporting model and clinic-level transparency conventions.
Canadian Fertility and Andrology Society et al., 2025·Canadian Fertility and Andrology Society - CARTR Plus
CARTR Plus 2025 annual report covering Canadian ART activity for treatment cycles completed in 2024. Reports cycles performed, single-embryo transfer rates, clinical pregnancy and live-birth rates, ART-conceived births, and multiple-pregnancy rates from participating CFAS member ART centers. Voluntary professional-society reporting from Canadian ART clinics.
Human Fertilisation and Embryology Authority, 2025·
# National Patient Survey 2024
Survey of UK fertility 2 September - 9 October 2024
Published: March 2025
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/vf5bxixp/national-patient-survey-2024-underlying-dataset.xlsx "Download the underlying dataset for the ‘National Patient Survey 2024’ report")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#main-points)
- [Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#introduction)
- [Section 1: Over 70% of patients were satisfied with treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-1)
- [Section 2: Almost 80% of patients spoke to a GP before treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-2)
- [Section 3: 73% had used an additional test, treatment or emerging technology](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-3)
- [Section 4: Around a quarter of respondents had used donor eggs, sperm, or embryos](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-4)
- [Section 5: 40% of those able to donate would be willing to donate to research](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-5)
- [Section 6: Familiarity with the HFEA increased to 68%](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-6)
- [Qualitative summary](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#qualitative-summary)
- [About our data](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#about-our-data)
## Main points
- Fertility patients’ satisfaction with most ...
Sweden national IVF registry report covering 2023 treatments. 26,500 treatments started at 23 clinics (6 public, 17 private). 5,804 live born children (5,508 IVF + 296 IUI-D). Fresh IVF delivery rate 27% per ET (own gametes). FET delivery rate 36.9% per ET. Cumulative delivery rate per OPU within 1 year: 45%. SET rate 97%. Multiple birth rate 1.7%. OHSS hospitalization rate 0.4%. 1,121 oocyte freezing cycles (865 social, 186 oncological). Patient satisfaction: medical care 92%, treatment 94%.
Merhi Z et al., 2025·American journal of stem cells
This report describes two women aged 45 and older who achieved live births following intraovarian administration of a novel combination of mechanically processed adipose nanofat rich in adipose-derived stem cells (ADSCs) and autologous platelet-rich plasma (PRP). Both patients had a history of prolonged infertility and multiple failed assisted reproductive technology cycles with in vitro fertilization (IVF). Case 1, a 46-year-old with diminished ovarian reserve and prior miscarriage, underwent adipose-PRP treatment after unsuccessful minimal stimulation IVF. Six months later, she conceived naturally and delivered a healthy infant at age 47. Case 2, a 45-year-old with endometriosis and multiple failed IVF attempts, conceived via frozen embryo transfer of her only euploid embryo produced three months after adipose-PRP treatment, resulting in the birth of a healthy infant. The combination approach was developed to comply with U.S. FDA minimal manipulation guidelines, avoiding enzymatic processing of adipose tissue. This report is, to our knowledge, the first to document natural conception in women with age over 45 following combined adipose nanofat ADSCs and PRP intraovarian injection, and among the few to describe live births at this age using autologous oocytes after such therapy. These findings suggest that adipose-PRP treatment may offer a promising regenerative option for women with extremely diminished ovarian reserve who desire genetically related offspring, though controlled studies are required to confirm long term safety, efficacy, and appropriate patient selection.
ICMART world report on global assisted reproductive technology activity in 2019. Reports utilization, effectiveness, and safety data submitted from national and regional registries worldwide. Pre-pandemic activity baseline. Authors: Dyer S, Chambers GM, Jwa SC, Baker VL, Banker M, de Mouzon J, Elgindy E, Fu B, Ishihara O, Kupka M, Zegers-Hochschild F, Adamson GD.
Almohammadi A et al., 2025·International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics
[BACKGROUND] Recurrent implantation failure (RIF) has a multifactorial etiology. An umbrella review was undertaken to evaluate the multiple proposed interventions. [OBJECTIVES] To summarize and assess the strength of evidence of interventions for RIF from published systematic reviews (SR) of randomized clinical trials (RCTs). [SEARCH STRATEGY] After prospective registration (PROSPERO CRD42023414255), a systematic search was conducted in the Cochrane Library, Scopus and Medline from inception until March 2024. [SELECTION CRITERIA] SRs of RCTs, with or without meta-analyses (MA), were included if they reported clinical pregnancy rates (CPR) or live birth rates (LBR). [DATA COLLECTION AND ANALYSIS] The methodological quality of the included SRs was appraised independently in duplicate using the AMSTAR 2 tool. For each intervention, the MAs of RCTs with statistically significant improvements were counted as a percentage of the total assessing the strength of evidence using the GRADE system. [MAIN RESULTS] A total of 47 SRs were included: 32 reviews covered immunomodulatory interventions, 10 (68 RCTs) covered uterine and endometrial interventions, one covered antibiotics, and four (69 RCTs) addressed mixed approaches, including laboratory interventions. AMSTAR 2 appraised 41 (88%) SRs as critically low or low, and 6 (12%) as moderate or high in quality. The SRs often had a level of overlap of RCTs (median 33.3%), inconsistent definitions of RIF, and varied comparisons for the interventions. Considering the significant meta-analytic evidence of high-moderate GRADE strength: Granulocyte colony-stimulating factor (G-CSF) showed improvement in CPR in 9/13 (69.2%) MAs and LBR in 1/7 (14%); intralipid infusion showed improvement in CPR in 4/6 (57.14%) MAs and LBR in 3/4 (75%); peripheral blood mononuclear cells (PBMC) showed improvement in CPR in 4/8 (50%) MAs and LBR 3/5 (60%); platelet-rich plasma (PRP) intervention showed improvement in CPR in 6/10 (60%) MAs and LBR in 1/5 (20%); human chorionic gonadotropins showed improvement in CPR in 3/3 (100%) MAs; growth hormone showed improvement in CPR in 1/1 (100%) MA; low molecular weight heparin showed improvement in CPR in 1/1 (100%) MAs and LBR in 1/2 (50%); hysteroscopy showed improvement in CPR in 1/2 (50%) MAs; and, intentional endometrial injury showed improvement in CPR in 3/4 (75%) MAs and LBR in 2/3 (66.66%). [CONCLUSIONS] Evidence syntheses of RCTs evaluating interventions for RIF suggest a consistent direction, with high to moderate strength, indicating that immunomodulatory treatments, including G-CSF, PBMC, PRP, intralipid infusion, and intentional endometrial injury are likely to be effective. However, this conclusion should be interpreted with caution due to the generally low methodological quality of the included studies and the clinical heterogeneity observed in most SRs.
Human Fertilisation and Embryology Authority, 2024·
# Family formations in fertility treatment 2022
Preliminary UK family type statistics for IVF and DI treatment, storage, and donation
Published: November 2024
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/zpjlvhnd/family-formations-in-fertility-treatment-2022-underlying-dataset.xlsx "Download the underlying dataset for the ‘Family formations in fertility treatment 2022’ report")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#main-points)
- [Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#introduction)
- [Section 1: The proportion of female same-sex couples and single patients having fertility treatment has changed](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-1)
- [Section 2: IVF birth rates highest among female same-sex couples](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-2)
- [Section 3: Single patients are starting IVF younger than previous years](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-3)
- [Section 4: Patient population changes between those storing eggs and thawing them](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-4)
- [Section 5: Average IVF multiple birth rate decreased across all family types](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-5)
- [Section 6: Female same-sex couples and single patients had the lowest levels of NHS funding](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-6)
- [Section 7: Up to two-thirds o...
Human Fertilisation and Embryology Authority, 2024·
# State of the fertility sector 2023/24
Annual publication on HFEA licensed clinics
(1st April 2023 – 31st March 2024)
Published: 1st October 2024
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/cjwjns5j/state-of-the-fertility-sector-2023-2024-underlying-dataset.xlsx "State of the fertility sector 2023-2024 - underlying dataset")
## Table of contents
- [How we regulate](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#how-we-regulate)
- [1\. Inspections in 2023/24](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-1)
- [2\. There were 226 non-compliances identified at inspection in 2023/24](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-2)
- [3\. In 2023/24, 135 clinics were licensed by the HFEA to provide fertility treatment, storage and/or research](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-3)
- [4\. Total incidents reduced by 8% compared to the previous financial year](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-4)
- [5\. Fewer Ovarian hyperstimulation syndrome (OHSS) incidents were reported in 2023/24](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-5)
- [6\. Patient complaints in 2023/24 were consistent with the previous financial year](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-6)
- [About our data](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#about-our-data)
## How we regulate
The Human Fertilisation and Embryology Authority (HFEA) is the independent regulator of fertility treatment and human embryo research in the United Ki...
Awareness of the age-related decline in fertility potential has increased the popularity of planned oocyte cryopreservation (POC). However, data regarding outcomes of POC, including rates of women returning to thaw oocytes, as well as pregnancy and live birth rates, are scarce and based mostly on small case series. POC was defined as cryopreservation exclusively for prevention of future age-related fertility loss. The primary outcome was live birth rate per patient. The secondary outcomes included the return to thaw rate and laboratory outcomes. A meta-regression analysis examining the association between live birth and age above 40 or below 35 was conducted. We conducted a systematic database search from inception to August 2022. The search included PubMed (MEDLINE) and EMBASE. Our search strategies employed a combination of index terms (Mesh) and free text words to compile relevant concepts. The systematic review and meta-regression were undertaken following registration of systematic review (PROSPERO registration number CRD42022361791) and were reported following guidelines of Preferred Reporting Items for Systematic Review and Meta-Analyses 2020 (PRISMA 2020). The database search yielded 3847 records. After the selection process, 10 studies, conducted from 1999 to 2020, were included. Overall, 8750 women underwent POC, with a mean cryopreservation age of 37.2 (±0.8). Of those, 1517 women returned to use their oocytes with a return rate of 11.1% (± 4.7%). The mean age at the time of cryopreservation for women who returned to use their oocytes was 38.1 (±0.4), with an average of 12.6 (±3.6) cryopreserved oocytes per woman. In a meta-analysis, the oocyte survival rate was 78.5% with a 95% CI of 0.74-0.83 (I2 = 93%). The live birth rate per patient was 28% with a 95% CI of 0.24-0.33 (I2 = 92%). Overall, 447 live births were reported. In a sub-group analysis, women who underwent cryopreservation at age ≥40 achieved a live birth rate per patient of 19% (95% CI 0.13-0.29, I2 = 6%), while women aged ≤35 years old or younger had a higher live birth rate per patient of 52% (95% CI 0.41-0.63, I2 = 7%).
Freezing and Storage · Embryo Freezing and Storage
Many cancer treatments pose a threat to fertility for patients. Semen cryopreservation before cancer treatment is an effective method to preserve fertility. There are sparse long-term data on the usage of samples from Canadian oncology sperm banks. A retrospective chart review of all oncology sperm banking samples at a Canadian academic fertility centre from 2001 to 2020 was conducted. From 2001 to 2020, 4521 samples were banked by 2504 patients. The most frequent diagnoses among these patients were testicular cancer (29.5%) and lymphoma (26.9%). Of these patients, only 81 (3.2%) patients returned to use their samples with intrauterine insemination (IUI) or in vitro fertilisation (IVF) treatment and 62 (2.5%) patients transferred their samples to another clinic. The time between banking and return for usage of the sperm ranged from 1 to 131 months with a median of 18 months after banking. A total of 66 IVF cycles (104 embryo transfers) and 101 IUI cycles from 67 patients were reviewed. Of the 67 couples who used their samples, 53.7% achieved a clinical pregnancy. The clinical pregnancy rate was 6.6% per cycle for IUI and 30.8% per embryo transfer for IVF. Higher sperm concentration or total motile count was not associated with a higher chance of pregnancy. Patients who conceived had on average 1.9 ± 0.8 (p=0.02) more usable embryos per cycle than those who did not conceive. Sperm cryopreservation provides a valuable option for patients with cancer to achieve parenthood after potentially gonadotoxic cancer treatment. However, the overall usage of banked oncology sperm samples is very low.
In vitro maturation (IVM) of oocytes represents an assisted reproductive technique that involves the minimal or absence of ovarian stimulation and is beneficial to specific groups of patients. It is based on the collection of immature cumulus-oocyte complexes (COCs) from antral follicles, which are cultured in vitro until they reach the metaphase II (MII) stage. Once maturation is completed, IVM oocytes are normally fertilized, as during a conventional IVF protocol. On the other hand, ovarian rejuvenation through the intraovarian platelet-rich plasma (PRP) injection represents an innovative procedure intended to restore ovarian fertility and development, and it is used to enhance ovarian stimulation outcomes. Here, we report a case of a 47-year-old woman who underwent an assisted reproductive technology cycle (ART) with PRP injection and IVM, which resulted in a successful pregnancy.
Human Fertilisation and Embryology Authority, 2024·
# Fertility treatment 2022: preliminary trends and figures
Preliminary UK statistics for IVF and DI treatment, storage, and donation
Published: July 2024
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/5jfpm1cw/fertility-treatment-2022-preliminary-trends-and-figures-underlying-dataset.xlsx "Fertility treatment 2022: preliminary trends and figures - underlying dataset")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#main-points)
- [Note on preliminary data](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#note-on-preliminary-data)
- [Section 1: Average IVF pregnancy rate using fresh embryo transfers increased](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#section-1)
- [Section 2: Average IVF pregnancy and birth rates using frozen embryo transfers similar to previous years](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#section-2)
- [Section 3: Average age at first IVF treatment increased above 35 years of age for first time](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#section-3)
- [Section 4: New egg and sperm donors increased by 21% from 2019 to 2022](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#section-4)
- [Section 5: Egg storage fastest growing treatment, but accounted for 5% of all cycles in 2022](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#section-5)
- [Section 6: Multiple births from IVF at lowest UK average yet of 4%](https://www.hfea.gov.uk/about-us/publications/research-and-data/fe...
Yamada R et al., 2024·Journal of internal medicine·
Open Access
Cardiovascular disease is a major cause of maternal mortality, but the extent to which infertility treatment is implicated in heart disease remains unclear. To evaluate the association between infertility treatment and postpartum heart disease. We designed a retrospective cohort study of patients who delivered in the United States between 2010 and 2018. The primary outcome was hospitalization within 12-month post-delivery due to heart disease (including ischemic heart disease, atherosclerotic heart disease, cardiomyopathy, hypertensive disease, heart failure, and cardiac dysrhythmias). We estimated the rate difference (RD) of hospitalizations among patients who conceived with infertility treatment and those who conceived spontaneously. Associations were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs), derived from Cox proportional hazards regression after adjustment for potential confounders. Infertility treatment was recorded in 0.9% (n = 287,813) of 31,339,991 deliveries. Rates of heart disease hospitalizations with infertility treatment and with spontaneous conception were 550 and 355 per 100,000, respectively (RD 195, 95% CI: 143-247; adjusted HR 1.99, 95% CI: 1.80-2.20). The most important increase in risk was observed for hypertensive disease (adjusted HR 2.16, 95% CI: 1.92-2.42). This increased risk was apparent as early as 30-day post-delivery (HR 1.61, 95% CI: 1.39-1.86), with progressively increasing risk up to a year. Although the absolute risk of postpartum heart disease hospitalization is low, infertility treatment is associated with an increased risk, especially for hypertensive disease. These findings highlight the importance of timely postpartum follow-ups in patients who received infertility treatment.
Vaidakis D et al., 2024·The Cochrane database of systematic reviews·
Open Access
Autologous platelet-rich plasma (PRP) consists of plasma and a concentrate of platelets extracted from fresh whole blood of the person being treated. Research has suggested that intrauterine or intraovarian infusion/injection of PRP before embryo transfer may improve endometrial receptivity and response to ovarian stimulation in women undergoing assisted reproduction. We compared these interventions to standard treatment, placebo, or other interventions (mechanical or pharmacological). To assess the effectiveness and safety of intrauterine and intraovarian infusion/injection of platelet-rich plasma in infertile women undergoing assisted reproductive technology cycles. We searched the Cochrane Gynaecology and Fertility Group's Specialised Register, CENTRAL, MEDLINE, Embase, and the Epistemonikos database in January 2023. We also searched the reference lists of relevant articles and contacted the trial authors and experts in the field for any additional trials. We included randomized controlled trials (RCTs) that evaluated the application of PRP in the uterine cavity, ovaries, or both versus no intervention, placebo, or any other intervention (either mechanical or pharmacological) in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles. We included 12 parallel-group RCTs that recruited a total of 1069 women. We identified three different comparison groups. Using GRADE, we assessed the certainty of evidence as very low for almost all outcomes. [Abridged for length: the two intrauterine PRP comparisons (nine RCTs versus no intervention or placebo; two RCTs versus intrauterine G-CSF) are omitted here; all were very low-certainty evidence. Full abstract at PubMed.] Intraovarian injection of platelet-rich plasma versus no intervention One RCT evaluated PRP injection into both ovaries versus no intervention; it was judged at high risk of bias for the two outcomes it reported. We are uncertain about the effect of intraovarian PRP injection compared with no intervention on ongoing pregnancy (OR 1.09, 95% CI 0.33 to 3.63; 73 women; very low-certainty evidence) and clinical pregnancy (OR 0.90, 95% CI 0.31 to 2.60; 73 women; very low-certainty evidence). The study examined no safety outcomes. AUTHORS' We are uncertain about the effect of intrauterine or intraovarian administration of PRP on outcomes of assisted reproduction technology in infertile women. The pooled results should be interpreted with caution. Only one of the 12 included studies was judged at low risk of bias. Other limitations of the included trials were failure to report live birth, poor reporting of methods, lack of prospective protocol registration, low precision due to the small number of enrolled participants, indirectness due to the specific subpopulations and settings studied, and insufficient or absent safety data.
To determine the association between fertility treatment, socioeconomic status (SES), and neonatal and post-neonatal mortality. Retrospective cohort study of all births (19,350,344) and infant deaths from 2014-2018 in the United States. The exposure was mode of conception-spontaneous vs fertility treatment. The outcome was neonatal (<28d), and post-neonatal (28d-1y) mortality. Multivariable logistic models were stratified by SES. The fertility treatment group had statistically significantly higher odds of neonatal mortality (high SES OR 1.59; CI [1.5, 1.68], low SES OR 2.11; CI [1.79, 2.48]) and lower odds of post-neonatal mortality (high SES OR 0.87, CI [0.76, 0.996], low SES OR 0.6, CI [0.38, 0.95]). SES significantly modified the effect of ART/NIFT on neonatal and post-neonatal mortality. Fertility treatment is associated with higher neonatal and lower post-neonatal mortality and SES modifies this effect. Socioeconomic policies and support for vulnerable families may help reduce rates of infant mortality.
Kupka MS et al., 2024·Fertility and Sterility·
Open Access
To report utilization, effectiveness, and safety of assisted reproductive technologies in 2015 and 2016. A retrospective, cross-sectional survey of 3,103 assisted reproductive technology clinics in 74 countries in 2015 and 3,249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries. Seventy-nine countries and >3,000 assisted reproductive technology clinics. PATIENT(S): Patients undergoing assisted reproductive technology procedures. INTERVENTION(S): Assisted reproductive technology. MAIN OUTCOME MEASURE(S): Outcomes on country, regional, and global levels. RESULT(S): Reported for 2015: 2,358,239 cycles with 548,652 infants born; for 2016: 2,807,963 cycles with 647,188 infants born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 infants; in 2016, ≥3,100,448 cycles resulted in ≥723,026 infants. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous treatment cycles were aged ≥40 years. Frozen-thawed embryo transfer (ET) cycles accounted for 47.0% and 51.9%, respectively, of all ETs in 2015 and 2016. Oocyte donation cycles accounted for 6.7% and 7.1% of all ETs in 2015 and 2016. Intracytoplasmic sperm injection was performed in 57.7% and 56.4% of autologous aspiration cycles in 2015 and 2016, respectively. The cumulative delivery rate per aspiration cycle for fresh and frozen-thawed ET was 32.4% in 2015 and 33.1% in 2016, respectively. The average number of transferred embryos was 1.70 in 2015 and 1.69 in 2016. The proportion of single ETs in fresh autologous cycles increased from 42.1% in 2015 to 44.0% in 2016. The twin delivery rate decreased from 16.0% in 2015 to 14.7% in 2016, and the triplet rate decreased from 0.6% in 2015 to 0.4% in 2016. The proportion of single ETs in frozen-thawed ET autologous treatment cycles was 62.2% in 2015 and 64.2% in 2016, with twin and triplet rates of 10.1% and 0.3% in 2015 and 10.0% and 0.2% in 2016, respectively. CONCLUSION(S): Utilization of assisted reproductive technology treatment and births per cycle increased from 2015 to 2016, although multiple births were reduced. An increasing proportion of frozen-thawed ET cycles, continuing wide variation in use of intracytoplasmic sperm injection, and an increase in single ET rates are reported.
Japan Society of Obstetrics and Gynecology et al., 2024·Japan Society of Obstetrics and Gynecology
日本産科婦人科学会 体外受精・胚移植等の臨床実施成績 2023年. JSOG ART annual registry report for 2023 from the Japan Society of Obstetrics and Gynecology (JSOG) ART Online Registration Committee. Reports IVF, ICSI, and frozen-embryo-transfer (FET) cycle volumes; cycles performed, oocyte retrieval cycles, freeze-all cycles, transfer cycles, pregnancy cycles, and live births by year and treatment type. Mandatory professional-society reporting from all JSOG-registered ART facilities in Japan, the world's largest mandatory single-country ART registry by cycle volume.
Katagiri Y et al., 2024·Reprod Med Biol·
Open Access
Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2022, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG). Reports per-cycle outcomes including pregnancy rates, live birth rates, and cycle volumes from JSOG-registered ART facilities. JSOG ART registry is mandatory for member clinics and represents one of the world's largest ART registries by cycle volume.
Canadian Fertility and Andrology Society et al., 2024·Canadian Fertility and Andrology Society - CARTR Plus
CARTR Plus 2024 annual report covering Canadian ART activity for treatment cycles completed in 2023. Reports cycles performed, single-embryo transfer rates, clinical pregnancy and live-birth rates, ART-conceived births, and multiple-pregnancy rates from participating CFAS member ART centers.
Katagiri Y et al., 2024·Reprod Med Biol·
Open Access
Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2021, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG). Reports per-cycle outcomes from JSOG-registered ART facilities.
Agence de la biomédecine, 2024·Agence de la biomédecine - AMP Vigilance
Rapport annuel d'AMP Vigilance 2023 de l'Agence de la biomédecine. 2023 ART vigilance report from the French Agence de la biomédecine. AMP Vigilance is the mandatory adverse-event surveillance system covering serious adverse events and reactions related to assisted reproduction practice in France. Reports cycle counts, vigilance signals, and incident classifications across French ART centers.
DIR Jahrbuch 2023 des Deutschen IVF-Registers. 2023 Annual Report of the German IVF Registry (Deutsches IVF-Register, DIR). Reports German ART cycle counts, treatment indications, embryo-transfer outcomes, pregnancy and live-birth rates by treatment type and age strata.
**STUDY ** What are the data and trends on ART and IUI cycle numbers and their outcomes, and on fertility preservation (FP) interventions, reported in 2019 as compared to previous years? **SUMMARY ** The 23rd ESHRE report highlights the rising ART treatment cycles and children born, alongside a decline in twin deliveries owing to decreasing multiple embryo transfers; fresh IVF or ICSI cycles exhibited higher delivery rates, whereas frozen embryo transfers (FET) showed higher pregnancy rates (PRs), and reported IUI cycles decreased while maintaining stable outcomes. **WHAT ** ART aggregated data generated by national registries, clinics, or professional societies have been gathered and analyzed by the European IVF-Monitoring (EIM) Consortium since 1997 and reported in a total of 22 manuscripts published in *Human Reproduction* and *Human Reproduction Open*. **STUDY DESIGN, SIZE, ** Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE each year. The data on treatment cycles performed between 1 January and 31 December 2019 were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons in one of the 44 countries that are members of the EIM Consortium. **PARTICIPANTS/MATERIALS, SETTING, ** Overall, 1487 clinics offering ART services in 40 countries reported, for the second time, a total of more than 1 million (1 077 813) treatment cycles, including 160 782 with IVF, 427 980 with ICSI, 335 744 with FET, 64 089 with preimplantation genetic testing (PGT), 82 373 with egg donation (ED), 546 with IVM of oocytes, and 6299 cycles with frozen oocyte replacement (FOR). A total of 1169 institutions reported data on IUI cycles using either husband/partner's semen (IUI-H; n = 147 711) or donor semen (IUI-D; n = 51 651) in 33 and 24 countries, respectively. Eighteen countries reported 24 139 interventions in pre- and post-pubertal patients for FP, including oocyte, ovarian tissue, semen, and testicular tissue banking. **MAIN ** In 21 countries (21 in 2018) in which all ART clinics reported to the registry 476 760 treatment cycles were registered for a total population of approximately 300 million inhabitants, allowing the best estimate of a mean of 1581 cycles performed per million inhabitants (range: 437–3621). Among the reporting countries, for IVF the clinical PRs per aspiration slightly decreased while they remained similar per transfer compared to 2018 (21.8% and 34.6% versus 25.5% and 34.1%, respectively). In ICSI, the corresponding PRs showed similar trends compared to 2018 (20.2% and 33.5%, versus 22.5% and 32.1%) When freeze-all cycles were not considered for the calculations, the clinical PRs per aspiration were 28.5% (28.8% in 2018) and 26.2% (27.3% in 2018) for IVF and ICSI, respectively. After FET with embryos originating from own eggs, the PR per thawing was at 35.1% (versus 33.4% in 2018), and with embryos originating from donated eggs at 43.0% (41.8% in 2018). After ED, the PR per fresh embryo transfer was 50.5% (49.6% in 2018) and per FOR 44.8% (44.9% in 2018). In IVF and ICSI together, the trend toward the transfer of fewer embryos continues with the transfer of 1, 2, 3, and ≥4 embryos in 55.4%, 39.9%, 2.6%, and 0.2% of all treatments, respectively (corresponding to 50.7%, 45.1%, 3.9%, and 0.3% in 2018). This resulted in a reduced proportion of twin delivery rates (DRs) of 11.9% (12.4% in 2018) and a similar triplet DR of 0.3%. Treatments with FET in 2019 resulted in twin and triplet DR of 8.9% and 0.1%, respectively (versus 9.4% and 0.1% in 2018). After IUI, the DRs remained similar at 8.7% after IUI-H (8.8% in 2018) and at 12.1% after IUI-D (12.6% in 2018). Twin and triplet DRs after IUI-H were 8.7% and 0.4% (in 2018: 8.4% and 0.3%) and 6.2% and 0.2% after IUI-D (in 2018: 6.4% and 0.2%), respectively. Eighteen countries (16 in 2018) provided data on FP in a total number of 24 139 interventions (20 994 in 2018). Cryopreservation of ejaculated sperm (n = 11 592 versus n = 10 503 in 2018) and cryopreservation of oocytes (n = 10 784 versus n = 9123 in 2018) were most frequently reported. **LIMITATIONS, ** Caution with the interpretation of results should remain as data collection systems and completeness of reporting vary among European countries.
Human Fertilisation and Embryology Authority, 2023·
# State of the fertility sector 2022/23
Annual publication on HFEA licensed centres
(1st April 2022 – 31st March 2023)
Published: 12th September 2023
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/2znoxhqv/state-of-the-fertility-sector-2022-2023-underlying-dataset.xlsx "State of the fertility sector 2022-2023 - underlying dataset")
## Table of contents
- [About this report](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2022-2023/#about-this-report)
- [1\. There were 85 inspections undertaken in 2022/23](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2022-2023/#section-1)
- [2\. Critical non-compliances have decreased to 2%](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2022-2023/#section-2)
- [3\. In 2022/23, 107 clinics were licensed by the HFEA to provide fertility treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2022-2023/#section-3)
- [4\. No Grade A incidents since 2020/21, and severe/critical OHSS incidents remained consistent with previous years](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2022-2023/#section-4)
- [5\. Patient complaints decreased in 2022/23](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2022-2023/#section-5)
- [About our data](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2022-2023/#about-our-data)
## About this report
The Human Fertilisation and Embryology Authority (HFEA) is the independent regulator of fertility treatment and human embryo research in the United Kingdom (UK). We aim to ensure that everyone receives high quality care in a licenced fertility clinic. We do this by licensing, monitoring, and inspecting fertility clinics and research centres [i](https://www.hfea.go...
Stroke accounts for 7% of pregnancy-related deaths in the US. As the use of infertility treatment is increasing, many studies have sought to characterize the association of infertility treatment with the risk of stroke with mixed results. To evaluate the risk of hospitalization from hemorrhagic and ischemic strokes in patients who underwent infertility treatment. DESIGN, SETTING, This population-based, retrospective cohort study used data abstracted from the Nationwide Readmissions Database, which stores data from all-payer hospital inpatient stays from 28 states across the US, from 2010 and 2018. Eligible participants included individuals aged 15 to 54 who had a hospital delivery from January to November in a given calendar year, and any subsequent hospitalizations from January to December in the same calendar year of delivery during the study period. Statistical analysis was performed between November 2022 and April 2023. Hospital delivery after infertility treatment (ie, intrauterine insemination, assisted reproductive technology, fertility preservation procedures, or use of a gestational carrier) or after spontaneous conception. The primary outcome was hospitalization for nonfatal stroke (either ischemic or hemorrhagic stroke) within the first calendar year after delivery. Secondary outcomes included risk of stroke hospitalization at less than 30 days, less than 60 days, less than 90 days, and less than 180 days post partum. Cox proportional hazards regression models were used to estimate associations, which were expressed as hazard ratios (HRs), adjusted for confounders. Effect size estimates were corrected for biases due to exposure misclassification, selection, and unmeasured confounding through a probabilistic bias analysis. Of 31 339 991 patients, 287 813 (0.9%; median [IQR] age, 32.1 [28.5-35.8] years) underwent infertility treatment and 31 052 178 (99.1%; median [IQR] age, 27.7 [23.1-32.0] years) delivered after spontaneous conception. The rate of stroke hospitalization within 12 months of delivery was 37 hospitalizations per 100 000 people (105 patients) among those who received infertility treatment and 29 hospitalizations per 100 000 people (9027 patients) among those who delivered after spontaneous conception (rate difference, 8 hospitalizations per 100 000 people; 95% CI, -6 to 21 hospitalizations per 100 000 people; HR, 1.66; 95% CI, 1.17 to 2.35). The risk of hospitalization for hemorrhagic stroke (adjusted HR, 2.02; 95% CI, 1.13 to 3.61) was greater than that for ischemic stroke (adjusted HR, 1.55; 95% CI, 1.01 to 2.39). The risk of stroke hospitalization increased as the time between delivery and hospitalization for stroke increased, particularly for hemorrhagic strokes. In general, these associations became larger for hemorrhagic stroke and smaller for ischemic stroke following correction for biases. In this cohort study, infertility treatment was associated with an increased risk of stroke-related hospitalization within 12 months of delivery; this risk was evident as early as 30 days after delivery. Timely follow-up in the immediate days post partum and continued long-term follow-up should be considered to mitigate stroke risk.
Outcomes and Effectiveness · Outcomes by Diagnosis
Endometriosis is a common finding among women with infertility, and women who are diagnosed with endometriosis are almost twice as likely to experience infertility. Mechanisms by which endometriosis causes infertility remain poorly understood. In this review, we evaluate the current literature on the impact of endometriosis on oocyte and embryo quality. The presence of endometriosis evidently reduces ovarian reserve, oocyte quality, and embryo quality; however, this does not appear to translate to a clear clinical impact. Analysis of data from large assisted reproduction technology registries has shown that women with endometriosis have a lower oocyte yield but no reduction in reproductive outcomes. There is a need for future studies in the form of well-designed randomized controlled trials to further evaluate the role of surgical and medical treatment options in women with endometriosis undergoing assisted conception.
Human Fertilisation and Embryology Authority, 2023·
# Fertility treatment 2021: preliminary trends and figures
Preliminary UK statistics for IVF and DI treatment, storage, and donation
Published: June 2023
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/5zzh25zw/fertility-treatment-2021-preliminary-trends-and-figures-underlying-dataset.xlsx "Fertility treatment 2021: preliminary trends and figures - underlying dataset")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#main-points)
- [Note on preliminary data](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#note-on-preliminary-data)
- [Section 1. Average IVF pregnancy rates using fresh embryo transfers increased for all ages](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#section-1)
- [Section 2. Average IVF pregnancy and birth rates using frozen embryo transfers increased over the past 30 years](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#section-2)
- [Section 3. Fertility treatments have returned to pre-pandemic levels](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#section-3)
- [Section 4. Multiple births from IVF at lowest UK average yet of 5%](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#section-4)
- [Section 5. Egg and embryo storage cycles continued to increase](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#section-5)
- [Section 6. Average age of IVF patients increased to 36 years](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-a...
H Petersen S et al., 2023·Hypertension (Dallas, Tex. : 1979)
Frozen embryo transfer (frozen-ET) is increasingly common because of improved cryopreservation methods and elective freezing of all embryos. Frozen-ET is associated with higher risk of hypertensive disorders in pregnancy than both natural conception and fresh embryo transfer (fresh-ET), but whether this is attributable to parental factors or treatment is unknown. Using the Medical Birth Registries of Denmark (1994-2014), Norway, and Sweden (1988-2015), linked to data from national quality registries and databases on assisted reproduction, we designed a population-based cohort study with within-sibship comparison. We included 4 426 691 naturally conceived, 78 300 fresh-ET, and 18 037 frozen-ET singleton pregnancies, of which 33 209 sibships were conceived using different conception methods. Adjusted odds ratios (aOR) of hypertensive disorders in pregnancy for fresh-ET and frozen-ET versus natural conception with 95% CI were estimated using multilevel logistic regression, where random effects provided conventional population-level estimates and fixed effects gave within-sibship estimates. Main models included adjustment for birth year, maternal age, parity, and country. Risk of hypertensive disorders in pregnancy was higher after frozen-ET compared to natural conception, both at population-level (7.4% versus 4.3%, aOR, 1.74 [95% CI, 1.61-1.89]) and within sibships (aOR, 2.02 [95% CI, 1.72-2.39]). For fresh-ET, risk was similar to natural conception, both at population-level (aOR, 1.02 [95% CI, 0.98-1.07]) and within sibships (aOR, 0.99 [95% CI, 0.89-1.09]). Frozen-ET was associated with substantially higher risk of hypertensive disorders in pregnancy, even after accounting for shared parental factors within sibships.
Japan Society of Obstetrics and Gynecology et al., 2023·Japan Society of Obstetrics and Gynecology
日本産科婦人科学会 体外受精・胚移植等の臨床実施成績 2022年. JSOG ART annual registry report for 2022 from the Japan Society of Obstetrics and Gynecology. Reports IVF, ICSI, and frozen-embryo-transfer cycle volumes and outcomes. Mandatory professional-society reporting from all JSOG-registered ART facilities in Japan.
Registries and Reporting · Cross-Registry Comparison
Zegers-Hochschild F et al., 2023·JBRA Assisted Reproduction
REDLARA (Red Latinoamericana de Reproduccion Asistida) annual registry report for treatment year 2021. REDLARA is a voluntary multi-country aggregation of ART centres across 16 Latin American nations, covering approximately 75% of regional ART cycles. Reports IVF, ICSI, frozen embryo transfer, oocyte donation, and intrauterine insemination outcomes. From 2010 onward most annual reports were published as papers in JBRA Assisted Reproduction. Earlier reports (1990s and 2000s) were standalone Spanish-language print/PDF registry documents. Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Human Fertilisation and Embryology Authority, 2023·
# Ethnic diversity in fertility treatment 2021
Preliminary UK ethnicity statistics for IVF and DI treatment, storage, and donation
Published: December 2023
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/5rgnpqsr/ethnic-diversity-in-fertility-treatment-2021-underlying-dataset.xlsx "Ethnic diversity in fertility treatment 2021 - underlying dataset")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#main-points)
- [Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#introduction)
- [Note on preliminary and ethnicity data](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#note-on-preliminary-and-ethnicity-data)
- [Section 1. IVF birth rates increased across all ethnic groups, though disparities remain](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#section-1)
- [Section 2. Black patients started fertility treatment later than other ethnic groups](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#section-2)
- [Section 3. DI predominantly used by White patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#section-3)
- [Section 4. Imported donor sperm and eggs vary by ethnicity](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#section-4)
- [Section 5. Multiple birth rate decreased in all ethnic groups, but remain highest for Black patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#section-5)
- [Section 6. Use of egg storage was similar across all ethnic groups](https://www.hfea.gov.uk/about-us/publications/res...
Katagiri Y et al., 2023·Reprod Med Biol·
Open Access
Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2020, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG).
Agence de la biomédecine, 2023·Agence de la biomédecine - AMP Vigilance
Rapport annuel d'AMP Vigilance 2022 de l'Agence de la biomédecine. 2022 ART adverse-event surveillance report from the French Agence de la biomédecine, covering serious adverse events and reactions in assisted reproduction during 2022.
Tire B et al., 2023·Journal of ovarian research·
Open Access
Telomeres are repetitive DNA sequences at eukaryotic chromosome ends and function in maintaining genome integrity and stability. These unique structures undergo shortening due to various factors including biological aging, consecutive DNA replication, oxidative stress, and genotoxic agents. Shortened telomeres can be lengthened by the enzyme telomerase and alternative lengthening of telomeres in germ cells, early embryos, stem cells, and activated lymphocytes. If telomeres reach to critical length, it may lead to genomic instability, chromosome segregation defects, aneuploidy, and apoptosis. These phenotypes also occur in the oocytes and early embryos, produced using assisted reproductive technologies (ARTs). Thus, a number of studies have examined the potential effects of ART applications such as ovarian stimulation, culture conditions, and cryopreservation procedures on telomeres. Herein, we comprehensively reviewed impacts of these applications on telomere length and telomerase activity in ART-derived oocytes and embryos. Further, we discussed use of these parameters in ART centers as a biomarker in determining oocyte and embryo quality.
Canadian Fertility and Andrology Society et al., 2023·Canadian Fertility and Andrology Society - CARTR Plus
CARTR Plus 2023 plenary slides presenting 2022 Canadian ART cycle data. Single-embryo transfer rates, clinical pregnancy and live-birth rates, ART-conceived births, and multiple-pregnancy rates by participating Canadian ART clinic.
DIR Jahrbuch 2022 Sonderausgabe für Paare des Deutschen IVF-Registers. 2022 patient-facing edition of the German IVF Registry annual report. Translates clinical-registry data into accessible information for couples considering or undergoing ART in Germany, including success-rate context and treatment options.
DIR Jahrbuch 2022 des Deutschen IVF-Registers. 2022 Annual Report of the German IVF Registry covering German ART cycle counts, treatment indications, embryo-transfer outcomes, and pregnancy/live-birth rates.
Hart RJ et al., 2022·Front Reprod Health·
Open Access
It is well established that there are increased pregnancy-related complications for a woman who conceives through assisted reproductive treatment (ART). Furthermore, it is known that the risk to the child born is greater, believed to be related to prematurity and growth restriction. Studies have also reported epigenetic changes in the DNA of offspring conceived through ART. In addition, it is believed that they have a greater risk of congenital malformations, although some of these risks may relate to underlying infertility, rather than the ART treatment per se. As a result, it may be expected that there is a greater risk to the longer-term health of the child who is born from ART; however, evidence about the long-term health of children conceived through ART is reassuring. Even though, it is recognised that many of the studies in this field come with limitations. Low numbers of participants is one of the major limitations, which makes subgroup analyses for diverse types of ART, or diverse types of infertility, not feasible. Furthermore, studies are often limited by short follow-up periods because of the difficulty and costs involved in longitudinal study designs. In addition, the rapid changes over time in ART limit the generalisability and significance of long-term findings. Well-designed studies investigating the long-term health outcomes of ART-conceived offspring and the potential influences of various aspects of the ART procedure, as well as studies of the potential underlying epigenetic mechanisms, are imperative. Furthermore, conclusions from childhood hospitalisation data from the United Kingdom, the long-term follow-up and quality of life study from researchers in Melbourne, and the data published from the Western Australian Growing Up Healthy Study will go a long way to help reassure current and prospective parents who may require ART to conceive.
Human Fertilisation and Embryology Authority, 2022·
# State of the fertility sector 2021/22
Annual publication on HFEA licensed clinics
Published: October 2022
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/lxkhzo04/state-of-the-fertility-sector-2021-2022-underlying-data.xlsx "State of the Fertility Sector 2021 - 2022 - underlying data")
## Table of contents
- [About this report](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-1)
- [1\. Changes to interim inspection themes](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-2)
- [2\. There were 105 inspections undertaken in 2021/22](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-3)
- [3\. In 2021/22, 104 clinics were licensed by the HFEA to provide fertility treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-4)
- [4\. No Grade A incidents since 2020/21, and severe OHSS remained consistent with previous years](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-5)
- [5\. Patient complaints decreased in 2021/22](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#section-6)
- [About our data](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2021-2022/#about-our-data)
## About this report
The Human Fertilisation and Embryology Authority (HFEA) is the independent regulator of fertility treatment and human embryo research in the United Kingdom (UK). We aim to ensure that everyone receives high quality care in a licenced fertility clinic. We do this by licensing, monitoring, and inspecting fertility clinics and providing free, clear and impartial information about fertility treatment, clinics, and egg, sperm, and embryo donation.
...
The aim was to investigate whether children born after assisted reproduction technology (ART), particularly after frozen-thawed embryo transfer (FET), are at higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. We performed a registry-based cohort study using data from the 4 Nordic countries: Denmark, Finland, Norway, and Sweden. The study included 7,944,248 children, out of whom 171,774 children were born after use of ART (2.2%) and 7,772,474 children were born after spontaneous conception, representing all children born between the years 1994 to 2014 in Denmark, 1990 to 2014 in Finland, 1984 to 2015 in Norway, and 1985 to 2015 in Sweden. Rates for any cancer and specific cancer groups in children born after each conception method were determined by cross-linking national ART registry data with national cancer and health data registries and population registries. We used Cox proportional hazards models to estimate the risk of any cancer, with age as the time scale. After a mean follow-up of 9.9 and 12.5 years, the incidence rate (IR) of cancer before age 18 years was 19.3/100,000 person-years for children born after ART (329 cases) and 16.7/100,000 person-years for children born after spontaneous conception (16,184 cases). Adjusted hazard ratio (aHR) was 1.08, 95% confidence interval (CI) 0.96 to 1.21, p = 0.18. Adjustment was performed for sex, plurality, year of birth, country of birth, maternal age at birth, and parity. Children born after FET had a higher risk of cancer (48 cases; IR 30.1/100,000 person-years) compared to both fresh embryo transfer (IR 18.8/100,000 person-years), aHR 1.59, 95% CI 1.15 to 2.20, p = 0.005, and spontaneous conception, aHR 1.65, 95% CI 1.24 to 2.19, p = 0.001. Adjustment either for macrosomia, birth weight, or major birth defects attenuated the association marginally. Higher risks of epithelial tumors and melanoma after any assisted reproductive method and of leukemia after FET were observed. The main limitation of this study is the small number of children with cancer in the FET group. Children born after FET had a higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. The results should be interpreted cautiously based on the small number of children with cancer, but the findings raise concerns considering the increasing use of FET, in particular freeze-all strategies without clear medical indications. ISRCTN 11780826.
Outcomes and Effectiveness · Outcomes by Diagnosis
Restorative reproductive medicine represents a comprehensive approach to subfertility (infertility and miscarriage) with investigations, diagnoses, and treatments combined with fertility charting to restore optimal reproductive function. Restorative reproductive medicine assumes that multiple factors need to be identified and treated (cycle optimization) for up to 12 cycles to achieve a successful pregnancy. Conception can occur during normal intercourse without intrauterine insemination or in vitro fertilization. A 35-year-old Croatian female presented for fertility treatment in May 2019 with a previous diagnosis of polycystic ovaries, infertility of 16 years duration, and 8 unsuccessful embryo transfers with in vitro fertilization and intracytoplasmic sperm injection. She was gravida 3 para 0, with 2 miscarriages after spontaneous conception at 5-6 weeks gestation in 2002 and 2004, followed by a miscarriage after in vitro fertilization at 12 weeks gestation in 2011. We initially found poor follicle function and suboptimal progesterone levels. Restorative reproductive medicine treatment resulted in conception after two cycles of treatment. This pregnancy ended in miscarriage at 7 weeks 4 days. Additional investigations found a balanced Robertsonian translocation (13, 14) and a uterine septum. We achieved repeat fertilization with restorative reproductive medicine after three cycles of treatment following resection of the uterine septum and ovulation induction with letrozole and human chorionic gonadotrophin. She had a full-term healthy pregnancy and live birth in 2021. We propose that a full evaluation of underlying factors, and up to 12 cycles of cycle optimization, should be offered to subfertile patients before considering in vitro fertilization treatment.
Sanders JN et al., 2022·Reprod Health·
Open Access
In vitro fertilization (IVF) births contribute to a considerable proportion of preterm birth (PTB) each year. However, there is no formal surveillance of adverse perinatal outcomes for less invasive fertility treatments. The study objective was to describe associations between fertility treatment (in vitro fertilization, intrauterine insemination, usually with ovulation drugs (IUI), or ovulation drugs alone) and preterm birth, compared to no treatment in subfertile women. The Fertility Experiences Study (FES) is a retrospective cohort study conducted at the University of Utah between April 2010 and September 2012. Women with a history of primary subfertility self-reported treatment data via survey and interviews. Participant data were linked to birth certificates and fetal death records to asses for perinatal outcomes, particularly preterm birth. A total 487 birth certificates and 3 fetal death records were linked as first births for study participants who completed questionnaires. Among linked births, 19% had a PTB. After adjustment for maternal age, paternal age, maternal education, annual income, religious affiliation, female or male fertility diagnosis, and duration of subfertility, the odds ratios and 95% confidence intervals (CI) for PTB were 2.17 (CI 0.99, 4.75) for births conceived using ovulation drugs, 3.17 (CI 1.4, 7.19) for neonates conceived using IUI and 4.24 (CI 2.05, 8.77) for neonates conceived by IVF, compared to women with subfertility who used no treatment during the month of conception. A reported diagnosis of female factor infertility increased the adjusted odds of having a PTB 2.99 (CI 1.5, 5.97). Duration of pregnancy attempt was not independently associated with PTB. In restricting analyses to singleton gestation, odds ratios were not significant for any type of treatment. IVF, IUI, and ovulation drugs were all associated with a higher incidence of preterm birth and low birth weight, predominantly related to multiple gestation births.
Cakiroglu Y et al., 2022·Aging (Albany NY)·
Open Access
The aim of the current study was to characterize ovarian reserve parameters and IVF outcomes in women with a history of poor ovarian response (POR) treated with intraovarian injection of autologous platelet rich plasma (PRP). Reproductive age women (N=510; age range 30-45yo) diagnosed with POR based on Poseidon criteria were included in the study. PRP treatment resulted in higher AFC, higher serum AMH, lower serum FSH, and a higher number of mature oocytes and cleavage and blastocyst stage embryos. After PRP injection, 22 women (4.3%) conceived spontaneously, 14 (2.7%) were lost to follow up, and 474 (92.9%) attempted IVF. Among women who attempted IVF, 312 (65.8%) generated embryos and underwent embryo transfer, 83 (17.5%) achieved a pregnancy, and 54 (11.4%) achieved sustained implantation/live birth (SI/LB). In total, of the 510 women with POR and mean age of 40.3, PRP resulted in improvement of ovarian reserve parameters, a pregnancy rate of 20.5% and SI/LB rate of 12.9%. Our findings suggest that PRP treatment may be considered in women with POR. For wider clinical application, its clinical efficacy will need to be demonstrated in prospective randomized clinical trials.
Sunderam S et al., 2022·MMWR Surveillance Summaries
Since the first US infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to have multiple births because multiple embryos might be transferred. Multiple births can pose substantial risks for both mothers and infants, including obstetric complications, preterm birth, and low birthweight. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2018 and compares birth outcomes that occurred in 2018 (resulting from ART procedures performed in 2017 and 2018) with outcomes for all infants born in the United States in 2018. 2018. In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from the 50 US states, the District of Columbia, and Puerto Rico. In 2018, a total of 203,119 ART procedures (range: 196 in Alaska to 26,028 in California) were performed in 456 US fertility clinics and reported to CDC. These procedures resulted in 73,831 live-birth deliveries (range: 76 in Puerto Rico and Wyoming to 9,666 in California) and 81,478 infants born (range: 84 in Wyoming to 10,620 in California). Nationally, among women aged 15-44 years, the rate of ART procedures performed was 3,135 per 1 million women.
Human Fertilisation and Embryology Authority, 2022·
# National Patient Survey 2021
Survey of UK fertility patients, 2 November – 7 December 2021
Published: April 2022
The key findings are published on this page with a statistical appendix available for download. A separate [Quality & Methodology report](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/patient-survey-2021-quality-and-methodology-report) provides details on survey methodology and patient profile.
[Download the underlying dataset as Excel Worksheet](https://www.hfea.gov.uk/media/lqwnb4lp/2022-04-07-national-patient-survey-underlying-data.xlsx "National Patient Survey Underlying Data").
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#main-points)
- [1\. Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#introduction)
- [2\. Recent experience of fertility treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#recent-experience-of-fertility-treatment)
- [3\. Experience of speaking to a GP about fertility concerns](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#experience-of-speaking-to-a-gp-about-fertility-concerns)
- [4\. Multiple embryo transfers](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#multiple-embryo-transfers)
- [5\. Use of donor eggs, sperm, or embryos](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#use-of-donor-eggs-sperm-or-embryos)
- [6\. Treatment add-ons](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#treatment-add-ons)
- [7\. Knowledge of HFEA & Information/support sources](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2021/#knowledge-of-hfea-information-support-sources)
- [About ou...
Agence de la biomédecine, 2022·Agence de la biomédecine
Rapport annuel d'AMP Vigilance 2021 publié par l'Agence de la biomédecine. Annual AMP (Medically Assisted Reproduction) Vigilance Report 2021 from the French Agence de la biomédecine.
Japan Society of Obstetrics and Gynecology et al., 2022·Japan Society of Obstetrics and Gynecology
日本産科婦人科学会 体外受精・胚移植等の臨床実施成績 2021年. JSOG ART annual registry report for 2021 from the Japan Society of Obstetrics and Gynecology. Reports IVF, ICSI, and frozen-embryo-transfer cycle volumes and outcomes. Mandatory professional-society reporting from all JSOG-registered ART facilities in Japan.
Industry, Cost and Access · Money Flows and Financial Incentives
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2021. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Katagiri Y et al., 2022·Reprod Med Biol·
Open Access
Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2019, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG).
Human Fertilisation and Embryology Authority, 2022·
# Trends in egg, sperm and embryo donation 2020
Statistics on donation and donor treatments in the UK fertility sector
Published: November 2022
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/ycjb2gnm/trends-in-egg-sperm-and-embryo-donation-2020-underlying-dataset.xlsx "Trends in egg, sperm and embryo donation 2020 - underlying dataset")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#main-points)
- [Foreword](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#foreword)
- [Section 1. Use of donor eggs, sperm and embryos has increased](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-1)
- [Section 2. Donor registrations have increased, though access to donors of ethnic minority backgrounds varies](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-2)
- [Section 3. Treatments using donor eggs, sperm and embryos less commonly funded by NHS](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-3)
- [Section 4. Donor eggs can increase birth rates for older patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-4)
- [Section 5. From 2023, donor-conceived people will be able to access information on their donors](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-5)
- [Section 6. Characteristics of egg and sperm donors have changed over time](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sperm-and-embryo-donation-2020/#section-6)
- [About our data](https://www.hfea.gov.uk/about-us/publications/research-and-data/trends-in-egg-sp...
Chromosome imbalance (aneuploidy) is the major cause of pregnancy loss and congenital disorders in humans. Analyses of small biopsies from human embryos suggest that aneuploidy commonly originates during early divisions, resulting in mosaicism. However, the developmental potential of mosaic embryos remains unclear. We followed the distribution of aneuploid chromosomes across 73 unselected preimplantation embryos and 365 biopsies, sampled from four multifocal trophectoderm (TE) samples and the inner cell mass (ICM). When mosaicism impacted fewer than 50% of cells in one TE biopsy (low-medium mosaicism), only 1% of aneuploidies affected other portions of the embryo. A double-blinded prospective non-selection trial (NCT03673592) showed equivalent live-birth rates and miscarriage rates across 484 euploid, 282 low-grade mosaic, and 131 medium-grade mosaic embryos. No instances of mosaicism or uniparental disomy were detected in the ensuing pregnancies or newborns, and obstetrical and neonatal outcomes were similar between the study groups. Thus, low-medium mosaicism in the trophectoderm mostly arises after TE and ICM differentiation, and such embryos have equivalent developmental potential as fully euploid ones.
Human Fertilisation and Embryology Authority, 2021·
# State of the fertility sector 2020/21
**Annual publication on HFEA licensed clinics**
Published: November 2021
[**Download the underlying dataset as .xlsx**](https://www.hfea.gov.uk/media/5czb4k2o/2024-02-26-state-of-the-sector-underlying-data.xlsx "State of the Sector 2020/21 underlying dataset").
## Table of contents
- [About this report](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#about-this-report)
- [HFEA regulatory response to COVID-19](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#hfea-regulatory-response-to-covid-19)
- [Maintaining regulatory oversight](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#maintaining-regulatory-oversight)
- [There were 77 inspections undertaken in 2020/21, taking a hybrid inspection approach](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#there-were-77-inspections-undertaken-in-2020-21-taking-a-hybrid-inspection-approach)
- [In 2020/21, 103 clinics were licensed by the HFEA to provide fertility treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#in-2020-21-103-clinics-were-licensed-by-the-hfea-to-provide-fertility-treatment)
- [The number of incidents in 2020/21 is broadly consistent with previous years](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#the-number-of-incidents-in-2020-21-is-broadly-consistent-with-previous-years)
- [The number of severe incidents of OHSS reported declined in 2020/21](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2020-2021/#the-number-of-severe-incidents-of-ohss-reported-declined-in-2020-21)
- [A total of 88 patient complaints were received about licensed clinics in 2...
Couple infertility is a pathology with an absolute number of cases growing markedly over the last decade in connection mainly with the increased age of couples wishing to conceive. Platelet-rich plasma (PRP) is an alternative treatment used for several years for experimental purposes. Yet, this method is not yet defined as a standard therapeutic option in the infertility protocol for poor responders in assisted human reproduction procedures. Thus, the present study is a retrospective study conducted between February 2019 and February 2020 to evaluate the effect of ovarian PRP injection in patients with a poor ovarian response (POR) to ovarian stimulation. Women (n=20; age 31-44 years) diagnosed with POR based on the European Society of Human Reproduction and Embryology criteria underwent ovarian injection with autologous PRP injection. Markers of ovarian reserve before, during the following two menstrual cycles, and at six months after treatment were followed as well as stimulation and fertilisation parameters before and post-treatment. PRP treatment resulted in increased antral follicle count and serum anti-Mullerian hormone, while levels of serum follicle-stimulating hormone and luteinising hormone were decreased. These changes were more pronounced during the 2nd menstrual cycle following treatment. By six months following the injection, their values return to pre-treatment levels and any small differences were not considered statistically significant. The average dose of gonadotropin used and duration remained statistically unchanged, but a significant increase in estradiol achieved by the day of the human chorionic gonadotropin trigger day was achieved. The cancellation rate decreased following PRP treatment while the number of collected oocytes, number of oocytes in metaphase II rose. The number of embryos (of A and B quality) resulting also increased but fell short of the significance level set (α=0.073). Following the PRP injection, two singleton pregnancies were achieved, resulting in live births at term without complications during pregnancy. Another pregnancy was achieved spontaneously 45 months following the PRP and a failed assisted human reproduction procedure. Although the group included a small number of women, the results indicate the potential benefits of an ovarian autologous PRP injection in women with POR. Positive results appear to be short-term for 2-6 months after the procedure.
Add-Ons and Adjuncts · Preimplantation Genetic Testing
Polygenic risk scores (PRSs) have been offered since 2019 to screen in vitro fertilization embryos for genetic liability to adult diseases, despite a lack of comprehensive modeling of expected outcomes. Here we predict, based on the liability threshold model, the expected reduction in complex disease risk following polygenic embryo screening for a single disease. A strong determinant of the potential utility of such screening is the selection strategy, a factor that has not been previously studied. When only embryos with a very high PRS are excluded, the achieved risk reduction is minimal. In contrast, selecting the embryo with the lowest PRS can lead to substantial relative risk reductions, given a sufficient number of viable embryos. We systematically examine the impact of several factors on the utility of screening, including: variance explained by the PRS, number of embryos, disease prevalence, parental PRSs, and parental disease status. We consider both relative and absolute risk reductions, as well as population-averaged and per-couple risk reductions, and also examine the risk of pleiotropic effects. Finally, we confirm our theoretical predictions by simulating 'virtual' couples and offspring based on real genomes from schizophrenia and Crohn's disease case-control studies. We discuss the assumptions and limitations of our model, as well as the potential emerging ethical concerns.
The 2019 Assisted Reproductive Technology (ART) Fertility Clinic and National Summary Report, prepared by the Centers for Disease Control and Prevention (CDC) under the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493), presents data submitted by 449 reporting US fertility clinics for ART cycles initiated during the 2019 reporting year. The Report includes data on a total of 330,773 ART cycles performed and 78,889 live-birth deliveries. Beginning with the 2019 reporting year, clinic-specific ART success rates are reported in the ART Success Rates by Clinic online application instead of in the printed annual report; the 2019 publication consolidates the previously separate fertility clinic and national summary reports. Standard age bands changed for the 2019 reporting year to less than 35, 35 to 37, 38 to 40, and over 40 years. National summary figures present noncumulative data on cycles performed in the reporting year. CDC estimates that NASS captures 97 to 98 percent of all ART cycles performed in the United States. The 2019 Report includes information on cumulative success rates per intended retrieval cycle, fresh and frozen embryo transfer outcomes, donor egg cycles, embryo banking, and gestational carrier cycles.
Hypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Assisted reproductive technology (ART) has been associated with adverse pregnancy outcomes, including HDP. However, the impact of multiple pregnancies, oocyte donation, as well as fresh and frozen embryo transfer needs to be further studied. We conducted a systematic review and meta-analyses to evaluate the association between ART and HDP or preeclampsia relative to spontaneous conception (SC).
We identified studies from EMBASE, MEDLINE, and Cochrane Library (up to April 8, 2020) and manually using structured search strategies. Cohort studies that included pregnancies after in vitro fertilization (IVF) with or without intracytoplasmic sperm fertilization (ICSI) relative to SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Numbers needed to harm (NNH) were calculated based on absolute risk differences between exposure and control groups.
Eighty-five studies were included after a screening of 1879 abstracts and 283 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.70; 95% CI 1.60-1.80; I2 = 80%) and multiple pregnancies (OR 1.34; 95% CI 1.20-1.50; I2 = 76%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.42; 95% CI 3.00-6.51; I2 = 83%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58-1.92; I2 = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33-1.53; I2 = 72%). The associations between IVF/ICSI pregnancies and SC were similar for preeclampsia. Most interventions had an NNH of 40 to 100, while singleton and multiple oocyte donation pregnancies had particularly low NNH for HDP (16 and 10, respectively).
Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.
Human Fertilisation and Embryology Authority, 2021·
# Fertility treatment 2019: trends and figures
UK statistics for IVF and DI treatment, storage, and donation
Published: May 2021
Fertility trends is our annual statistical release. The key findings are published on this page with a statistical appendix available for download.
[**Download the underlying dataset as .xlsx**](https://www.hfea.gov.uk/media/jvqloejj/2021-05-13-fertility-treatment-2019-trends-and-figures-underlying-data.xlsx "2021 05 Fertility Treatment 2019 Trends and Figures Underlying Data").
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2019-trends-and-figures/#mainpoints)
- [30 years of the Human Fertilisation and Embryology Authority (HFEA)](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2019-trends-and-figures/#introduction)
- [Section 1. IVF birth rates in 2019 were three times higher than in 1991](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2019-trends-and-figures/#Section1)
- [Section 2. Great progress has been made in the reduction of multiple births, which now stands at 6%](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2019-trends-and-figures/#Section2)
- [Section 3. Single embryo transfer is now common practice](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2019-trends-and-figures/#Section3)
- [Section 4. Frozen embryo transfers have increased in use](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2019-trends-and-figures/#Section4)
- [Section 5. The use of donor eggs and sperm has increased](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2019-trends-and-figures/#Section5)
- [Section 6. Fertility treatment has enabled more people to have families later](https://www.hfea.gov.uk/about-us/publications/research-and-dat...
To study how the attributes of mosaicism identified during preimplantation genetic testing for aneuploidy relate to clinical outcomes, in order to formulate a ranking system of mosaic embryos for intrauterine transfer. Compiled analysis. Multi-center. PATIENT(S): A total of 5,561 euploid blastocysts and 1,000 mosaic blastocysts used in clinical transfers in patients undergoing fertility treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation (gestational sac), ongoing pregnancy, birth, and spontaneous abortion (miscarriage before 20 weeks of gestation). RESULT(S): The euploid group had significantly more favorable rates of implantation and ongoing pregnancy/birth (OP/B) compared with the combined mosaic group or the mosaic group affecting only whole chromosomes (implantation: 57.2% vs. 46.5% vs. 41.8%; 52.3% vs. 37.0% vs. 31.3%), as well as lower likelihood of spontaneous abortion (8.6% vs. 20.4% vs. 25%). Whole-chromosome mosaic embryos with level (percent aneuploid cells) <50% had significantly more favorable outcomes than the ≥50% group (implantation: 44.5% vs. 30.4%; 36.1% vs. 19.3%). Mosaic type (nature of the aneuploidy implicated in mosaicism) affected outcomes, with a significant correlation between number of affected chromosomes and unfavorable outcomes. This ranged from mosaicism involving segmental abnormalities to complex aneuploidies affecting three or more chromosomes (implantation: 51.6% vs. 30.4%; 43.1% vs. 20.8%). Combining mosaic level, type, and embryo morphology revealed the order of subcategories regarding likelihood of positive outcome. CONCLUSION(S): This compiled analysis revealed traits of mosaicism identified with preimplantation genetic testing for aneuploidy that affected outcomes in a statistically significant manner, enabling the formulation of an evidence-based prioritization scheme for mosaic embryos in the clinic.
Fertility preservation is an important aspect of quality of life in oncological patients, and in men is achieved by semen cryopreservation prior to treatment. Results of in vitro fertilization (IVF) procedures in healthy infertile couples are comparable, regardless of whether fresh or cryopreserved semen is used, but are scarce in male oncological patients. We performed a retrospective analysis of IVF/intracytoplasmic sperm injection (IVF/ICSI) procedures in infertile couples where men had been treated for cancer in the past. We additionally compared the results of IVF/ICSI procedures with respect to the type of semen used (fresh, cryopreserved). We compared the success rates of 214 IVF/ICSI cycles performed in the years 2004-2018. Pregnancy (30.0% vs. 21.4%; p = 0.12) and live-birth rates (22.3% vs. 17.9%; p = 0.43) per oocyte aspiration were similar between the groups in fresh cycles; however embryo utilization (48.9% vs. 40.0%; p = 0.006) and embryo cryopreservation rates (17.3% vs. 12.7%; p = 0.048) were significantly higher in the cryopreserved semen group. The cumulative pregnancy rate (60.6% vs. 37.7%; p = 0.012) was significantly higher, and the live-birth rate (45.1% vs. 34.0%; p = 0.21) non-significantly higher, in the cryopreserved semen group. The success of IVF/ICSI procedures in couples where the male partner was treated for cancer in the past are the same in terms of pregnancies and live-births in fresh cycles regardless of the type of semen used. However, embryo utilization and embryo cryopreservation rates are significantly higher when cryopreserved semen is used, leading to a significantly higher cumulative number of couples who achieved at least one pregnancy.
Safety and Risks · Ovarian Hyperstimulation Syndrome
Ovarian hyperstimulation syndrome (OHSS) is one of the major complications of assisted reproductive technology treatment. We assumed that it had declined in recent years owing to the options of new preventive strategies. The aim of the present study was to investigate the annual incidence of OHSS in Denmark in the course of a 17-year period. This was a national register-based historical cohort study including all women with an OHSS diagnosis admitted to Danish hospitals between 2001 and 2017. Data included information on all OHSS diagnoses, duration of hospital stay, early pregnancy complications and other complications like thromboembolism and ovarian torsion. The annual number of initiated stimulated in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles was based on the annual reporting by the Danish Fertility Society. From 2001 to 2017, a total of 2,261 (1.2%) women with an OHSS admission were identified among 186,168 stimulated IVF/ICSI cycles. The annual incidence of OHSS varied from 0.9% to 1.2-1.4% with no overall change over time (p = 0.24. Early OHSS (defined as OHSS without a pregnancy in the cycle) was seen in 48.5% of the events, late OHSS (defined as OHSS with a pregnancy in the cycle) in 51.2% of cycles. Among all women with OHSS, 75% were hospitalised for more than 24 hours, with mean 4.3 and 6.2 days in hospital for early and late OHSS, respectively. The annual incidence of severe OHSS leading to a hospital admission remained stable for 17 years, which suggests that OHSS preventive actions like use of antagonist cycles, agonist triggering and freeze all should be better implemented in Denmark. none. not relevant.
Ishihara O et al., 2021·Reprod Med Biol·
Open Access
Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2018, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG).
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2020. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Human Fertilisation and Embryology Authority, 2021·
# Multiple births in fertility treatment 2019
UK multiple birth statistics for IVF and DI fertility treatment
Published: February 2022
[Download the underlying dataset as Excel Worksheet](https://www.hfea.gov.uk/media/ikninm5o/2022-01-25-multiple-births-in-fertility-treatment-underlying-supplementary-data-tables.xlsx "2022 01 25 Multiple Births In Fertility Treatment Underlying Supplementary Data Tables").
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#main-points)
- [History of multiple births in the UK](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#history-of-multiple-births-in-the-uk)
- [Section 1. Multiple births reduced following cross-sector collaborative efforts](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-1)
- [Section 2. Single embryo transfers increased most among young patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-2)
- [Section 3. Largest improvements in multiple birth rate among youngest and oldest patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-3)
- [Section 4. Multiple embryo transfers put younger patients at greatest risk of multiple birth](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-4)
- [Section 5. Greater risk of multiple births when using donor eggs](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-5)
- [Section 6. Multiple birth rates higher among Black patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-6)
- [Section 7. Higher multiple birth rate...
Human Fertilisation and Embryology Authority, 2021·
# Impact of COVID-19 on fertility treatment 2020
UK statistics for IVF and DI treatment, storage and donation
Published: May 2022
[Download the underlying dataset as Excel Worksheet](https://www.hfea.gov.uk/media/rhih4yyx/impact-of-covid-19-on-fertility-treatment-2020-underlying-dataset.xlsx "Impact of COVID-19 on fertility treatment 2020 - Underlying dataset").
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#main-points)
- [Foreword](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#foreword)
- [HFEA regulatory response to the COVID-19 pandemic](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#hfea-regulatory-response-to-the-covid-19-pandemic)
- [1\. NHS-funded IVF treatment slower to recover](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#section-1)
- [2\. Treatments decreased by 20% from 2019 to 2020](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#section-2)
- [3\. Greater decrease in IVF cycles among younger patients and patients in heterosexual relationships](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#section-3)
- [4\. Egg donor registrations decreased by 23% from 2019 to 2020](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#section-4)
- [5\. Impact of COVID-19 varied by nation and English region](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#section-5)
- [6\. COVID-19 caused delays in GP appointments and fertility treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertil...
Agence de la biomédecine, 2021·Agence de la biomédecine
Rapport annuel d'AMP Vigilance 2020 publié par l'Agence de la biomédecine. Document de surveillance pour les activités d'Assistance Médicale à la Procréation en France couvrant les incidents et effets indésirables. Annual AMP (Medically Assisted Reproduction) Vigilance Report 2020 from the French Agence de la biomédecine, the national mandatory ART registry covering adverse events and safety surveillance for licensed AMP activities in France.
Registries and Reporting · Cross-Registry Comparison
What were the utilization, effectiveness and safety of practices in assisted reproductive technologies (ART) globally in 2014 and what global trends could be observed? The estimated total number of ART cycles conducted in 76 participating countries in 2014 was 1.93 million representing ∼66% of global activity, with 5-year trends including an increase in success rates and proportion of frozen embryo transfer (FET) cycles, improvement in cumulative live birth rates per aspiration, a continued increase in single embryo transfer (SET) and thus a reduction in multiple birth rates, an increase in preimplantation genetic testing and stabilization in the use of intracytoplasmic sperm injection (ICSI). ART is widely practiced throughout the world but continues to be characterized by significant disparities in utilization, practice, effectiveness and safety. The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) annual world report series provides an important instrument for tracking trends in ART treatment and for providing clinical and public health data to ART professionals, health authorities, patients and the general public. STUDY DESIGN, SIZE, A retrospective, cross-sectional survey on ART procedures performed globally during 2014 was carried out. A new method for calculating ART utilization rates and number of babies born was introduced in this latest ICMART world report. PARTICIPANTS/MATERIALS, SETTING, Overall, 76 countries and 2 746 ART centres submitted data through national and regional ART registries on ART cycles performed during 2014 and their treatment and pregnancy outcomes. ART cycles and outcomes are described at a country level, regionally and globally. Aggregate country data are processed and analyzed based on methods developed by ICMART. MAIN A total of 1 629 179 ART cycles were reported for the treatment year 2014. After imputing data for missing values and non-reporting centres in reporting countries, an estimated 1 929 905 cycles resulted in >439 039 babies in reporting countries. From 2010 to 2014, the number of reported non-donor aspirations and FET cycles increased by 37.3% and 67.5%, respectively. The proportion of women aged ≥40 years undergoing non-donor ART increased from 23.2% in 2010 to 27.0% in 2014. ICSI, as a percentage of non-donor aspiration cycles, remained relatively stable at 64.8%. The IVF/ICSI combined delivery rates per fresh aspiration and FET cycle were 19.9% and 24.3%, respectively. In fresh non-donor cycles, SET increased from 30.0% in 2010 to 40.0% in 2014, while the average number of transferred embryos decreased from 1.95 to 1.73-but with wide country variation. The rate of twin deliveries following fresh non-donor transfers continued to decrease, from 20.4% in 2010 to 16.2% in 2014, and the triplet rate decreased from 1.1% to 0.5%. In FET non-donor cycles in 2014, the SET rate was 61.6%, with an average of 1.43 embryos transferred, resulting in twin and triplet rates of 10.1% and 0.2%, respectively. The cumulative delivery rate per aspiration increased from 27.1% in 2010 to 32.1% in 2014. The overall perinatal mortality rate per 1 000 births was 19.4 following fresh IVF/ICSI cycles and 9.5 following FET cycles. Among reporting countries, oocyte donation cycles represented 7.3% of all embryo transfers (89 751 transfer cycles) and resulted in 39 278 babies. LIMITATIONS, The data presented are dependent on the quality and completeness of data submitted by individual countries to ICMART directly or through regional registries. This report covers approximately two-thirds of world ART activity. China is a major contributor of global cycles missing from this report. Continued efforts to improve the quality and consistency of ART data reported by registries are still needed, including the use of internationally agreed standard definitions (The International Glossary of Infertility and Fertility Care). A new method was introduced in this report to calculate ART utilization and number of babies born following ART; therefore, these results are not directly comparable with previous reports. The ICMART world reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment effectiveness and safety continue to increase globally, the wide disparities in access to treatment, procedures performed and embryo transfer practices warrant attention by clinicians and policymakers. The new method for estimating ART utilization and number of babies born provided more conservative estimates compared to the previuos method. STUDY FUNDING/COMPETING INTEREST(S): ICMART receives unrestricted grants from Abbott and Ferring Pharmaceuticals. ICMART also acknowledges financial support from the following organization
Registries and Reporting · Cross-Registry Comparison
To report the utilization, effectiveness, and safety of practices in assisted reproductive technology (ART) globally in 2013 and assess global trends over time. Retrospective, cross-sectional survey on the utilization, effectiveness, and safety of ART procedures performed globally during 2013. Seventy-five countries and 2,639 ART clinics. PATIENT(S): Women and men undergoing ART procedures. INTERVENTION(S): All ART. MAIN OUTCOME MEASURE(S): The ART cycles and outcomes on country-by-country, regional, and global levels. Aggregate country data were processed and analyzed based on methods developed by the International Committee for Monitoring Assisted Reproductive Technology (ICMART). RESULT(S): A total of 1,858,500 ART cycles were conducted for the treatment year 2013 across 2,639 clinics in 75 participating countries with a global participation rate of 73.6%. Reported and estimated data suggest 1,160,474 embryo transfers (ETs) were performed resulting in >344,317 babies. From 2012 to 2013, the number of reported aspiration and frozen ET cycles increased by 3% and 16.4%, respectively. The proportion of women aged >40 years undergoing nondonor ART increased from 25.2% in 2012 to 26.3% in 2013. As a percentage of nondonor aspiration cycles, intracytoplasmic sperm injection (ICSI) was similar to results for 2012. The in vitro fertilization (IVF)/ICSI combined delivery rates per fresh aspiration and frozen ET cycles were 24.2% and 22.8%, respectively. In fresh nondonor cycles, single ET increased from 33.7% in 2012 to 36.5% in 2013, whereas the average number of transferred embryos was 1.81-again with wide country variation. The rate of twin deliveries after fresh nondonor transfers was 17.9%; the triplet rate was 0.7%. In frozen ET cycles performed in 2013, single ET was used in 57.6%, with an average of 1.49 embryos transferred and twin and triplet rates of 10.8% and 0.4%, respectively. The cumulative delivery rate per aspiration was 30.4%, similar to that in 2012. Perinatal mortality rate per 1,000 births was 22.2% after fresh IVF/ICSI and 16.8% after frozen ET. The data presented depended on the quality and completeness of the data submitted by individual countries. This report covers approximately two-thirds of world ART activity. Continued efforts to improve the quality and consistency of reporting ART data by registries are still needed. CONCLUSION(S): Reported ART cycles, effectiveness, and safety increased between 2012 and 2013 with adoption of a better method for estimating unreported cycles.
The 2018 Assisted Reproductive Technology (ART) Fertility Clinic Success Rates Report, prepared under the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493), presents data submitted to the Centers for Disease Control and Prevention (CDC) by 456 reporting fertility clinics in the United States, Puerto Rico, and the District of Columbia for ART cycles initiated during the 2018 reporting year. The report includes 203,119 ART cycles, 73,831 live-birth deliveries, and 81,478 infants born through ART. Clinic-specific data are presented for each reporting clinic and include fresh and frozen ART cycles using patients' own eggs and donor eggs, broken out by patient age band (less than 35, 35 to 37, 38 to 40, 41 to 42, and over 42 years). The 2018 Report introduced data suppression rules to suppress the publication of small numbers (1 through 4) to reduce the risk of patient identification. The Report also presents national summary figures and clinic table summaries, including cumulative success rates that combine fresh and frozen embryo transfers from a single oocyte retrieval. CDC estimates that the proportion of all ART cycles reported to the National ART Surveillance System (NASS) represents 97 to 98 percent of all ART cycles performed in the United States.
Infertility affects \~20% of the couples in the world. Assisted reproductive technologies (ARTs) are currently the most common treatment option for infertility. Nevertheless, ARTs may be associated with complications for mothers and/or offspring. Natural procreative technology (NaProTechnology) is a natural treatment which minimizes these risks by seeking to identify the causes of infertility to enable better treatments. This narrative review summarizes the complications related to ARTs and clarifies how the NaProTechnology approach can help ARTs to achieve better results or be used in alternative to ARTs. Data in the literature indicate that NaProTechnology is a natural approach for treating infertility. The percentage of live births obtained by NaProTechnology is similar to that of ARTs. An extensive search for the genetic defects causing infertility or subfertility through genetic testing can help both ARTs and NaProTechnology to achieve successful pregnancies. By discovering the underlying causes of infertility, genetic tests enable better family counseling, like the implications of transmitting risk- and disease-alleles to future generations.
Human Fertilisation and Embryology Authority, 2020·
# State of the fertility sector 2019/2020
**Annual publication on our regulatory work**
Published: November 2020
[**Download the underlying data set as.xlsx (47KB)**](https://www.hfea.gov.uk/media/3289/state-of-the-sector-2019-20-underlying-data.xlsx)
* * *
### About this report
We are the independent regulator of fertility treatment and human embryo research in the United Kingdom (UK). We aim to ensure that everyone who steps into a fertility clinic, and everyone born as a result of treatment, receives high quality care. We do this by licensing, monitoring and inspecting fertility clinics and providing free, clear and impartial information about fertility treatment, clinics, and egg, sperm and embryo donation.
State of the Sector is our annual report, which summarises what we have seen through our regulatory work during the year. The report is compiled from information gathered from our inspections throughout the year and uses other sources of information including our Register of fertility treatments, incident reports and patient feedback mechanisms.
In 2019/20, we introduced a [**Clinical Governance Quarterly Update**](https://portal.hfea.gov.uk/knowledge-base/clinic-focus/) which provides clinics with detailed insight into non-compliances in a more timely manner to help clinics improve compliance and prepare for inspections. As a result, the State of the Sector report this year provides a high-level overview of sector-wide compliance, reporting on the absolute number of inspections, non-compliances, incidents and complaints.
* * *
### Impact of COVID-19 on the fertility sector
This report looks at the financial year 2019/20 (1 April 2019 – 31 March 2020), predominantly covering the period before any COVID-19 restrictions were put in place. As COVID-19 caused unprecedented demand on the NHS during the initial wave of the pandemic, the Human Fertilisation and Embryology Authority (HFEA) made the difficult decision to publish [**General Direction 0014**](https://po...
Safety and Risks · Ovarian Hyperstimulation Syndrome
Schirmer DA 3rd et al., 2020·Fertility and Sterility
To assess trends, predictors, and perinatal outcomes of ovarian hyperstimulation syndrome (OHSS) associated with in vitro fertilization (IVF) cycles in the United States. Retrospective cohort study using National Assisted Reproductive Technology Surveillance System (NASS) data. Not applicable. PATIENT(S): Fresh autologous and embryo-banking cycles performed from 2000 to 2015. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): OHSS, first-trimester loss, second-trimester loss, stillbirth, low birth weight, and preterm delivery. RESULT(S): The proportion of IVF cycles complicated by OHSS increased from 10.0 to 14.3 cases per 1,000 from 2000 to 2006, and decreased to 5.3 per 1,000 from 2006 to 2015. The risk of OHSS was highest for cycles with more than 30 oocytes retrieved (adjusted risk ratio [aRR] 3.85). OHSS was associated with a diagnosis of ovulatory disorder (aRR 2.61), tubal factor (aRR 1.14), uterine factor (aRR 1.17) and cycles resulting in pregnancy (aRR 3.12). In singleton pregnancies, OHSS was associated with increased risk of low birth weight (aRR 1.29) and preterm delivery (aRR 1.32). In twin pregnancies, OHSS was associated with an increased risk of second-trimester loss (aRR 1.81), low birth weight (aRR 1.06), and preterm delivery (aRR 1.16). CONCLUSION(S): Modifiable predictive factors for OHSS include number of oocytes retrieved, pregnancy following fresh embryo transfer, and the type of medication used for pituitary suppression during controlled ovarian hyperstimulation. Patients affected by OHSS had a higher risk of preterm delivery and low birth weight. Clinicians should take measures to reduce the risk of OHSS whenever possible.
Registries and Reporting · Cross-Registry Comparison
---
title: "ART in Europe, 2016: results generated from European registries by ESHRE"
source_file: "eshre-eim-2016-source.pdf"
pages: 17
extracted_date: "2026-04-24"
figures_extracted: 3
tables_extracted: 5
review_flags: 2
citation: "Wyns C et al. ART in Europe, 2016: results generated from European registries by ESHRE. Hum Reprod Open. 2020;2020(3):hoaa032. doi:10.1093/hropen/hoaa032"
---
Human Fertilisation and Embryology Authority, 2020·
# Fertility treatment 2018: trends and figures
**UK statistics for IVF and DI treatment, storage, and donation**
Published: 30 June 2020
Fertility trends is our annual statistical release. The key findings are published on this page with a statistical appendix available for download.
[**Download the underlying data set in .xlsx (151kb)**](https://www.hfea.gov.uk/media/3293/underlying-data-tables-fertility-trends-2018.xlsx "download the data as .xlsx").
[**Download a PDF version of this report (1.04mb)**](https://www.hfea.gov.uk/media/3158/fertility-treatment-2018-trends-and-figures.pdf "Fertility treatment 2018: trends and figures").
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#mainpoints)
- [Section 1. IVF birth rates have increased for patients under 43 years](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#birthrates)
- [Section 2. Birth rates were above 20% per embryo transferred on average in the first three cycles](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#birthrates2)
- [Section 3. Using donor eggs can result in high birth rates for older patients, but they are not widely used](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#donoreggs)
- [Section 4. The multiple birth rate decreased further to 8% in 2018](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#multiplebirths)
- [Section 5. Transferring more than one embryo could result in a multiple birth rate over 30%](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2018-trends-and-figures/#multiplebirths2)
- [Section 6. Embryo and egg storage have increased as freezing becomes more common](https://www.hfea...
To assess infant (<1 year) and childhood (1-18 years) mortality in singletons conceived through assisted reproductive techniques (ART) versus naturally conceived singletons.
Nationwide prospective study.
Sweden. PATIENT(S): All singleton liveborn infants born from 1983 to 2012 in Sweden identified using the Medical Birth Register (N = 2,847,108), of whom 43,506 were conceived through ART treatments including in vitro fertilization with and without intracytoplasmic sperm injection. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Infant (<1 year) and childhood (1-18 years) mortality. RESULT(S): Data on ART treatment and covariates were retrieved from population-based registers using the unique personal identity number assigned to all permanent residents in Sweden. Cox proportional hazards models estimated the hazard ratios (HRs) with 95% confidence intervals (CIs) as measures of association between ART treatments and death. The analyses were adjusted for maternal characteristics, infertility, child sex, and birth cohort and were restricted to individuals with complete information on covariates for fully adjusted analysis. Compared with naturally conceived singletons, higher infant mortality risks were seen in infants conceived through ART (adjusted HR 1.45; 95% CI, 1.19-1.77), especially after transfer of cryopreserved embryos (adjusted HR 2.30; 95% CI, 1.46-3.64). Early neonatal mortality risk (deaths during the first week) was increased in children born after transfer of blastocysts (HR 2.40; 95% CI, 1.05-5.48). No increased mortality risk was observed between the ages of 1 and 18 years. CONCLUSION(S): Singletons conceived through ART had an increased risk of infant mortality from birth up to 1 year of life, predominantly in the early neonatal period and in pregnancies after transfer of frozen and thawed embryos.
Human Fertilisation and Embryology Authority, 2020·
# Ethnic diversity in fertility treatment 2018
UK ethnicity statistics for IVF and DI fertility treatment
Published: March 2021
[**Download the underlying dataset as .xlsx (27kb)**](https://www.hfea.gov.uk/media/3348/2021-03-03-bame-report-suppl_mental-underlying-data-final.xlsx "download the underlying data as .xlsx").
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#mainpoints)
- [Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#introduction)
- [Section 1. IVF birth rates lowest for patients of Black ethnicities](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section1)
- [Section 2. Multiple birth rate higher on average for Black patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section2)
- [Section 3. White egg donors most commonly used across all ethnic groups](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section3)
- [Section 4. Fewer Asian egg and sperm donors compared to UK Asian population](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section4)
- [Section 5. Asian patients represent a larger proportion of IVF users](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section5)
- [Section 6. Variation in NHS-funded IVF cycles between cycles in larger in younger age groups](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section6)
- [Section 7. Black patients start IVF later than other ethnic groups](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversit...
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2019. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Human Fertilisation and Embryology Authority, 2020·
# Family formations in fertility treatment 2018
UK IVF and DI statistics for heterosexual, female same-sex and single Published: 22 September 2020
[**Download the underlying data set in .xlsx (144KB)**](https://www.hfea.gov.uk/media/3294/family-formations-2018-complete-underlying-data-tables.xlsx).
[**Download a PDF version of this report (976KB)**](https://www.hfea.gov.uk/media/3234/family-formations-in-fertility-treatment-2018.pdf "Family formations 2018").
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#mainpoints)
- [Section 1. In vitro fertilisation (IVF) increasingly used over donor insemination (DI) for single patients and patients in female same-sex relationships](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#Section1)
- [Section 2. IVF birth rates increased most for patients in female same-sex relationship as average age declined](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#Section2)
- [Section 3. DI birth rates lowest for single patients due to higher average age](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#Section3)
- [Section 4. Egg freezing most used by single patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#Section4)
- [Section 5. NHS-funded cycles were more common for patients in heterosexual relationships](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#Section5)
- [Section 6. Patients in female same-sex relationships used cost-reducing egg share programme at the highest rate](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2018/#...
Ishihara O et al., 2020·Reprod Med Biol·
Open Access
Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2017, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG).
Sunderam S et al., 2020·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
Assisted Reproductive Technology Surveillance - United States, 2017. Sunderam S, Kissin DM, Zhang Y, Jewett A, Boulet SL, Warner L, Kroelinger CD, Barfield WD. Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to have multiple-birth infants because multiple embryos may be transferred. Multiple births can pose substantial risks for both mothers and infants, including obstetric complications, preterm birth (<37 weeks), and low birthweight (<2,500 g). This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2017 and compares birth outcomes that occurred in 2017 (resulting from ART procedures performed in 2016 and 2017) with outcomes for all infants born in the United States in 2017. 2017. In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from the 50 states, the District of Columbia, and Puerto Rico. In 2017, a total of 196,454 ART procedures (range: 162 in Alaska to 24,179 in California) with at least one embryo transferred were performed in 448 U.S. fertility clinics and reported to CDC. These procedures resulted in 68,908 live-birth deliveries (range: 67 in Puerto Rico to 8,852 in California) and 78,052 infants born (range: 85 in Puerto Rico to 9,926 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years) was 3,040. ART use rates exceeded the national rate in 14 states (Connecticut, Delaware, District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Utah, Vermont, and Virginia). ART use exceeded 1.5 times the national rate in seven states (Connecticut, the District of Columbia, Illinois, Maryland, Massachusetts, New Jersey, and New York). Nationally, among all ART transfer procedures, the average number of embryos transferred increased slightly with increasing age (1.3 among women aged <35 years, 1.4 among women aged 35-37 years, and 1.5 among women aged >37 years). This year, single-embryo transfer (SET) rates among all embryo-transfer procedures are presented instead of elective single-embryo transfer procedures previously reported. Nationally, SET rates were 67.3% (range: 38.9% in South Dakota to 90.4% in Delaware), 65.0% (range: 23.6% in Puerto Rico to 89.4% in Delaware), and 60.0% (range: 28.6% in Puerto Rico to 83.1% in Delaware) among women aged <35 years, aged 35-37 years, and aged >37 years, respectively. In 2017, ART contributed to 1.9% of all infants born in the United States (range: 0.4% in Puerto Rico to 5.0% in Massachusetts). Approximately 73.6% of ART-conceived infants were singleton infants. Overall, ART contributed to 14.7% of all multiple births, including 14.7% of all twin infants and 17.3% of all triplets and higher-order infants. ART-conceived twins accounted for approximately 96.5% (18,890 of 19,570) of all ART-conceived infants born in multiple deliveries. The percentage of multiple births was higher among infants conceived with ART (26.4%) than among all infants born in the total birth population (3.4%). Approximately 25.5% of ART-conceived infants were twins, and 0.9% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 4.5% of all low birthweight (<2,500 g) infants. Among ART-conceived infants, 20.2% had low birthweight, compared with 8.3% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (27.8%) than among all infants born in the total birth population (9.9%). The percentage of low birthweight among singletons was 8.1% among ART-conceived infants and 6.6% among all infants born. The percentage of preterm births among ART-conceived singleton infants was 14.0%, compared with 8.1% among all singleton infants. The percentages of small for gestational age infants was 7.6% among ART-conceived infants, compared with 9.9% among all infants. Although singleton infants accounted for the majority of ART-conceived infants, multi
Maleki-Hajiagha A et al., 2020·Journal of reproductive immunology
Prior studies have provided conflicting results regarding the use of platelet-rich plasma (PRP) in women undergoing in-vitro fertilization (IVF) or intracytoplasmic injection (ICSI). The objective of this study was to evaluate the effect of the intrauterine infusion of PRP on the outcome of embryo transfer (ET) in women undergoing IVF/ICSI. We searched databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Clinical Trials (CENTRAL). Meta-analysis using a random-effects model was performed to calculate the pooled estimates. Seven studies involving 625 patients (311 cases and 314 controls) were included. The probability of chemical pregnancy (n = 3, risk ratio (RR): 1.79, 95 % confidence intervals (CI): 1.29, 2.50; P < 0.001, I2 = 0 %), clinical pregnancy (n = 7, RR: 1.79, 95 % CI: 1.37, 2.32; P < 0.001, I2 = 16 %), and implantation rate (n = 3, RR: 1.97, 95 % CI: 1.40, 2.79; P < 0.001, I2 = 0 %) was significantly higher in women who received PRP compared with control. There was no difference between women who received PRP compared with control group regarding miscarriage (RR: 0.72, 95 % CI: 0.27, 1.93; P = 0.51, I2 = 0 %). Following the intervention, endometrial thickness increased in women who received PRP compared to control group (SMD: 1.79, 95 % CI: 1.13, 2.44; P < 0.001, I2 = 64 %). The findings of this systematic review suggest that PRP is an alternative treatment strategy in patients with thin endometrium and recurrent implantation failure (RIF). Further prospective, large, and high quality randomized controlled trials (RCTs) are needed to identify the subpopulation that would most benefit from PRP.
Nazari L et al., 2020·Human fertility (Cambridge, England)
Repeated implantation failure is a major challenge in reproductive medicine and despite several methods that have been described for management, there is little consensus on which is the most effective. This study was conducted to evaluate the effectiveness of autologous platelet-rich plasma in improving the pregnancy rate in repeated implantation failure. Between 2016 and 2017, a total of 138 patients who failed to conceive after 3 or more embryo transfers with high quality embryos and candidate for frozen-thawed embryo transfer were assessed for eligibility to enter the study. Intrauterine infusion of 0.5 ml platelet-rich plasma (PRP) that contained platelets at 4-5 times higher concentration than peripheral blood was performed 48 h before blastocyst transfer. A control group received standard treatment. Ninety-seven patients completed the study procedure. There were no significant differences between the two groups in terms of age, body mass index and number of previous embryo transfers. The chemical pregnancy rate was higher in the PRP group than control group (53.06% versus 27.08%, respectively; p value: 0.009). Clinical pregnancy rate was higher in PRP group than control group (44.89% versus 16.66%, respectively; p value: 0.003). In conclusion, intrauterine platelet-rich plasma may be effective in the improvement of pregnancy outcome in repeated implantation failure.
An increasing number of children worldwide are born after the use of fertility treatment, although it remains unclear whether the treatment affects the risk of childhood cancer and whether any associations observed are due to the use of specific drugs, the use of specific procedures, or the underlying infertility. To examine the association between different types of fertility treatments and cancer risk in children. DESIGN, SETTING, A retrospective cohort study based on Danish population-based registry data and the Danish Infertility Cohort (individual record linkage) that included 1 085 172 children born in Denmark between January 1, 1996, and December 31, 2012, linked with parental information. There were a total of 2217 children diagnosed with cancer (follow-up occurred during 1996-2015). Maternal fertility treatment during the index pregnancy, including the use of fertility drugs (clomiphene [n = 33 835], gonadotropins [n = 57 136], gonadotropin-releasing hormone analogs [n = 38 653], human chorionic gonadotropin [n = 68 181], progesterone [n = 41 628], and estrogen [n = 16 948]) and assisted reproductive technology (in vitro fertilization [n = 19 448], intracytoplasmic sperm injection [n = 13 417], and frozen embryo transfer [n = 3356]). Each exposure was examined separately and compared with children born to fertile women. Hazard ratios and incidence rate differences for childhood cancer. After 12.2 million person-years of follow-up (mean, 11.3 years), the incidence rate of childhood cancer was 17.5 per 100 000 for children born to fertile women (n = 910 291) and 44.4 per 100 000 for children born after the use of frozen embryo transfer (n = 3356). Compared with children born to fertile women, the use of frozen embryo transfer was associated with an elevated risk of childhood cancer (14 cancer cases; hazard ratio, 2.43 [95% CI, 1.44 to 4.11]; incidence rate difference, 26.9 [95% CI, 2.8 to 51.0] per 100 000), mainly due to an increased risk of leukemia (5 cancer cases; incidence rate, 14.4 per 100 000; hazard ratio, 2.87 [95% CI, 1.19 to 6.93]; incidence rate difference, 10.1 [95% CI, -4.0 to 24.2] per 100 000) and sympathetic nervous system tumors (<5 cancer cases; hazard ratio, 7.82 [95% CI, 2.47 to 24.70]). There were no statistically significant associations with the use of the other types of fertility treatment examined. Among children born in Denmark, the use of frozen embryo transfer, compared with children born to fertile women, was associated with a small but statistically significant increased risk of childhood cancer; this association was not found for the use of other types of fertility treatment examined.
Add-Ons and Adjuncts · Preimplantation Genetic Testing
To evaluate the benefit of next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) for embryo selection in frozen-thawed embryo transfer. Randomized controlled trial. Not applicable. PATIENT(S): Women aged 25-40 years undergoing IVF with at least two blastocysts that could be biopsied. INTERVENTION(S): Randomization for single frozen-thawed embryo transfer with embryo selection based on PGT-A euploid status versus morphology. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate (OPR) at 20 weeks' gestation per embryo transfer. RESULT(S): A total of 661 women (average age 33.7 ± 3.6 years) were randomized to PGT-A (n = 330) or morphology alone (n = 331). The OPR was equivalent between the two arms, with no significant difference per embryo transfer (50% [137/274] vs. 46% [143/313]) or per intention to treat (ITT) at randomization (41.8% [138/330] vs. 43.5% [144/331]). Post hoc analysis of women aged 35-40 years showed a significant increase in OPR per embryo transfer (51% [62/122] vs. 37% [54/145]) but not per ITT. CONCLUSION(S): PGT-A did not improve overall pregnancy outcomes in all women, as analyzed per embryo transfer or per ITT. There was a significant increase in OPR per embryo transfer with the use of PGT-A in the subgroup of women aged 35-40 years who had two or more embryos that could be biopsied, but this was not significant when analyzed by ITT. CLINICAL NCT02268786.
Al-Jebari Y et al., 2019·BMJ (Clinical research ed.)
To compare the risk and severity of prostate cancer between men achieving fatherhood by assisted reproduction and men conceiving naturally. National register based cohort study. Sweden from January 1994 to December 2014. 1 181 490 children born alive in Sweden during 1994-2014 to the same number of fathers. Fathers were grouped according to fertility status by mode of conception: 20 618 by in vitro fertilisation (IVF), 14 882 by intra-cytoplasmic sperm injection (ICSI), and 1 145 990 by natural conception. Prostate cancer diagnosis, age of onset, and androgen deprivation therapy (serving as proxy for advanced or metastatic malignancy). Among men achieving fatherhood by IVF, by ICSI, and by non-assisted means, 77 (0.37%), 63 (0.42%), and 3244 (0.28%), respectively, were diagnosed as having prostate cancer. Mean age at onset was 55.9, 55.1, and 57.1 years, respectively. Men who became fathers through assisted reproduction had a statistically significantly increased risk of prostate cancer compared with men who conceived naturally (hazard ratio 1.64, 95% confidence interval 1.25 to 2.15, for ICSI; 1.33, 1.06 to 1.66, for IVF). They also had an increased risk of early onset disease (that is, diagnosis before age 55 years) (hazard ratio 1.86, 1.25 to 2.77, for ICSI; 1.51, 1.09 to 2.08, for IVF). Fathers who conceived through ICSI and developed prostate cancer received androgen deprivation therapy to at least the same extent as the reference group (odds ratio 1.91; P=0.07). Men who achieved fatherhood through assisted reproduction techniques, particularly through ICSI, are at increased risk for early onset prostate cancer and thus constitute a risk group in which testing and careful long term follow-up for prostate cancer may be beneficial.
Outcomes and Effectiveness · Outcomes by Diagnosis
Wang R et al., 2019·The Cochrane database of systematic reviews·
Open Access
Clinical management for unexplained infertility includes expectant management as well as active treatments, including ovarian stimulation (OS), intrauterine insemination (IUI), OS-IUI, and in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection (ICSI).Existing systematic reviews have conducted head-to-head comparisons of these interventions using pairwise meta-analyses. As this approach allows only the comparison of two interventions at a time and is contingent on the availability of appropriate primary evaluative studies, it is difficult to identify the best intervention in terms of effectiveness and safety. Network meta-analysis compares multiple treatments simultaneously by using both direct and indirect evidence and provides a hierarchy of these treatments, which can potentially better inform clinical decision-making. To evaluate the effectiveness and safety of different approaches to clinical management (expectant management, OS, IUI, OS-IUI, and IVF/ICSI) in couples with unexplained infertility. We performed a systematic review and network meta-analysis of relevant randomised controlled trials (RCTs). We searched electronic databases including the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, the Cochrane Central Register of Studies Online, MEDLINE, Embase, PsycINFO and CINAHL, up to 6 September 2018, as well as reference lists, to identify eligible studies. We also searched trial registers for ongoing trials. We included RCTs comparing at least two of the following clinical management options in couples with unexplained infertility: expectant management, OS, IUI, OS-IUI, and IVF (or combined with ICSI). Two review authors independently screened titles and abstracts identified by the search strategy. We obtained the full texts of potentially eligible studies to assess eligibility and extracted data using standardised forms. The primary effectiveness outcome was a composite of cumulative live birth or ongoing pregnancy, and the primary safety outcome was multiple pregnancy. We performed a network meta-analysis within a random-effects multi-variate meta-analysis model. We presented treatment effects by using odds ratios (ORs) and 95% confidence intervals (CIs). For the network meta-analysis, we used Confidence in Network Meta-analysis (CINeMA) to evaluate the overall certainty of evidence. We included 27 RCTs (4349 couples) in this systematic review and 24 RCTs (3983 couples) in a subsequent network meta-analysis. Overall, the certainty of evidence was low to moderate: the main limitations were imprecision and/or heterogeneity.Ten RCTs including 2725 couples reported on live birth. Evidence of differences between OS, IUI, OS-IUI, or IVF/ICSI versus expectant management was insufficient (OR 1.01, 95% CI 0.51 to 1.98; low-certainty evidence; OR 1.21, 95% CI 0.61 to 2.43; low-certainty evidence; OR 1.61, 95% CI 0.88 to 2.94; low-certainty evidence; OR 1.88, 95 CI 0.81 to 4.38; low-certainty evidence). This suggests that if the chance of live birth following expectant management is assumed to be 17%, the chance following OS, IUI, OS-IUI, and IVF would be 9% to 28%, 11% to 33%, 15% to 37%, and 14% to 47%, respectively. When only including couples with poor prognosis of natural conception (3 trials, 725 couples) we found OS-IUI and IVF/ICSI increased live birth rate compared to expectant management (OR 4.48, 95% CI 2.00 to 10.1; moderate-certainty evidence; OR 4.99, 95 CI 2.07 to 12.04; moderate-certainty evidence), while there was insufficient evidence of a difference between IVF/ICSI and OS-IUI (OR 1.11, 95% CI 0.78 to 1.60; low-certainty evidence).Eleven RCTs including 2564 couples reported on multiple pregnancy. Compared to expectant management/IUI, OS (OR 3.07, 95% CI 1.00 to 9.41; low-certainty evidence) and OS-IUI (OR 3.34 95% CI 1.09 to 10.29; moderate-certainty evidence) increased the odds of multiple pregnancy, and there was insufficient evidence of a difference between IVF/ICSI and expectant management/IUI (OR 2.66, 95% CI 0.68 to 10.43; low-certainty evidence). These findings suggest that if the chance of multiple pregnancy following expectant management or IUI is assumed to be 0.6%, the chance following OS, OS-IUI, and IVF/ICSI would be 0.6% to 5.0%, 0.6% to 5.4%, and 0.4% to 5.5%, respectively.Trial results show insufficient evidence of a difference between IVF/ICSI and OS-IUI for moderate/severe ovarian hyperstimulation syndrome (OHSS) (OR 2.50, 95% CI 0.92 to 6.76; 5 studies; 985 women; moderate-certainty evidence). This suggests that if the chance of moderate/severe OHSS following OS-IUI is assumed to be 1.1%, the chance following IVF/ICSI would be between 1.0% and 7.2%. AUTHORS' There is insufficient evidence of differences in live birth between expectant management and the other four interventions (OS, IUI, OS-IUI, and IVF/ICSI). Compared to expectant management/IUI, OS may increase the odds of multiple pregnancy, and OS-IUI probably increases the odds of multiple pregnancy. Evidence on differences between IVF/ICSI and expectant management for multiple pregnancy is insufficient, as is evidence of a difference for moderate or severe OHSS between IVF/ICSI and OS-IUI.
Gleicher N et al., 2019·Hum Reprod Open·
Open Access
With steadily improving pregnancy and live birth rates, IVF over approximately the first two and a half decades evolved into a highly successful treatment for female and male infertility, reaching peak live birth rates by 2001-2002. Plateauing rates, thereafter, actually started declining in most regions of the world. We here report worldwide IVF live birth rates between 2004 and 2016, defined as live births per fresh IVF/ICSI cycle started, and how the introduction of certain practice add-ons in timing was associated with changes in these live birth rates. We also attempted to define how rapid worldwide 'industrialization' (transition from a private practice model to an investor-driven industry) and 'commoditization' in IVF practice (primary competitive emphasis on revenue rather than IVF outcomes) affected IVF outcomes. The data presented here are based on published regional registry data from governments and/or specialty societies, covering the USA, Canada, the UK, Australia/New Zealand (combined), Latin America (as a block) and Japan. Changes in live birth rates were associated with introduction of new IVF practices, including mild stimulation, elective single embryo transfer (eSET), PGS (now renamed preimplantation genetic testing for aneuploidy), all-freeze cycles and embryo banking. Profound negative associations were observed with mild stimulation, extended embryo culture to blastocyst and eSET in Japan, Australia/New Zealand and Canada but to milder degrees also elsewhere. Effects of 'industrialization' suggested rising utilization of add-ons ('commoditization'), increased IVF costs, reduced live birth rates and poorer patient satisfaction. Over the past decade and a half, IVF, therefore, has increasingly disappointed outcome expectations. Remarkably, neither the profession nor the public have paid attention to this development which, therefore, also has gone unexplained. It now urgently calls for evidence-based explanations.
Sermondade N et al., 2019·Human reproduction update·
Open Access
A worldwide increase in the prevalence of obesity has been observed in the past three decades, particularly in women of reproductive age. Female obesity has been clearly associated with impaired spontaneous fertility, as well as adverse pregnancy outcomes. Increasing evidence in the literature shows that obesity also contributes to adverse clinical outcomes following in vitro fertilization (IVF) procedures. However, the heterogeneity of the available studies in terms of populations, group definition and outcomes prevents drawing firm conclusions. A previous meta-analysis published in 2011 identified a marginal but significant negative effect of increased female body mass index (BMI) on IVF results, but numerous studies have been published since then, including large cohort studies from national registries, highlighting the need for an updated review and meta-analysis. Our systematic review and meta-analysis of the available literature aims to evaluate the association of female obesity with the probability of live birth following IVF. Subgroup analyses according to ovulatory status, oocyte origin, fresh or frozen-embryo transfer and cycle rank were performed. A systematic review was performed using the following key words: ('obesity', 'body mass index', 'live birth', 'IVF', 'ICSI'). Searches were conducted in MEDLINE, EMBASE, Cochrane Library, Eudract and clinicaltrial.gov from 01 January 2007 to 30 November 2017. Study selection was based on title and abstract. Full texts of potentially relevant articles were retrieved and assessed for inclusion by two reviewers. Subsequently, quality was assessed using the Newcastle-Ottawa Quality Assessment Scales for patient selection, comparability and assessment of outcomes. Two independent reviewers carried out study selection and data extraction according to Cochrane methods. Random-effect meta-analysis was performed using Review Manager software on all data (overall analysis), followed by subgroup analyses. A total of 21 studies were included in the meta-analysis. A decreased probability of live birth following IVF was observed in obese (BMI ≥ 30 kg/m2) women when compared with normal weight (BMI 18.5-24.9 kg/m2) women: risk ratio (RR) (95% CI) 0.85 (0.82-0.87). Subgroups analyses demonstrated that prognosis was poorer when obesity was associated with polycystic ovary syndrome, while the oocyte origin (donor or non-donor) did not modify the overall interpretation. Our meta-analysis clearly demonstrates that female obesity negatively and significantly impacts live birth rates following IVF. Whether weight loss can reverse this deleterious effect through lifestyle modifications or bariatric surgery should be further evaluated.
Wang T et al., 2019·International journal of cancer
Prior studies on the association between fertility treatment and childhood cancer risk have generated inconsistent results. We performed a systematic review and meta-analysis of observation studies to summarize the evidence regarding the relation of fertility treatment with childhood cancer risk. A systematic literature search of several databases was conducted through April 2018 to identify relevant studies. The outcomes of interest included overall cancer, haematological malignancies, neural tumours, other solid tumours, and eight specific cancers. The overall risk estimates and corresponding 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Sixteen cohort and thirteen case-control studies were included. Results showed that children conceived by fertility treatment had significantly higher risk for developing overall cancer (relative risk [RR]: 1.16, 95% CI: 1.01, 1.32), haematological malignancies (RR: 1.39, 95% CI: 1.21, 1.60) and other solid tumours (RR: 1.57, 95% CI: 1.14, 2.16). For specific cancers, fertility treatment was associated with a significantly increased risk of leukaemia (RR: 1.31, 95% CI: 1.09, 1.57) and hepatic tumours (RR: 2.26, 95% CI: 1.32, 3.85). Sensitivity analysis validated evidence of the robustness of the findings. The results may demonstrate a possible association between fertility treatment and an increased risk of cancer among the offspring. However, the findings cannot say whether this increased risk is due to the subfertility itself or to the fertility treatment. Further research is needed to address the underlying mechanisms.
Almasi-Hashiani A et al., 2019·BMC Pregnancy Childbirth·
Open Access
The objective of this systematic review and meta-analyses was to assess the risk of preeclampsia among women who conceived with assisted reproductive technology (ART). We searched the ISI Web of Knowledge, Medline/PubMed, Scopus, and Embase (from inception to May 2017) for English language articles using a list of key words. In addition, reference lists from identified studies and relevant review articles were also searched. Data extraction was performed by two authors, and the study quality was assessed using the Newcastle-Ottawa Scale. Random-effects model meta-analysis was applied to pool the relative risks (RR) across studies. A total of 48 studies (5 case-control studies and 43 cohort studies) were included in this meta-analysis. The Cochran Q test and I(2) statistics revealed substantial heterogeneity (Q = 26,313.92, d.f. = 47, p < 0.001 and I(2) = 99.8%). Meta-analysis showed a significant increase in preeclampsia in women who conceived by ART compared with those who conceived spontaneously (RR = 1.71, 95% CI = 1.11-2.62, p = 0.015). The findings of this systematic review indicate that the use of ART treatment is associated with a 1.71-fold increase in preeclampsia.
The prevalence of poor response to gonadotropin stimulation is approximately 9-24% in women undergoing in vitro fertilization. Interestingly, due to containing a variety of growth factors, platelet-rich plasma (PRP) can play an important role in tissue regeneration and healing. Thus, in this research, we aimed to investigate the intra-ovarian injection of PRP in women with poor ovarian response. To this goal, 23 poor responders constituted the study population, from among whom 19 women were enrolled. These patients underwent ovarian stimulation according to the Shanghai protocol. Immediately after the first follicular puncture, 2 mL of PRP was injected into each ovary. 1 day after the first puncture and PRP injection, the second stimulation was initiated. Then, oocyte retrieval was followed. About 2-3 months after the first cycle, the patients underwent another treatment with ovarian stimulation according to the Shanghai protocol and then, follicular puncture was performed. The mean numbers of oocytes before and after PRP injection were 0.64 and 2.1, respectively. Two patients experienced spontaneous conceptions. The third case achieved clinical pregnancy and delivered a healthy baby in June 2018. The results of this study appeared to be the first report on the effects of intra-ovarian PRP injection on the increase of ovarian responses, even on the spontaneous conceptions of women with poor ovarian response.
von Versen-Höynck F et al., 2019·Hypertension (Dallas, Tex. : 1979)
In vitro fertilization involving frozen embryo transfer and donor oocytes increases preeclampsia risk. These in vitro fertilization protocols typically yield pregnancies without a corpus luteum (CL), which secretes vasoactive hormones. We investigated whether in vitro fertilization pregnancies without a CL disrupt maternal circulatory adaptations and increase preeclampsia risk. Women with 0 (n=26), 1 (n=23), or >1 (n=22) CL were serially evaluated before, during, and after pregnancy. Because increasing arterial compliance is a major physiological adaptation in pregnancy, we assessed carotid-femoral pulse wave velocity and transit time. In a parallel prospective cohort study, obstetric outcomes for singleton livebirths achieved with autologous oocytes were compared between groups by CL number (n=683). The expected decline in carotid-femoral pulse wave velocity and rise in carotid-femoral transit time during the first trimester were attenuated in the 0-CL compared with combined single/multiple-CL cohorts, which were similar (group-time interaction: P=0.06 and 0.03, respectively). The blunted changes of carotid-femoral pulse wave velocity and carotid-femoral transit time from prepregnancy in the 0-CL cohort were most striking at 10 to 12 weeks of gestation ( P=0.01 and 0.006, respectively, versus 1 and >1 CL). Zero CL was predictive of preeclampsia (adjusted odds ratio, 2.73; 95% CI, 1.14-6.49) and preeclampsia with severe features (6.45; 95% CI, 1.94-25.09) compared with 1 CL. Programmed frozen embryo transfer cycles (0 CL) were associated with higher rates of preeclampsia (12.8% versus 3.9%; P=0.02) and preeclampsia with severe features (9.6% versus 0.8%; P=0.002) compared with modified natural frozen embryo transfer cycles (1 CL). In common in vitro fertilization protocols, absence of the CL perturbed the maternal circulation in early pregnancy and increased the incidence of preeclampsia.
Human-assisted reproductive technologies (ART) are a widely accepted treatment for infertile couples. At the same time, many studies have suggested the correlation between ART and increased incidences of normally rare imprinting disorders such as Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Silver-Russell syndrome (SRS). Major methylation dynamics take place during cell development and the preimplantation stages of embryonic development. ART may prevent the proper erasure, establishment, and maintenance of DNA methylation. However, the causes and ART risk factors for these disorders are not well understood. A nationwide epidemiological study in Japan in 2015 in which 2777 pediatrics departments were contacted and a total of 931 patients with imprinting disorders including 117 BWS, 227 AS, 520 PWS, and 67 SRS patients, were recruited. We found 4.46- and 8.91-fold increased frequencies of BWS and SRS associated with ART, respectively. Most of these patients were conceived via in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and showed aberrant imprinted DNA methylation. We also found that ART-conceived SRS (ART-SRS) patients had incomplete and more widespread DNA methylation variations than spontaneously conceived SRS patients, especially in sperm-specific methylated regions using reduced representation bisulfite sequencing to compare DNA methylomes. In addition, we found that the ART patients with one of three imprinting disorders, PWS, AS, and SRS, displayed additional minor phenotypes and lack of the phenotypes. The frequency of ART-conceived Prader-Willi syndrome (ART-PWS) was 3.44-fold higher than anticipated. When maternal age was 37 years or less, the rate of DNA methylation errors in ART-PWS patients was significantly increased compared with spontaneously conceived PWS patients. We reconfirmed the association between ART and imprinting disorders. In addition, we found unique methylation patterns in ART-SRS patients, therefore, concluded that the imprinting disorders related to ART might tend to take place just after fertilization at a time when the epigenome is most vulnerable and might be affected by the techniques of manipulation used for IVF or ICSI and the culture medium of the fertilized egg.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2018. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Canadian Fertility and Andrology Society; BORN Ontario, 2019·CFAS / BORN Ontario
CARTR Plus annual report containing final treatment cycle and pregnancy outcome data for 2016 and preliminary treatment cycle data for 2017. Presented at the Canadian Fertility and Andrology Society Annual Meeting (Montreal, September 2018). The Canadian Assisted Reproductive Technologies Register Plus (CARTR Plus) is a voluntary professional society database operated by CFAS in collaboration with BORN Ontario, capturing IVF/ART cycle outcomes from Canadian fertility clinics.
Ishihara O et al., 2019·Reprod Med Biol·
Open Access
Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2016, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG).
Sills ES et al., 2019·International journal of molecular and cellular medicine
One explanation for why downstream gonadotropin protocol changes during IVF commonly arrive too late to have significant effects is that embryo development actually begins during oogenesis. Thus, efforts to modify the chromosomal status of blastocysts must address the ovarian milieu well in advance of follicular recruitment. A 42 year old woman with primary infertility of 3 year duration attended with her partner. Five previous IVF cycles had produced 20 embryos, but all had genetic abnormalities and no embryo transfer was performed. Karyotypes and all lab tests were normal for both partners. 3 months before her IVF here, she received isolated platelet-derived growth factors injected into both ovaries as a cell-free, enriched substrate. Genetic assessments were via whole genome amplification and DNA tagmentation and PCR adapter sequences. Comprehensive chromosomal screening was carried out by dual-indexed sequencing of pooled libraries on the MiSeq™ platform. From this IVF cycle one euploid 46, XY blastocyst was produced and vitrified on the day of trophectoderm biopsy. 9 days after frozen embryo transfer, serum human chorionic gonadotropin was 250 mIU/ml and a transvaginal ultrasound at 6 week gestation confirmed a single intrauterine pregnancy with fetal heart at 153/min. A healthy male infant was delivered by c-section at 39 weeks' gestation. While cellular and molecular events directing the oocyte-to-embryo transition are incompletely characterized, processes related to ovarian stem cell differentiation, mitochondrial dynamics, and mRNA storage, translation, and degradation likely are relevant. It appears that intraovarian application of autologous platelet-derived growth factors, when used before IVF, can impact oocyte integrity and facilitate euploid blastocyst development. Although research on intraovarian injection of autologous activated platelet rich plasma has already shown improved quantitative IVF responses, this is the first description of qualitative improvements in embryo genetics after intraovarian injection of autologous platelet-derived growth factors.
Bay B et al., 2019·BJOG : an international journal of obstetrics and gynaecology
To assess the risk of stillbirth in low-risk in vitro fertilisation (IVF) pregnancies. Register-based national cohort study. Denmark 2003-2013. Cohort of 425 732 singleton pregnancies including 10 235 conceived following IVF/intracytoplasmic sperm injection (ICSI), 4521 conceived following intrauterine insemination (IUI), and 410 976 spontaneously conceived. Information on pregnancy, obstetrical risk factors, stillbirth, and fertility treatment was obtained from the Danish national health registers for all pregnancies after gestational week 21+6 . We estimated the overall and gestational age-specific risk of stillbirth in low-risk term pregnancies following IVF, ICSI, and IUI. Further, we estimated the association between stillbirth and IVF and ICSI respectively as well as fresh or frozen-thawed embryo transfer. Risk of stillbirth. The number of stillbirths in spontaneously conceived and IVF/ICSI low-risk term pregnancies was 525 (0.1%) and 35 (0.3%), respectively. In multivariate analysis, the risk of stillbirth in pregnancies following IVF/ICSI was increased (odds ratio 2.1, 95% CI 1.4-3.1). The risk of stillbirth was correspondingly increased in time-to-event analyses taking risk time for each fetus into account from gestational week 37 and onwards (hazard ratio 2.4, 95% CI 1.6-3.6). In sub-analyses, the risk of stillbirth was increased for pregnancies following ICSI (odds ratio 2.2, 95% CI 1.2-3.1), but not IVF (odds ratio 1.7, 95% CI 0.9-3.1). We found a systematically increased risk of stillbirth in low-risk term pregnancies following IVF/ICSI. Whether the risk was related to the treatment or to underlying subfertility is uncertain. The results may indicate a need for obstetrical surveillance for these pregnancies when reaching term. Increased risk of stillbirth in low-risk term pregnancies following fresh cycle IVF/ICSI.
Sunderam S et al., 2019·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
Assisted Reproductive Technology Surveillance - United States, 2016. Sunderam S(1), Kissin DM(1), Zhang Y(1), Folger SG(1), Boulet SL(2), Warner L(1), Callaghan WM(1), Barfield WD(1). (1)Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC. (2)Emory University School of Medicine, Atlanta, Georgia. Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g). This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2016 and compares birth outcomes that occurred in 2016 (resulting from ART procedures performed in 2015 and 2016) with outcomes for all infants born in the United States in 2016. 2016. In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico). In 2016, a total of 197,706 ART procedures (range: 162 in Wyoming to 24,030 in California) with the intent to transfer at least one embryo were performed in 463 U.S. fertility clinics and reported to CDC. These procedures resulted in 65,964 live-birth deliveries (range: 57 in Puerto Rico to 8,638 in California) and 76,892 infants born (range: 74 in Alaska to 9,885 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years), a proxy measure of the ART use rate, was 3,075. ART use rates exceeded the national rate in 14 reporting areas (Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Utah, and Virginia). ART use exceeded 1.5 times the national rate in nine states, including three (Illinois, Massachusetts, and New Jersey) that also had comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four oocyte retrievals). Nationally, among ART transfer procedures for patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age (1.5 among women aged <35 years, 1.7 among women aged 35-37 years, and 2.2 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 42.7% (range: 8.3% in North Dakota to 83.9% in Delaware). In 2016, ART contributed to 1.8% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.7% in Massachusetts). ART also contributed to 16.4% of all multiple-birth infants, including 16.2% of all twin infants and 19.4% of all triplets and higher-order infants. ART-conceived twins accounted for approximately 96.5% (21,455 of 22,233) of all ART-conceived infants born in multiple deliveries. The percentage of multiple-birth infants was higher among infants conceived with ART (31.5%) than among all infants born in the total birth population (3.4%). Approximately 30.4% of ART-conceived infants were twins and 1.1% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 5.0% of all low birthweight (<2,500 g) infants. Among ART-conceived infants, 23.6% had low birthweight compared with 8.2% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (29.9%) than among all infants born in the total birth population (9.9%). The percentage of ART-conceived infants who had low birthweight was 8.7% among singletons, 54.9% among twins, and 94.9% among triplets and higher-order multiples; the corresponding percentages among all infants born were 6.2% among singletons, 55.4% among twins, and 94.6% among triplets and higher-order multiples. The percentage of ART-conceived infants who were born preterm was 13.7% among singletons, 64.2% among twins, and 97.0% among triplets and higher-order infants; t
Eftekhar M et al., 2018·Taiwanese journal of obstetrics & gynecology·
Open Access
[OBJECTIVE] One of the important aspects involved in achieving optimal outcomes after assisted reproductive treatment (ART) is the endometrium. Some cycles are cancelled due to inadequate endometrial growth in ART. In this clinical trial, we evaluated the effectiveness of platelet-rich plasma (PRP) in the treatment of thin endometrium. [MATERIALS AND METHODS] In this randomized clinical trial, 83 women with poor endometrial response to standard hormone replacement therapy (HRT) (endometrium thickness < 7 mm) in the 13th day of the cycle in a frozen-thawed embryo transfer (FET) were entered in two groups. In the PRP group (n = 40), in addition to HRT, 0.5-1 cc of PRP was infused into the uterine cavity on the 13th day of HRT cycle. The control group (n = 43) was only received HRT. If endometrial thickness failed to increase after 48 h, PRP infusion was repeated in the same cycle. When the endometrium thickness reached ≥7 mm, embryo transfer was done. Finally, endometrial thickness, chemical, clinical, and ongoing pregnancy rates were compared between two groups. [RESULTS] Endometrial thickness increased significantly to 8.67 ± 0.64 in PRP group than in controls (p = 0.001). This increase was higher in women who conceived in PRP group (p value: 0.031). The implantation rate and per-cycle clinical pregnancy rate were significantly higher in PRP group (p = 0.002 and 0.044, respectively (p = 0.002). [CONCLUSION] PRP may be effective in improving the endometrial growth, and possibly pregnancy outcomes in women with a thin endometrium.
Alternative ovarian stimulation protocols for in vitro fertilisation (IVF) have grown in popularity. Yet, patient populations best suited for these protocols have not been defined. Our objective was, therefore, to determine national IVF utilisation patterns and live birth rates of various ovarian stimulation protocols. Retrospective cohort study. Academic-affiliated private fertility centre. Aggregate data published by Society for Assisted Reproductive Technology for autologous IVF cycles performed in the USA during 2014 and 2015 were analysed. IVF cycles were stratified based on ovarian stimulation protocol: 205 705 conventional stimulations, 4397 minimal stimulations, 2785 natural cycles and 514 in vitro maturation (IVM) cycles. Repeat cycles could not be determined in this analysis. Utilisation patterns and age-specific live birth rates for various ovarian stimulation protocols. With advancing female age, utilisation of conventional stimulation protocols decreased, while minimal stimulation and natural cycle IVF increased. Diminished ovarian reserve diagnoses were in all age groups less prevalent in patients undergoing conventional stimulation than with all other protocols. Live birth rates were highest with conventional stimulation at 42.4%, 33.1%, 22.1%, 11.7% and 3.9% for <35, 35-37, 38-40, 41-42 and >42 female age groups, respectively. The difference in live birth rates between conventional stimulation and other protocols widened with advancing age from 1.6-fold to 3.9-fold among women <35 years of age, reaching 4.4-fold to 6.6-fold among women >42 years of age. In comparison to conventional stimulation IVF-minimal stimulation, natural cycle IVF and IVM protocols offer lower but still acceptable live birth rates among young women. These alternative protocols are frequently used in older women and those with diminished ovarian reserve, despite their lower live birth rates. The reasons for this apparent incongruity warrant further careful exploration.
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title: "ART in Europe, 2014: results generated from European registries by ESHRE"
source_file: "eshre-eim-2014-source.pdf"
doi: "10.1093/humrep/dey242"
journal: "Human Reproduction, pp. 1-16, 2018"
pages: 16
extracted_date: "2026-04-24"
figures_extracted: 3
tables_extracted: 5
review_flags: 3
authors: "Ch. De Geyter, C. Calhaz-Jorge, M.S. Kupka, C. Wyns, E. Mocanu, T. Motrenko, G. Scaravelli, J. Smeenk, S. Vidakovic, V. Goossens"
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A significant increase in the use of intracytoplasmic sperm injection (ICSI) since its introduction in 1992 has been observed worldwide, including beyond its original intended use for severe male factor infertility. Concerns regarding ICSI include the effects of poor quality spermatozoa on offspring health and future fertility, and of the technique itself. The health and development of ICSI-conceived children beyond early infancy have not been comprehensively assessed. A systematic review of health outcomes of ICSI-conceived offspring beyond the neonatal period compared to spontaneously conceived (SC) offspring. PubMed, OVID Medline/Embase, InformIT, Web of Science, and ProQuest databases were searched for studies reporting on health outcomes in ICSI-conceived offspring beyond 28 days after birth. Physical and psychosocial health. The search strategy yielded 2826 articles. Of these, 2580 were not relevant or did not meet inclusion criteria and 138 were duplicates. One hundred and eight full-text papers were evaluated further, and 48 satisfied the inclusion criteria. Most studies reported on neurodevelopment during early infancy and childhood with reassuring results. Growth, vision, and hearing of ICSI and SC offspring also appear comparable, although important differences in general physical health, and particularly metabolic and reproductive health have been described, including recently poorer semen quality among ICSI-conceived young adult men compared to SC peers. Whilst neurodevelopment, growth, vision, and hearing appear similar between ICSI and SC children, evidence suggests differences in general physical health, and metabolic and reproductive endpoints. The clinical significance of many findings, however, remains unclear, and further prospective, large, and good quality studies with a focus on all these health outcomes in ICSI-conceived young adults are required.
Levi-Setti PE et al., 2018·Fertility and Sterility·
Open Access
To assess complications encountered after transvaginal oocyte retrieval procedures. Retrospective analysis. University hospital, fertility center. PATIENT(S): A total of 23,827 consecutive transvaginal oocyte retrieval procedures in 12,615 patients. INTERVENTION(S): Oocyte retrieval procedures performed between June 1996 and October 2016. MAIN OUTCOME MEASURE(S): All oocyte retrieval complications. Those requiring hospital admission for at least 24 hours were considered severe. RESULT(S): A total of 96 patients (0.76 %) suffered complications, with hospital admission necessary for 71 patients (0.56 %). When calculated per retrieval, the overall complication rate was 0.4%, whereas 0.29% was the admission rate, with an average duration of hospital stay of 2.77 ± 2.5 days. A surgical procedure was necessary for 24 patients (0.1% per retrieval and 0.19% per patient). Multivariate analysis showed a significant correlation between complications and women age, body mass index (BMI), the number oocyte retrieved, and the mean time to complete oocyte retrieval. The incidence of complications was significantly higher for physicians who had performed <250 retrievals compared with those who had completed >250 retrievals (odds ratio 0.63, 95% confidence interval 0.40-0.99). CONCLUSION(S): Oocyte retrieval can be considered a safe procedure but is not without risks. The most important, identifiable, risk factors for the occurrence of complications are: [1] high number of oocytes retrieved, [2] a long duration of the procedure and mean time per oocyte retrieved, [3] inexperience of the surgeon, [4] younger patients with a lesser BMI, and [5] history of prior abdominal or pelvic surgery or pelvic inflammatory disease. CLINICAL NCT03282279.
Sills ES et al., 2018·Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
Platelets modulate clinically relevant yet incompletely understood tissue regeneration processes, and platelet rich plasma (PRP) has been previously used with some success in various non-reproductive medical contexts. Here, we extended PRP application to ovarian tissue with a view to document impact on ovarian reserve among women attending for infertility treatment. PRP was freshly isolated from patients (n= 4) with diminished ovarian reserve as determined by at least one prior IVF cycle canceled for poor follicular recruitment response or estimated by serum AMH and/or FSH, no menses for ≥1 year. Immediately following substrate isolation and activation with calcium gluconate, approximately 5 mL of autologous PRP was injected into each ovary under direct transvaginal sonogram guidance. For each study subject, AMH, FSH, and serum estradiol data were recorded at two-week intervals post-PRP and compared to baseline (pre-PRP) values. In this pilot group, mean (±SD) patient age was 42 ± 4 years with infertility duration reported as 60 ± 25 months. Following this protocol of intraovarian PRP administration, increases in serum AMH (p = .17), decreases in FSH (p < .01), or both, were observed in all cases, sufficient to permit retrieval of 5.3 ± 1.3 MII oocytes. IVF occurred 78 ± 22 (range = 59-110) days after activated PRP injection, and results appeared independent of patient age, infertility duration, baseline platelet concentration or pretreatment antral follicle count. Each patient had at least one blastocyst suitable for cryopreservation. While autologous PRP has been successfully applied therapeutically to various tissues to accelerate healing and wound repair, this is the first description of direct injection of activated PRP into the human ovary of poor prognosis IVF patients. Evidence of improved ovarian function was noted in all who received intraovarian PRP, possibly as early as two months after treatment. Additional research is needed to clarify (and enhance) which PRP components are responsible for altered ovarian function, and to identify predictive characteristics for patients most likely to benefit from this intervention.
Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g) infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2015 and compares birth outcomes that occurred in 2015 (resulting from ART procedures performed in 2014 and 2015) with outcomes for all infants born in the United States in 2015. Period Covered: 2015. Description of System: In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System, a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico).
In 2015, a total of 182,111 ART procedures (range: 135 in Alaska to 23,198 in California) with the intent to transfer at least one embryo were performed in 464 U.S. fertility clinics and reported to CDC. These procedures resulted in 59,334 live-birth deliveries (range: 55 in Wyoming to 7,802 in California) and 71,152 infants born (range: 68 in Wyoming to 9,176 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years), a proxy measure of the ART utilization rate, was 2,832. ART use exceeded the national rate in 13 reporting areas (California, Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Virginia). Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.6 among women aged <35 years, 1.8 among women aged 35-37 years, and 2.3 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 34.7% (range: 11.3% in Puerto Rico to 88.1% in Delaware). In 2015, ART contributed to 1.7% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.5% in Massachusetts). ART also contributed to 17.0% of all multiple-birth infants, 16.8% of all twin infants, and 22.2% of all triplets and higher-order infants. The percentage of multiple-birth infants was higher among infants conceived with ART (35.3%) than among all infants born in the total birth population (3.4%). Approximately 34.0% of ART-conceived infants were twins and 1.0% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 5.1% of all low birthweight infants. Among ART-conceived infants, 25.5% had low birthweight, compared with 8.1% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (31.2%) than among all infants born in the total birth population (9.7%). Among singletons, the percentage of ART-conceived infants who had low birthweight was 8.7% compared with 6.4% among all infants born. The percentage of ART-conceived infants who were born preterm was 13.4% among singletons compared with 7.9% among all infants. Interpretation: Multiple births from ART contributed to a substantial proportion of all twins, triplets, and higher-order infants born in the United States. For women aged <35 years, who are typically considered good candidates for eSET, the national average of 1.6 embryos was transferred per ART procedure. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four cycles of IVF), three (Illinois, Massachusetts, and New Jersey) had rates of ART use exceeding 1.5 times the national rate. This type of mandated insurance coverage has been associated with greater use of ART and likely accounts for some of the difference in per capita ART use observed among states. Public Health Action: Twins account for the majority of ART-conceived multiple births. Reducing the number of embryos transferred and increasing use of eSET when clinically appropriate could help reduce multiple births and related adverse health consequences for both mothers and infants. State-based surveillance of ART might be useful for monitoring and evaluating maternal and infant health outcomes of ART in states with high ART use.
The most common complication during oocyte retrieval is vaginal bleeding, which is largely controlled by buffer application. In conclusion, the oocyte retrieval process can be considered a safe procedure.
Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2015, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG).
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2017. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Canadian Fertility and Andrology Society; BORN Ontario, 2018·CFAS / BORN Ontario
CARTR Plus annual report. Presented at the Canadian Fertility and Andrology Society Annual Meeting in September 2017, reporting Canadian ART cycle outcomes.
Registries and Reporting · Cross-Registry Comparison
To study the perinatal outcomes between singleton live births achieved with the use of commissioned versus spontaneously conceived embryos carried by the same gestational surrogate. Retrospective cohort study. Academic in vitro fertilization center. PATIENT(S): Gestational surrogate. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy outcome, gestational age at birth, birth weight, perinatal complications. RESULT(S): We identified 124 gestational surrogates who achieved a total of 494 pregnancies. Pregnancy outcomes for surrogate and spontaneous pregnancies were significantly different (P<.001), with surrogate pregnancies more likely to result in twin pregnancies: 33% vs. 1%. Miscarriage and ectopic rates were similar. Of these pregnancies, there were 352 singleton live births: 103 achieved from commissioned embryos and 249 conceived spontaneously. Surrogate births had lower mean gestational age at delivery (38.8 ± 2.1 vs. 39.7 ± 1.4), higher rates of preterm birth (10.7% vs. 3.1%), and higher rates of low birth weight (7.8% vs. 2.4%). Neonates from surrogacy had birth weights that were, on average, 105 g lower. Surrogate births had significantly higher obstetrical complications, including gestational diabetes, hypertension, use of amniocentesis, placenta previa, antibiotic requirement during labor, and cesarean section. CONCLUSION(S): Neonates born from commissioned embryos and carried by gestational surrogates have increased adverse perinatal outcomes, including preterm birth, low birth weight, hypertension, maternal gestational diabetes, and placenta previa, compared with singletons conceived spontaneously and carried by the same woman. Our data suggest that assisted reproductive procedures may potentially affect embryo quality and that its negative impact can not be overcome even with a proven healthy uterine environment.
Late preterm infants are at risk for short-term morbidities. We report that late preterm singletons conceived with fertility treatment have increased risk for admission to the neonatal intensive care unit and respiratory support compared with spontaneously conceived infants. Fertility treatment may be a risk factor to consider in managing late preterm infants.
To explore the relationship between the type of clinician (generalist vs subspecialist) initially seen by infertile women, the treatment received, and the time to pregnancy. We analyzed mixed-mode questionnaire data from 867 women with primary infertility enrolled into a retrospective cohort through population- and fertility clinic-based sampling. We compared women presenting first to generalist providers with women presenting first to fertility subspecialists, with the main outcomes of receiving in vitro fertilization (IVF), time to pregnancy, and live birth. The first contact for most (84%) women with infertility was a generalist provider. Only 8% of women sought care first from a fertility subspecialist, and these women were older and had been trying longer to conceive. Women who presented first to a generalist provider were less likely to receive IVF (adjusted odds ratio, 0.48; 95% confidence interval, 0.28-0.82), were equally likely to achieve pregnancy, and had similar times to pregnancy (adjusted hazard ratio, 1.11; 95% confidence interval, 0.80-1.53) compared with women who presented first to a subspecialist. Generalist providers are frequently the first point of care for women with difficulty conceiving and are uniquely positioned to promote the balanced management of infertility.
To establish how medically assisted reproduction (MAR) clinics report success rates on their websites. Websites of private and NHS clinics offering in vitro fertilisation (IVF) in the UK. We identified clinics offering IVF using the Choose a Fertility Clinic facility on the website of the Human Fertilisation and Embryology Authority (HFEA). Of 81 clinics identified, a website could not be found for 2, leaving 79 for inclusion in the analysis. PRIMARY Outcome measures reported by clinic websites. The numerator and denominator included in the outcome measure were of interest. 53 (67%) websites reported their performance using 51 different outcome measures. It was most common to report pregnancy (83% of these clinics) or live birth rates (51%). 31 different ways of reporting pregnancy and 9 different ways of reporting live birth were identified. 11 (21%) reported multiple birth or pregnancy rates. 1 clinic provided information on adverse events. It was usual for clinics to present results without relevant contextual information such as sample size, reporting period, the characteristics of patients and particular details of treatments. Many combinations of numerator and denominator are available for the purpose of reporting success rates for MAR. The range of reporting options available to clinics is further increased by the possibility of presenting results for subgroups of patients and for different time periods. Given the status of these websites as advertisements to patients, the risk of selective reporting is considerable. Binding guidance is required to ensure consistent, informative reporting.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2016. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Irahara M et al., 2017·Reprod Med Biol·
Open Access
Multi-decade summary report covering assisted reproductive technology (ART) cycles performed in Japan from 1992 through 2014, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG). Provides longitudinal trends in cycle volume, treatment-type stratification, and outcomes from JSOG-registered ART facilities.
Sunderam S et al., 2017·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
Assisted Reproductive Technology Surveillance - United States, 2014. Sunderam S(1), Kissin DM(1), Crawford SB(1), Folger SG(1), Jamieson DJ(1), Warner L(1), Barfield WD(1). (1)Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC. Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks to both mothers and infants, including obstetric complications, preterm delivery, and low birthweight infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2014 and compares birth outcomes that occurred in 2014 (resulting from ART procedures performed in 2013 and 2014) with outcomes for all infants born in the United States in 2014. 2014. In 1996, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico). In 2014, a total of 169,568 ART procedures (range: 124 in Wyoming to 21,018 in California) with the intent to transfer at least one embryo were performed in 458 U.S. fertility clinics and reported to CDC. These procedures resulted in 56,028 live-birth deliveries (range: 52 in Wyoming to 7,230 in California) and 68,782 infants born (range: 64 in Wyoming to 8,793 in California). Nationally, the total number of ART procedures performed per million women of reproductive age (15-44 years), a proxy measure of the ART usage rate, was 2,647 (range: 364 in Puerto Rico to 6,726 in Massachusetts). ART use exceeded the national average in 13 reporting areas (Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Virginia). Eight reporting areas (Connecticut, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Jersey, and New York) had rates of ART use exceeding 1.5 times the national average. Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.7 among women aged <35 years, 1.9 among women aged 35-37 years, and 2.3 among women aged >37 years). Among women aged <35 years, who typically are considered to be good candidates for elective single embryo transfer (eSET) procedures, the national eSET rate was 28.5% (range: 4.3% in Puerto Rico to 67.9% in Delaware). In 2014, ART contributed to 1.6% of all infants born in the United States (range: 0.4% in Puerto Rico to 4.7% in Massachusetts) and 18.3% of all multiple-birth infants (range: 5.5% in Alaska and West Virginia to 37.3% in Hawaii), including 18.0% of all twin infants (range: 5.2% in some states to 36.2% in Hawaii) and 26.4% of all triplets and higher-order infants (range: 0% in some states to 65.2% in Hawaii). Percentages of live births that were multiple-birth deliveries were higher among infants conceived with ART (39.4%; range: 11.5% in Delaware to 55.6% in Puerto Rico) than among all infants born in the total birth population (3.5%; range: 2.2% in Puerto Rico to 4.4% in New Jersey). Approximately 38.0% of ART-conceived infants were twin infants, and 2.0% were triplets and higher-order infants. ART-conceived twins accounted for approximately 95.3% of all ART-conceived infants born in multiple deliveries. Nationally, infants conceived with ART contributed to 5.5% of all low birthweight (<2,500 g) infants (range: 1.2% in West Virginia to 14.2% in Massachusetts). Among ART-conceived infants, 27.8% were low birthweight (range: 10.6% in Delaware to 44.4% in Puerto Rico), compared with 8.0% among all infants (range: 5.9% in Alaska to 11.3% in Mississippi). ART-conceived infants contributed to 4.7% of all preterm (<37 weeks) infants (range: 1.2% in Puerto Rico to 13.4% in Massachusetts). Percentages of preterm births were higher among infants conceived with ART (33.2%; range: 18.9% in the District of Columbia to 45.9% in Puerto Rico) than among all infants born in the total birth population (11.3%; range: 8.5% in California to 16.0% in Mississippi). The percentage of ART-c
Wdowiak A et al., 2016·Videosurgery and Other Miniinvasive Techniques·
Open Access
In vitro fertilization (IVF) is a method of treatment for infertility in selected indications. Recent years have brought dynamic development of technologies related to IVF. This article presents problems pertaining to the safety of technology with respect to the patient, as well as the embryo, based on an analysis of scientific reports and our own experience. Invasiveness of the IVF procedure for the woman and the embryo varies on an individual basis. Minimization of the invasiveness of IVF requires experience of the staff performing the procedure, especially with respect to the assessment of risk for an individual patient. Technologies related to IVF are constantly being improved, and the effectiveness of the selected individual treatment methods is not always scientifically confirmed.
Kathpalia SK et al., 2016·Medical journal, Armed Forces India·
Open Access
Many infertile couples need treatment in different forms including Assisted Reproductive Techniques. In Vitro Fertilization and Embryo Transfer is the most advanced method of infertility treatment. Management of these pregnancies is difficult as the couples and treating doctors have undue concern and apprehension and worry about outcome of such pregnancies. This study was undertaken to find out the complications and mode of delivery and if there is a need to manage them at tertiary care centers. 130 cases were included in the study after pregnancy was confirmed in this prospective study. These cases were followed throughout pregnancy and labour. Pregnancy, labour, and neonatal complications were noted. Incidence of primary infertility was more common. Mean age of patient was more. All the cases were provided standard routine antenatal care. Multiple pregnancies and preterm labour were more frequent in the study group. A large number of cases delivered vaginally. A large number of pregnancies terminated in vaginal delivery, thereby indicating that these pregnancies though high risk can have vaginal delivery. They can be managed at any hospital once clinical pregnancy is confirmed.
Masoudian P et al., 2016·American journal of obstetrics and gynecology
The purpose of this study was to determine whether pregnancies that were achieved via oocyte donation, compared with pregnancies achieved via other assisted reproductive technology methods or natural conception, demonstrate increased risk of preeclampsia or gestational hypertension. Comparative studies of pregnancies that were achieved with oocyte donation vs other methods of assisted reproductive technology or natural conception with preeclampsia or gestational hypertension were included as 1 of the measured outcomes. Abstracts and unpublished studies were excluded. Two reviewers independently selected studies, which were assessed for quality with the use of methodological index for non-randomized studies, and extracted the data. Statistical analysis was conducted. Of the 523 studies that were reviewed initially, 19 comparative studies met the predefined inclusion and exclusion criteria and were included in the metaanalysis, which allowed for analysis of a total of 86,515 pregnancies. Our pooled data demonstrated that the risk of preeclampsia is higher in oocyte-donation pregnancies compared with other methods of assisted reproductive technology (odds ratio, 2.54; 95% confidence interval, 1.98-3.24; P < .0001) or natural conception (odds ratio, 4.34; 95% confidence interval, 3.10-6.06; P < .0001). The risk of gestational hypertension was also increased significantly in oocyte donation pregnancies in comparison with other methods of assisted reproductive technology (odds ratio, 3.00; 95% confidence interval, 2.44-3.70; P < .0001) or natural conception (odds ratio, 7.94; 95% confidence interval, 1.73-36.36; P = .008). Subgroup analysis that was conducted for singleton and multiple gestations demonstrated a similar risk for preeclampsia and gestational hypertension in both singleton and multiple gestations. This metaanalysis provides further evidence that supports that egg donation increases the risk of preeclampsia and gestational hypertension compared with other assisted reproductive technology methods or natural conception.
To provide a detailed description of the current oocyte vitrification status as a means of elective fertility preservation (EFP).
Retrospective observational multicenter study.
Private university-affiliated center.
PATIENT(S): A total of 1,468 women who underwent EFP because of age or having associated a medical condition other than cancer (January 2007 to April 2015).
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Survival and cumulative live birth rate (CLBR) per consumed oocyte.
RESULT(S): Mean age was higher with EFP due to age versus having an associated medical reason (37.7 y [95% confidence interval (CI) 36.5-37.9] vs. 35.7 y [95% CI 34.9-36.3]). In total, 137 patients (9.3%) returned to use their oocytes. Overall survival rate was 85.2% (95% CI 83.2-87.2). Live birth rate per patient was higher in women ≤35 years old than ≥36 years old (50% [95% CI 32.7-67.3] vs. 22.9% [95% CI 14.9-30.9]). CLBR was higher and increased faster in younger women. The gain in CLBR was sharp from 5 (15.4%, 95% CI -4.2 to 35.0) to 8 oocytes (40.8%, 95% CI 13.2-68.4), with an 8.4% gain per additional oocyte, in the ≤35-year-old group. The increase was slower with 10-15 oocytes, reaching a plateau CLBR of 85.2%. A milder increase (4.9% gain) was observed in the ≥36-year-old group (from 5.1% [95% CI -0.6 to 10.7] to 19.9% [95% CI 8.7-31.1] when 5-8 oocytes were consumed), reaching the plateau with 11 oocytes (CLBR 35.6%). Forty babies were born.
CONCLUSION(S): At least 8-10 metaphase II oocytes are necessary to achieve reasonable success. Numbers should be individualized in women >36 years old. We suggest encouraging women who are motivated exclusively by a desire to postpone childbearing because of age, to come at younger ages to increase success possibilities.
Humphries LA et al., 2016·American Journal of Obstetrics and Gynecology
We conducted a systematic review to evaluate the influence of race and ethnicity on clinical pregnancy and live birth outcomes after in vitro fertilization (IVF).StudyWe searched PubMed, EMBASE, Web of Science, CINAHL, POPLINE, and Cochrane Central, and hand-searched relevant articles published through July 22, 2015.Study appraisal and synthesis methodsTwo reviewers independently evaluated abstracts to identify studies that compared clinical pregnancy rates and live birth rates for ≥2 racial and/or ethnic groups after nondonor IVF cycles. Twenty-four studies were included. All 5 US registry-based studies showed that black, Hispanic, and Asian women had lower clinical pregnancy rates and/or live birth rates after IVF, compared with white women. Similarly, most clinic-specific studies reported significant disparities in these primary outcomes, potentially attributable to differences in infertility diagnosis, spontaneous abortion, and obesity. Studies varied with respect to definitions of race/ethnicity, inclusion of first cycles vs multiple cycles for individual women, and collected covariates. Most studies were limited by sample size, inadequate adjustment for confounding, selection bias, and extensive missing data. Although current evidence points to race and ethnicity, especially black race, as strong predictors of poorer outcomes after IVF, the utility of results is constrained by the limitations described.
Hua R et al., 2016·Nan fang yi ke da xue xue bao = Journal of Southern Medical University
To investigate the associations of occupational, educational and residential factors with the outcomes of in vitro fertilization -embryo transfer (IVF-ET). A retrospective analysis was conducted among 3998 patients undergoing the first treatment with IVF-ET and 3064 perinatal infants in our center between January, 2010 and June, 2014. The relation of the patients' occupation, educational background, and residence registry with IVF-ET outcomes was analyzed. The risk of abortion in the first trimester was significantly higher in female patients engaged in agriculture (OR=4.319, P=0.047). Occupation and educational background of the patients and their spouse were related with the incidence of ectopic pregnancy following IVF-ET. The total incidence rate of perinatal birth defects was 2.1% in this cohort, and was the highest in Shenzhen (5.5%) but this difference was not statistically significant (P>0.05). The patients' occupation and educational background are related with the outcomes of IVF-ET, suggesting the importance of health education and prenatal examination.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2015. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
To determine whether there are any increases in pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies after assisted reproductive technology (ART) compared with those conceived naturally. Meta-analysis. University-affiliated teaching hospital. PATIENT(S): Singleton pregnancies conceived with ART and naturally. INTERVENTION(S): PubMed, Google Scholar, Cochrane Libraries and Chinese database were searched through March 2015 to identify studies that met pre-stated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators. MAIN OUTCOME MEASURE(S): Pregnancy-related complications and adverse pregnancy outcomes. RESULT(S): Fifty cohort studies comprising 161,370 ART and 2,280,241 spontaneously conceived singleton pregnancies were identified. The ART singleton pregnancies had a significantly increased risk of pregnancy-induced hypertension (relative risk [RR] 1.30, 95% confidence interval [CI] 1.04-1.62; I(2) = 79%), gestational diabetes mellitus (RR 1.31, 95% CI 1.13-1.53; I(2) = 6%), placenta previa (RR 3.71, 95% CI 2.67-5.16; I(2) = 72%), placental abruption (RR 1.83, 95% CI 1.49-2.24; I(2) = 22%), antepartum hemorrhage (RR 2.11, 95% CI 1.86-2.38; I(2) = 47%), postpartum hemorrhage (RR 1.29, 95% CI 1.06-1.57; I(2) = 65%), polyhydramnios (RR 1.74, 95% CI 1.24-2.45; I(2) = 0%), oligohydramnios (RR 2.14, 95% CI 1.53-3.01; I(2) = 0%), cesarean sections (RR 1.58, 95% CI 1.48-1.70; I(2) = 92%), preterm birth (RR 1.71, 95% CI 1.59-1.83; I(2)=80%), very preterm birth (RR 2.12, 95% CI 1.73-2.59; I(2) = 90%), low birth weight (RR 1.61, 95% CI 1.49-1.75; I(2) = 80%), very low birth weight (RR 2.12, 95% CI 1.84-2.43; I(2) = 67%), small for gestational age (RR 1.35, 95% CI 1.20-1.52; I(2) = 82%), perinatal mortality (RR 1.64, 95% CI 1.41-1.90; I(2)=45%), and congenital malformation (RR 1.37, 95% CI 1.29-1.45; I(2)=41%). Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed. CONCLUSION(S): The ART singleton pregnancies are associated with higher risks of adverse obstetric outcomes. Obstetricians should manage these pregnancies as high risk.
Registries and Reporting · Cross-Registry Comparison
Dyer S et al., 2016·Human reproduction (Oxford, England)
20. International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010. Dyer S(1), Chambers GM(2), de Mouzon J(3), Nygren KG(4), Zegers-Hochschild F(5), Mansour R(6), Ishihara O(7), Banker M(8), Adamson GD(9). (1)Department of Obstetrics & Gynaecology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa silke.dyer@uct.ac.za. (2)National Perinatal Epidemiology and Statistics Unit, University of New South Wales, Sydney, Australia. (3)Institut National de la Santé et de la Recherche Médicale Service de Gynécologie Obstétrique II et de Médecine de la Reproduction, Groupe Hospitalier Cochin-Saint Vincet de Paul, Paris, France. (4)Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. (5)Clinica las Condes and Program of Ethics and Public Policies in Human Reproduction, University Diego Portales, Santiago, Chile. (6)Egyptian IVF-ET Center, Cairo, Egypt. (7)Department of Obstetrics and Gynaecology, Saitama Medical University, Moroyama, Japan. (8)Nova IVI Fertility, Chennai, India. (9)Palo Alto Medical Foundation Fertility Physicians of North California, San Jose, CA, USA. Comment in Hum Reprod. 2016 Jul;31(7):1381-2. doi: 10.1093/humrep/dew092. What were utilization, outcomes and practices in assisted reproductive technology (ART) globally in 2008, 2009 and 2010? Global utilization and effectiveness remained relatively constant despite marked variations among countries, while the rate of single and frozen embryo transfers (FETs) increased with a concomitant slight reduction in multiple birth rates. ART is widely practised in all regions of the world. Monitoring utilization, an approximation of availability and access, as well as effectiveness and safety is an important component of universal access to reproductive health. STUDY DESIGN, SIZE, This is a retrospective, cross-sectional survey on utilization, effectiveness and safety of ART procedures performed globally from 2008 to 2010. PARTICIPANTS, SETTING, Between 58 and 61 countries submitted data from a total of nearly 2500 ART clinics each year. Aggregate country data were processed and analyzed based on forms and methods developed by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). Results are presented at country, regional and global level. MAIN For the years 2008, 2009 and 2010, >4 461 309 ART cycles were initiated, resulting in an estimated 1 144 858 babies born. The number of aspirations increased by 6.4% between 2008 and 2010, while FET cycles increased by 27.6%. Globally, ART utilization remained relatively constant at 436 cycles/million in 2008 and 474 cycles/million population in 2010, but with a wide country range of 8-4775 cycles/million population. ICSI remained constant at around 66% of non-donor aspiration cycles. The IVF/ICSI combined delivery rate (DR) per fresh aspiration was 19.8% in 2008; 19.7% in 2009 and 20.0% in 2010, with corresponding DRs for FET of 18.8, 19.7 and 20.7%. In fresh non-donor cycles, single embryo transfer increased from 25.7% in 2008 to 30.0% in 2010, while the average number of embryos transferred fell from 2.1 to 1.9, again with wide regional variation. The rates of twin deliveries following fresh non-donor transfers were, in 2008, 2009 and 2010, 21.8, 20.5 and 20.4%, respectively, with a corresponding triplet rate of 1.3, 1.0 and 1.1%. Fresh IVF and ICSI carried a perinatal mortality rate per 1000 births of 22.8 (2008), 19.2 (2009) and 21.0 (2010), compared with 15.1, 12.8 and 14.6/1000 births following FET in the same periods of observation. The proportion of women aged 40 years or older undergoing non-donor ART increased from 20.8 to 23.2% from 2008 to 2010. LIMITATIONS, The data presented are reliant on the quality and completeness of data submitted by individual countries. This report covers approximately two-thirds of the world ART activity. The ICMART World Reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment continues to increase globally, the wide disparities in access to treatment and embryo transfer practices warrant attention by clinicians and policy makers. The authors declare no conflict of interest and no specific support from any organizations in relation to this manuscript. ICMART acknowledges financial support from the following organizations: American Society for Reproductive Medicine; European Society for Human Reproduction and Embryology; Fertility Society of Australia; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproduccion Asistida; Society for Assisted Re
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
Comment in BMJ. 2015 Dec 23;351:h6913. doi: 10.1136/bmj.h6913. JAMA. 2015 Dec 22-29;314(24):2627-9. doi: 10.1001/jama.2015.17297. The likelihood of achieving a live birth with repeat in vitro fertilization (IVF) is unclear, yet treatment is commonly limited to 3 or 4 embryo transfers. To determine the live-birth rate per initiated ovarian stimulation IVF cycle and with repeated cycles. DESIGN, SETTING, Prospective study of 156,947 UK women who received 257,398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed up until June 2012. In vitro fertilization, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers. Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted, and conservative cumulative live-birth rates were estimated, reflecting 0%, 30%, and 100%, respectively, of women who discontinued due to poor prognosis and having a live-birth rate of 0 had they continued. Among the 156,947 women, the median age at start of treatment was 35 years (interquartile range, 32-38; range, 18-55), and the median duration of infertility for all 257,398 cycles was 4 years (interquartile range, 2-6; range, <1-29). In all women, the live-birth rate for the first cycle was 29.5% (95% CI, 29.3%-29.7%). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth cycle, with 65.3% (95% CI, 64.8%-65.8%) of women achieving a live birth by the sixth cycle. In women younger than 40 years using their own oocytes, the live-birth rate for the first cycle was 32.3% (95% CI, 32.0%-32.5%) and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (95% CI, 67.8%-68.9%). For women aged 40 to 42 years, the live-birth rate for the first cycle was 12.3% (95% CI, 11.8%-12.8%), with 6 cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (95% CI, 29.7%-33.3%). For women older than 42 years, all rates within each cycle were less than 4%. No age differential was observed among women using donor oocytes. Rates were lower for women with untreated male partner-related infertility compared with those with any other cause, but treatment with either intracytoplasmic sperm injection or sperm donation removed this difference. Among women in the United Kingdom undergoing IVF, the cumulative prognosis-adjusted live-birth rate after 6 cycles was 65.3%, with variations by age and treatment type. These findings support the efficacy of extending the number of IVF cycles beyond 3 or 4.
In vitro fertilization (IVF) is a method known almost all over the world, by which modern man is trying to cope with the problem of infertility. The aim of this article is to show the eugenic roots of in vitro and to attempt to reconciliate the supporters and opponents of this controversial procedure at a NaProTechnological plane. In order to achieve this, the author characterizes IVF from the technical, medical and legal point of view. Then, the article shows the relationship between the in vitro procedure and eugenic thought. The third section contextualizes the problem of artificial insemination in the contemporary, human uncritical faith in technological progress. The last part of this article directs the reader's attention towards NaProTechnology – a method of infertility treatement which can engage both the supporters and the opponents of IVF.
To investigate perinatal outcomes associated with fertility treatments, including assisted reproductive technology (ART), intrauterine insemination with ovulation stimulation (IUI), and ovulation stimulation alone (OS). Population-representative cross-sectional survey of women with live births, 2004-2008. Florida, Maryland, and Utah, USA. 21 803 women, weighted to represent 1 022 597 women. Survey and birth certificate data were analysed with logistic regression models adjusted for age, education, race, income, and parity, using separate models for singletons and all births. We used two referent groups: (1) women who never used fertility treatment and (2) subfertile women conceiving without treatment. Preterm birth (<37 weeks), very preterm birth (<34 weeks), low birthweight (<2500 g), and very low birthweight (<1500 g). Referent group 1: In singletons, ART was associated with preterm birth (OR 3.28; 95% CI 1.74, 6.20) and low birthweight (OR 2.91; 95% CI 1.99, 4.26). OS was also associated with low birthweight (OR 1.62; 95% CI 1.19, 2.19). Including all births, treatment was associated with preterm birth and low birthweight: ART (OR 6.21; 95% CI 4.21, 9.16 and OR 6.51; 95% CI 4.85, 8.73); IUI (OR 2.10; 95% CI 1.24, 3.56 and OR 2.41; 95% CI 1.54, 3.76); OS (OR 1.40; 95% CI 1.01, 1.94 and OR 2.10; 95% CI 1.60, 2.75), respectively. Referent group 2: ART was associated with both outcomes in all births, but not singletons. Preterm birth and low birthweight associated with fertility treatments are largely attributable to multiple gestation, but are also related to underlying subfertility. Preterm birth is associated with subfertility, and with fertility treatments through multiple gestation.
To provide an up-to-date comparison of pregnancy-related complications and adverse pregnancy outcomes of multiple pregnancies generated with assisted reproductive technology (ART) vs. spontaneous conception. Meta-analysis. University-affiliated teaching hospital.Patient(s)Multiple pregnancies conceived by ART or naturally.Intervention(s)Searches through October 2014 were conducted on PubMed, Google Scholar, Cochrane Libraries, China Biology Medicine disc, Chinese Scientific Journals Fulltext Database, China National Knowledge Infrastructure, and Wanfang Data, to identify studies that met prestated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators.Main outcome measure(s)Pregnancy-related complications and adverse pregnancy outcomes.Result(s)Thirty-nine cohort studies involving 146,008 multiple births were included in the meta-analysis. Multiple pregnancies from ART were associated with a higher risk of premature rupture of membranes (relative risk [RR] = 1.20, 95% confidence interval [CI]: 1.05-1.37; I(2) = 15%); pregnancy-induced hypertension (RR = 1.11, 95% CI: 1.04-1.19; I(2) = 6%); gestational diabetes mellitus (RR = 1.78, 95% CI: 1.25-2.55; I(2) = 42%); preterm birth (RR = 1.08, 95% CI: 1.03-1.14; I(2) = 83%); very preterm birth (RR = 1.18, 95% CI: 1.04-1.34; I(2) = 79%); low birth weight (RR = 1.04, 95% CI: 1.01-1.07; I(2) = 47%); very low birth weight (RR = 1.13, 95% CI: 1.01-1.25; I(2) = 62%); and congenital malformation (RR = 1.11, 95% CI: 1.02-1.22; I(2) = 30%). The relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded similar results. No evidence of publication bias was observed.Conclusion(s)Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests that multiple pregnancies generated via ART, vs. spontaneous conception, are associated with higher risks of pregnancy-related complications and adverse pregnancy outcomes. Further research is needed to determine which aspect of ART poses the most risk and how this risk can be minimized.
Schliep KC et al., 2015·Fertil Steril·
Open Access
To assess the effects of both male and female body mass index (BMI), individually and combined, on IVF outcomes.
Prospective cohort study.
University fertility center. PATIENT(S): All couples undergoing first fresh IVF cycles, 2005-2010, for whom male and female weight and height information were available (n = 721 couples). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryologic parameters, clinical pregnancy, and live birth incidence. RESULT(S): The average male BMI among the study population was 27.5 ± 4.8 kg/m(2) (range, 17.3-49.3 kg/m(2)), while the average female BMI (n = 721) was 25.2 ± 5.9 kg/m(2) (range, 16.2-50.7 kg/m(2)). Neither male nor female overweight (25-29.9 kg/m(2)), class I obese (30-34.9 kg/m(2)), or class II/III obese (≥35 kg/m(2)) status was significantly associated with fertilization rate, embryo score, or incidence of pregnancy or live birth compared with normal weight (18.5-24.9 kg/m(2)) status after adjusting for male and female age, partner BMI, and parity. Similar null findings were found between combined couple BMI categories and IVF success. CONCLUSION(S): Our findings support the notion that weight status does not influence fecundity among couples undergoing infertility treatment. Given the limited and conflicting research on BMI and pregnancy success among IVF couples, further research augmented to include other adiposity measures is needed.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2014. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Sunderam S et al., 2015·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
Assisted Reproductive Technology Surveillance - United States, 2013. Sunderam S, Kissin DM, Crawford SB, Folger SG, Jamieson DJ, Warner L, Barfield WD; Centers for Disease Control and Prevention (CDC). Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks to both mothers and infants, including obstetric complications, preterm delivery, and low birthweight infants. This report provides state-specific information for the United States (including Puerto Rico) on ART procedures performed in 2013 and compares infant outcomes that occurred in 2013 (resulting from ART procedures performed in 2012 and 2013) with outcomes for all infants born in the United States in 2013. 2013. In 1996, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia [DC], and Puerto Rico). In 2013, a total of 160,521 ART procedures (range: 109 in Wyoming to 20,299 in California) with the intent to transfer at least one embryo were performed in 467 U.S. fertility clinics and were reported to CDC. These procedures resulted in 53,252 live-birth deliveries (range: 47 in Alaska to 6,979 in California) and 66,691 infants (range: 61 in Alaska to 8,649 in California). Nationally, the total number of ART procedures performed per million women of reproductive age (15-44 years), a proxy measure of the ART usage rate, was 2,521 (range: 352 in Puerto Rico to 7,688 in DC). ART use exceeded the national rate in 13 reporting areas (California, Connecticut, Delaware, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Virginia, and DC). Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.8 among women aged <35 years, 2.0 among women aged 35-37 years, and 2.5 among women aged >37 years). Among women aged <35 years, who typically are considered to be good candidates for elective single embryo transfer (eSET) procedures, the national eSET rate was 21.4% (range: 4.0% in Idaho to 77.5% in Delaware). In 2013, ART contributed to 1.6% of all infants born in the United States (range: 0.2% in Puerto Rico to 4.8% in Massachusetts) and 18.7% of all multiple-birth infants (range: 4.5% in Puerto Rico to 35.7% in Massachusetts), including 18.5% of all twin infants (range: 4.5% in Mississippi to 35.3% in Massachusetts) and 25.2% of all triplet and higher-order infants (range: 0% in several reporting areas to 51.5% in New Jersey). Multiple-birth deliveries were higher among infants conceived with ART (41.1%; range: 20.4% in Delaware to 61.6% in Wyoming) than among all infants born in the total birth population (only 3.5%; range: 1.8% in Puerto Rico to 4.5% in Massachusetts and New Jersey). Approximately 39% of ART-conceived infants were twin infants, and 2% were triplet and higher-order infants. ART-conceived twins accounted for approximately 95.4% of all ART-conceived infants born in multiple deliveries. Nationally, infants conceived with ART contributed to 5.8% of all low birthweight (<2,500 grams) infants (range: 0.9% in Puerto Rico to 15.1% in Massachusetts). Among ART-conceived infants, 29.1% were low birthweight (range: 18.3% in Delaware to 42.6% in Louisiana), compared with 8.0% among all infants (range: 5.8% in Alaska to 11.5% in Mississippi). ART-conceived infants contributed to 4.6% of all preterm (<37 weeks) infants (range: 0.6% in Puerto Rico to 13.3% in Massachusetts). Preterm birth rates were higher among infants conceived with ART (33.6%; range: 22.3% in DC to 50.7% in Louisiana) than among all infants born in the total birth population (11.4%; range: 8.8% in California to 16.6% in Mississippi). The percentage of ART-conceived infants who were low birthweight was 9.0% (range: 5.1% in Mississippi to 19.7% in Puerto Rico) among singletons and 56.3% (range: 48.3% in Maine to 72.4% in Puerto Rico) among twins; the corresponding percentages among all infants born were 6.3% for singletons (range: 4.6% in Alaska to 9.6% in Mississippi and Puerto Rico) and 55.3% for twins (range: 43.6% in Alas
Hyrapetian M et al., 2014·Journal of reproductive immunology
In vitro fertilisation (IVF) and other assisted reproductive therapies (ART) offer hope to subfertile couples worldwide. At least 5 million ART children have been born to date. Their health is an issue that is increasingly relevant: first, to those children and young adults themselves; second, to couples considering fertility treatment; and third, to the general population as ART has progressed from experimental treatment to routine practice. Many concerns about the potential risks to these children have been voiced with varying degrees of supportive evidence. This article summarises some key long-term data. Current evidence suggests that ART does increase risk of: higher order pregnancy (with its inherent pre- and perinatal risks); prematurity and low birth weight; congenital malformations in particular of the male urogenital system; imprinting disorders. Reassuringly, evidence points away from an increased overall cancer risk or differences in neurodevelopmental outcomes. Many unknowns remain, including future fertility and cardiovascular risks and risk of cerebral palsy.
Increasing numbers of children are being conceived by assisted reproductive technology (ART). A number of studies have highlighted an altered epigenetic status in gametes from infertile couples and the possibility of an increased risk of imprinting defects and somatic epigenetic changes in ART conceived children, but the results have been heterogeneous. We performed a systematic review of existing studies to compare the incidence of imprinting disorders and levels of DNA methylation in key imprinted genes in children conceived through in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with those in children conceived spontaneously. A detailed search strategy was used to conduct electronic literature searches (spanning 1978 to 2013) on Medline, EMBASE, the Cochrane Library and Web of Science. Abstracts of relevant conference papers were identified. As randomized trials are not feasible in this context, we included observational (cohort and case-control) studies comparing outcomes in children conceived through ART with those conceived spontaneously, irrespective of the language of publication. The outcome measures were DNA methylation and the incidence of imprinting disorders. A total of 351 publications were identified by the initial search. Of these, 26 were excluded as duplicates and 241 were excluded after reviewing the abstracts, then of those remaining 66 were excluded after review of the full text. A total of 18 papers were included in the review. Apart from one case-control study, all were cohort studies. There was a degree of clinical heterogeneity in terms of the study population, type of infertility treatment, and samples obtained from exposed and unexposed children. DNA methylation levels were either presented as categorical data (hypo-, hyper- or normally methylated DNA) or continuous data (i.e. percentage of methylated DNA). The combined odds ratio (95% confidence intervals) of any imprinting disorder in children conceived through ART was 3.67 (1.39, 9.74) in comparison with spontaneously conceived children. Meta-analysis of data from relevant studies revealed that the weighted mean difference (95% confidence intervals) in methylation percent between IVF/ICSI versus spontaneously conceived children were as follows: H19: -0.46(-1.41, 0.49), PEG1-MEST: 0.47 (-2.07, 3.01), GRB10: -0.05 (-0.43, 0.33), IGF2: -0.15 (-1.09, 0.79), -0.55 (-1.55, 0.46), KvDMR/KCNQ10T1: -0.16 (-0.34, 0.02) and PEG3: -0.24 (-1.72, 1.24). There was an increase in imprinting disorders in children conceived though IVF and ICSI but insufficient evidence for an association between ART and methylation in other imprinted genes. Heterogeneity in the types of fertility treatment, the imprinted regions studied, the tissues used and the methods of measurement, reduce our ability to assess the full effect of ART on DNA methylation and imprinting. More controlled studies, using standardized methodologies, in larger, better clinically defined populations are needed.
Hansen M et al., 2014·Seminars in Fetal and Neonatal Medicine·
Open Access
Pooled odds ratios from meta-analyses of infants born following assisted reproductive technologies (ART) compared with non-ART singletons show increases in low birth weight, preterm birth, small for gestational age, and birth defects. Although there have been small reductions in recent data, odds associated with these outcomes are still higher for ART singletons. Both ART procedures and underlying infertility contribute to these increased risks. Outcomes appear better for frozen-thawed compared with fresh embryo transfers, but are poorer than for non-ART infants. There is a concerning increase in large-for-gestational-age infants born following frozen-thawed embryo transfer and limited data on the effects of embryo vitrification used instead of slow-freezing techniques. Using large datasets, we now need to investigate risks of individual birth defects and disentangle the inter-related effects of different types of infertility and the multiple aspects of ART. Greater understanding of the causes of adverse ART outcomes and identification of modifiable risk factors may lead to further reductions in the disparities in outcome between ART and non-ART infants.
Uyar A et al., 2014·Current Opinion in Obstetrics & Gynecology·
Open Access
Purpose of reviewGenomic imprinting refers to preferential allele-specific gene expression. DNA methylation-based molecular mechanisms regulate establishment and maintenance of parental imprints during early embryo development and gametogenesis. Because of the coincident timing, a potential association between assisted reproductive technology (ART) procedures and imprinting defects has been investigated in various studies. In this review, we provide an overview of genomic imprinting and present a summary of the relevant clinical data. Recent findings: ART procedures affect DNA methylation pattern, parental imprinting status, and imprinted gene expression in the mouse embryo. In humans, several case series suggested an association between ART and imprinting disorders, with a three-fold to six-fold higher prevalence of ART use among children born with Beckwith-Wiedemann syndrome compared to the general population. However, more recent studies failed to support these findings and could not demonstrate an association between imprinting disorders and ARTs, independent of subfertility. ART procedures may affect methylation status of imprinted regions in the DNA, leading to imprinting disorders. Although the low prevalence of imprinting disorders makes it challenging to perform conclusive clinical trials, further studies in large registries are required to determine the real impact of ARTs on their occurrence.
We reviewed the occurrence of prematurity, low birth weight, multiple gestations, frequency of stillbirths and maternity care-associated variables including hospital stay and hospital charges of women conceiving using assisted reproductive technology (ART) or artificial insemination (AI) compared with women with a history of infertility who conceived naturally, and all other naturally conceived pregnancies in California at non-federal hospitals between 2009 and 2011. At a single center, infants born after ART/AI were compared with infants provided care in the normal nursery. Publically available inpatient data sets from the California Office of Statewide Health Planning and Development for years 2009-2011 using data from all California non-federal hospitals were used to determine the impact of ART on a variety of pregnancy-related outcomes and infant characteristics. Infant data from a single center was used to determine hospital charges for infants delivered over an 18-month period to compare the hospital and physician charges indexed to similar charges for infants admitted to the 'normal' newborn nursery. Among ART/AI pregnancies, there was a 4-5-fold increase in stillbirths, compared with a 2-3-fold increase among women with infertility compared with other naturally conceiving women. ART/AI pregnancies underwent more cesarean sections (fourfold), and a near fourfold increase in the rate of preterm deliveries. Multiple gestations were increased 24-27-fold compared with naturally conceived pregnancies. Maternal hospital stay and hospital charges were increased among those undergoing ART/AI. Infant charges were increased multi-fold for singletons, twins and triplets delivered after ART/AI compared with naturally conceived infants. Multiple births, preterm births and a higher overall rate of fetal anomalies were found in California after ART/AI for 2009-2011. Cesarean section rates, longer length of maternal stay and hospital charges among women receiving ART/AI could be lowered if emphasis on elective single embryo transfers was a higher priority among providers. Charges for the care of infants delivered after ART/AI are substantially higher than among naturally conceived infants born late preterm or at term. Families seeking ART/AI need to be informed of the impact of these adverse pregnancy outcomes, including neonatal outcomes and charges for medical care for their infant(s), when considering ART/AI.
The aim of the article was to investigate the relationship between pregnancy complications, infertility and assisted reproductive technologies (ART). The study was conducted on 1331 couples with complicated reproductive history. It is found that miscarriage and other complications of pregnancy depend rather on the etiopathogenesis of infertility than on the technique of ART. The highest frequency of complications of pregnancy was diagnosed in women with endocrine disorders. In case of congenital malformations in the fetus the frequency of birth defects was 3.6% after in vitro fertilization (IVF) and 1.8% in case of spontaneous pregnancy. It was found an increased risk of birth defects in singleton boys conceived by IVF.
The indications for IVF have expanded from tubal disorders to many causes of subfertility, including unexplained. But with limited evidence underpinning its extended remit Esme Kamphuis and colleagues explain how the risks could outweigh the benefits.
Clomiphene citrate (CC) is the first line drug for ovulation induction but because of its peripheral antiestrogenic effect, letrozole was introduced as the 2nd line drug. It lacks the peripheral antiestrogenic effect and is associated with similar or even higher pregnancy rates. Since letrozole is a drug for breast cancer, its use for the purpose of ovulation induction became controversial in the light of studies indicating an increased incidence of congenital malformations. To evaluate and compare the incidence of congenital malformations among offsprings of infertile couples who conceived naturally or with clomiphene citrate or letrozole treatment. A retrospective cohort study done at a tertiary infertility centre. A total of 623 children born to infertile women who conceived naturally or following clomiphene citrate or letrozole treatment were included in this study. Subjects were sorted out from medical files of both mother and newborn and follow up study was done based on the information provided by parents through telephonic conversations. Babies with suspected anomaly were called and examined by specialists for the presence of major and minor congenital malformations. Other outcomes like multiple pregnancy rate and birth weight were also studied. Overall, congenital malformations, chromosomal abnormalities were found in 5 out of 171 (2.9%) babies in natural conception group and 5 out of 201 babies in the letrozole group (2.5%) and in 10 of 251 babies in the CC group (3.9%). There was no significant difference in the overall rate of congenital malformations among children born to mothers who conceived naturally or after letrozole or CC treatment. Congenital malformations have been found to be comparable following natural conception, letrozole and clomiphene citrate. Thus, the undue fear against letrozole may be uncalled for.
1. Endocrinology. 2014 May;155(5):1956-69. doi: 10.1210/en.2013-2081. Epub 2014
Mar 31. Use of a mouse in vitro fertilization model to understand the developmental
origins of health and disease hypothesis. Feuer SK(1), Liu X, Donjacour A, Lin W, Simbulan RK, Giritharan G, Piane LD,
Kolahi K, Ameri K, Maltepe E, Rinaudo PF. Author information:
(1)Department of Obstetrics, Gynecology and Reproductive Sciences (S.K.F., X.L.,
A.D., W.L., R.K.S., G.G., L.D.P., K.K., P.F.R.), and Department of Pediatrics
(K.A., E.M.), University of California San Francisco, San Francisco, California
94143; Nevada Center for Reproductive Medicine (G.G.), Reno, Nevada 89511;
Obstetric and Gynecology Department (L.D.P.), University of Turin, Turin, Italy;
and Oregon Health & Science University (K.K.), Portland, Oregon 97239. The Developmental Origins of Health and Disease hypothesis holds that
alterations to homeostasis during critical periods of development can predispose
individuals to adult-onset chronic diseases such as diabetes and metabolic
syndrome. It remains controversial whether preimplantation embryo manipulation,
clinically used to treat patients with infertility, disturbs homeostasis and
affects long-term growth and metabolism. To address this controversy, we have
assessed the effects of in vitro fertilization (IVF) on postnatal physiology in
mice. We demonstrate that IVF and embryo culture, even under conditions
considered optimal for mouse embryo culture, alter postnatal growth trajectory,
fat accumulation, and glucose metabolism in adult mice. Unbiased metabolic
profiling in serum and microarray analysis of pancreatic islets and insulin
sensitive tissues (liver, skeletal muscle, and adipose tissue) revealed broad
changes in metabolic homeostasis, characterized by systemic oxidative stress and
mitochondrial dysfunction. Adopting a candidate approach, we identify
thioredoxin-interacting protein (TXNIP), a key molecule involved in integrating
cellular nutritional and oxidative states with metabolic response, as a marker
for preimplantation stress and demonstrate tissue-specific epigenetic and
transcriptional TXNIP misregulation in selected adult tissues. Importantly,
dysregulation of TXNIP expression is associated with enrichment for H4
acetylation at the Txnip promoter that persists from the blastocyst stage
through adulthood in adipose tissue. Our data support the vulnerability of
preimplantation embryos to environmental disturbance and demonstrate that
conception by IVF can reprogram metabolic homeostasis through metabolic,
transcriptional, and epigenetic mechanisms with lasting effects for adult growth
and fitness. This study has wide clinical relevance and underscores the
importance of continued follow-up of IVF-conceived offspring. 10.1210/en.2013-2081
PMC3990843
24684304 [Indexed for MEDLINE]
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2013. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Canadian Fertility and Andrology Society; BORN Ontario, 2014·CFAS / BORN Ontario
CARTR Plus annual report covering Canadian ART cycle outcomes; presented at CFAS Annual Meeting October 2015 with 2013 birth outcomes and 2011-2014 cycle data. The Canadian Assisted Reproductive Technologies Register Plus (CARTR Plus) is a voluntary professional society database operated by CFAS in collaboration with BORN Ontario.
Kupka MS et al., 2014·Human reproduction (Oxford, England)
Jul 27. Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHRE†. Kupka MS(1), Ferraretti AP(2), de Mouzon J(2), Erb K(2), D'Hooghe T(2), Castilla JA(2), Calhaz-Jorge C(2), De Geyter C(2), Goossens V(2); European IVF-Monitoring Consortium, for the European Society of Human Reproduction and Embryology. Collaborators: Grunwald KM, Neulen J, Rösing B, Weisenborn U, Rau R, Schro B, Eid R, Hiller K-, Bauer T, Kraus H, Bayreuth K, Todorow S, Struller D, Etien C, Temme DH, Kentenich H, Siemann A, Stief G, Tandler-Schneider A, Remberg B, Tewordt S, Bloechle M, Marr S, Awwadeh H, Mutz A, Roth B, Kadgien C, Hannen R, Stoll CF, Jantke A, Spindeldreher S, Stegelmann A, Nowshari M, Sydow P, Peet DJ, Sydow C, Bergmann-Hensel U, Pfüller B, Bartley J, Scheiber I, Schmiady H, Ebert PA, Völklein K, Harms B, Baban N, Hilland U, Giesner Y, van der Ven H, van der Ven K, Bohlen U, Montag M, Prietl G, Drost O, Schmidt EH, Stutterheim Av, Finger T, Meyer-Ströh S, Jogschies P, Geistert D, Shugair L, Lahl A, Chemnitz S, Gabert A, Bauer K, Saager G, Leyendecker G, Bilgicyildirim A, Inacker M, Kroiss HJ, Bernhardt E, Braüker A, Vornehm H, Wilhelm E, Dieterle S, Neuer A, Greb R, Held HJ, Distler W, Keck G, Gouma E, Kru JS, Hess A, Mikat-Drozdzynski B, Schanz A, Hirchenhain J, Scholtes M, Marx K, Kisler S, Behler M, Pfeiffer S, Hubert P, Emde T, Yildirim-Assaf S, Frauena, Hamori M, Behrens R, Hammel A, Van Uem J, Beckmann MW, Müller A, Dittrich R, Katzorke T, Propping D, Wohlers S, Bielfeld P, Costea J, Wiegratz I, Merz E, Siebzehnru E, Weidner A, Weitzell, Thiemann, Wetzka, Geisthövel F, Friebel S, Hanjalic-Beck A, Zahradnik HP, Ina Walter-Göbel, Fiseler K, Hinney B, Michelmann HW, Moltrecht R, Hübner S, Welcker T, Sakin-Kaindl F, Mittmann S, Schulzeck P, Tobler M, Rostek J, Tigges J, Friol K, Gnoth C, Behre HM, Kaltwaser P, Seliger E, Horn, Michel u Partner, Bispink, Horn, Michel, Gohmann, Aytekin, Acar-Nosit, Kocak S, List P, Weidner U, Fischer R, Martina, Müseler-Albers, Arendt HP, Bühler K, Schill T, Schippert, Basler, Parta-Kehry W, Parta S, Tesarz F, Seehaus D, Tho C, Strowitzki T, Toth B, Algermissen, Justus, Wilke, Graf, Hildesheim, Fritzsche H, Reiher JP, Hoffmann A, Weiss J, Hoppe I, Wetzel V, Tetens F, Schlüter G, Willi MJ, Schmidt O, Hinrichsen M, Felberbaum R, Gerhard OA, Hiltensberger D, Kousehlar M, von Otte S, Schulz V, Völckers M, Eckel H, Schmutzler A, Salmassi A, Brandenburg K, Bonhoff A, Carstensen A, Merzenich M, Palm S, Pu I, Dannhof M, Keck C, Foth D, Ko U, Rahimi G, Moers C, Orth I, Leer K, von der Burg W, Alexander H, Weber W, Hmeidan FA, Jogschies P, Shugair L, Geistert D, Lahl A, Gabert A, Bauer K, Saager G, Griesinger G, Schultze-Mosgau A, Diedrich K, Schmidt T, Schmidt C, Motzkus N, Nickel I, Richter E, Kleinstein J, Brössner A, Sütterlin M, Schaffelder R, St Bussen, Schüttler J, Gentili, Sc RS, Passuello V, Kölbl H, Emig R, Mettlin S, Hadji P, Wagner U, Ziller V, Buurman O, Dumschat M, Menkhaus R, Heidecker B, Döhmen G, Schalk T, Bogenhausen AR, Berg D, Lesoine B, Kupka MS, Papadopoulos P, Thaler CJ, von Schönfeldt V, Friese K, Lacher H, Puchta J, Michna S, Pauer HU, Fiedler K, von Hertwig I, Würfel W, Laubert I, Santjohanser C, Völker S, Meri O, Krüsmann J, Bollmann W, Brückner T, Noss U, Belkien L, Niehoff C, Kiesel, Kreimer M, Kliesch, Sudik R, Kissing-Pahl K, Beran J, Müller B, Munzer-Neuwinger B, Neuwinger J, Licht P, Manolopoulos K, Oldenburg T, Hennefründ J, Boppert H, Heeder M, Jibril S, Pohlig G, Coordes I, Schneider M, Pforzheim K, Peuten V, Boehm S, Lehnert M, Recklinghausen K, Seifert B, Bals-Pratsch M, Luckhaus J, Müller H, Busecke A, Bossow A, Thaele M, Happel L, Giebel A, Nassar N, Otte M, Fuchs U, Maleika F, Harrer S, B D, Trier P, Satari M, Wissenschaftspark JP, Göhring, Göhring U, Göhring I, Lawrenz B, Neunhoeffer E, Gagsteiger, Sterzik K, Strehler E, Hancke K, Seemann B, Isachenko E, Rosenbusch B, Wetzlar V, Hajimohammad A, Oels B, Schorsch M, Hahn T, Adasz G, Schilberz K, Frambach T, Bernar T, Mai R, Schmitt W, Mulfinger L. (1)ESHRE Central Office, Meerstraat 60, Grimbergen B-1852, Belgium mail@prof-kupka.de. (2)ESHRE Central Office, Meerstraat 60, Grimbergen B-1852, Belgium. The 14th European IVF--monitoring (EIM) report presents the results of medically assisted reproduction treatments including assisted reproductive technology (ART) cycles and intrauterine insemination (IUI) cycles initiated in Europe during 2010: are there changes in the trends compared with previous years? Despite some fluctuations in the number of countries reporting, the overall number of ART cycles has continued to increase year by year, and while pregnancy rates in 2010 remained similar to those reported in 2009, the number of transfers with multiple embryos (three or more) further declined. Since 1997, ART data in Europe have been collected and reported in 13 manuscripts, published in Human Reproduction. STUDY D
Williams CL et al., 2013·The New England journal of medicine
Accurate population-based data are needed on the incidence of cancer in children born after assisted conception. We linked data on all children born in Britain between 1992 and 2008 after assisted conception without donor involvement with data from the United Kingdom National Registry of Childhood Tumours to determine the number of children in whom cancer developed before 15 years of age. Cohort cancer rates were compared with population-based rates in Britain over the same period, with stratification for potential mediating and moderating factors, including sex, age at diagnosis, birth weight, singleton versus multiple birth, parity, parental age, type of assisted conception, and cause of parental infertility. The cohort consisted of 106,013 children born after assisted conception (700,705 person-years of observation). The average duration of follow-up was 6.6 years. Overall, 108 cancers were identified, as compared with 109.7 expected cancers (standardized incidence ratio, 0.98; 95% confidence interval [CI], 0.81 to 1.19; P=0.87). Assisted conception was not associated with an increased risk of leukemia, neuroblastoma, retinoblastoma, central nervous system tumors, or renal or germ-cell tumors. It was associated with an increased risk of hepatoblastoma (standardized incidence ratio, 3.64; 95% CI, 1.34 to 7.93; P=0.02; absolute excess risk, 6.21 cases per 1 million person-years) and rhabdomyosarcoma (standardized incidence ratio, 2.62; 95% CI, 1.26 to 4.82; P=0.02; absolute excess risk, 8.82 cases per 1 million person-years), with hepatoblastoma developing in 6 children and rhabdomyosarcoma in 10 children. The excess risk of hepatoblastoma was associated with low birth weight. There was no increase in the overall risk of cancer among British children born after assisted conception during the 17-year study period. Increased risks of hepatoblastoma and rhabdomyosarcoma were detected, but the absolute risks were small. (Funded by Cancer Research UK and others.).
Farhangniya M et al., 2013·International journal of fertility & sterility
In many countries, 1 to 3% of newborn infants are conceived by assisted reproductive techniques (ART). Despite the success of ART, there is concern about the risk of congenital malformations among these infants. We report our experience to determine whether use of ART is associated with an increase in major congenital malformations or adverse pregnancy outcomes. Historical cohort study of major congenital malformations (MCM) was performed in 978 births from January 2008 to December 2010. The data for this analysis were derived from a Tehran's ART linked data file by simple sampling method. In our study, the risk of congenital malformations was compared in 326 ART infants and 652 naturally conceived (NC) infants. We also performed multiple logistic regression analyses to calculate the odds ratio (OR) and 95% confidence intervals (CI) for the independent association of ART on each outcome. We found 56 infants with major congenital malformations, these included 29 NC infants (4.4%) and 27 ART infants (8.3%). In comparison with NC infants, ART infants had a significant 1.94-fold increased risk of MCM.After adjustment for maternal age, infant's sex stillbirth, abortion and type of delivery, we found a relatively small difference in risk (OR=2.04). In this study the majority (94.3%) of all infants were normal but 5.7% of infants had at least one MCM. The prevalence rate for the intracytoplasmic sperm injection (ICSI) was 6.5% for the In vitro fertilisation (IVF) group was 15.9% or 2.73-fold higher than ICSI group (P=0.018). Also we ignore the possible role of genotype and other unknown factors in causing more malformations in ART infants. Other studies have shown a slightly increased risk of major congenital malformations in pregnancies resulting from ART. Likewise, this study reports a greater risk of MCMs in ART infants than in naturally conceived infants. We also found evidence of a difference in risk of MCMs between IVF and ICSI. Musculoskeletal and urogenital malformations were the most reported MCMs in ART infants according to organs and systems classification.
Novak C et al., 2013·Seminars in Reproductive Medicine
Health disparities are observed in all fields of medicine and reproductive health is not immune to this phenomenon. The incidence of women using infertility treatments to conceive is increasing. Women undergoing assisted reproduction appear to be at increased risk of adverse outcomes, and minority women tend to be at even greater risk. This article examines several adverse obstetrical outcomes including preterm birth, congenital malformations, and preeclampsia among women receiving infertility treatments compared with those who conceive spontaneously. It will further examine societal costs associated with these procedures.
Kelley-Quon LI et al., 2013·Journal of Pediatric Surgery
Management of congenital malformations comprises a large part of pediatric surgical care. Despite increasing utilization of assisted reproductive technology (ART) and fertility-related services (FRS), associations with birth defects are poorly understood. Infants born after ART or FRS were identified from the California Linked Birth Cohort Dataset from 2006 to 2007 and compared to propensity matched infants conceived naturally. Factors associated with major congenital malformations were evaluated using Firth logistic regression. With a cohort of 4,795 infants born after ART and 46,025 naturally conceived matched controls, major congenital malformations were identified in 3,463 infants. Malformations were increased for ART infants (9.0% vs. 6.6%, p<0.001). After adjusting for infant and maternal factors, ART infants exhibited increased odds of major malformations overall (OR 1.25, 95% CI 1.12-1.39), specifically defects of the eye (OR 1.81, 95% CI 1.04-3.16), head and neck (OR 1.37, 95% CI 1.00-1.86), heart (OR 1.41, 95% CI 1.22-1.64), and genitourinary system (OR 1.40, 95% CI 1.09-1.82). The likelihood of birth defects was increased for multiples (OR 1.35, 95% CI 1.18-1.54) and not singletons. Odds of congenital malformation after FRS alone (n=1,749) were non-significant. ART contributes a significant risk of congenital malformation and may be more pronounced for multiples. Accurate counseling for parents considering ART and multidisciplinary coordination of care prior to delivery are warranted.
Lu YH et al., 2013·Journal of Zhejiang University SCIENCE B·
Open Access
Children conceived via assisted reproductive technologies (ART) are nowadays a substantial proportion of the population. It is important to follow up these children and evaluate whether they have elevated health risks compared to naturally conceived (NC) children. In recent years there has been a lot of work in this field. This review will summarize what is known about the health of ART-conceived children, encompassing neonatal outcomes, birth defects, growth and gonadal developments, physical health, neurological and neurodevelopmental outcomes, psychosocial developments, risk for cancer, and epigenetic abnormalities. Most of the children conceived after ART are normal. However, there is increasing evidence that ART-conceived children are at higher risk of poor perinatal outcome, birth defects, and epigenetic disorders, and the mechanism(s) leading to these changes have not been elucidated. Continuous follow-up of children after ART is of great importance as they progress through adolescence into adulthood, and new ART techniques are constantly being introduced.
Human Fertilisation and Embryology Authority, 2013·HFEA Statistical Releases
HFEA annual statistical release presenting information about cycles started in 2010 and 2011, with longer-term trends back to 1991. Includes tables on IVF/ICSI cycles, donor insemination, multiple birth rates from 2009 and 2010, age-stratified live birth rates per cycle started, and patient demographics. The HFEA Register, established under the Human Fertilisation and Embryology Act 1990, contains records of every licensed fertility treatment in the UK since 1991. The 2011 report supersedes earlier annual statistical releases by HFEA covering treatment years up through 2010.
To review the literature and present original data to answer the question of whether in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is associated with an increase in imprinted diseases in offspring. If the answer is positive, to investigate whether there is a causal relationship between IVF or ICSI and the imprinted diseases. Review study. RESULT(S): Eight epidemiologic studies were suitable to calculate the weighted relative risk for the birth of a child with Beckwith-Wiedemann syndrome following IVF or ICSI compared with the risk in the normal population. This relative risk was 5.2 (95% CI 1.6-7.4). In one study the relative risk was corrected for parents' fertility problems and no significant association was found. Data on the Silver-Russell syndrome are too sparse to draw conclusions, but a positive association with IVF or ICSI treatment is probable. No significant associations were found between the incidences of the Angelman and Prader-Willi syndromes and IVF or ICSI treatments. Children with Prader-Willi syndrome or Angelman syndrome are more likely to be born to parents with fertility problems. All retinoblastomas in children born after IVF or ICSI could be explained by de novo mutations in the RB1 gene and were not associated with imprinted genes. Imprinted diseases result from methylation errors already present in sperms or oocytes. There is no proof of a causal relationship between imprinted diseases and IVF or ICSI treatments. CONCLUSION(S): Imprinting disorders are more prevalent after human IVF or ICSI. Future studies should correct for fertility problems in the affected and comparison groups. It is highly improbable that assisted reproduction technologies cause imprinted diseases in humans.
Worldwide, more than 5 million children have been born after assisted reproductive technology (ART), and in many developed countries ART infants represent more than 1% of the birth cohorts. It is well known that ART children are at increased risk of congenital malformations even after adjustment for known confounders such as maternal age. The proportion of ART children is not negligible, and knowledge about the causes of the higher risk of congenital malformations is crucial to develop prevention strategies to reduce the future risk in ART children. The aim of this review is to summarize the literature on the association between ART and congenital anomalies with respect to subfertility, fertility treatment other than ART, and different ART methods including intracytoplasmic sperm injection, blastocyst culture, and cryotechniques. Trends over time in ART and congenital anomalies will also be discussed.
Barnhart KT, 2013·Fertility and Sterility·
Open Access
Interrogating the association between assisted reproductive technologies (ART) and perinatal outcome is complicated but very important. This is an introduction to a series of articles that review this potential association with an eye toward etiology of risk, and what aspects of in vitro fertilization (IVF) can be modified to reduce this risk. When an association is not due to chance (i.e., statistically significant), one must also consider how the association may be affected due to bias or confounding. Despite lack of the perfect study, perinatal consequences of ART are apparent, even though the vast majority of children conceived with ART are healthy. Pregnancy after IVF is altered as evidenced by risk of preterm delivery, low birth weight among infants, and an alerted prevalence of preeclampsia. The long-term clinical implications of ART, such as childhood development and metabolism, have not been established and ongoing study is proceeding. The risk attributed to multiple births is iatrogenic and needs to be minimized. Optimizing the environment at the time a woman conceives will likely have an effect on gestation as well as the health of children. Reproduction effects health and health effects reproduction.
Canadian Fertility and Andrology Society, 2013·CFAS
Canadian ART Register (CARTR) annual report for 2012. In 2012, 32 of 33 Canadian assisted reproductive technology (ART) clinics participated in CARTR. Voluntary professional society database operated by the Canadian Fertility and Andrology Society. This is the predecessor to the CARTR Plus partnership with BORN Ontario.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2012. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Kochanski A et al., 2013·Journal of Neonatal-Perinatal Medicine
The question of genetic alterations resulting from assisted reproductive technologies (ART) in humans is examined within the organization of the human genome. Increased rates of birth defects have been reported among children conceived using ART; however, questions remain and controversy exists regarding how "infertility" predisposes to birth defects. ART has been shown to be associated with an increased number of chromosomal alterations especially in the X chromosome. There is increased risk for embryonal tumors among ART conceived children, as well as, imprinting disorders (Beckwith-Wiedemann and Angelman Syndromes). Genetic studies of children conceived using ART reveal a larger (genome-wide) scale of methylation defects that encompass hundreds of genes. Genes involved in carcinogenesis and developmental pathways appear altered and may impact on later development of chronic illness, although these data are very preliminary. ART may create novel mutations by different chromosomal and molecular mechanisms; however, these techniques also enable propagation of pre-existing mutations that are associated with impaired fertility. While older maternal age is often associated with female infertility and chromosomal aneuploidy, sperm from older men have more new gene mutations. The prevalence of birth defects is increased when ART is used for conception. These data are summarized by large meta-analyses or from multi-year national registries. Whether the increased number of birth defects is due to ART procedures themselves or are a consequence of the impaired fertility of the parents is discussed. Long-term evaluation of children conceived using ART and/or ovarian hyper-stimulation is needed to determine whether alterations during embryonic development may increase the prevalence of chronic diseases in adulthood.
Ferraretti AP et al., 2013·Human reproduction (Oxford, England)
9. Assisted reproductive technology in Europe, 2009: results generated from European registers by ESHRE. Ferraretti AP(1), Goossens V, Kupka M, Bhattacharya S, de Mouzon J, Castilla JA, Erb K, Korsak V, Nyboe Andersen A; European IVF-Monitoring (EIM) Consortium for the European Society of Human Reproduction and Embryology (ESHRE). Collaborators: Strohmer H, Bogaerts K, Kyurkchiev S, Vrcic H, Pelekanos M, Rezabek K, Erb K, Gissler M, Royere D, Bühler K, Tarlatzis BC, Kosztolanyi G, Bjorgvinsson H, Mocanu E, Scaravelli G, Lokshin V, Arajs M, Gudleviciene Z, Lazarevski S, Moshin V, Simic TM, Hazekamp JT, Kurzawa R, Calhaz-Jorge C, Rugescu I, Korsak V, Radunovic N, Tomazevic T, Hernandez JH, Karlström PO, Weder M, Lambalk C, Veselovsky V, Baranowski R. (1)ESHRE Central Office, Grimbergen, Belgium. annapia.ferraretti @sismer.it The 13th European in vitro fertilization (IVF)-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2009: are there any changes in the trends compared with previous years? Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year and, while pregnancy rates in 2009 remained similar to those reported in 2008, the number of transfers with multiple embryos (3+) and the multiple delivery rates declined. Since 1997, ART data in Europe have been collected and reported in 12 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1st January and 31st December are collected on a yearly basis; the data are collected by the National Registers, when existing, or on a voluntary basis. PARTICIPANTS/MATERIALS SETTING, From 34 countries (-2 compared with 2008), 1005 clinics reported 537 463 treatment cycles including: IVF (135 621), intracytoplasmic sperm injection (ICSI, 266 084), frozen embryo replacement (FER, 104 153), egg donation (ED, 21 604), in vitro maturation (IVM, 1334), preimplantation genetic diagnosis/screening (PGD/PGS, 4389) and frozen oocyte replacements (FOR, 4278). European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor (IUI-D) semen were reported from 21 and 18 countries, respectively. A total of 162 843 IUI-H (+12.7%) and 29 235 IUI-D (+17.3%) cycles were included. Data available from each country are presented in the tables; total values (as numbers and percentages) refer to those countries where all data have been reported. MAIN In 21 countries where all clinics reported to the ART register, a total of 399 020 ART cycles were performed in a population of 373.8 million, corresponding to 1067 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.9 and 32.9%, respectively and for ICSI, the corresponding rates were 28.7 and 32.0%. In FER cycles, the pregnancy rate per thawing was 20.9%; in ED cycles, the pregnancy rate per transfer was 42.3%. The delivery rate after IUI-H was 8.3 and 13.4% after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 24.2, 57.7, 16.9 and 1.2%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.8, 19.4 and 0.8%, respectively, resulting in a total multiple delivery rate of 20.2%, compared with 21.7% in 2008, 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.0% (12.7% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 10.4/0.7% and 10.3/0.5%, following treatment with husband and donor semen, respectively. LIMITATIONS, The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. The 13th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than half a million of cycles reported in 2009. The use of ICSI has reached a plateau. Pregnancy and delivery rates after IVF and ICSI remained relatively stable compared with 2008 and 2007. The number of multiple embryo transfers (3+ embryos) and the multiple delivery rate have shown a clear decline.
Registries and Reporting · Cross-Registry Comparison
Sullivan EA et al., 2013·Human reproduction (Oxford, England)
(ICMART) world report: assisted reproductive technology 2004. Sullivan EA(1), Zegers-Hochschild F, Mansour R, Ishihara O, de Mouzon J, Nygren KG, Adamson GD. Author information:
(1)National Perinatal Statistics and Epidemiology Unit, School of Women's and Children's Health, University of New South Wales, Randwick Hospitals Campus, McNevin Dickson Building Room Level 2, Randwick, NSW 2031, Australia. e.sullivan@unsw.edu.au Have changes in assisted reproductive technology (ART) practice and outcomes occurred globally between 2003 and 2004?
Globally, ART practice has changed with an increasing prevalence of the use of ICSI rather than conventional IVF. In 2004, a small but increasing number of countries are incorporating single embryo transfer. There remain unacceptably high rates of three or more embryo transfers in select countries resulting in multiple births and adverse perinatal outcomes.
World data on the availability, effectiveness and safety of ART have been published since 1989. The number of embryos transferred is a major determinant of the iatrogenic increase in multiple pregnancies and is highly correlated with the likelihood of multiple birth and excess perinatal morbidity and mortality.
STUDY DESIGN, SIZE, Cross-sectional survey of countries and regions undertaking surveillance of ART procedures started in 2004 and their corresponding outcomes.
PARTICIPANTS/MATERIALS, SETTING, Of total, 2184 clinics from 52 reporting countries and regions. Number of ART clinics, types of cycles and procedures, pregnancy, delivery and multiple birth rates and perinatal outcomes.
MAIN A total of 954 743 initiated cycles resulted in an estimated 237 809 babies born. This was a 2.3% increase in the number of reported cycles from 2003. The availability of ART varied by country and ranged from 14 to 3844 treatment cycles per million population. Over one-third (37.2%) of ART clinics performed <100 cycles per year with only 19.9% performing ≥ 500 cycles per year. Of all cycles, 60.6% were ICSI. Frozen embryo transfers (FETs) represented 31% of the initiated cycles. The overall delivery rate per fresh aspiration for IVF and ICSI was 20.2% compared with 16.6% per FET. The average number of embryos transferred was 2.35. Single (16.3%) and double embryo transfers accounted for 73.2% of cycles. The overall proportion of deliveries with twins and triplets from IVF and ICSI was 25.1 and 1.8%, respectively, but varied widely by country and region. The proportion of premature deliveries per fresh aspiration for IVF and ICSI was 33.7% compared with 26.3% per FET. The perinatal death rate was 25.8 per 1000 births for fresh aspiration for IVF and ICSI compared with 14.2 per 1000 births per FET.
LIMITATIONS, Data are incomplete with seven countries not providing data to the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) in 2004 that had in 2003. The validity of data reflects current data collection practice. In 2004, 79.3% of the clinics in participating countries reported to their national or regional registries and to ICMART. In addition, the number of ART cycles per million population is a measure which is affected by a country's government policy, regulation, funding and the number of service providers.
ART practice, effectiveness and outcomes vary markedly internationally. Notably, the increasing proportion of cycles that are FET, the change in practice to single embryo transfer and the cessation of the transfer of three or more embryos in some countries has resulted in improved perinatal outcomes with minimal impact on pregnancy rates.
STUDY FUNDING/COMPETING INTEREST(S): ICMART receives financial support from ASRM, ESHRE, FSA, Japan Society for Reproductive Medicine, REDLARA, MEFS and SART. 10.1093/humrep/det036
23442757 [Indexed for MEDLINE]
Sunderam S et al., 2013·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
Sunderam S, Kissin DM, Crawford S, Anderson JE, Folger SG, Jamieson DJ, Barfield WD; Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC.
Tararbit K et al., 2012·Human Reproduction·
Open Access
Are the risks of hypoplastic left heart syndrome, transposition of great arteries, tetralogy of Fallot (TOF) and coarctation of the aorta increased in infants conceived by different assisted reproductive techniques (ARTs)?Study answerARTs, and particularly intracytoplasmic sperm injection (ICSI), are specifically associated with a higher risk of TOF.What is already knownARTs are associated with an increase in the overall risk of birth defects. The risk for congenital heart defects (CHDs) associated with ARTs has been evaluated as a whole but there is limited information on the risks for specific CHDs. STUDY DESIGN, We conducted a case-control study using population-based data from the Paris registry of congenital malformations for the period 1987-2009 and a cohort study of CHD (EPICARD) on 1583 cases of CHDs and 4104 malformed controls with no known associations with ARTs. ARTs included ovulation induction only, IVF and ICSI. Exposure to ARTs was significantly higher for TOF than controls (6.6 versus 3.5%, P = 0.002); this was not the case for the other three CHDs. ARTs (all methods combined) were associated with a 2.4-fold higher odds of TOF after adjustment for maternal characteristics, paternal age and year of birth [adjusted odds ratios (OR): 2.4, 95% confidence interval (CI): 1.5-3.7] with the highest risk associated with ICSI (adjusted OR: 3.0, 95% CI: 1.0-8.9). No statistically significant associations were found for the other CHDs. Our study cannot disentangle to what extent the observed associations between the risk of TOF and ARTs are due to causal effects of ARTs and/or the underlying infertility problems of couples who conceive following ART. The developmental basis of the specific association between the risk of TOF and ARTs need to be further investigated.
Children who are born after assisted reproduction (ART) have a slightly increased risk of being born preterm, of having low birthweight and a higher perinatal mortality than spontaneously conceived children. The higher rate of multiple births among women having had ART can to some extent explain this. However, adverse outcomes persist even in ART singletons. The characteristics of the infertile parents have negative effects on the outcome, but also the hormone stimulation and the in vitro techniques are thought to play a role. A milder hormone stimulation and elective single embryo transfer, which reduces the number of multiples after ART, have improved the overall health of children born as a result of ART.
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
Luke B et al., 2012·The New England journal of medicine·
Open Access
Live-birth rates after treatment with assisted reproductive technology have traditionally been reported on a per-cycle basis. For women receiving continued treatment, cumulative success rates are a more important measure. We linked data from cycles of assisted reproductive technology in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for the period from 2004 through 2009 to individual women in order to estimate cumulative live-birth rates. Conservative estimates assumed that women who did not return for treatment would not have a live birth; optimal estimates assumed that these women would have live-birth rates similar to those for women continuing treatment. The data were from 246,740 women, with 471,208 cycles and 140,859 live births. Live-birth rates declined with increasing maternal age and increasing cycle number with autologous, but not donor, oocytes. By the third cycle, the conservative and optimal estimates of live-birth rates with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age and to 6.6% and 11.3% for those 43 years of age or older. When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3). At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used. Our results indicate that live-birth rates approaching natural fecundity can be achieved by means of assisted reproductive technology when there are favorable patient and embryo characteristics. Live-birth rates among older women are lower than those among younger women when autologous oocytes are used but are similar to the rates among young women when donor oocytes are used. (Funded by the National Institutes of Health and the Society for Assisted Reproductive Technology.).
There is an increased incidence of rare imprinting disorders associated with assisted reproduction technologies (ARTs). The identification of epigenetic changes at imprinted loci in ART infants has led to the suggestion that the techniques themselves may predispose embryos to acquire imprinting errors and diseases. However, it is still unknown at what point(s) these imprinting errors arise, or the risk factors. In 2009 we conducted a Japanese nationwide epidemiological study of four well-known imprinting diseases to determine any association with ART. Using bisulfite sequencing, we examine the DNA methylation status of 22 gametic differentially methylated regions (gDMRs) located within the known imprinted loci in patients with Beckwith-Wiedemann syndrome (BWS, n=1) and also Silver-Russell syndrome (SRS, n= 5) born after ART, and compared these with patients conceived naturally. We found a 10-fold increased frequency of BWS and SRS associated with ART. The majority of ART cases showed aberrant DNA methylation patterns at multiple imprinted loci both maternal and paternal gDMRs (5/6), with both hyper- and hypomethylation events (5/6) and also mosaic methylation errors (5/6). Although our study may have been limited by a small sample number, the fact that many of the changes were mosaic suggested that they occurred after fertilization. In contrast, few of the patients who were conceived naturally exhibited a similar pattern of mosaic alterations. The differences in methylation patterns between the patients who were conceived naturally or after ART did not manifest due to the differences in the disease phenotypes in these imprinting disorders. A possible association between ART and BWS/SRS was found, and we observed a more widespread disruption of genomic imprints after ART. The increased frequency of imprinting disorders after ART is perhaps not surprising given the major epigenetic events that take place during early development at a time when the epigenome is most vulnerable.
To describe the characteristics of women seeking infertility treatment and the types of fertility treatment sought within a population-based sample. We analyzed data from the cross-sectional Pregnancy Risk Assessment Monitoring System (PRAMS) of women with a live birth using data from seven states. Logistic regression was used to determine factors associated with infertility treatment utilization. Infertility treatment was reported by 10.5% of women who were trying to become pregnant. The most common treatment reported was fertility enhancing drugs (29%), followed by assisted reproductive technology including in vitro fertilization (21%), and artificial insemination together with fertility enhancing drugs (15%). Some women reported using other types of treatment (23%). The PRAMS data provide insights into the use of infertility treatment among women giving birth in the United States. Further research is needed to understand the true prevalence of infertility, factors that influence treatment choices, and the longitudinal impact of infertility treatment on outcomes.
Outcomes and Effectiveness · Outcomes by Diagnosis
Pandian Z et al., 2012·Cochrane Database Syst Rev·
In vitro fertilisation (IVF) is a widely accepted treatment for unexplained infertility (NICE 2004), which affects up to a third of all infertile couples. With estimated live birth rates (LBRs) per cycle varying from 33.1% in women aged under 35 years down to 12.5% in women aged between 40 and 42 years (HFEA 2011), its effectiveness has not been rigorously evaluated in comparison with other treatments. With increasing awareness of the role of expectant management, less-invasive procedures such as intrauterine insemination (IUI), and concerns about multiple pregnancies and costs associated with IVF, it is important to evaluate the effectiveness of IVF against other treatment options in couples with unexplained infertility. To evaluate the effectiveness and safety of IVF compared to expectant management, clomiphene citrate, IUI alone and intrauterine insemination plus controlled ovarian stimulation (IUI+SO). Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, first quarter), MEDLINE (1970 to July 2011), EMBASE (1985 to July 2011) and reference lists of articles were searched. Relevant conference proceedings were handsearched. Authors were contacted.
Selection Criteria: Randomised controlled trials (RCTs) were included. LBR per woman was the primary outcome.
Data Collection and Analysis: Two review authors independently assessed eligibility and quality of trials. MAIN Six RCTs were included in the final analysis. LBR per woman was significantly higher with IVF (45.8%) than expectant management (3.7%) (odds ratio (OR) 22.00, 95% confidence interval (CI) 2.56 to 189.37, 1 RCT, 51 women). There were no comparative data for clomiphene citrate. There was no evidence of a significant difference in LBR between IVF and IUI alone (OR 1.96, 95% CI 0.88 to 4.36, 1 RCT, 113 women), 40.7% with IVF versus 25.9% with IUI. In studies comparing IVF versus IUI+SO, LBR per woman did not differ significantly between the groups among treatment-naive women (OR 1.09, 95% CI 0.74 to 1.59, 2 RCTs, 234 women) but was significantly higher in a large RCT of women pretreated with IUI + clomiphene citrate (OR 2.66, 95% CI 1.94 to 3.63, 1 RCT, 341 women). These three studies could not be pooled due to high heterogeneity (I(2) = 84%). There was no evidence of a significant difference in multiple pregnancy rate (MPR) or ovarian hyperstimulation syndrome (OHSS) between the two treatments (OR 0.64, 95% CI 0.31 to 1.29, 3 RCTs, 351 women; OR 1.53, 95% CI 0.25 to 9.49, 1 RCT, 118 women, respectively). AUTHORS' IVF may be more effective than IUI+SO. Due to paucity of data from RCTs the effectiveness of IVF for unexplained infertility relative to expectant management, clomiphene citrate and IUI alone remains unproven. Adverse events and the costs associated with these interventions have not been adequately assessed.
Skora D et al., 2012·Seminars in Reproductive Medicine
Since the advent of ART, much research has focused on the potential adverse for resultant harm. Prematurity, low birth-weight, PIH, congenital malformations, and CP are closely tied to multiple gestation. With the increase in elective single embryo transfer, there will be a reduction in adversity related to multiple birth. It is understood that underlying causes of infertility, including advanced maternal age, PCOS, thyroid disease, and uterine fibroids, predispose to adverse outcomes. However, imprinting abnormalities do not appear to stem from multiple births, and thus the need to consider the association between fertility treatment and methylation disorders remains essential. These, as well as risks of multi-fetal gestation, must be discussed with patients when considering using assisted reproduction.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2011. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Canadian Fertility and Andrology Society, 2012·CFAS
Canadian ART Register (CARTR) annual report for 2011. In 2011, 31 of 32 Canadian ART clinics participated in CARTR. Voluntary professional society database operated by the Canadian Fertility and Andrology Society.
Ferraretti AP et al., 2012·Human reproduction (Oxford, England)
10. Assisted reproductive technology in Europe, 2008: results generated from European registers by ESHRE. Ferraretti AP(1), Goossens V, de Mouzon J, Bhattacharya S, Castilla JA, Korsak V, Kupka M, Nygren KG, Nyboe Andersen A; European IVF-monitoring (EIM); Consortium for European Society of Human Reproduction and Embryology (ESHRE). (1)ESHRE Central Office, Meerstraat 60, B-1852 Grimbergen, Belgium. annapia.ferraretti@sismer.it This 12th European IVF-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2008. From 36 countries (3 more compared with 2007), 1051 clinics reported 532 260 treatment cycles including: IVF (124 539), ICSI (280 552), frozen embryo replacements (FER, 97 120), egg donation (ED, 13 609), in vitro maturation (IVM, 562), preimplantation genetic diagnosis/screening (PGD/PGS, 2875) and frozen oocyte replacements (FOR, 4080). Overall, this represents a 7.9% increase in the activity since 2007, which is mainly related to an increase in cycles from almost all registers and only partially to the new countries entering EIM (Estonia, Kazakhstan, Moldova and Romania, 5480 cycles in total). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI-D) semen were reported from 27 and 21 countries, respectively. A total of 144 509 IUI-H (+1.5%) and 24 960 IUI-D (-4.3%) cycles were included. In 19 countries where all clinics reported to the ART register, a total of 350 143 ART cycles were performed in a population of 369.8 million, corresponding to 947 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.5 and 32.5%, respectively, and for ICSI the corresponding rates were 28.7 and 31.9%. In FER cycles, the pregnancy rate per thawing was 19.3%. The delivery rate after IUI was 9.1% for IUI-H and 13.8% for IUI-D. In IVF and ICSI cycles, one, two, three and four or more embryos were transferred in 22.4, 53.2, 22.3 and 2.1%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 78.3, 20.7 and 1.0%, respectively, resulting in a total multiple delivery rate of 21.7%, compared with 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.7% (13.4% twins and 0.3% triplets). In women undergoing IUI, twin and triplet deliveries occurred in 10.6% and 0.7% with IUI-H and in 9.4 and 0.3% with IUI-D, respectively. In comparison with previous years, there was an increase in the reported number of ART cycles in Europe. For the first time in 5 years, the pregnancy rates failed to show a year-on-year increase. Compared with 2007, the number of transfers of multiple embryos (3+) and a multiple delivery rate showed a marginal decline.
de Mouzon J et al., 2012·Human reproduction (Oxford, England)
17. Assisted reproductive technology in Europe, 2007: results generated from European registers by ESHRE. de Mouzon J(1), Goossens V, Bhattacharya S, Castilla JA, Ferraretti AP, Korsak V, Kupka M, Nygren KG, Andersen AN; European IVF-Monitoring (EIM); Consortium for the European Society on Human Reproduction and Embryology (ESHRE). (1)ESHRE Central Office, Meerstraat 60, B-1852 Grimbergen, Belgium. jacques.demouzon@inserm.fr This 11th European IVF-monitoring report presents the results of assisted reproductive technology (ART) treatments initiated in Europe during 2007. From 33 countries, 1029 clinics reported 493 184 treatment cycles: IVF (120 761), ICSI (256 642), frozen embryo replacement (91 145), egg donation (15 731), preimplantation genetic diagnosis/preimplantation genetic screening (4638), in vitro maturation (660) and frozen oocytes replacements (3607). Overall, this represents a 7.6% increase since 2006, mostly related to an increase in all registers. IUI using husband/partner's (IUI-H) and donor (IUI-D) semen was reported from 23 countries: 142 609 IUI-H (+6.2%) and 26 088 IUI-D (+7.2%). In 18 countries where all clinics reported, 376 971 ART cycles were performed in a population of 425.6 million (886 cycles per million). The clinical pregnancy rates per aspiration and per transfer were 29.1 and 32.8% for IVF, and 28.6 and 33.0% for ICSI. Delivery rate after IUI-H was 10.2% in women aged < 40 years. In IVF/ICSI cycles, 1, 2, 3 and ≥4 embryos were transferred in 21.4, 53.4, 22.7 and 2.5% of cycles, with no decline in the number of embryos per transfer since 2006. The proportion of multiple deliveries (22.3: 21.3% twin and 1.0% triplet), did not decrease compared with 2006 (20.8%) and 2005 (21.8%). In women < 40 years undergoing IUI-H, twin deliveries occurred in 11.7% and triplets in 0.5%. In comparison with previous years, the reported number of ART cycles in Europe increased in 2007; pregnancy rates increased marginally, but the earlier decline in the number of embryos transferred and multiple births did not continue.
To report a child with Beckwith-Wiedemann syndrome (BWS) born after assisted reproductive technology (ART) to an HIV serodiscordant couple. Case report. Academic medical center.Patient(s)A child with BWS born after ART to an HIV serodiscordant couple.Intervention(s)Assisted reproductive techniques.Main outcome measure(s)ART and HIV.Result(s)Since 2003, it has been suggested that there is an association between ART and BWS, which is a congenital overgrowth syndrome characterized by macrosomia, macroglossia, visceromegaly, umbilical and abdominal wall abnormalities, and an increased risk of developing embryonal tumors in childhood. It is a multigenic disorder resulting from genetic or epigenetic alterations of genes on chromosome 11p15. Methylation errors account for 50%-60% of sporadic cases and almost 100% of cases born after ART. We report the birth of a child diagnosed with BWS arising from an ART cycle to an HIV serodiscordant couple with no history of infertility. This case cannot constitute conclusive evidence but it raises various questions.Conclusion(s)Assisted reproductive technology seems to be in the causal pathway but a male/female factor or an iatrogenic factor is also possible.
Ståhl O et al., 2011·Journal of the National Cancer Institute
The potential mutagenic effects of cancer therapies and the growing number of young male cancer survivors have given rise to concern about the health of their offspring. We identified all singleton children born alive in Denmark between 1994 and 2004 and in Sweden between 1994 and 2005 (n = 1,777,765). Of the 8670 children with a paternal history of cancer, 8162 were conceived naturally and 508 were conceived using assisted reproductive technologies (ARTs) (in vitro fertilization or intracytoplasmatic sperm injection). Of the 1,769,095 children without a paternal history of cancer, 25,926 were conceived using ARTs. Associations between paternal history of cancer and risk of adverse birth outcomes of children conceived naturally or by ARTs were investigated using log-linear binomial models, yielding risk ratios (RRs) with 95% confidence intervals (CIs). All statistical tests were two-sided. The offspring of male cancer survivors were more likely to have major congenital abnormalities than the offspring of fathers with no history of cancer (RR = 1.17, 95% CI = 1.05 to 1.31, P = .0043, 3.7% vs 3.2%). However, the mode of conception (natural conception or ARTs) did not modify the association between paternal history of cancer and risk of congenital abnormalities (natural conception, RR = 1.17, 95% CI = 1.04 to 1.31; ARTs, RR = 1.22, 95% CI = 0.80 to 1.87, P(interaction) = .84). We observed a statistically significant but modest increase in the risk of major congenital abnormalities among offspring of males with a history of cancer, independent of the mode of conception.
The purpose of the present study was to evaluate the relative risk (RR) of multiple births for birth defects after assisted reproductive technology (ART) using Japanese nationwide data from 2004 to 2008 with singletons as the reference group. In multiples compared to singletons, the percentage of birth defects per pregnancy were significantly higher (RR = 1.88, 95% confidence interval (CI) 1.60-2.13), the percentage of birth defects per live birth was not significantly higher (RR = 0.90, 95% CI 0.78-1.05 or RR = 0.94, 95% CI 0.81-1.10), and the early neonatal mortality rate was significantly higher (RR = 2.68, 95% CI 1.52-4.70 or RR = 2.80, 95% CI 1.60-4.92). The early neonatal mortality per 10,000 live births was slightly higher in ART (5.09) than in the general population (3.86). We concluded that the impact of birth defects after ART would be larger in families with multiples compared to families with singletons, since the mean number of children would be larger in the former.
Canadian Fertility and Andrology Society, 2011·CFAS
Canadian ART Register (CARTR) annual report for 2010. A total of 18,454 cycles was reported to CARTR. Voluntary professional society database operated by the Canadian Fertility and Andrology Society.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2010. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
We report the complications observed after transvaginal oocyte retrieval guided by ultrasound in 7,098 IVF cycles. The frequency of severe complications in our patients was 0.08%, of which four cases were intraperitoneal bleeding (0.06%) and two were cases of ovarian abscess (0.003%).
To estimate the risk of congenital heart defects (CHD) associated with assisted reproductive technologies (ART).Methods and resultsWe used data from the Paris Registry of Congenital Malformations on 5493 cases of CHD and 3847 malformed controls for which no associations with ART were reported in the literature. Assisted reproductive technologies included inductors of ovulation only, in vitro fertilization, and intracytoplasmic sperm injection. Exposure to ART was higher for cases than controls (4.7 vs. 3.6%, P= 0.008) and was associated with a 40% increase in the maternal age, socioeconomic factors, and year of birth-adjusted odds of CHD without chromosomal abnormalities [adjusted odds ratio (OR) 1.4, 95% confidence interval (CI) 1.1-1.7]. Assisted reproductive technologies were specifically associated with significant increases in the odds of malformations of the outflow tracts and ventriculoarterial connections (adjusted OR 1.7, 95% CI 1.2-2.4) and of cardiac neural crest defects and double outlet right ventricle (adjusted OR 1.7, 95% CI 1.1-2.7). In general, we found specific associations between methods of ART and subcategories of CHD. Cases with CHD were more likely to have been conceived following ART when compared with malformed controls. This higher risk for CHD varied specifically according to the method of ART and the type of CHD and may be due to ART per se and/or the underlying infertility of couples.
To compare the risk of preterm delivery, low birth weight, and admission of the newborn to a neonatal intensive care unit (NICU) in women pregnant after fertility treatment and subfertile women with the risk in fertile women. Prospective follow-up study. Aarhus University Hospital, Skejby, Denmark, 1989-2006. PATIENT(S): A total of 20,080 liveborn singletons. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm delivery, low birth weight, and admission of the newborn to a NICU. RESULT(S): After adjustment we found a statistically significantly increased risk of preterm delivery and very preterm delivery in women who conceived after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) compared with fertile women. Compared with fertile women, the risk of preterm delivery and very preterm delivery was not statistically significantly different in women pregnant after non-IVF assisted reproductive treatment (non-IVF ART) or subfertile women. We found no association between IVF/ICSI and the risk of low birth weight at term or admittance to the NICU. CONCLUSION(S): The increased risk of preterm delivery after IVF/ICSI may be due to the fertility treatment or unknown characteristics in the couples who undergo IVF/ICSI.
To describe two children diagnosed with Beckwith-Wiedemann Syndrome (BWS) arising from a spontaneous conception and an assisted reproductive technology (ART) cycle from one patient with a long-standing history of subfertility. Case report. Academic medical center.Patient(s)Two children with the morphologic features of BWS as a result of a spontaneous conception and an ART cycle from the same patient.Intervention(s)Assisted reproductive technology.Main outcome measure(s)Neonatal and pediatric morphologic evaluation by geneticists.Result(s)Two children with the morphologic features consistent with the criteria for the diagnosis of BWS.Conclusion(s)Patients with subfertility may be carriers for genetic disorders that can be passed to a child with or without the use of assisted reproductive technologies (ART). The use of ART may bypass natural selection mechanisms.
Wisborg K et al., 2010·Human reproduction (Oxford, England)
Previous studies have indicated that the risk of stillbirth is increased in singleton pregnancies achieved after assisted reproduction technology (ART). However, no previous study fully accounted for factors with potential influence on the risk of stillbirth. Further, whether fertility treatment, the possible reproductive pathology of the infertile couples or other characteristics related to being subfertile may explain a possible association with stillbirth remains unclear. This study compares the risk of stillbirth in women pregnant after fertility treatment (IVF/ICSI and non-IVF ART) and subfertile women with that in fertile women. We used prospectively collected data from the Aarhus Birth Cohort, Denmark and included information about 20 166 singleton pregnancies (1989-2006). Outcome measure was stillbirth. The risk of stillbirth in women who conceived after IVF/ICSI was 16.2 per thousand ( per thousand) and in women who conceived after non-IVF ART 2.3 per thousand. In fertile and subfertile women, the risk of stillbirth was 3.7 per thousand and 5.4 per thousand, respectively. Compared with fertile women, women who conceived after IVF/ICSI had more than four times the risk of stillbirth [odds ratio (OR): 4.44, 95% confidence interval (CI): 2.38-8.28], and adjustments for maternal age, BMI, education, smoking habits and alcohol and coffee intake during pregnancy had only minor impact on the findings (OR: 4.08; 95% CI: 2.11-7.93). The risk of stillbirth in women who conceived after non-IVF ART and in women who conceived spontaneously with a waiting time to pregnancy of a year or more was not significantly different from the risk in women with a shorter time to pregnancy. Compared with fertile women, women who conceived by IVF/ICSI had an increased risk of stillbirth that was not explained by confounding. Our results indicate that the increased risk of stillbirth seen after fertility treatment is a result of the fertility treatment or unknown factors pertaining to couples who undergo IVF/ICSI.
Arendt J et al., 2010·Bulletin de la Societe des sciences medicales du Grand-Duche de Luxembourg
The first chapter analyses the ART methods of the Centre Hospitalier of Luxembourg, in the department of reproductive medicine between 2001 and 2009. The second chapter examines the techniques individually, their influence on pregnancy outcomes, the complications on offsprings and their health. The results coincide with literature in that risks are acceptable as long as good medical and biological conditions are maintained. Multiple pregnancies remain the most frequent complication, particularly once out of IVF. These are analysed separately as well as the pregnancies after egg and semen donation.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2009. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Canadian Fertility and Andrology Society, 2010·CFAS
Canadian ART Register (CARTR) annual report for 2009. A total of 16,315 cycles was reported to CARTR. Voluntary professional society database operated by the Canadian Fertility and Andrology Society.
de Mouzon J et al., 2010·Human reproduction (Oxford, England)
22. Assisted reproductive technology in Europe, 2006: results generated from European registers by ESHRE. de Mouzon J(1), Goossens V, Bhattacharya S, Castilla JA, Ferraretti AP, Korsak V, Kupka M, Nygren KG, Nyboe Andersen A; European IVF-monitoring (EIM) Consortium, for the European Society of Human Reproduction and Embryology (ESHRE). Collaborators: Glozheni O, Strohmer H, Bogaerts K, Kyurkchiev S, Pelekanos M, Rezabek K, Erb K, Gissler M, de Mouzon J, Shojaei T, Buhler K, Tarlatzis B, Kosztolanyi G, Bjorgvinsson H, Mocanu E, Scaravelli G, Lejins V, Gudleviciene Z, Lazarevski S, Simic TM, Lambalk C, Hazekamp JT, Kuczynski W, Calhaz-Jorge C. (1)ESHRE Central Office, Meerstraat 60, B-1852 Grimbergen, Belgium. jacques.demouzon@inserm.fr In this 10th European IVF-monitoring (EIM) report, the results of assisted reproductive techniques from treatments initiated in Europe during 2006 are presented. Data were mainly collected from existing national registers. From 32 countries, 998 clinics reported 458 759 treatment cycles including: IVF (117 318), ICSI (232 844), frozen embryo replacement (FER, 86 059), egg donation (ED, 12 685), preimplantation genetic diagnosis/screening (6561), in vitro maturation (247) and frozen oocytes replacements (3498). Overall this represents a 9.7% increase in activity since 2005, which is partly due to an increase in registers (seven more countries with complete coverage). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI-D) semen were reported from 22 countries. A total of 134 261 IUI-H and 24 339 IUI-D cycles were included. In 20 countries, where all clinics reported to the IVF register, a total of 359 110 assisted reproductive technology (ART) cycles were performed in a population of 422.5 million, corresponding to 850 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 29.0 and 32.4%, respectively. For ICSI, the corresponding rates were 29.9 and 33.0%. After IUI-H the delivery rate was 9.2% in women below 40. After IVF and ICSI the distribution of transfer of one, two, three and four or more embryos was 22.1, 57.3, 19.0 and 1.6%, respectively. Compared with 2005, fewer embryos were replaced per transfer, but significant national differences in practice were apparent. The proportion of singleton, twin and triplet deliveries after IVF and ICSI combined was 79.2, 19.9 and 0.9%, respectively. This gives a total multiple delivery rates of 20.8% compared with 21.8% in 2005 and 22.7% in 2004. IUI-H in women below 40 years of age resulted in 10.6% twin and 0.6% triplet pregnancies. Compared with previous years, the reported number of ART cycles in Europe has increased, pregnancy rates have increased marginally, even though fewer embryos were transferred and the multiple delivery rates have declined.
To test consumables and other products used during oocyte collection, sperm preparation, IUI, embryo culture, and IVF-embryo transfer for their possible reprotoxic properties. A prospective 4-year survey of reprotoxicity testing of consumables and other products used in assisted reproductive technologies (ART). Private infertility center in a university-affiliated teaching hospital. INTERVENTION(S): Thirty-six products of 72 different brands, including plastics, syringes, tubing, and surgical gloves were analyzed for their reprotoxicity in 350 human sperm survival tests (SpST). MAIN OUTCOME MEASURE(S): The SpST index: percentage progressive motility of test sample/percentage progressive motility of control sample after 24 and 96 hours. RESULT(S): Thirteen of 36 products were found to be reprotoxic: an SpST index <0.85 was noted 24 and 96 hours after exposure. These products included eight brands of unpowdered surgical gloves, two types of hysterometers and one type of tubing attached to the oocyte collection needle, one type of ovum pickup procedure needle, and one type of embryo transfer catheter. One type of condom used for ultrasound, one type of sterile Pasteur pipette and petri dish, as well as the cover of a specimen container, were reprotoxic. CONCLUSION(S): The SpST is an inexpensive, easy, and reliable method to identify potential reprotoxic products and consumables used in ART procedures. These data underline the importance of the inclusion of the SpST in a continuous quality control (QC) program of ART outcome.
Delaying conception has increased the demand on assisted reproduction. Currently, more than 1% of children are conceived through assisted reproductive technologies (ART) worldwide and this number is likely to continue increasing. Like any other medical intervention ART is associated with both short-term and long-term complications. The major short-term complications include ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. OHSS is difficult to predict, but meticulous preventive strategies and protocols are being developed that may limit it. Most of the morbidities in children born after ART are related to multiple pregnancies. New laboratory methodologies may allow the transfer of fewer embryos to maintain satisfactory live birth rates while reducing the risk of multiple pregnancies. In vitro fertilization may be associated with a slight increased risk for birth defects. Analysis of possible risks from these techniques is confounded by factors of underlying parental subfertility, fertility treatments and multiple births. The long-term sequelae remain largely undetermined. All outcomes of ART, including pregnancy rates and adverse complications, need to be compared with standard non-ART when deciding the appropriate course of treatment. The importance of counselling should never be ignored in any treatment decision.
Pearson KR et al., 2009·Fertil Steril·
Open Access
Among 2,245 women, those who experienced a chemical pregnancy that failed to progress to a clinically recognized pregnancy or a spontaneous abortion on their first IVF cycle were more likely to discontinue IVF treatment than those whose first cycle ended before embryo transfer or who did not have a positive pregnancy test after transfer. However, among women who did continue to a second IVF cycle, those who had at least a chemical pregnancy on the first cycle were more likely to have a live birth on the second attempt than those women who had failed before conception in the first cycle (34% success rate compared with 21%, respectively).
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
To model the cumulative probability of pregnancy among couples with subfertility without a definitive diagnosis, according to different treatment strategies. A beta distribution of fecundity was fitted that reproduced the cumulative probability of pregnancy in prospective studies of natural fertility, and this distribution was applied to simulated cohorts starting with one million couples each. Probabilities of pregnancy were generated for each cycle of each couple. Simulation study. PATIENT(S): Hypothetic subfertile population. INTERVENTION(S): After 2 or 4 years of attempting pregnancy and diagnostic evaluation to exclude anovulation, tubal obstruction, and severe male factor, simulated treatments were applied to the remaining nonpregnant couples, with treatment effects based on published literature. MAIN OUTCOME MEASURE(S): Simulated cumulative probability of pregnancy. RESULT(S): Initially, the cumulative probability of pregnancy was highest for early treatment with IVF, but over time, conservative treatment or frequent intercourse approached the same cumulative probability. CONCLUSION(S): In couples without clear indications for IVF, the main benefit of early IVF may be to shorten time to pregnancy, a benefit that must be weighed against costs and potential adverse outcomes. Couples should be encouraged to maintain regular intercourse to maximize chances of pregnancy, even after unsuccessful treatment attempts.
With >1% of US births occurring following use of assisted reproductive technology (ART), it is critical to examine whether ART is associated with birth defects. We analyzed data from the National Birth Defects Prevention Study, a population-based, multicenter, case-control study of birth defects. We included mothers of fetuses or live-born infants with a major birth defect (case infants) and mothers who had live-born infants who did not have a major birth defect (control infants), delivered during the period October 1997-December 2003. We compared mothers who reported ART use (IVF or ICSI) with those who had unassisted conceptions. Multiple logistic regression was used to adjust for the following confounders: maternal race/ethnicity, maternal age, smoking and parity; we stratified by plurality. ART was reported by 1.1% of all control mothers, and by 4.5% of control mothers 35 years or older. Among singleton births, ART was associated with septal heart defects (adjusted odds ratio [aOR] = 2.1, 95% confidence intervals [CI] 1.1-4.0), cleft lip with or without cleft palate (aOR = 2.4, 95% CI 1.2-5.1), esophageal atresia (aOR = 4.5, 95% CI 1.9-10.5) and anorectal atresia (aOR = 3.7, 95% CI 1.5-9.1). Among multiple births, ART was not significantly associated with any of the birth defects studied. These findings suggest that some birth defects occur more often among infants conceived with ART. Although the mechanism is not clear, couples considering ART should be informed of all potential risks and benefits.
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
Outcomes of in vitro fertilization (IVF) treatment are traditionally reported as pregnancies per IVF cycle. However, a couple's primary concern is the chance of a live birth over an entire treatment course. We estimated cumulative live-birth rates among patients undergoing their first fresh-embryo, nondonor IVF cycle between 2000 and 2005 at one large center. Couples were followed until either discontinuation of treatment or delivery of a live-born infant. Analyses were stratified according to maternal age and performed with the use of both optimistic and conservative methods. Optimistic methods assumed that patients who did not return for subsequent IVF cycles would have the same chance of a pregnancy resulting in a live birth as patients who continued treatment; conservative methods assumed no live births among patients who did not return. Among 6164 patients undergoing 14,248 cycles, the cumulative live-birth rate after 6 cycles was 72% (95% confidence interval [CI], 70 to 74) with the optimistic analysis and 51% (95% CI, 49 to 52) with the conservative analysis. Among patients who were younger than 35 years of age, the corresponding rates after six cycles were 86% (95% CI, 83 to 88) and 65% (95% CI, 64 to 67). Among patients who were 40 years of age or older, the corresponding rates were 42% (95% CI, 37 to 47) and 23% (95% CI, 21 to 25). The cumulative live-birth rate decreased with increasing age, and the age-stratified curves (< 35 vs. > or = 40 years) were significantly different from one another (P<0.001). Our results indicate that IVF may largely overcome infertility in younger women, but it does not reverse the age-dependent decline in fertility.
Canadian Fertility and Andrology Society, 2009·CFAS
Canadian ART Register (CARTR) annual report for 2008. A total of 15,000 cycles was reported to CARTR. Voluntary professional society database operated by the Canadian Fertility and Andrology Society.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2008. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Registries and Reporting · Cross-Registry Comparison
International Committee for Monitoring Assisted Reproductive Technology et al., 2009·Human reproduction (Oxford, England)
International Committee for Monitoring Assisted Reproductive Technology(1); de Mouzon J, Lancaster P, Nygren KG, Sullivan E, Zegers-Hochschild F, Mansour R, Ishihara O, Adamson D. Author information:
(1)INSERM U569, Hôpital de Bicêtre, 82 rue du Général Leclerc, 94276 Le Kremlin Bicêtre Cedex, Paris, France. Erratum in Hum Reprod. 2010 May;25(5):1345. The International Committee for Monitoring Assisted Reproductive Technology's (ICMART) Eighth World Report analyzes assisted reproductive technology (ART) practice and results for the year 2002 from 53 countries by type of ART, women's age, number of embryos transferred and multiple births. Over 601,243 initiated cycles resulted in a delivery rate (DR) per aspiration of 22.4% for conventional IVF, 21.2% for ICSI and a DR per transfer of 15.3% for frozen embryo transfer. For conventional IVF and ICSI, there was an overall twin rate of 25.7% per delivery and a triplet rate of 2.5%. The number of babies born worldwide through ART in 2002 was estimated to range between 219,000 and 246,000. There were wide variations in availability, DRs and multiple birth rates across the countries. Compared with the previous report (year 2000), there was a large increase in the number of cycles and a slight increase in the DR. There was a marginal decline in the mean number of embryos transferred and in the multiple DRs. 10.1093/humrep/dep098
19474459 [Indexed for MEDLINE]
Nyboe Andersen A et al., 2009·Human reproduction (Oxford, England)
18. Assisted reproductive technology and intrauterine inseminations in Europe, 2005: results generated from European registers by ESHRE. The European IVF Monitoring Programme (EIM), for the European Society of Human Reproduction and Embryology (ESHRE). Nyboe Andersen A(1), Goossens V, Bhattacharya S, Ferraretti AP, Kupka MS, de Mouzon J, Nygren KG; European IVF-monitoring (EIM) Consortium, for the European Society of Human Reproduction and Embryology (ESHRE). Collaborators: Glozheni O, Candeur M, Kyurkchiev S, Radakovic B, Rezabek K, Erb K, Tiitinen A, De Mouzon J, Shojaei T, Bühler K, Tarlatzis B, Urbancsek J, Bjorgvinsson H, Mocanu E, Scaravelli G, Lejins V, Gudleviciene Z, Lazarevski S, Simic TM, Lambalk C, Hazekamp JT, Kuczynski W, Calhaz-Jorge C, Korsak V, Radunovic N, Marsik L, Tomazevic T, Hernandez J, Karlcstrom PO, Weder M, Isikoglu M, Veselovsky V, Baranowsk R. (1)ESHRE Central Office, Meerstraat 60 B-1852, Grimbergen, Belgium. anders.nyboe.andersen@rh.regionh.dk Comment in Hum Reprod. 2010 Mar;25(3):805-6; author reply 806-7. doi: 10.1093/humrep/dep388. Results of assisted reproductive techniques from treatments initiated in Europe during 2005 are presented in this ninth report. Data were mainly collected from existing national registers. From 30 countries, 923 clinics reported 418 111 treatment cycles including: IVF (118 074), ICSI (203 329), frozen embryo replacement (79 140), oocyte donation (ED, 11 475), preimplantation genetic diagnosis/screening (5846) and in vitro maturation (247). Overall, this represents a 13.6% increase since 2004, partly due to inclusion of 28 417 cycles from Turkey. European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 21 countries and included 128 908 IUI-H and 20 568 IUI-D cycles. In 16 countries where all clinics reported to the IVF register, 1115 cycles were performed per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 26.9% and 30.3%, respectively. For ICSI, the corresponding rates were 28.5% and 30.9%. After IUI-H, the clinical pregnancy rate was 12.6% per insemination in women <40. After IVF and ICSI, the distribution of transfer of one, two, three and four or more embryos was 20.0%, 56.1%, 21.5% and 2.3%, respectively. Huge differences exist between countries. The distribution of singleton, twin and triplet deliveries after IVF and ICSI was 78.2%, 21.0% and 0.8%, respectively. This gives a total multiple delivery rate of 21.8% compared with 22.7% in 2004 and 23.1% in 2003. In women <40 years of age, IUI-H was associated with a twin and triplet pregnancy rate of 11.0% and 1.1%, respectively. Compared with earlier years, there was an increase in the reported number of ART cycles in Europe. Although fewer embryos were transferred per treatment, there was a marginal increase in pregnancy rates and a reduction in multiple deliveries.
To investigate the risks of chromosome mutation after ART for couples with comparable genetic backgrounds. Prospective clinical observational study. In vitro fertilization center at a tertiary-care, university-affiliated teaching hospital.Patient(s)Ninety-seven male children whose fathers have normal spermatogenesis were recruited, including 19 babies conceived through IVF, 18 babies conceived through intracytoplasmic sperm injection (ICSI), and 60 naturally conceived babies, as well as the babies' fathers.Intervention(s)Collection of peripheral and umbilical cord blood samples.Main outcome measure(s)The Yq genetic status of the babies and fathers according to 13 Y-specific markers covering four azoospermia factor (AZF) subregions, the karyotype, and the neonatal examination.Result(s)We found that all children had a normal 46, XY karyotype, but de novo Y-chromosome microdeletions were identified in 1 (5.3%) of 19 IVF offspring and in 3 (16.7%) of 18 ICSI offspring. The incidence of de novo Y-chromosome microdeletion in male children conceived through ICSI or IVF was statistically significantly higher than that in those conceived naturally (10.8% vs. 0). In four babies with microdeletion, one was complicated, with hypospadias.Conclusion(s)Our results, for the first time, indicate that risks of gene mutation may increase in the ART offspring, even though their fathers have normal spermatogenesis and genetic background. Hence, intense attention should be placed on genetic safety in the ART children, and the benefits and risks of adopting ART should be balanced gingerly.
Outcomes and Effectiveness · Outcomes by Diagnosis
To determine the effect of luteinized unruptured follicle (LUF) cycles on frozen thawed embryo transfer (FET).
A retrospective analysis comparing the clinical outcomes after FET among 144 cases of luteinized unruptured follicle (LUF) cycles and 866 cases of ovulation cycles.
Reproductive medical center, Beijing China. Chinese infertile women who underwent FET. None. Clinical pregnancy rate (PR), implantation rate. The implantation rate, clinical pregnancy rate, on-going pregnancy rate and live birth rate in LUF group were 12.76% (49/384), 27.78% (40/144), 24.31% (35/144) and 19.44% (28/144), respectively, and in ovulation group, 14.74% (332/2251), 31.29% (271/866), 28.29% (245/866) and 22.23% (193/866), respectively (p > 0.05). LUF does not affect the clinical outcomes of FET. Patients of LUF should be included in FET treatment.
In vitro fertilization used in combination with intracytoplasmic sperm injection allows otherwise sterile couples to become parents. Despite recent studies on the safety of these technologies, there is still only an incomplete picture of the risks associated with the usage of these assisted reproductive techniques to offspring. The risk of multiple gestations continues to be of major concern because of its association with low birth weight, preterm delivery, and increased perinatal mortality. This article outlines the risks associated with in vitro fertilization/intracytoplasmic sperm injection as a well-defined treatment for couples with severe male factor infertility.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2007. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Andersen AN et al., 2008·Human reproduction (Oxford, England)
14. Assisted reproductive technology in Europe, 2004: results generated from European registers by ESHRE. Andersen AN(1), Goossens V, Ferraretti AP, Bhattacharya S, Felberbaum R, de Mouzon J, Nygren KG; European IVF-monitoring (EIM) Consortium; European Society of Human Reproduction and Embryology (ESHRE). (1)ESHRE Central Office, Meerstraat 60, B-1852 Grimbergen, Belgium. anyboea@rh.dk European results of assisted reproductive techniques from treatments initiated during 2004 are presented in this eighth report. Data were mainly collected from existing national registers. From 29 countries, 785 clinics reported 367,066 treatment cycles including: IVF (114,672), ICSI (167,192), frozen embryo replacement (FER, 71,997), egg donation (ED, 10 334), preimplantation genetic diagnosis/screening (PGD/PGS, 2701) and in vitro maturation (IVM, 170). Overall, this represents only a marginal increase since 2003, due to a huge reduction in treatments in Germany. European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 20 countries. A total of 115,980 cycles (IUI-H, 98,388; IUI-D, 17,592) were included. In 14 countries where all clinics reported to the IVF register, a total of 248,937 ART cycles were performed in a population of 261.6 million, corresponding to 1095 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 26.6% and 30.1%, respectively. For ICSI, the corresponding rates were 27.1% and 29.8%. After IUI-H, the clinical pregnancy rate was 12.6% in women below 40. After IVF and ICSI, the distribution of transfer of 1, 2, 3 and 4 or more embryos was 19.2%, 55.3%, 22.1% and 3.3%, respectively. Compared with 2003, fewer embryos were transferred, but huge differences still existed between countries. The distribution of singleton, twin and triplet deliveries after IVF and ICSI combined was 77.2%, 21.7% and 1.0%, respectively. This gives a total multiple delivery rate of 22.7% compared with 23.1% in 2003 and 24.5% in 2002. After IUI-H in women below 40 years of age, 11.9% were twin and 1.3% triplet gestations. Compared with earlier years, the reported number of ART cycles in Europe increased and the pregnancy rates increased marginally, even though fewer embryos were transferred and the multiple delivery rates were reduced.
Add-Ons and Adjuncts · Preimplantation Genetic Testing
Pregnancy rates in women of advanced maternal age undergoing in vitro fertilization (IVF) are disappointingly low. It has been suggested that the use of preimplantation genetic screening of cleavage-stage embryos for aneuploidies may improve the effectiveness of IVF in these women. We conducted a multicenter, randomized, double-blind, controlled trial comparing three cycles of IVF with and without preimplantation genetic screening in women 35 through 41 years of age. The primary outcome measure was ongoing pregnancy at 12 weeks of gestation. The secondary outcome measures were biochemical pregnancy, clinical pregnancy, miscarriage, and live birth. Four hundred eight women (206 assigned to preimplantation genetic screening and 202 assigned to the control group) underwent 836 cycles of IVF (434 cycles with and 402 cycles without preimplantation genetic screening). The ongoing-pregnancy rate was significantly lower in the women assigned to preimplantation genetic screening (52 of 206 women [25%]) than in those not assigned to preimplantation genetic screening (74 of 202 women [37%]; rate ratio, 0.69; 95% confidence interval [CI], 0.51 to 0.93). The women assigned to preimplantation genetic screening also had a significantly lower live-birth rate (49 of 206 women [24%] vs. 71 of 202 women [35%]; rate ratio, 0.68; 95% CI, 0.50 to 0.92). Preimplantation genetic screening did not increase but instead significantly reduced the rates of ongoing pregnancies and live births after IVF in women of advanced maternal age. (Current Controlled Trials number, ISRCTN76355836 [controlled-trials.com].).
Kagami M et al., 2007·Journal of Assisted Reproduction and Genetics·
Open Access
The prevalence of low birth weight (LBW) is increased in subjects born after assisted reproduction technology (ART), and defective imprinting has frequently been identified in patients with Beckwith-Wiedermann and Angelman syndromes conceived by ART. Thus, we examined methylation pattern in a girl born after ART who had Silver-Russell syndrome (SRS) which can be caused by maternal uniparental disomy for chromosome 7 and by hypomethylation of the differentially methylated region (DMR) of H19. We examined methylation status of 31 cytosines at the CpG dinucleotides in the DMR of PEG1/MEST on 7q32.2 and 23 cytosines at the CpG dinucleotides in the DMR of H19 on 11p15, using leukocyte genomic DNA. Eight of the 31 cytosines in the patient and four of the 31 cytosines in the father were hypermethylated in the PEG1/MEST-DMR. In the H19-DMR, no abnormal methylation pattern was identified in the patient. The results suggest that hypermethylation of paternally expressed genes including PEG1/MEST, which usually have growth-promoting effects, may be relevant to LBW in subjects conceived by ART.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2006. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Andersen AN et al., 2007·Human reproduction (Oxford, England)
30. Assisted reproductive technology in Europe, 2003. Results generated from European registers by ESHRE. Andersen AN(1), Goossens V, Gianaroli L, Felberbaum R, de Mouzon J, Nygren KG. (1)Central Office, European Society of Human Reproduction and Embryology, Meerstraat 60, B-1852 Grimbergen, Belgium. bruno.vandeneede@eshre.com European results of assisted reproductive techniques (ARTs) from treatments initiated during 2003 are presented in this seventh report. Data were mainly collected from already existing national registers. From 28 countries, 725 clinics reported 365 103 treatment cycles with: IVF 132 932, ICSI 162 149, frozen embryo replacement (FER) 60 412, oocyte donation (OD) 7548, PGD/PGS 1956 and IVM 109. Overall, this represents a 13% increase since 2002. For the third time, results on European data on intrauterine inseminations (IUIs) were reported from 19 countries. A total of 99 577 cycles (IUI-H, 82 834; IUI-D, 16 743) were included. In those 15 countries where all clinics reported to the register, a total of 284 765 cycles were performed in a population of 278.7 million, corresponding to 1022 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 26.1 and 29.6%, respectively. For ICSI, the corresponding rates were 26.5 and 28.7%. After IUI-H, the clinical pregnancy rate was 12.2% in women below 40 years and 8.8% in women > or =40 years. After IVF and ICSI, the distribution of transfer of one, two, three and four or more embryos was 15.7, 55.9, 24.9 and 3.5%, respectively. Compared to the year 2002, fewer embryos were transferred, but huge differences still exist between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 76.7, 22.0 and 1.1%, respectively. This gives a total multiple delivery rate of 23.1% compared with 24.5% in 2002. The range of triplet deliveries after IVF and ICSI varied from 0.0 to 4.4% between countries. After IUI-H in women below 40 years of age, 11.4% were twin and 2.2% triplet gestations.
Racial disparity in assisted reproductive technology (ART) outcomes has been reported but remains controversial. Reasons for the disparity are unclear, and access to care has been suggested as a causative factor. In this study, we sought to examine minority utilization of ART in the Department of Defense (DoD) compared with minority utilization in the U.S. ART population. Outcomes from ART were compared between Caucasian (Cau) and African American (AA) patients, and etiologies of disparity were examined. Retrospective cohort study. University-based ART program. PATIENT(S): A total of 1,457 patients undergoing first-cycle fresh, nondonor ART. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live birth rate, implantation rate, spontaneous abortion rate. RESULT(S): Within the DoD population, AA women had a fourfold increase in utilization of ART services relative to the U.S. ART population. In this equal-access-to-care setting, AA women experienced a clinically significant decrease in live birth rate that did not reach statistical significance (29.6% vs. 35.8%, risk ratio [RR] 0.83, 95% confidence interval [CI] 0.67-1.02) and a statistically significant increase in spontaneous abortions compared with Cau women (25% vs. 15.9%, RR 1.57, 95% CI 1.05-2.36). This might be explained, in part, by a higher prevalence of uterine leiomyomas in AA women (30.8% AA vs. 10.7% Cau, RR 2.85, 95% CI 2.06-3.95). For both AA and Cau women, the presence of fibroids at baseline ultrasound was associated with reductions in clinical pregnancy rates (35% with leiomyomas vs. 43.2% without leiomyomas, RR 0.74, 95% CI 0.51-0.98), live birth rates (26.2% vs. 36.0%, RR 0.63, 95% CI 0.44-0.90), and implantation rates (25.6% vs. 31.1% RR 0.82, 95% CI 0.69-0.98). CONCLUSION(S): Utilization of ART services among AA women increased when access to care was improved. A clinically significant reduction in live birth rate and statistically significant increase in spontaneous abortion rate was observed in AA women compared with Cau women. Leiomyomas were three times more prevalent in AA women and reduced ART success, regardless of race. The persistence of racial differences in an equal-access-to-care environment might be explained, in part, by the increased prevalence of leiomyomas in AA women.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2005. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
A meta-analysis was performed on 11 cohort studies of Assisted Reproductive Technologies (ART) and subsequent childhood cancer, published up to February 2005, which reported comparable, nonoverlapping data, and then restricted to eight studies which presented a similar research design. The overall Standardised Incidence Ratio was 1.33 (95% CI 0.62-2.85), and 0.77 (95% CI 0.41-1.42) when the analysis was restricted to eight studies. No evidence of publication bias was observed for the overall analysis. The data are consistent with a lack of increase in risk of childhood cancer, though the amount of data on ART and cancer is still limited; larger multicentric studies as well as a pooled analysis on the available data are warranted.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2004. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Niemitz EL et al., 2004·Am J Hum Genet·
Open Access
A surprising set of recent observations suggests a link between assisted reproductive technology (ART) and epigenetic errors--that is, errors involving information other than DNA sequence that is heritable during cell division. An apparent association with ART was found in registries of children with Beckwith-Wiedemann syndrome, Angelman syndrome, and retinoblastoma. Here, we review the epidemiology and molecular biology behind these studies and those of relevant model systems, and we highlight the need for investigation of two major questions: (1) large-scale case-control studies of ART outcomes, including long-term assessment of the incidence of birth defects and cancer, and (2) investigation of the relationship between epigenetic errors in both offspring and parents, the specific methods of ART used, and the underlying infertility diagnoses. In addition, the components of proprietary commercial media used in ART procedures must be fully and publicly disclosed, so that factors such as methionine content can be assessed, given the relationship in animal studies between methionine exposure and epigenetic changes.
This study was undertaken to determine proportions of very-low-birth-weight (VLBW) multiple birth infants receiving neonatal intensive care whose mothers received various types of infertility treatment and to evaluate infertility treatment-associated morbidity and mortality. Study infants were multiples with birth weight 401 to 1500 g cared for in Cincinnati neonatal intensive care units from January 1996 to December 2000. Data were obtained retrospectively from the National Institute for Child Health and Human Development Neonatal Research Network registry. Use of infertility treatment (in vitro fertilization, injection or oral ovulation, and intrauterine insemination) was determined by maternal interview or chart review. The generalized estimating equation approach to logistic regression was used. The study included 382 infants of 212 mothers: 201=spontaneous conception (53%), 93=in vitro fertilization (24%), 55=injection (14%), 15=oral (4%), and 18=intrauterine insemination (5%). Neither gestational age nor birth weight differed between groups. More female (58%, P=.003) and white infants (95%, P<.001) resulted from infertility treatment-induced pregnancies than from spontaneous pregnancies. Advancing gestational age significantly decreased odds for all outcomes. Of VLBW multiples receiving neonatal intensive care, 47% are associated with infertility treatment. Infertility treatment does not influence outcomes in VLBW multiples.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2003. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
This review addresses questions related to medicosocial concerns surrounding the care of women with multiple births and their infants. Relevant articles and texts on twin and triplet pregnancies were reviewed. Population-based data were selected for inclusion whenever possible. Relevant tables were simplified from original sources. The review clarifies obstetric and perinatal questions in a manner that is helpful to clinicians and their patients.
Treatment for infertility using assisted reproductive technologies (ART) is highly successful and has been used to help a steadily growing number of couples worldwide. In 1999, in the United States, more than 86,000 treatment cycles were performed resulting in the birth of more than 30,000 babies. Despite this widespread application, few follow-up studies of children conceived through ART have been performed, and more rigorous investigation of this important issue has clearly been needed. In recent months, three studies linking ART with several complications have been published in high profile and widely read general medical journals: Schieve et al. (1) reported that singletons conceived using ART were at an increased risk for low birth weight, whereas Hansen et al. (2) suggested an increased risk of major birth defects. Finally, Stromberg et al. (3) concluded that children conceived through IVF have an increased risk of neurological problems, especially cerebral palsy.
The importance of these studies is obvious as they provide clues of possible risks associated with ART. However, they are all retrospective analyses of data collected through registries and therefore are vulnerable to biases inherent to such study design. We must be careful not to overinterpret the data by concluding that the use of ART, whether from gamete or embryo manipulation or use of medications, is the direct cause of the complications—the observed associations may simply be explained by one or more confounders, such as an underlying infertility-related condition in the treated women. This short communication is an attempt to place these three articles in proper perspective for the clinician and to provide the impetus for conducting further studies to determine the true nature of the described associations.
At the outset, it should be stated that a major weakness of all three studies is the lack of proper controls. If the aim of a study is to determine whether a cause and effect relationship exists between the process of IVF and a specific outcome (i.e., low birth weight, major birth defects, neurological problems), the appropriate control population is that of babies born to infertile women achieving pregnancies by methods other than IVF. None of the three studies specifically included such a control population.
To determine the number of embryos stored at assisted reproductive technology (ART) clinics in the United States and their current disposition. A targeted survey instrument sent by the SART-RAND team to all medical practices providing in vitro fertilization services in the United States. The SART-RAND team surveyed all 430 ART practices in the United States. Of these practices, 340 returned surveys for analysis. The data from these surveys were merged with data taken from the 1999 SART dataset, which contains information about practice size and success rates. Responding clinics reported a total of 396,526 embryos in storage as of April 11, 2002. The vast majority of the embryos (88.2%) were targeted for patient use. Small numbers of embryos were available for research, donation, destruction, quality assurance, or other uses. Nearly 400,000 embryos are stored in the United States, the majority of which (88.2%) are targeted for patient use. Few are available for research (2.8%), limiting possible conversion into embryonic stem cell lines.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2002. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Wright VC et al., 2003·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
MMWR 2003 Oct 3; 52(39):942. In 1996, CDC initiated data collection regarding assisted reproductive technology (ART) procedures performed in the United States to determine medical center-specific pregnancy success rates, as mandated by the Fertility Clinic Success Rate and Certification Act (FCSRCA) (Public Law 102-493, October 24, 1992). ART includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization and related procedures). Patients who undergo ART treatments are more likely to deliver multiple-birth infants than women who conceive naturally. Multiple births are associated with increased risk for mothers and infants (e.g., pregnancy complications, premature delivery, low-birthweight infants, and long-term disability among infants). 2000. CDC contracts with a professional society, the Society for Assisted Reproductive Technology (SART), to obtain data from fertility medical centers located in the United States. Since 1997, CDC has compiled data related to ART procedures. The Assisted Reproductive Technology Surveillance System was initiated by CDC in collaboration with the American Society for Reproductive Medicine, the Society for Assisted Reproductive Technology, and The National Infertility Association. In 2000, a total of 25,228 live-birth deliveries and 35,025 infants resulting from 99,629 ART procedures were reported to CDC from 383 medical centers that performed ART in the United States and U.S. territories. Nationally, 75,516 (76%) of ART treatments were freshly fertilized embryos using the patient's eggs; 13,312 (13%) were thawed embryos using the patient's eggs; 7,919 (8%) were freshly fertilized embryos from donor eggs; and 2,882 (3%) were thawed embryos from donor eggs. The national live-birth delivery per transfer rate was 30.8%. The five states that reported the highest number of ART procedures were California (13,194), New York (11,239), Massachusetts (8,041), Illinois (7,323), and New Jersey (5,506). These five states also reported the highest number of live-birth deliveries and infants born as a result of ART. Overall, 47% of women undergoing ART-transfer procedures using freshly fertilized embryos from their own eggs were aged <35 years; 23% were aged 35-37 years; 19% were aged 38-40 years; 7% were aged 41-42 years; and 4% were aged >42 years. Among ART treatments in which freshly fertilized embryos from the patient's eggs were used, substantial variation in patient age, infertility diagnoses, history of past infertility treatment, and past births was observed. Nationally, live-birth rates were highest for women aged <35 years (38%). The risk for a multiple-birth delivery was highest for women who underwent ART-transfer procedures using freshly fertilized embryos from either donor eggs (40%) or from their own eggs (35%). Among women who underwent ART-transfer procedures using freshly fertilized embryos from their own eggs, further variation by patient age and number of embryos transferred was observed. Of the 35,025 infants born, 44% were twins, and 9% were triplet and higher order multiples, for a total multiple-infant birth rate of 53%. Patient's residing in states with the highest number of live-birth deliveries also reported the highest number of infants born in multiple-birth deliveries. Whether an ART procedure was successful (defined as resulting in a pregnancy and live-birth delivery) varied according to different patient and treatment factors. Patient factors included the age of the woman undergoing ART, whether she had previously given birth, whether she had previously undergone ART, and the infertility diagnosis of both the female and male partners. Treatment factors included whether eggs were from the patient or a woman serving as an egg donor, whether the embryos were freshly fertilized or previously frozen and thawed, how long the embryos were kept in culture, how many embryos were transferred, and whether various specialized treatment procedures were used in conjunction with ART. ART poses a major risk for multiple births. This risk varied according to the patient's age, the type of ART procedure performed, and the number of embryos transferred. In addition, the increased risk for multiple births has a notable population impact in certain states. As use of ART and ART success rates continue to increase, ART-related multiple births are an increasingly important public health problem nationally and in many states. The proportion of infants born through ART in 2000 that were multiple births (53%) was substantially higher than in the general U.S. population during the same period. Data in this report indicate a need to reduce multiple births associated with ART. Efforts should be made to limit the number of embryos transferred for patients undergoing ART. In addition, continued research and survei
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
To examine the cumulative conception rate and live birth rate in women undergoing IVF and to assess the influence of prognostic factors on cumulative conception rate and discontinuation of treatment. Retrospective analysis of data from couples undergoing IVF. Assisted conception unit of a university hospital. PATIENT(S): Two thousand fifty-six patients undergoing 2708 cycles of IVF from April 1992 to March 1999. MAIN OUTCOME MEASURE(S): Cumulative conception rate by age, number of oocytes retrieved, and embryos transferred, and the influence of these factors on dropout rates. RESULT(S): The cumulative conception rate and cumulative live birth rate after four attempts were 75% and 66%, respectively. The cumulative conception rate differed significantly between women 35 years of age or younger and those older than 35 years who had five or more oocytes retrieved (83% vs. 63%). When fewer than five oocytes were retrieved in women 35 years of age or younger, the cumulative conception rate decreased to 33%. Overall, 36% of patients continued treatment after the first attempt; these patients were more likely to have more than five oocytes retrieved and more than two embryos available for transfer. The cumulative conception rate was greater when the female partner was 35 years of age or younger and had more than five oocytes retrieved and more than two embryos were available for transfer. These factors influenced dropout rates.
Outcomes and Effectiveness · Outcomes by Diagnosis
To investigate the IVF outcome for patients with endometriosis. Meta-analysis. Academic research center. PATIENT(S): A MEDLINE search and review of the literature were performed. Patients were classified by level of endometriosis, and controls were classified according to the indication for IVF. INTERVENTION(S): Bivariate analysis and multivariate logistic regression was used to estimate overall effect and control for confounding. MAIN OUTCOME MEASURE(S): Pregnancy rates, fertilization rate, implantation rates, and numbers of oocytes retrieved. RESULT(S): Twenty-two published studies were included in the overall analysis. The chance of achieving pregnancy was significantly lower for endometriosis patients (odds ratio, 0.56; 95% confidence interval, 0.44-0.70) when compared with tubal factor controls. Multivariate analysis also demonstrated a decrease in fertilization and implantation rates, and a significant decrease in the number of oocytes retrieved for endometriosis patients. Pregnancy rates for women with severe endometriosis were significantly lower than for women with mild disease (odds ratio, 0.60; 95% confidence interval, 0.42-0.87). CONCLUSION(S): Patients with endometriosis-associated infertility undergoing IVF respond with significantly decreased levels of all markers of reproductive process, resulting in a pregnancy rate that is almost one half that of women with other indications for IVF. These data suggest that the effect of endometriosis is not exclusively on the receptivity of the endometrium but also on the development of the oocyte and embryo.
It is not known whether infants conceived with use of intracytoplasmic sperm injection or in vitro fertilization have a higher risk of birth defects than infants conceived naturally. We obtained data from three registries in Western Australia on births, births after assisted conception, and major birth defects in infants born between 1993 and 1997. We assessed the prevalence of major birth defects diagnosed by one year of age in infants conceived naturally or with use of intracytoplasmic sperm injection or in vitro fertilization. Twenty-six of the 301 infants conceived with intracytoplasmic sperm injection (8.6 percent) and 75 of the 837 infants conceived with in vitro fertilization (9.0 percent) had a major birth defect diagnosed by one year of age, as compared with 168 of the 4000 naturally conceived infants (4.2 percent; P<0.001 for the comparison between either type of technology and natural conception). As compared with natural conception, the odds ratio for a major birth defect by one year of age, after adjustment for maternal age and parity, the sex of the infant, and correlation between siblings, was 2.0 (95 percent confidence interval, 1.3 to 3.2) with intracytoplasmic sperm injection, and 2.0 (95 percent confidence interval, 1.5 to 2.9) with in vitro fertilization. Infants conceived with use of assisted reproductive technology were more likely than naturally conceived infants to have multiple major defects and to have chromosomal and musculoskeletal defects. Infants conceived with use of intracytoplasmic sperm injection or in vitro fertilization have twice as high a risk of a major birth defect as naturally conceived infants.
The increased risk of low birth weight associated with the use of assisted reproductive technology has been attributed largely to the higher rate of multiple gestations associated with such technology. It is uncertain, however, whether singleton infants conceived with the use of assisted reproductive technology may also have a higher risk of low birth weight than those who are conceived spontaneously. We used population-based data to compare the rates of low birth weight (less-than-or-equal 2500 g) and very low birth weight (<1500 g) among infants conceived with assisted reproductive technology with the rates in the general population. We studied 42,463 infants who were born in 1996 and 1997 and conceived with assisted reproductive technology and used as a comparison group 3,389,098 infants born in the United States in 1997. Among singleton infants born at 37 weeks of gestation or later, those conceived with assisted reproductive technology had a risk of low birth weight that was 2.6 times that in the general population (95 percent confidence interval, 2.4 to 2.7). The use of assisted reproductive technology was associated with an increased rate of multiple gestations; however, its use was not associated with a further increase in the risk of low birth weight in multiple births. Among twins, the ratio of the rate of low birth weight after the use of assisted reproductive technology to the rate in the general population was 1.0 (95 percent confidence interval, 1.0 to 1.1). Infants conceived with assisted reproductive technology accounted for 0.6 percent of all infants born to mothers who were 20 years of age or older in 1997, but for 3.5 percent of low-birth-weight and 4.3 percent of very-low-birth-weight infants. The use of assisted reproductive technology accounts for a disproportionate number of low-birth-weight and very-low-birth-weight infants in the United States, in part because of absolute increases in multiple gestations and in part because of higher rates of low birth weight among singleton infants conceived with this technology.
To evaluate the safety of ICSI, this study compared data of IVF and ICSI children by collecting data on neonatal outcome and congenital malformations during pregnancy and at birth. The follow-up study included agreement to genetic counselling and eventual prenatal diagnosis, followed by a physical examination of the children after 2 months, after 1 year and after 2 years. 2840 ICSI children (1991-1999) and 2955 IVF children (1983-1999) were liveborn after replacement of fresh embryos. ICSI was carried out using ejaculated, epididymal or testicular sperm. In the two cohorts, similar rates of multiple pregnancies were observed. ICSI and IVF maternal characteristics were comparable for medication taken during pregnancy, pregnancy duration and maternal educational level, whereas maternal age was higher in ICSI and a higher percentage of first pregnancies and first children born was observed in the ICSI mothers. Birthweight, number of neonatal complications, low birthweight, stillbirth rate and perinatal death rate were compared between the ICSI and the IVF groups and were similar for ICSI and IVF. Prematurity was slightly higher in the ICSI children (31.8%) than in the IVF children (29.3%). Very low birthweight was higher in the IVF pregnancies (5.7%) compared with ICSI pregnancies (4.4%). Major malformations (defined as those causing functional impairment or requiring surgical correction), were observed at birth in 3.4% of the ICSI liveborn children and in 3.8% of the IVF children (P = 0.538). Malformation rate in ICSI was not related to sperm origin or sperm quality. The number of stillbirths (born > or =20 weeks of pregnancy) was 1.69% in the ICSI group and 1.31% in the IVF group. Total malformation rate taking into account major malformations in stillborns, in terminations and in liveborns was 4.2% in ICSI and 4.6% in IVF (P = 0.482). The comparison of ICSI and IVF children taking part in an identical follow-up study did not show any increased risk of major malformations and neonatal complications in the ICSI group.
To estimate the relationship of assisted reproductive technologies and ovulation-inducing drugs with preeclampsia in multiple gestations. This historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously. Between January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty-nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at the P <.05 level. Women who conceive multiple gestations through assisted reproductive technologies have a 2.1-fold higher risk of preeclampsia than those who conceive spontaneously.
There is an absence of population-based long-term studies on the risk of neurological sequelae in children born after in-vitro fertilisation (IVF). Our aim was to compare the frequency of such problems between IVF-born children and controls. We did a population-based retrospective cohort study in which we compared development of neurological problems in 5680 children born after IVF, with 11360 matched controls. For 2060 twins born after IVF, a second set of controls (n=4120), all twins, were selected. We obtained data on neurological problems from the records of the Swedish habilitation centres. Children born after IVF are more likely to need habilitation services than controls (odds ratio 1.7, 95% CI 1.3-2.2). For singletons, the risk was 1.4 (1.0-2.1). The most common neurological diagnosis was cerebral palsy, for which children born after IVF had an increased risk of 3.7(2.0-6.6), and IVF singletons of 2.8 (1.3-5.8). Suspected developmental delay was increased four-fold (1.9-8.3) in children born after IVF. Twins born after IVF did not differ from control twins with respect to risk of neurological sequelae. Low-birthweight and premature infants were more likely to need habilitation than fullterm babies. Maternal age did not affect risk. Our study suggests that children born after IVF have an increased risk of developing neurological problems, especially cerebral palsy. These risks are largely due to the high frequency of twin pregnancies, low birthweight, and prematurity among babies born after IVF. To limit these risks, we recommend that only one embryo should be transferred during IVF.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2001. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Outcomes and Effectiveness · Outcomes by Diagnosis
To investigate differences in immature oocyte maturation, fertilization, and pregnancy rates among women with unstimulated normal ovaries, polycystic ovaries (PCOs), or PCOS. Prospective observational study. University fertility clinic. PATIENT(S): One hundred forty-four women undergoing 180 in vitro oocyte maturation treatment cycles. INTERVENTION(S): Transvaginal immature oocyte recovery from unstimulated ovaries 36 hours after hCG priming. In vitro oocyte maturation and fertilization. Fresh embryo transfer. MAIN OUTCOME MEASURE(S): Immature oocytes collected, metaphase II oocytes, and embryos produced. Implantation and pregnancy rates. RESULT(S): The overall oocyte maturation and fertilization rates attained were 80.3% (1,222 of 1,522) and 76.5% (935 of 1,222), respectively. Significantly fewer immature oocytes were retrieved from normal ovaries (5.1 +/- 3.7) compared with the PCO (10.0 +/- 5.1) or PCOS (11.3 +/- 9.0) groups. Fertilization and cleavage rates were comparable among the three groups. The implantation, pregnancy, and live birth rates per transfer for normal ovaries were 1.5%, 4.0%, and 2.0%, respectively; for PCOs 8.9%, 23.1%, 17.3%, respectively; and for women with PCOS 9.6%, 29.9%, and 14.9%, respectively. CONCLUSION(S): Immature oocytes retrieved from normal ovaries, PCOs, or women with PCOS, when using hCG priming before oocyte retrieval, have a similarly high maturation, fertilization, and cleavage potential. In vitro maturation is a useful treatment option, particularly for women with PCOs.
To compare the karyotype of babies conceived through ICSI with that of naturally conceived babies. Prospective controlled study. The Egyptian IVF-ET Center, Cairo, Egypt. PATIENT(S): Four hundred and thirty babies conceived through ICSI and 430 babies conceived naturally. INTERVENTION(S): ICSI and karyotyping. MAIN OUTCOME MEASURE(S): Abnormal karyotype. RESULT(S): Four hundred and thirty consecutive babies conceived through ICSI who were delivered in one hospital had 15 abnormal karyotypes (3.5%). Of the 15 babies, 7 were of female phenotype and 8 of male phenotype. Six babies had sex chromosome anomalies, 8 had autosomal anomalies, and 1 had combined sex chromosome and autosomal anomalies. A control group of 430 consecutive babies conceived naturally who were delivered in one hospital had no abnormal karyotype. The difference between the two groups was significant (P<.001). CONCLUSION(S): ICSI carries a small but significant increased risk of abnormal karyotyping to the offspring. This risk appears to be equally distributed between autosomal and sex chromosome anomalies.
There have been reports suggesting that children born after in-vitro fertilisation by intracytoplasmic sperm injection (ICSI) are at increased risk of neurodevelopmental delay. We have undertaken a case-control study of this issue. We studied 208 singleton children conceived by ICSI and a control group of 221 normally conceived singleton children. Children were recruited from 22 fertility centres and local nurseries throughout the UK. Controls were selected to match cases as closely as possible for social class, maternal educational attainment, region, sex, and race. The primary outcome measure was neurodevelopmental scoring; secondary measures were perinatal outcomes, postnatal health, and congenital abnormalities. A single examiner assessed all the children. A follow-up rate of 90% for the ICSI group was achieved at a mean age of 17 months. No difference between the study children and controls was found in mean neurodevelopmental scores (98.08 [SD 10.93] vs 98.69 [9.99]) or any subscales on the Griffiths' scales of mental development. Perinatal outcome was similar apart from a higher rate of caesarean section (73 [35.1%] vs 53 [24.0%], p=0.015) and a lower mean birthweight (3163 [SD 642] vs 3341 [606] g, p=0.013) in the study group. Rates of major congenital abnormality were also similar overall (ten [4.8%] study vs ten [4.5%] control), although there were significantly more congenital anomalies among children born to fathers with oligozoospermia than in other children. This population study did not show any significant difference between children conceived after ICSI and their naturally conceived peers in terms of physical health and development.
Transvaginal ultrasonic follicle puncture has now become the method of choice for oocyte retrieval among most in vitro fertilization (IVF) units. The procedure, which involves puncture then aspiration of ovarian follicles, inevitably results in damage to the fine vascular network of blood vessels on the ovarian surface and theca interna layer, and tends to produce varying degrees of blood loss. The transvaginal ultrasonically guided retrieval of oocytes can be considered noncomplicated when the procedure does not result in injury to iliac vessels, trauma to pelvic viscera, or iatrogenic pelvic infections (1, 2), which would necessitate laparoscopy and or laparotomy. The aim of our study was to quantify the amount of blood loss that should be considered “normal” after noncomplicated transvaginal ultrasonically guided retrieval of oocytes, to characterize the factors that are related to the amount of blood loss, and to identify the patients who have the highest risk of hemorrhage.
Before beginning our study, we performed a power analysis of potential participants. We established the sample size after evaluating the number of women of fertile age in our area, and we used the previous years’ data to calculate the prevalence of sterility problems and the percentage of women who had undergone in vitro fertilization. Thus, our prospective study was based on a sample of 220 women, 25 to 42 years old, who underwent assisted reproduction from January 1998 to May 1999. We excluded the women who had mild or severe ovarian hyperstimulation syndrome or thrombocytopenia, those who were taking anticoagulant drugs, and those who were overweight (body mass index 25 to 30) or obese (body mass index greater than 30). The study was approved by the local hospital ethics committee and all of the participants gave written informed consent.
Zuppa AA et al., 2001·Eur J Obstet Gynecol Reprod Biol·
Over the last 10 years, diffusion of assisted reproduction techniques (ovarian stimulation, IVF, GIFT) has led to an increased incidence of multiple pregnancies and consequently, of the related obstetric-neonatal problems. In this study, multiple births have been studied, with particular reference to the twin births occurring in the Gemelli hospital, Rome. The hospital is also a reference centre for obstetric pathologies and infertility treatment. In particular, attention has been focused on neonatal outcome, comparing twins born from spontaneous and assisted pregnancies. 228 neonates from spontaneous twin pregnancies and 32 from assisted twin pregnancies were taken into consideration with regard to: premature birth, low birth-weight, intrauterine growth retardation, weight discordance, Apgar score, major neonatal diseases, and mortality. Results showed a significant higher incidence of prematurity and low birth-weight, as well as a significant lower gestational age, occurring more frequently in twins resulting from assisted pregnancies than in twins from spontaneous pregnancies. Furthermore, the incidence of severe depression at birth and respiratory disease was significantly higher in twins from assisted pregnancies than in those from spontaneous pregnancies, despite similar gestational age and birth-weight.
To investigate the contributions of ovulation-inducing drugs and assisted reproductive technologies to multiple birth. This historic prospective study was conducted in a cohort of 13,151 women who delivered after 20 weeks' gestation between October 1996 and December 1999. The study setting was a Colorado health maintenance organization. Cases were women who were pregnant as a result of exposure to treatment with either assisted reproductive technologies or ovulation induction in the absence of assisted reproductive technologies. The main outcome measure was multiple birth. There was a significant association between assisted conception and multiple birth. Compared with women with naturally conceived pregnancies, there was a 25-fold likelihood (95% confidence interval 18, 35, P <.001) of multiple birth among women exposed to any of those treatments. In the total cohort the proportion of multiple births attributable to those treatments was 33%. After adjusting for the use of assisted conception and other covariates, we found no association between advanced maternal age and multiple birth. In this cohort, assisted reproductive interventions were strongly associated with multiple birth. Although a higher proportion of older women sought assisted reproductive technologies, we did not find an independent relationship between advanced maternal age and multiple birth. The increasing number of multiple births attributable to assisted conception raises public health concerns regarding multiple gestation-related maternal and infant morbidities.
The potential risk of transmitting chromosomally abnormal spermatozoa from infertile males into oocytes through intracytoplasmic sperm injection (ICSI) has prompted us to investigate the male pronuclei of tripronuclear zygotes (3PN) obtained after ICSI. To specify the type of anomalies, we used triple colour fluorescent in-situ hybridization (FISH) with three specific probes for chromosomes X, Y and 18. From a total of 163 paternal complements of ICSI-3PN zygotes, 90 (55.2%) had Y-chromosome signals. Eighty-three of these were normal, four had the disomy XY and three were diploid. In the remaining 73 ICSI-3PN zygotes without Y-chromosome signals, the origin of paternal pronuclei was extrapolated through chromosome constitution of the first polar body. Five anomalies were found in this group of zygotes, giving a total rate of numerical chromosome aberrations for fertilizing spermatozoa of 7.4%. In contrast to ICSI, only two disomies (1.5%) were found in the control group of IVF-3PN zygotes. Compared with the incidence of chromosome anomalies between paternal-derived
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2000. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
In the United States, pregnancies associated with assisted reproductive technology (ART) or ovulation-inducing drugs are more likely to result in multiple births than spontaneously conceived pregnancies (1). In addition, triplet and higher-order multiple births are at greater risk than singleton births to be preterm (< or = 37 completed weeks' gestation), low birthweight (LBW) (i.e., < or = 2500 g), or very low birthweight (i.e., < 1500 g), resulting in higher infant morbidity and mortality (2). Because preterm and LBW infants often require costly neonatal care and long-term developmental follow-up, the continuing increase in triplet and higher-order multiple births causes concern among health-care providers and policymakers (3). This report provides estimates of the contribution of ART and ovulation-inducing drugs to these birth outcomes for 1996 and 1997, and summarizes trends during 1980-1997, which indicate that the ratio of triplet and higher-order multiple births has more than quadrupled and that a large proportion of this increase can be attributed to ART or the use of ovulation-inducing drugs.
To maximize pregnancy rates, physicians who perform IVF, often transfer multiple embryos, which increases the multiple birth risk. Multiple birth infants are at significant risk for a number of adverse outcomes including preterm delivery, low birth weight, congenital malformations, fetal and infant deaths and long term morbidity and disability among survivors. Since the ultimate goal for an IVF treatment is the birth of a healthy infant, an important issue for all kinds of assisted reproductive technologies (ART) must be the reduction or elimination of multiple pregnancies. In this article, different strategies to avoid multiple births in ART are discussed.
To quantify the contribution of in vitro fertilization (IVF) on changes in the rates of low birth weight (LBW), preterm delivery, very low birth weight, and multiple births during the past 3 years. Data on IVF pregnancies from 1994 to 1996 within Alberta were reviewed. Population data were obtained from the Provincial notice of a live or stillbirth. The IVF component of increased LBW rate in the province was 17.8% for infants <2500 g and 43.5% for those born <1500 g. IVF accounted for 10.5% of the provincial rate increase in deliveries <37 weeks' gestation and 66.2% of those <30 weeks' gestation. IVF accounted for 21.4% of the twins and all of the sets of triplets in the province. During a 3-year period IVF has affected the incidence of LBW, preterm delivery, and multiple birth. IVF is a substantial contributor to changes in very low birth weight and delivery before 30 weeks, which is partly related to multiple births.
Outcomes and Effectiveness · Outcomes by Diagnosis
The aim of this study was to report the outcome of all clinical pregnancies obtained after intracytoplasmic sperm injection (ICSI) performed during a 5 year period at two fertility clinics, with special reference to delivery outcome associated with different sperm origin and quality and the transfer of fresh or frozen-thawed pre-embryos. A total of 1293 clinical pregnancies was analysed. Deliveries occurred in 75.9% (n = 982) and early spontaneous abortion, late spontaneous abortion and ectopic pregnancy in 21.4, 1.0 and 1.2% respectively. Multiple birth occurred in 21.3% (208 sets of twins and one set of triplets) of the deliveries, with the highest incidence in the epididymal sperm group (30.2%) and lowest in the cryopreserved group (13.7%). A total of 1192 infants was born. Preterm birth occurred in 15.7% of all deliveries. Preterm birth was not related to sperm origin or quality but was related to multiple birth. The prematurity rate was 8.4%, 42.3% and 100% for singletons, twins and triplets respectively. Singleton infants born after cryopreservation as embryos had a significantly higher birthweight than the ejaculated sperm group with fresh embryo transfer. The perinatal mortality rate was 11.7 per 1000 born infants. Eighty-seven of the 1192 infants (7.3%) had a malformation, 40 of which were minor. The perinatal mortality rate and the malformation rate were similar in the different subgroups. Prenatal karyotyping was performed on 149 fetuses (12.5%) and abnormal results were found in four cases (2.7%). In conclusion, obstetric outcome of ICSI pregnancies was similar to that of conventional IVF and was not influenced by sperm origin or quality. The high incidence of multiple births is still the major concern.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1999. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
To maximize birth rates, physicians who perform in vitro fertilization (IVF) often transfer multiple embryos, but this increases the multiple-birth risk. Live-birth and multiple-birth rates may vary by patient age and embryo quality. One marker for embryo quality is cryopreservation of extra embryos (if embryos are set aside for cryopreservation, higher quality embryos may have been available for transfer). To examine associations between the number of embryos transferred during IVF and live-birth and multiple-birth rates stratified by maternal age and whether extra embryos were available (ie, extra embryos cryopreserved). Retrospective cohort of 300 US clinics reporting IVF transfer procedures to the Centers for Disease Control and Prevention in 1996. A total of 35554 IVF transfer procedures. Live-birth and multiple-birth rates (percentage of live births that were multiple). A total number of 9873 live births were reported (multiple births from 1 pregnancy were counted as 1 live birth). The number of embryos needed to achieve maximum live- birth rates varied by age and whether extra embryos were cryopreserved. Among women 20 to 29 years and 30 to 34 years of age, maximum live-birth rates (43 % and 36%, respectively) were achieved when 2 embryos were transferred and extra embryos were cryopreserved. Among women 35 years of age and older, live-birth rates were lower overall and regardless of whether embryos were cryopreserved, live-birth rates increased if more than 2 embryos were transferred. Multiple-birth rates varied by age and the number of embryos transferred, but not by whether embryos were cryopreserved. With 2 embryos transferred, multiple-birth rates were 22.7%, 19.7%, 11.6%, and 10.8% for women aged 20 to 29, 30 to 34, 35 to 39, and 40 to 44 years, respectively. Multiple-birth rates increased as high as 45.7% for women aged 20 to 29 years and 39.8% for women aged 30 to 34 years if 3 embryos were transferred. Among women aged 35 to 39 years, the multiple-birth rate was 29.4% if 3 embryos were transferred. Among women 40 to 44 years of age, the multiple-birth rate was less than 25% even if 5 embryos were transferred. Based on these data, the risk of multiple births from IVF varies by maternal age and number of embryos transferred. Embryo quality was not related to multiple birth risk but was associated with increased live-birth rates when fewer embryos were transferred.
Donor Gametes and Surrogacy · Donor Conceived Outcomes
Pregnancies achieved from oocyte, sperm or embryo donation are unique, since they have resulted from donor gametes that are immunologically foreign to the mother. Thus, studying the obstetric outcome of such pregnancies may shed some light on the pathophysiology of preeclampsia, particularly in women conceiving with donated embryos, since the entire fetal genome is allogenic in these pregnancies. In this retrospective cohort study, a total of 144 women were studied. Of these, 72 were infertility patients who had conceived as a result of sperm, ovum or embryo donation and the other 72 women were age- and parity-matched control patients who became pregnant with their own gametes, either spontaneously, or following intrauterine insemination with their partner's spermatozoa. Study patients were divided into three groups depending on the origin of the donated gametes. Group 1 consisted of pregnancies achieved by intrauterine insemination with washed donor spermatozoa (n = 33). Group 2 included women who conceived using donated oocytes (n = 27) and group 3 consisted of women who conceived as a result of embryo donation (n = 12). The incidence of pregnancy-induced hypertension in the donated gametes study group was 12.5% (9/72) compared with 2.8% (2/72) in the control group. In addition, pre-eclampsia was diagnosed in 18.1% (13/72) of the donated gametes study group compared to 1.4% (1/72) in the age- and parity-matched controls. The increased incidence of gestational hypertension in pregnancies resulting from donated gametes gives evidence for a maternal genetic component, with an equally strong fetal influence, in the complicated aetiology of gestational hypertension, and pre-eclampsia in particular.
Outcomes and Effectiveness · Outcomes by Diagnosis
This meta-analysis was intended to evaluate differences in pregnancy rates after in-vitro fertilization (IVF) in tubal fertility with and without hydrosalpinx. It examined nine published retrospective comparative series and five series published as abstracts for which additional information was obtained. In all, these studies involved 5592 patients (1004 with hydrosalpinx and 4588 with tubal infertility without hydrosalpinx). The main outcome measures were rates of pregnancy, implantation, live delivery, and early pregnancy loss. Pregnancy rates were significantly lower in the presence of hydrosalpinx: 31.2% for the tubal sterility group without hydrosalpinx and 19.7% for the group with hydrosalpinx (odds ratio: 0.64; 95% confidence interval: 0.56, 0.74). Similarly, the implantation rate and the delivery rate per transfer in the hydrosalpinx group were only slightly more than half those of the non-hydrosalpinx group (implantation: 8.5 and 13.7%, respectively; delivery: 13.4 and 23.4%). The incidence of early pregnancy loss was also higher in the hydrosalpinx group (43.7%) than in the control group (31.1%). This meta-analysis makes it clear that hydrosalpinx present during IVF-embryo transfer has negative consequences on the rates of pregnancy, implantation, live delivery, and early pregnancy loss. It would be premature, nonetheless, to conclude that routine salpingectomy should be performed on all patients with hydrosalpinx.
A variety of embryo-based technologies used in farm animal reproduction, including embryo culture, nuclear transfer, embryo-somatic cell co-culture and asynchronous embryo transfer can lead to the production of large offspring; the so-called large calf/lamb syndrome. In some cases, abnormalities in the fetus and newborn are apparent. The nature of these associations is explored with emphasis on the biological differences between in-vivo- and in-vitro-produced embryos. A unifying framework and research programme aimed at explaining anomalies in early embryo development is then proposed in terms of the response of somatic cells and embryos to cellular stress. The review concludes with a caution against developments in assisted conception technologies, in man and domestic animals, being determined too much by the needs of commerce at the expense of research on the molecular, biochemical and physiological basis of early mammalian development.
To determine whether IVF or a standard infertility treatment algorithm results in better outcome and/or lower cost when used as first-line therapy for couples with infertility. Prospective, randomized clinical study. University-affiliated infertility clinic. PATIENT(S): Couples with newly diagnosed infertility and no prior treatment. INTERVENTION(S): Couples were randomized to undergo either IVF (group 1, n = 46) or a standard infertility treatment algorithm (group 2, n = 50) as initial therapy for infertility. MAIN OUTCOME MEASURE(S): Pregnancy rates and costs per couple, per month of treatment, and per pregnancy. RESULT(S): Pregnancy rates were higher in group 2 than in group 1. Costs per couple were not statistically different, although a trend toward higher costs was apparent in group 1, reflected by a higher median cost per clinical pregnancy established and a higher cost per month of treatment. Whereas cost differences between the groups diminished over time, pregnancy rates remained the same. CONCLUSION(S): In vitro fertilization currently does not represent an appropriate first-line treatment option for couples with infertility. The use of a standard infertility treatment algorithm results in a higher pregnancy rate and lower cost and therefore should be the preferred treatment approach.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1998. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
To investigate the incidence of complications in the use of assisted reproductive technology in the management of infertile couples. Retrospective study. The Egyptian IVF & ET Center, Maadi, Cairo, Egypt. PATIENT(S): Two thousand nine hundred twenty-four patients underwent IVF-ET or intracytoplasmic sperm injection (ICSI) in 3,500 cycles. INTERVENTION(S): IVF-ET, ICSI, ejaculate sperm, epididymal sperm aspiration, and testicular sperm extraction. MAIN OUTCOME MEASURE(S): Complications of the procedure and complications of pregnancy in 702 patients. RESULT(S): Fifteen hundred ovum pickups for IVF-ET and 2,000 ovum pickups for ICSI were performed. Clinical pregnancy occurred in 1,078 patients (30.8%). Four groups of complications were identified. Complications of the procedure occurred in 291 patients (8.3%). Complications of pregnancy included ectopic pregnancy in 1.9%, heterotopic pregnancy in 0.2%. abortion in 20.6%, multiple pregnancy in 28%, pregnancy-induced hypertension in 10%, preterm labor in 21.5%, low birth weight in 30.5%, and intrauterine death in 2%. Coincidental complications occurred in five patients (0.15%). Other complications that were difficult to measure included psychological breakdown and socioeconomic problems. CONCLUSION(S): Assisted reproductive technology is effective for the management of infertility and has an acceptable incidence of complications. Complications rarely endanger the life of the patient. When this line of treatment is offered, the indications should be definitive. Patients should be monitored properly and measures should be taken to minimize the incidence of complications.
Ovarian stimulation for in-vitro fertilization (IVF) causes development of several cohorts of follicles. At the time of oocyte collection, oocytes are thus retrieved from a wide range of follicles of different sizes and developmental stages. A relationship between size of follicles and pregnancy rates has earlier been demonstrated. The aim of the present study was to compare fertilization, cleavage and pregnancy rates between oocytes retrieved from large and small follicles in conventional IVF and intracytoplasmic sperm injection (ICSI). A total of 200 conventional IVF patients and 175 ICSI patients underwent oocyte retrieval where oocytes from both large and small follicles were collected. A follicle with a volume of > or = 2 ml, corresponding to a follicular diameter > or = 16 mm as determined by ultrasound, was regarded as a large follicle. Only one cycle from each patient was included. Fertilization and cleavage rates were calculated per patient for oocytes from large and small follicles. The mean fertilization and cleavage rates for conventional IVF and ICSI cycles were calculated. Comparison of pregnancy rates was performed for patients receiving embryos derived from oocytes of only large or only small follicles. For conventional IVF patients, fertilization rates were 71.4 and 58.1% (P < 0.01, Wilcoxon paired test) for oocytes of large and small follicles respectively. The corresponding cleavage rates were 95.4 and 93.9% respectively. The pregnancy rate for the two groups was 47% (60/127) and 15% (2/13) (P < 0.05, chi2 test). For ICSI patients the fertilization rate was 72.0 and 71.1% for oocytes of large and small follicles respectively. The corresponding cleavage rate was 93.0 and 91.1%. The pregnancy rate in the two groups was 41% (46/113) and 42% (5/12). The results show that oocytes from smaller follicles also yield fertilization and pregnancies, although in conventional IVF to a lesser extent than oocytes from larger follicles. For IVF cycles, a higher proportion of immature oocytes (which are normally not included in the ICSI procedure) in the group of oocytes from small follicles is most probably the explanation for the lower fertilization rate. The decrease in pregnancy rate with oocytes from small follicles in the IVF cycles was not observed in the ICSI cycles. The possibility of evaluating the degree of oocyte maturation prior to fertilization may be an advantage of the ICSI technique. This suggests that the disadvantages of oocytes from small follicles might be overcome by means of ICSI.
Neonatal outcome of in vitro fertilization (IVF) pregnancies has been described by different authors, but several issues have yet to be resolved. The aim of the present study was to evaluate neonates conceived in vitro and to direct special attention to neonatal morbidity and prevalence of minor abnormalities. The information that has been accumulated so far is scant. The first 100 babies conceived in vitro, and subsequently born in our institute, were investigated and compared with the general, spontaneously conceived newborn population. All infants were examined by a senior neonatologist, and the data that were recorded included gestational age at delivery, birth weight, gender, major malformations, minor congenital abnormalities, neonatal mortality, and neonatal morbidity (including asphyxia, jaundice, meconium aspiration, hypoglycemia, and hypocalcemia). The data indicate that the IVF neonates assessed had a higher rate of low birth weight (37%), twinning (30%), and preterm birth (20%) in comparison with the general reference population (p < 0.05). However, no differences were encountered either in the rate of small for gestational age infants or the incidence of major malformations and minor abnormalities between these groups of newborns. The overall neonatal morbidity in IVF babies was found to exceed that of the general population. Nevertheless, at birth, there were no clinical pathognomonic signs typical of IVF babies, although more detailed metabolic, endocrine, and neurobehavioral studies are still required to confirm that newborns conceived in vitro do not differ from those conceived spontaneously in any of these respects.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1997. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Donor Gametes and Surrogacy · Sperm and Embryo Donation
Reports suggest that there is an increased incidence of preeclampsia after a previously normal pregnancy if there is a change in paternity. We hypothesize that there is a higher incidence of preeclampsia (proteinuric hypertension) in women conceiving by intrauterine insemination with donor sperm versus intrauterine insemination with partner sperm. This was a retrospective cohort study. In women with primary infertility all pregnancies achieved by either partner or donor intrauterine insemination carried to birth of a fetus (> 20 weeks) were identified. The medical records were examined for the maternal and pregnancy outcome data. The relative risk and 95% confidence interval were calculated for the risk of preeclampsia. The baseline data were compared with t tests, chi 2 analysis and Fisher's exact test where appropriate. Forty-four patients in the partner intrauterine insemination group and 37 in the donor insemination group were identified as having primary infertility. Three cases of mild preeclampsia were found in the partner insemination program and nine cases of preeclampsia (five severe, four mild) in the donor insemination program (relative risk 1.85, 95% confidence interval 1.20 to 2.85). There is a higher incidence of preeclampsia in women conceiving by intrauterine insemination with washed donor sperm compared with intrauterine insemination with washed partner sperm. This supports, indirectly, an immunologic basis for preeclampsia. The antigenic factor would appear to be located on the sperm as opposed to the seminal fluid itself.
To report the occurrence of an unusual case of successful pregnancy achieved by oocyte donation in a woman > 60 years of age. Case report. University-based assisted reproductive technology program. PATIENT(S): Sixty-three-year old nulligravida, married for 16 years to her 60-year-old husband. Throughout her infertility treatment, the patient was believed to be 10 years younger, as she claimed. She revealed her true age of 63 only upon being referred for obstetric care at 13 weeks of gestational age. INTERVENTION(S): Oocyte donation, IVF, embryo cryopreservation, and ET. MAIN OUTCOME MEASURE(S): Attainment of pregnancy and subsequent delivery. RESULT(S): The patient underwent two cycles of oocyte donation. During the second attempt, the fresh transfer resulted in a clinical miscarriage at approximately 8 weeks of gestational age. A subsequent transfer of three frozen-thawed embryos resulted in an ongoing singleton gestation. The pregnancy was complicated by gestational diabetes (controlled by diet) and mild pregnancy-induced hypertension. Delivery by cesarean section at 38 weeks of gestational age resulted in the birth of a healthy female infant weighing 2,844 g with Apgar scores of 9 and 9. CONCLUSION(S): This case demonstrates that the uterus is capable of supporting nidation and subsequent gestation for many years beyond natural menopause. It shows that other aspects of human physiology are capable of adapting to the stresses and changes of pregnancy sufficiently well to achieve a normal birth at the age of 63 years. This case also exemplifies the difficulty in attempting to regulate the age of recipients in oocyte donation. As in other aspects of human life, when age limits are applied to the provision of certain services, human beings whose age falls outside of these limits become motivated to deceive the providers of those services to avail themselves of the services.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1996. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Donor Gametes and Surrogacy · Sperm and Embryo Donation
To compare single women, lesbian couples, and heterosexual couples receiving therapeutic donor insemination (TDI). Chart review followed by anonymous mail questionnaires to donor insemination recipients and their partners. Infertility clinic in a university hospital. One hundred fifteen women receiving donor insemination were identified by chart review. Too few single women responded for reliable comparison. Lesbian women were similar to married women in age, education, duration, and outcome of donor insemination. When considering alternatives to TDI, married women were more likely to consider adoption and lesbians were most likely to consider using a known semen donor or having intercourse with a man aware of their desire to have a child. Married couples were less likely to tell others, including the child, about conception by donor insemination. They were also less likely to support disclosing identifying data about the donor to the child. Lesbians were more likely to report stress in their relationships as a result of TDI. Married men were most likely to support mandatory counseling before TDI initiation.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1995. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
To describe the characteristics of pregnancies and children at birth resulting from IVF-ET and to assess whether they differ from those after natural conception. Prospective multicenter survey. A national registry, representing 80% of all French IVF-ET activity for the period 1986 to 1990. Data on 7,024 pregnancies, 5,371 deliveries, and 6,879 newborn infants. A form is completed for every clinical pregnancy. Spontaneous abortion, ectopic pregnancy, multiple pregnancy, prematurity, hypotrophy, perinatal and neonatal mortality, and congenital malformations rates. The spontaneous abortion and ectopic pregnancy rates were, respectively, 17.6% and 5.8%. More than a quarter (26.8%) of the deliveries were multiple births. The preterm birth rate (29.3%), the low birth weight rate (36.2%), and the perinatal and neonatal mortality rates were higher than the national average. The rate of malformations (2.8%) was comparable with the general population (2.1%). Assisted conception frequently results in multiple pregnancy, and this is the main determinant of pregnancy outcome. Nevertheless, it is not the only risk factor for prematurity, which is also more frequent among IVF singleton newborn. The prevalence of congenital malformations is not higher than after natural conception.
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
The last decade has transformed the physician's approach to infertility. The development of IVF for its treatment has so improved our capacity to overcome this most distressing of disabilities that we now need to revise many of our working ideas on how it can come about. This is not because new causes have been discovered. Rather, an appreciation has been gained of how apparently minor disturbances can combine to cause a major disruption in the expectation of pregnancy.
At the best of times-and sometimes, no doubt, at the worst of times getting pregnant is a matter of chance. The parameter that describes this chance is the monthly probability of conception, known among epidemiologists as fecundability (f) (probability of achieving pregnancy in one menstrual cycle), and is similar to "monthly fecundity" (monthly probability of a live birth in one cycle exposed to the risk of pregnancy) (1). Like every statistic in biology, fecundability has a wide distribution of values in the population (modeled in Fig. 1). Figure 1 also illustrates a group of couples with a fecundability value of zero-meaning complete infertility, or sterility, which affects perhaps 5% of couples attempting to achieve a pregnancy.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1994. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1993. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
To compare the effect of fertility drugs and IVF on the outcome of triplet pregnancies. Prospective clinical study. A single university medical center. One hundred six consecutive triplet pregnancies treated from 1984 through 1992. The frequency of pregnancy loss, livebirths, and antenatal and neonatal complications was compared in spontaneous, clomiphene citrate (CC), menotropins, and IVF triplet pregnancies. Eighty-one of the 106 (76.4%) triplet pregnancies progressed beyond 25 weeks, comprising 6 of 7 (85.7%) spontaneous pregnancies, 13 of 16 (81.2%) CC induced, 44 of 56 (78.6%) menotropin induced, and 18 of 27 (66.6%) IVF gestations. There were no significant differences in the stillbirth and neonatal mortality rates according to the mode of conception. The mean gestational ages and the mean birth weights were similar in the four groups. The frequency of premature contractions, premature rupture of membranes, cesarean section, and neonatal complications were similar in the ovulation induction and IVF pregnancies. Triplet pregnancies after ovulation induction and IVF have a similar outcome.
To assess the outcome of pregnancy following assisted conception. Cohort descriptive study. Unit of Reproductive Medicine, Ninewells Hospital and Medical School. One hundred and forty-eight consecutive assisted conceptions. Patient characteristics and outcome of pregnancy. Seventy-nine percent of mothers were aged between 26 and 35 years (mean 31.4). The main causes of infertility were tubal (48%), unexplained (35%), anovulatory (8%) and male factor (8%). Primary infertility accounted for 61% of cases and 82% of pregnancies occurred within 3 treatment cycles. Thirty-five (24%) pregnancies miscarried before 14 weeks and 7 (5%) between 15 and 24 weeks gestation. One hundred and three pregnancies resulted in 136 liveborn infants. There was one neonatal death. Thirty-five babies were admitted to SCBU. Antenatally, 13% of patients were admitted to hospital with hypertension and 8% with APH; 50% of multiple and 13% of singleton pregnancies were delivered prematurely, 68% following preterm labour. There were 28 sets of twins (four miscarried at less than 24 weeks) and four sets of triplets. Multiple pregnancy was not associated with cause of infertility, treatment, age or ovarian hyperstimulation syndrome. Seventy-eight per cent of singletons and 50% of multipara were delivered vaginally. Our data confirm the high incidence of pregnancy loss and preterm delivery associated with assisted conception once allowing for the high rate of multiple pregnancies. The effect of assisted conception programme on health services is discussed.
To limit the high number of multiple pregnancies in an IVF program. In Vitro Fertilization Laboratory, Fertility Department, Public Hospital. The number of embryos transferred was limited to two instead of three. Limiting the number of embryos transferred to only two did not influence the take home baby rate but eliminated triplet and quadruplet gestations. Moreover, the number of patients with good quality supernumerary embryos available for cryopreservation increased. To reduce the high frequency of multiple gestations in an IVF program, the number of embryos replaced should be limited to a maximum of two.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1992. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
To compare the obstetric outcome of in vitro fertilization pregnancies with normally conceived pregnancies. The obstetric outcome of in vitro fertilization pregnancies achieved in 763 British residents at two in vitro fertilization clinics resulting in the births of 961 babies were compared by means of the relative risk statistic with a control group of naturally conceived primiparous pregnancies matched by maternal age and multiplicity of pregnancy. Twenty-five percent of in vitro fertilization pregnancies were multiple pregnancies. The incidence of singleton term breech presentation was similar to that among controls. As compared with controls there was an increased incidence among in vitro fertilization pregnancies of vaginal bleeding and hypertension requiring hospitalization (p less than 0.001) and cesarean births (p less than 0.001) and, among in vitro fertilization singleton pregnancies, an increased incidence of intrauterine growth retardation (p less than 0.05), placenta previa (p less than 0.05), and preterm delivery (p less than 0.001). The congenital malformation, stillbirth, and perinatal mortality rates were comparable with maternal age-standardized national rates. Although the majority of in vitro fertilization pregnancies have a satisfactory obstetric outcome, there are a number of increased obstetric risks that may reflect the history of infertility, the relatively high incidence of poor obstetric history, and the lower threshold for obstetric intervention in in vitro fertilization patients.
To review the maternal morbidity and neonatal morbidity and mortality associated with in vitro fertilization (IVF) multiple pregnancies. Retrospective analysis of data collected from office and hospital records and from questionnaires sent to patients, their obstetricians, and pediatricians. Patients (all with private insurance carriers) enrolled in an academic IVF program (The Jones Institute for Reproductive Medicine). PATIENTS, All IVF pregnancies resulting in one or more gestational sacs on the initial ultrasound at 6 to 7 weeks were reviewed. The frequency and severity of obstetrical and neonatal complications and the perinatal mortality of IVF twins, triplets, and quadruplets were compared. These were also compared with non-IVF multiple pregnancies. From 1982 to 1990, 629 IVF pregnancies progressed beyond 20 weeks; 115 twins (18.3%), 15 triplets (2.4%), and 4 quadruplets (0.6%). There was a high incidence of antenatal complications such as abortions (30.3%, 42%, and 20%), premature labor (41.5%, 92.3%, and 75%), pregnancy-induced hypertension (17.0%, 38.6%, and 50%), and gestational diabetes mellitus (3.1%, 38.5%, and 25%) for twins, triplets, and quadruplets, respectively. The mean gestational age at delivery was 35.5 +/- 3.7, 31.8 +/- 2.7, and 31.0 +/- 1.7 weeks, respectively. There was also a proportionate progressive increase in neonatal complications. The mean weights were 2,473 +/- 745, 1,666 +/- 441 and 1,414 +/- 368 g, respectively. Twins (22.7%), 64.1% of triplets, and 75% of quadruplets needed admission to the neonatal intensive care unit and remained for an average of 12.0 +/- 2.3, 17.4 +/- 14.0, and 57.8 +/- 17.9 days, respectively. There was no difference in the mean Apgar scores or the incidence of congenital malformations in the three groups. The corrected perinatal mortality rates were 38.5, 0.0, and 0.0 per thousand live births, respectively. Triplet and quadruplet IVF pregnancies have increased obstetrical and neonatal complications compared with IVF twins. The perinatal mortality and the incidence of congenital malformations are, however, comparable in all three groups.
The Medical Research Council In-Vitro Fertilization (IVF) Register report on births resulting from assisted conception in Great Britain demonstrated a high incidence of preterm and low birthweight babies. This incidence remained high even when the analysis was restricted to singleton babies. The present paper investigates possible risk factors for prematurity, low birthweight and small-for-gestational-age (SGA) in singleton IVF births. Thirteen per cent of singleton IVF babies were preterm, 11% low birthweight and 17% small-for-gestational-age. Analysis by multiple regression indicated that hypertension during pregnancy was an independent risk for preterm delivery, low birthweight and SGA, bleeding during pregnancy for preterm delivery, and the number of embryos transferred and the type of infertility for low birthweight.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1991. DIR is the German national IVF/ICSI registry, founded 1982. Phase B historical-archive source.
Ninety pregnancies conceived by infertile couples using assisted reproductive technologies and 86 pregnancies conceived by infertile couples with routine infertility treatment were analyzed to determine the outcome of and the complications experienced during the pregnancies. Pregnancies ending after 24 weeks' gestation were evaluated for the following complications: pregnancy-induced hypertension, diabetes mellitus, preterm labor, premature rupture of membranes, placenta previa, and fetal growth retardation. A matched control group of normal fertile patients admitted to the obstetric service at Vanderbilt University Medical Center was used to compare the incidence of pregnancy complications among the groups. In the group treated by assisted reproduction, 81 pregnancies were singleton and nine were multiple gestations, whereas in the routine group, 84 were singleton and two were multiple gestations. In the group treated by assisted reproduction, 29 of 90 gestations (32%) ended before 24 weeks, compared with 18 of 86 (21%) in the routine group, a nonsignificant difference. Mean birth weight and gestational age were similar among the three groups for singleton gestations. Among multiple gestations, the mean (+/- standard error of the mean [SEM]) birth weights were 2513 +/- 115, 724 +/- 57, and 2282 +/- 132 g in the group treated by assisted reproduction, the group receiving routine methods, and the control group, respectively (P less than .001 when those treated by routine methods were compared with the other two groups). The mean (+/- SEM) gestational ages were 36 +/- 1.2, 26.5 +/- 2.0, and 35.5 +/- 1.2 weeks, respectively (P less than .01 comparing those treated by routine methods and the other two groups).(ABSTRACT TRUNCATED AT 250 WORDS)
Donor Gametes and Surrogacy · Sperm and Embryo Donation
Ten years' experience of artificial insemination with cryopreserved donor semen for 1023 courses in 783 women resulting in 572 pregnancies is reported. A simple approach with multiple inseminations timed on the basis of cycle length, temperature charts, mucus symptoms and signs was used. The life table pregnancy rate was 61% after 12 cycles of treatment and 75% after 24 cycles. Women had a significantly higher rate of pregnancy in second and subsequent courses of treatment, and the pregnancy rate for treatment beyond 12 cycles was significantly less successful. Women over 35 years of age were significantly less successful.
Donor Gametes and Surrogacy · Sperm and Embryo Donation
From our study of 234 cases of AID with fresh semen, we conclude the following: (1) women who do not have other infertility problems, such as ovulatory dysfunction or evidence of tubal disease, have approximately a 90% chance of pregnancy if they stay in the program for up to 12 cycles; (2) with even greater persistence (i.e., greater than 12 cycles), it is predicted that virtually 100% of these women would conceive, but this conclusion is based on extrapolated data and therefore must be interpreted with caution; (3) women with ovulatory dysfunction who are treated with CC during their AID cycles ultimately achieve the same likelihood of pregnancy as women with normal ovulatory function, but at a slower rate; and (4) women with one patent tube (possibly a marker for generalized tubal damage) have a poorer outcome from AID than those with bilaterally patent tubes, from the standpoint of both the ultimate likelihood of pregnancy and the pregnancy rate per cycle.
Donor Gametes and Surrogacy · Sperm and Embryo Donation
Artificial insemination with donor sperm (AID) has been a major form of treatment among infertile couples with defects in sperm production. In this report, we review our experience from 1980-1985. A total of 108 patients underwent AID, with 75 resultant pregnancies. Of patients achieving pregnancy, 47% became pregnant after the third cycle and 92% by the twelfth cycle. A higher success rate and/or smaller number of AID cycles were positively associated with patient age of 35 or less and negatively associated with endometriosis. This information is useful in counseling couples interested in pursuing AID.
The technique for reduction of the number of embryos was applied in a patient who conceived following IVF and transfer of six embryos. On the 10th week of gestation, the number of embryos was reduced from five to three by an U/S-guided intra-uterine procedure. Two healthy girls and a boy were delivered in the 36th week by cesarean section. No trace of the other two fetuses was found. The moral and technical aspects of partial preventive termination of multiple pregnancy are discussed.
Donor Gametes and Surrogacy · Sperm and Embryo Donation
Factors influencing the probability of conception after artificial insemination with donor semen were investigated in a series of 80 infertile couples. Overall, 46 pregnancies were achieved for a crude pregnancy rate of 58%. Life table analysis showed a cumulative probability of conception of 97.1% at the end of 12 cycles and an average fecundability of 15.1%. These results were achieved using a single insemination per cycle and individualizing the day of insemination based on the woman's basal body temperature. Women who had been pregnant previously had a significantly better fecundability than nulligravid women (P less than .05). The overall rates of conception in those women who required therapy for ovulatory dysfunction were the same as normal women although the fecundability was somewhat lower. Women who had abdominal pathology had an overall conception rate of 23%.
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
Data on 575 couples undergoing 1057 consecutive cycles of in vitro fertilization (IVF) were used to calculate cumulative pregnancy rates for repeated IVF cycles. Excluding preclinical abortions and couples in whom the male partner had poor semen parameters, calculated cumulative pregnancy rates for cycles 1 to 6 were 13.6%, 24.8%, 37.2%, 47.8%, 52.2%, and 59.6%, respectively. A parametric model used to fit these data yielded a strong correlation between observed and predicted pregnancy rates (r = 0.99, P less than 0.001). Predicted cumulative pregnancy rates after 9 and 12 cycles were 75% and 84%, respectively. Excluding preclinical abortions, the pregnancy rate per cycle was approximately constant, at approximately 15% over repeated cycles. As the cost of IVF declines and as treatment cycles become more easily tolerated, persistence in IVF can lead to successful pregnancy for a large proportion of couples.
The effect of clomiphene citrate (CC) on the incidence of congenital malformations in newborn infants was assessed from the outcome of 1034 pregnancies after CC-induced ovulation recorded at nine university hospitals in a 5-year period. Of these pregnancies, 14.2% ended in abortion, 0.5% in ectopic pregnancy, 0.1% in molar pregnancy, and 1.6% in stillbirth. In all, 935 infants were born, and 21 (2.3%) showed visible malformations. This incidence of malformations was not significantly different from that in 30,033 infants (1.7%) after spontaneous ovulation (spontaneous ovulation group), and the types of malformations after CC treatment were similar to e those in the spontaneous ovulation group. These data indicate that CC has no teratogenic effect.
Lifshitz K et al., 2026·International urology and nephrology·
Open Access
Paternity rates among testicular cancer survivors are reduced. The patient journey, from fertility preservation at diagnosis to attempted paternity or use of assisted reproductive technologies (ART), contains two key gaps in the literature. While baseline semen impairment is well recognized, the relationship between disease stage, tumor pathology, and semen quality remains inconsistent. In addition, prior studies have largely excluded sex-cord stromal tumors, lacked healthy comparators, and rarely performed pathology-specific analyses within the same clinical stage. Reported paternity rates vary widely (6-21%), yet real-world data on ART utilization and live-birth outcomes remain limited. We conducted a retrospective cohort study (2017-2023) at a single tertiary academic referral center within a healthcare system that provided full coverage for sperm cryopreservation for 5 years and ART for up to 2 live births. Primary outcomes included baseline semen parameters by tumor histology and clinical stage, pathology-specific comparisons within each stage, and post-treatment utilization of cryopreserved sperm. Secondary outcomes were ART pregnancy and live-birth rates. The semen parameters were compared with those of healthy sperm donor candidates. The cohort included 126 men (mean age 36.6 ± 10.9 years; 83 seminoma, 35 non-seminoma, 8 sex-cord stromal tumors). Compared with 100 healthy donor candidates, testicular cancer patients demonstrated significantly impaired baseline semen quality across all parameters except volume (all p ≤ 0.01). Post-thaw semen quality was further reduced, with lower motility rates (17.5% vs 44.1%) and total motile counts (1.1 vs 7.8 million), highlighting greater motility and total motile count loss following cryopreservation. Sex-cord stromal tumors exhibited the poorest semen parameters. Semen quality did not differ by stage overall; pathology-specific differences were observed only in stage II disease, favoring non-seminoma tumors (p ≤ 0.05). Overall, 69% (n = 91) elected sperm cryopreservation. Among those, the median number of vials initially frozen was 15 (IQR 10-18), with a mean of 11.6 ± 4.3 vials per patient (range 1-18). During a median follow-up of 5.3 years (IQR: 3.9-6.8), only 8% (n = 7) used their vials for ART, undergoing a median (IQR) of 2.5 (1-4) cycles per couple (15 cycles recorded among 6 of 7 couples; cycle count missing for one couple), resulting in 12 pregnancies and an overall live-birth rate of 67%: 2/2, 100%, 6/10, 60%. Testicular cancer significantly impairs semen quality, with important variation by tumor pathology rather than stage. These findings underscore the need for accurate counseling: fertility preservation often enables future use primarily through IVF and supports banking multiple vials to mitigate freeze-thaw losses.
Parnell T et al., 2026·Journal of Restorative Reproductive Medicine
To evaluate adherence to published American Society for Reproductive Medicine (ASRM) and American Urological Association (AUA) infertility evaluation and treatment recommendations among commercially insured infertility patients who subsequently underwent in vitro fertilization (IVF), and to assess whether observed care gaps support the need for a restorative reproductive medical framework.
A retrospective claims-based analysis was performed using MarketScan® Commercial Claims and Encounter Data between January 1, 2021, and December 31, 2024. Approximately five million commercially insured members were evaluated. Patients with infertility-related diagnoses who subsequently underwent IVF were identified. Claims were analyzed for evidence of selected diagnostic testing, medical treatment, or surgical interventions recommended by ASRM or AUA/ASRM guidance for specific infertility-related diagnoses before IVF initiation. Cumulative adherence rates were assessed up to nine months following initial infertility diagnosis and compared with the timing of initiating IVF.
IVF initiation started early and consistently preceded completion of most recommended evaluations and treatments. By 3 months, the proportion of patients with IVF initiation ranged from 28% to 39% across different infertility-related diagnoses, while adherence to most recommended interventions remained low. Overall, by 9 months, IVF utilization had reached 70–85%, while many recommended evaluations and treatments remained below 40% adherence, with several interventions remaining below 15%. Observed care gaps (percentage of patients receiving IVF prior to other evaluation or treatment recommendations) ranged from approximately 13% to 78% for most recommended evaluations and treatments, with several measures demonstrating gaps over 50% of patients.
These findings suggest substantial divergence between published infertility-care recommendations and observed practice patterns. From the perspective of restorative reproductive medicine (RRM), the gaps are clinically important because many recommended steps are directed toward identifying, correcting, restoring, or preserving reproductive function and anatomy before offering or initiating IVF treatment. Limitations to these data include lack of individualized patient medical data, preferences, or circumstances, and not capturing any treatment that was not reimbursed by commercial insurance (i.e., any cash payment for services). In addition, the recommendations assessed have variable levels of underlying evidence, and likely vary in the level of their acceptance among practicing clinicians.
Many commercially insured infertility patients progressed to IVF without documented evidence of diagnostic evaluation or therapeutic interventions recommended in ASRM and AUA/ASRM guidance. These findings raise important questions regarding the implementation of adequate evaluation before IVF and the extent to which patients receive meaningful opportunities for diagnosis-directed treatment of potentially reversible causes of infertility. The findings further suggest an important role for RRM as a quality-of-care framework focused on comprehensive evaluation, correction of underlying dysfunction, preservation of reproductive anatomy and physiology, and optimization of patient-centered fertility care, prior to considering IVF.
Barbato M et al., 2026·Frontiers in Reproductive Health
Couple infertility is a common clinical condition that is too often treated with assisted reproductive techniques (ARTs) without a proper evaluation of both male and female factors. To improve the likelihood of natural conception, fertility awareness methods (FAMs) are widely used. We performed a multicenter prospective study enrolling couples with primary idiopathic infertility who were seeking natural conception. Participants were followed for 12 months using FAMs, and their outcomes were compared with those of couples who only used ARTs. The aim of our study was to evaluate the pregnancy rate after 12 months among couples with idiopathic infertility using FAMs compared with those who immediately pursued ARTs. We evaluated 41 couples in the FAM group and 56 couples in the ART group. In the FAM group, we reported a pregnancy rate (PR) of 51.22%. Among women aged <34 years, we reported a PR of 90.9%, while it decreased to 36.7% among women aged 35-39 years. In the ART group, 10 couples achieved pregnancy (PR 17.8%). Within this group, we reported a PR of 30% among women aged <34 years and 17.4% among women aged 35-39 years. After 12 months of unprotected intercourse without spontaneous conception in women younger than 35 years or after 6 months in women aged 35-39 years, couples should undergo a complete multidisciplinary diagnostic evaluation involving both the male and female partners. If a diagnosis of idiopathic infertility is established at the end of this process, couples (especially younger ones) may be advised to wait an additional 12 months while using FAMs, as no advantage has been observed with direct access to ARTs. They could then be referred to ART if a spontaneous pregnancy is not achieved during this period.
Human Fertilisation and Embryology Authority, 2025·
# Overview of HFEA public consultation on Choose a Fertility Clinic 2025
Consultation held August-September 2025 on clinic’s main profile statistics on the Choose a Fertility Clinic webpage
Published: December 2025
## Table of contents
- [Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/overview-of-hfea-public-consultation-on-choose-a-fertility-clinic-2025/#introduction)
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/overview-of-hfea-public-consultation-on-choose-a-fertility-clinic-2025/#main-points)
- Summary of findings from the consultation
- [Section 1: Overview of response groups](https://www.hfea.gov.uk/about-us/publications/research-and-data/overview-of-hfea-public-consultation-on-choose-a-fertility-clinic-2025/#section-1)
- [Section 2: Main profile page statistic: which was the preferred rate?](https://www.hfea.gov.uk/about-us/publications/research-and-data/overview-of-hfea-public-consultation-on-choose-a-fertility-clinic-2025/#section-2)
- [Section 3: Presenting a combined rate](https://www.hfea.gov.uk/about-us/publications/research-and-data/overview-of-hfea-public-consultation-on-choose-a-fertility-clinic-2025/#section-3)
- [Section 4: Inclusion of different treatment types](https://www.hfea.gov.uk/about-us/publications/research-and-data/overview-of-hfea-public-consultation-on-choose-a-fertility-clinic-2025/#section-4)
- [Section 5: Additional considerations for the HFEA](https://www.hfea.gov.uk/about-us/publications/research-and-data/overview-of-hfea-public-consultation-on-choose-a-fertility-clinic-2025/#section-5)
- [About the HFEA](https://www.hfea.gov.uk/about-us/publications/research-and-data/overview-of-hfea-public-consultation-on-choose-a-fertility-clinic-2025/#about-the-hfea)
## The HFEA has a statutory duty to provide information to the public about fertility treatment. Using the data collected from licensed fertility clinics, we publish verified information on th...
Chavez-Badiola A et al., 2025·Journal of assisted reproduction and genetics·
Open Access
The economics of IVF operations remain opaque despite growing prevalence and substantial investment in fertility services. Traditional accounting methods often fall short by failing to capture the complex relationship between biological inputs (number of eggs and embryos processed), skilled labor, and equipment utilization, creating a distorted view across different procedures and patient characteristics. This paper presents Activity-Based Costing (ABC) as a methodological framework for understanding true IVF laboratory costs. We demonstrate a use case with an analysis of data from five IVF laboratories (600-2200 annual egg retrieval cycles) across different US regions including time studies of 500 + procedures at each site, with theoretical projections to 4000 annual egg retrieval cycles based on queuing theory. We identify significant cost elasticity with biological inputs; costs increase by 55% for egg freezing when the number of eggs per patient triples, and by 30% for complex IVF procedures (such as those requiring embryo biopsy) when egg count per patient doubles. We also describe substantial scale effects, with marginal lab costs 40% higher in centers performing 500 yearly egg retrieval cycles versus 2000-cycle centers, and 4000-cycle centers estimated to achieve 13-40% lower costs per procedure than operations performing 500 retrieval cycles annually. Finally, we show labor efficiency increases by 30% between centers performing 500 and 2000 annual egg retrieval cycles, an observation supported by a queuing rule of thumb (QROT) analysis, with capital utilization also improving dramatically. ABC enables evidence-based pricing, capacity planning, technology assessment, and consolidation strategizing. ABC is intended to inform operational efficiency, not clinical treatment, ensuring that quality of care and patient outcomes remain the primary considerations in fertility services.
Chronic Endometritis · Endometritis and Reproductive Outcomes
Chen L et al., 2025·Frontiers in reproductive health
[OBJECTIVE] To analyze the effect of autologous platelet-rich plasma (PRP) intrauterine perfusion on the clinical outcomes of frozen-thawed embryo transfer in patients with chronic endometritis. [METHODS] A retrospective continuous cohort of 219 patients diagnosed with chronic endometritis at the Reproductive Medicine Center of Affiliated Hospital of Putian University between January 2020 and December 2022, undergoing their first frozen-thawed embryo transfer cycle, was included. All patients received standardized oral doxycycline treatment after diagnosis. Based on whether they received PRP intrauterine perfusion prior to embryo transfer, patients were divided into an observation group (PRP group, n=103) and a control group (non-PRP group, n = 116). Outcome measures included live birth rate per transfer cycle, clinical pregnancy rate per transfer cycle, and early miscarriage rate per clinical pregnancy. [RESULTS] All patients underwent endometrial preparation using a hormone replacement therapy (HRT) protocol. Endometrial thickness on the day before transformation was significantly higher in the PRP group compared to the control group (10.58 ± 1.78 mm vs. 9.79 ± 1.58 mm, P = 0.001). The PRP group exhibited significantly higher clinical pregnancy rate per transfer cycle and live birth rate per transfer cycle than the control group (58.25% vs. 40.52%, P = 0.038; 52.43% vs. 34.48%, P = 0.007). The difference in early miscarriage rate per clinical pregnancy between the PRP group and the control group was not statistically significant (8.33% vs. 14.89%, P = 0.86). The live birth rate per transfer cycle in the single-PRP subgroup was significantly lower than in the multiple-PRP subgroup (44.62% vs. 65.79%, P = 0.038). There were no statistically significant differences in clinical pregnancy rate per transfer cycle or early miscarriage rate per clinical pregnancy between the single-PRP and multiple-PRP subgroups (52.31% vs. 68.42%, P = 0.110; 11.76% vs. 3.85%, P = 0.377). [CONCLUSION] For patients diagnosed with chronic endometritis undergoing their first frozen-thawed blastocyst transfer after standardized antibiotic treatment, adjunctive PRP intrauterine perfusion therapy improves pregnancy outcomes.
Sanuie Farimani M et al., 2025·International journal of reproductive biomedicine
Female infertility, especially in those individuals with poor ovarian response (POR), is a challenge in the field of infertility and sterility. Recently, intra-ovarian platelet-rich plasma (IO-PRP) administration has been suggested as a possible co-treatment. This study aimed to investigate the biodemographic characteristics of individuals who experienced spontaneous pregnancy following IO-PRP. In this cross-sectional study, out of 1548 women diagnosed with POR who underwent IO-PRP, 596 individuals who completed their 2-yr follow-up period, were included. Different types of demographic and pre-intervention laboratory data (blood levels of anti-Müllerian hormone, luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, and their spouses' sperm analysis results) were collected from the files. Each individual was classified into a certain group according to the POSEIDON criteria, and their data were compared. The results showed that 50 (8.39%) spontaneous pregnancies were observed. However, 8 were excluded from further analyses due to missing data in their critical variables. The most prevalent POSEIDON group was 4, with a prevalence of 17/42 (40.47%). Among the POSEIDON groups, covariates including the age of the individuals and their spouses, body mass index, anti-Müllerian hormone, and antral follicle/oocytes count following the latest IO-PRP significantly differed (p < 0.001, p < 0.001, p = 0.039, p < 0.001, and p = 0.022, respectively). The spontaneous pregnancy rate following IO-PRP among women with POR was low. However, significant differences in biodemographic and hormonal characteristics were observed between the groups with and without spontaneous pregnancy which could be useful in leading future studies on this subject.
Michaelsen MP et al., 2025·BJOG: An International Journal of Obstetrics and Gynaecology
To study the association between previous use of levonorgestrel intrauterine system (LNG-IUS) and endometrial thickness (EMT) in women undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Multicentre historical cohort study. Eight Danish public and private fertility clinics. 12786 women aged 18-46 years contributing with an EMT measurement from 22 464 different IVF/ICSI treatment cycles between 2000 and 2021. Exposure was previous use of LNG-IUS, combined oral contraceptive pills (OCPs), progestogen-only pills (POPs), no/other contraception or combined, cumulated use of contraception when more contraceptives had been used during the inclusion period. LNG-IUS use was categorised into 0-3 years, >3-6 years, >6-9 years and >9 years. Mixed effect logistic regression adjusted for age, BMI, smoking, educational level, total FSH dose and fertility clinic was used. EMT (< 7 mm vs >= 7 mm). Statistically significantly higher odds of EMT >= 7 mm were found for OCPs [OR 3.53 (95% CI 1.29-9.65)], POPs [OR 6.43 (95% CI 1.45-28.63)] and no/other contraception [OR 6.67 (95% CI 2.37-18.74)] relative to LNG-IUS in IVF/ICSI cycles. All duration categories of ever use of LNG-IUS were associated with significantly lower odds of EMT >= 7 mm compared to no/other contraception. Previous use of LNG-IUS was associated with decreased endometrial growth in women undergoing IVF/ICSI.
Weibring K et al., 2024·Frontiers in endocrinology
The possibility of future parenthood is a highly relevant issue for patients of reproductive age facing oncologic treatment. This study aimed to investigate how fatherhood was achieved in a patient cohort of adolescents and young adults (AYAs) banking semen at time of cancer diagnosis and to determine the effectiveness of cryopreservation aimed at fertility preservation in the cohort. Observational cohort study examining AYAs with a cancer diagnosis who underwent semen banking for fertility preservation at Karolinska University Hospital 1988-2020, as part of the Stockholm regional fertility preservation program. This cohort is being prospectively followed since time of referral to the program, with most individuals included when presenting with primary cancers (Study Registration: ClinicalTrials.gov NTC04602962). Individuals achieving adulthood in the cohort were followed-up regarding their reproductive outcomes by linking to the Swedish Multi-generation Register, to identify fatherhood through natural conception or adoption, and to the Swedish National Quality Registry for Assisted Reproduction to identify parenthood through medical assistance, including the use of own sperm either cryopreserved or fresh, or donor sperm. Of the 1,378 patients referred during the study period, 1,357 were eligible for fatherhood analysis (aged >20 years at the end of follow-up, December 31, 2021). In total, 493 men became fathers following cancer treatment: 399 (81%) did so naturally, 87 (18%) via assisted reproductive techniques (including two using donor sperm), and 7 (1%) through adoption. Of the 92 patients who used their cryopreserved sperm for assisted reproductive techniques, 34 (37%) successfully fathered a child. The patients may have had children prior to cryopreservation. A large proportion of AYA cancer survivors achieved fatherhood through natural conception in this cohort, whereas less than 1 in 5 survivors needed medical assistance to conceive. Although a low utilization rate of cryopreserved sperm was found in this cohort, its use was highly effective in the group that developed infertility. At present there are no standardized predictors of testicular toxicity after cancer treatment, and inter-individual variability is high. Further research is needed to identify patients at risk of infertility who would benefit from fertility preservation.
Human Fertilisation and Embryology Authority, 2024
The HFEA Code of Practice gives guidance to clinics about the proper conduct of activities licensed under the Human Fertilisation and Embryology Act 1990 (as amended). The 9th edition (effective 26 October 2023) was further amended for version 9.4 (effective 1 October 2024). The Code consolidates statutory regulations, license conditions, and HFEA guidance covering: clinic governance, staff training and qualifications, identity checks and consent, gamete and embryo storage, donor recruitment and screening, donation arrangements, treatment licensing, pre-implantation genetic testing, multiple births policy, surrogacy, witnessing procedures, traceability, adverse incidents reporting, complaints, research licensing, and information disclosure. Compliance with the Code is a statutory requirement for all UK clinics licensed by the HFEA. Version 9.4 includes updated guidance on donor compensation (effective October 2024) and known donation for people with undetectable HIV (effective November 2024).
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology, 2024·Fertil Steril
The use of preimplantation genetic testing for aneuploidy (PGT-A) in the United States has been increasing steadily. Moreover, the underlying technology used for 24-chromosome analysis continues to evolve rapidly. The value of PGT-A as a routine screening test for all patients undergoing in vitro fertilization has not been demonstrated. Although some earlier single-center studies reported higher live-birth rates after PGT-A in favorable-prognosis patients, recent multicenter, randomized control trials in women with available blastocysts concluded that the overall pregnancy outcomes via frozen embryo transfer were similar between PGT-A and conventional in vitro fertilization. The value of PGT-A to lower the risk of clinical miscarriage is also unclear, although these studies have important limitations. This document replaces the document of the same name, last published in 2018.
[BACKGROUND] Thin endometrium (TE) is a common cause of female infertility in clinical practice. Platelet-rich Plasma (PRP) therapy becomes a novel treatment for thin endometrium; however, its clinical application remains controversial. This meta-analysis aims to evaluate the therapeutic effects of intrauterine autologous PRP infusion in women with thin endometrium through relevant randomized controlled trials (RCTs). [METHODS] We systematically searched studies published in English from inception until June 2024 in databases such as PubMed, The Cochrane Library, Embase, Web of Science, and MEDLINE. Search terms included "Platelet-Rich Plasma," "thin endometrium," "endometrial thickness," "infertility," "pregnancy," "reproduction," and "adverse reactions". RCTs identified through the search were subjected to systematic review and meta-analysis, and data were analyzed using fixed-effects or random-effects models based on heterogeneity. [RESULTS] Eight RCTs involving 678 patients with thin endometrium were included. Patients receiving PRP infusion demonstrated significantly superior outcomes compared to the control group in endometrial thickness (MD: 1.23, 95%CI: 0.87 to 1.59, P = 0.000), clinical pregnancy rate (RR: 2.04, 95%CI: 1.52 to 2.76, P = 0.000), live birth rate (RR: 2.46; 95%CI: 1.57 to 3.85, P = 0.000), cycle cancellation rate (RR: 0.46, 95%CI: 0.23 to 0.93, P = 0.000), and embryo implantation rate (RR: 2.71; 95%CI: 1.91 to 3.84, P = 0.000). There were no statistically significance in spontaneous abortion rate (RR: 0.85, 95%CI: 0.40 to 1.78, P = 0.659), chemical pregnancy rate (RR: 1.84, 95%CI: 0.72 to 4.72, P = 0.204) and endometrial vascular improvement rate (RR: 1.10; 95%CI: 0.89 to 1.38, P = 0.367) between the two groups. The limitations of this study includes that, we only included single lauguage for literature research, the sample size and heterogeneity which could cause criteria bias. [CONCLUSION] Intrauterine PRP infusion may be an effective and safe treatment for women with thin endometrium. Further high-quality, large-sample, randomized controlled trials are needed to validate the reliability of our results. [TRIAL REGISTRATION] The review protocol is registered on PROSPERO with registration number CRD42023490421, and no modifications were made to the information provided at registration.
Ethics Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org, 2024·Fertility and sterility
Planned oocyte cryopreservation is an ethically permissible procedure that may help individuals avoid future infertility. Because planned oocyte cryopreservation is new and evolving, it is essential that those considering using it be informed about the uncertainties regarding its efficacy and long-term effects. This replaces the document of the same name, last published in 2017.
Platelet-rich plasma (PRP) is a concentrated platelet preparation known for its regenerative properties due to the various growth factors it contains. Its application in the medical field, including dentistry, gynecology, and plastic surgery, has surged. In obstetrics and gynecology, PRP has shown promise in improving low libido, vaginal rejuvenation, ovarian reserve, and endometrial receptivity. This study presents a 29-year-old woman experiencing primary infertility attributed to low levels of anti-Müllerian hormone alongside the presence of asthenozoospermia in her husband's semen. After failed intrauterine insemination as well as in vitro fertilization (IVF), attempts at laparoscopic PRP treatment were administered before the second IVF cycle to enhance ovarian reserve and quality. The PRP treatment led to an increased follicle count, improved oocyte quality, and a successful pregnancy outcome in the second IVF cycle. PRP treatment promises to be effective in fertility treatments, potentially increasing ovarian reserve, improving oocyte quality, and enhancing successful pregnancy outcomes. This case report highlights its beneficial impact on a couple facing primary infertility, providing hope for patients with similar reproductive challenges.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Practice Committee of the American Society for Reproductive Medicine, 2024·Fertility and Sterility
Ovarian hyperstimulation syndrome is a serious complication associated with assisted reproductive technology. This systematic review aims to identify who is at high risk for developing ovarian hyperstimulation syndrome, along with evidence-based strategies to prevent it and replaces the document of the same name last published in 2016.
Does sperm cryopreservation serve as a feasible and effective method for preserving fertility in adult male patients with cancer? Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer. Sperm cryopreservation is the only way to efficiently preserve male fertility. It is an important procedure in ART. Recently, due to remarkable advances in cancer treatment, an increasing number of studies have reported the outcomes of sperm cryopreservation in patients with cancer. We conducted an extensive literature search for relevant studies published through to 31 December 2021, in the following databases: CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science. The search terms used were '(cryopreservation OR freeze OR freezing OR banking OR cryostorage OR storage) AND (sperm OR semen OR spermatozoon) AND (cancer OR tumor OR malignancy OR neoplasm)'. We included all studies that reported offering or attempting to cryopreserve sperm before or during cancer treatment in male patients considered at risk of treatment-related fertility impairment. We evaluated the eligibility of all data in each study. The major exclusion criteria were as follows: non-cancer patients; pediatric and adolescent cancer patients; not reporting the use of cryopreserved sperm; use of fresh semen for ART; not reporting the number of patients with cancer offered sperm cryopreservation or attempting to do so before or during treatment; using an experimental fertility preservation technique such as preservation of testicular tissue or spermatogonial stem cells; duplicate data; abstracts, case report, comments, reviews, or editorials; insufficient data reported. The quality of the included studies was assessed using the Newcastle-Ottawa scale and the Methodological Index for Non-Randomized Studies. This meta-analysis included 69 non-randomized studies, with 32 234 patients referred for sperm analysis and 23 178 patients cryopreserving at least one sperm sample. The pooled failed-to-cryopreserve rate was 10% (95% CI, 8-12%), and the sperm disposal and sperm use rates were 23% (95% CI, 16-30%) and 9% (95% CI, 8-10%), respectively. The pregnancy, miscarriage, and delivery rates were 28% (95% CI, 22-33%), 13% (95% CI, 10-17%), and 20% (95% CI, 15-25%), respectively. Subgroup analysis showed higher pregnancy and delivery rates, as well as a lower failed-to-cryopreserve rate, in recent studies compared to those released a decade ago. The studies from Asia reported higher sperm disposal and pregnancy rates than in other continents. Our analysis showed clinical pregnancy rates per cycle of 34% (27-41%), 24% (14-35%), and 9% (5-15%) and delivery rates per cycle of 23% (17-30%), 18% (11-26%), and 5% (1-9%) for ICSI, IVF, and IUI, respectively. As with all meta-analyses, some limitations should be considered. The first limitation of our study is that the data span 36 years. During this time, the World Health Organization has revised its sperm analysis standards, and other important changes have been made. There is also a limitation in that the outcome does not analyze the correlation between the type of cancer and sperm quality. Many of the earlier studies were limited by small sample sizes and a lack of control groups. Furthermore, almost all studies did not consider the severity of the disease, which could potentially have a substantial impact on the results. Consequently, further research should evaluate the effect of the type of cancer and, in particular, the severity of the condition on sperm quality in order to draw more precise conclusions. Similarly, it is inappropriate that most studies failed to differentiate between patients with different types of tumors and instead drew generalized conclusions that are presumed to apply to all patients with cancer. In the present analysis, we did not have in-depth information on patients' disease, and although extensive efforts were made to conduct a thorough systematic review and meta-analysis of the outcomes for patients with various types of tumors, the results must be acknowledged as being subject to bias. However, the use of average results obtained in each study, without the patient-level data, might also represent a source of bias. Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer. The observed utilization rate of frozen sperm at 9% may underestimate the actual usage, as the short follow-up period is inadequate for obtaining comprehensive data on the use of frozen sperm in young cancer survivors. ART plays an important role in fertility preservation and the achievement of pregnancy, with this meta-analysis showing that ICSI delivers better clinical outcomes than IVF or IUI in patients with cancer undergoing fertility preservation. This work was supported by the National Natural Science Foundation of China (grant no. 82001634, 81960550), and the China Post
The role of sperm DNA fragmentation index (DFI) in investigating fertility, embryonic development, and pregnancy is of academic interest. However, there is ongoing controversy regarding the impact of DFI on pregnancy outcomes and the safety of offspring in the context of Assisted Reproductive Technology (ART). In this study, we conducted an analysis of clinical data obtained from 6330 patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) at the reproductive medical center of The First People's Hospital of Shangqiu and The Affiliated Hospital of Zhengzhou University. The patients was stratified into two distinct groups: IVF group and ICSI group, Within each group, patients were further classified into three subgroups. group A (< 15%) included 3123 patients, group B (15-30%) included 561 patients, and group C (≥ 30%) included 46 patients. group A (< 15%) included 1967 patients, group B (15-30%) included 462 patients, and group C (≥ 30%) included 171 patients. Data were collected and subjected to statistical analysis. There were no significant differences in the basic characteristics among the three groups, and the sperm DFI did not significantly affect the fertilization rates, pregnancy rates, stillbirth rates and the number of birth defects. However, the incidences of miscarriage rates in IVF/ICSI groups with DFI > 30% and DFI 15-30% were significantly higher than those in IVF/ICSI groups with DFI < 15%, and the miscarriage rates in ICSI group with DFI > 30% were significantly higher than DFI 15-30% group, the smooth fitting curve shows that there is a positive correlation between miscarriage rates and sperm DFI (OR 1.095; 95% CI 1.068-1.123; P < 0.001). The birth weight of infants in the IVF/ICSI groups with DFI > 30% and DFI 15-30% exhibited a statistically significant decrease compared to those in the IVF/ICSI groups with DFI < 15%. Furthermore, the birth weight of infants in the ICSI group with DFI > 30% was lower than that of the DFI 15-30% group. The smooth fitting curve analysis demonstrates a negative association between birth weight and sperm DFI (OR 0.913; 95% CI 0.890-0.937; P < 0.001). Sperm DFI has an impact on both miscarriage rates and birth weight in assisted reproductive technology. The smooth fitting curve analysis reveals a positive correlation between miscarriage rates and DFI, while a negative correlation is observed between birth weight and DFI.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Moon KY et al., 2023·Taiwan J Obstet Gynecol·
Open Access
This study aimed to investigate the impact of thyroid autoantibodies and serum TSH levels on clinical IVF outcomes. This study included 260 Korean women scheduled for their first IVF between 2013 and 2017. Serum levels of thyroid hormone, TSH, and antibody for thyroid peroxidase and thyroglobulin were measured just before the first ovarian stimulation. Clinical pregnancy rate (PR), ongoing PR, and miscarriage rate were analyzed according to thyroid autoimmunity and serum TSH levels. The primary outcome was ongoing PR beyond 12 weeks of gestation. The ongoing PR and miscarriage rates were similar between women with positive (n = 29) and negative autoantibodies (n = 186). In women with subclinical hypothyroidism (serum TSH ≥4.2 μIU/mL), ongoing PR was significantly lower than euthyroid women (22.2%, vs. 44.7%, p = 0.045), but miscarriage rate was similar. The group with serum TSH ≥3.4 μIU/mL showed a significantly lower ongoing PR (23.9% vs. 46.7%, p = 0.005) and significantly higher miscarriage rate (38.9% vs. 14.1%, p = 0.020). In multivariate logistic regression analysis, serum TSH ≥3.4 μIU/mL was an independent unfavorable predictor for ongoing PR (odds ratio 0.375, p = 0.013). Thyroid autoantibodies did not affect clinical IVF outcomes, but women with serum TSH ≥3.4 μIU/mL demonstrated poor IVF outcomes.
Environmental Exposures · Plastics and Microplastics
The exposure to plastic derivatives during human life is deleterious. Infants conceived using ART (IVF or ICSI) have twice as many risks of major birth defects compared to naturally conceived infants. Could plastic ware used during ART trigger defects in the fetal development? Three groups of blastocysts were transferred to pseudopregnant mice. One was obtained after IVF and embryo development in plastic ware, the second in glass ware. The third, was obtained in vivo by natural mating. On day 16.5 of pregnancy, females were sacrificed and fetal organs collected for gene expression analysis. Fetal sex was determined by RT-PCR. RNA was extracted from a pool of five placental or brain samples coming from at least two litters from the same group and analyzed by hybridisation onto the mouse Affymetrix 430.2.0 GeneChips, confirmed by RT-qPCR for 22 genes. This study highlights a major impact of plastic ware on placental gene expression (1121 significantly deregulated genes), while glassware was much closer to in vivo offspring (only 200 significantly deregulated genes). Gene Ontology indicated that the modified placental genes were mostly involved in stress, inflammation and detoxification. A sex specific analysis revealed in addition a more drastic effect on female than male placentas. In the brains, whatever the comparison, less than 50 genes were found deregulated. Embryos incubated in plastic ware resulted in pregnancy with massive alterations of placental gene expression profile in concerted biological functions. There were no obvious effects on the brains. Besides other effects, this suggests that plastic ware in ART could be a cause of the increased level of pregnancy disorders observed recurrently in ART pregnancies. This study was funded by two grants from the Agence de la Biomedecine in 2017 and 2019.
Endometrial receptivity (ER) is a key factor required for the successful implantation of the embryo. However, the evaluation of ER is challenging, as a nondisruptive sampling of endometrial biomaterial by conventional methods is only possible outside of the embryo transfer (ET) cycle. We propose a novel approach for the assessment of ER-microbiological and cytokine profiling of menstrual blood aspirated directly from the uterine cavity at the beginning of the cryo-ET cycle. The aim of the pilot study was to evaluate its prognostic potential regarding the outcome of the in vitro fertilization procedure. Samples collected from a cohort of 42 patients undergoing cryo-ET were analyzed by a multiplex immunoassay (48 various cytokines, chemokines, and growth factors) and a real-time PCR assay (28 relevant microbial taxa and 3 members of the Herpesviridae family). Significant differences between groups of patients who achieved and did not achieve pregnancy were observed for G-CSF, GRO-α, IL-6, IL-9, MCP-1, M-CSF, SDF-1α, TNF-β, TRAIL, SCF, IP-10, and MIG (p < 0.05), whereas microbial profiles were not associated with the outcome of cryo-ET. It appeared that levels of IP-10 and SCGF-β were significantly lower (p < 0.05), in patients with endometriosis. Menstrual blood may provide great opportunities to noninvasively investigate various parameters of the endometrium.
Chronic Endometritis · Endometritis and Reproductive Outcomes
Li J et al., 2023·Frontiers in cell and developmental biology
Chronic endometritis (CE) has been considered to reduce uterine receptivity and negatively affect reproductive outcomes for in vitro fertilization-embryo transfer (IVF-ET) patients, especially for people undergoing recurrent implantation failure (RIF). To investigate the effects of antibiotic and platelet-rich plasma (PRP) therapy on pregnancy outcomes following frozen-thawed embryo transfer (FET) in RIF patients with CE, endometrial specimens of 327 patients with RIF obtained by endometrial scratching during mid-luteal phase were immunostained by multiple myeloma oncogene-1 (Mum-1)/syndecan-1 (CD138). RIF patients with CE were given antibiotics and PRP treatment. According to the Mum-1+/CD138+ plasmacytes after treatment, patients were divided into persistent weak positive CE (+) group, CE (-) group and non-CE group. FET was performed and the basic characteristics and pregnancy outcomes of patients in three groups were compared. Among 327 RIF patients, 117 patients were complicated with CE, the prevalence was 35.78%. The prevalence of strong positive was 27.22% and that of weak positive was 8.56%. 70.94% patients with CE converted to negative after treatment. There was no significant difference in the basic characteristics, including age, BMI, AMH, AFC, infertility years, infertility types, number of previous transplant cycles, endometrial thickness on transplantation day and number of transplanted embryos (p > 0.05); The positive rate of hCG, clinical pregnancy rate and implantation rate in CE (-) group were significantly increased compared with the weak CE (+) group and non-CE group (p < .01), and the live birth rate also improved (p < .05). Whereas, the rate of early abortion in CE (-) group was 12.70%, which was higher than that in weak CE (+) group and non-CE group (p < .05). After multivariate analysis, number of previous failed cycles and CE remained independent factors associated with live birth rate, while only CE remained to be the independent factor of clinical pregnancy rate. It is recommended to perform CE-related examination for patients with RIF. Antibiotic and PRP treatment can significantly improve pregnancy outcomes of patients with CE negative conversion in FET cycle.
Agence de la biomédecine, 2023·Agence de la biomédecine
Rapport annuel d'activité 2022 de l'Agence de la biomédecine. Annual activity report covering Agence de la biomédecine activities including AMP (Medically Assisted Reproduction) registry operations for 2022.
This article is a case study illuminating the experience of a cradle Catholic who pursued a career in the field of Assisted Reproductive Technology (ART) as a laboratory director and embryologist. Twenty years after leaving the field, the observations leading to the crisis of conscience are further amplified by the reports of social, legal, ethical, and medical consequences of the technology. These consequences are explored in detail and can serve as a mini-review of the published scientific literature describing the obstetrical complications, peri-natal outcomes, and the long-term health effects on the offspring. This paper provides the documented evidence that can be used by the religious and medical community for shepherding the flock. The disordered approach to patient care is evidenced by five serious consequences resulting from the use of the technology. These include multiple pregnancy and selective reduction, abandoned and discarded embryos, adverse health effects to the women and children, legal and ethical problems, and human experimentation. An explanation for the adverse consequences can be found by exploring and applying the principles of Natural Law. Natural Law, as embraced by the Catholic Church, can be used as a starting point for conversion of heart for many who struggle with the immorality of ART. Deterring use of the technology coupled with increased motivation by scientist and health professionals to pursue restorative approaches within a moral framework offer our best solution to the treatment of infertility. Natural Law and the consequences of violating it provide evidence that science and medicine should not be practiced in a vacuum void of ethical and moral boundaries grounded in divine Wisdom.
Thyroid and Metabolic Function · Insulin and Metabolism
Endocrine disorders negatively influence the ovarian function, and increasing incidence of endocrine diseases with age may have further negative effects on pregnancy rate. Prospective cohort study of 231 consecutively enrolled patients underwent IVF treatment. In patients with known endocrine disorders, the laboratory parameters were corrected before IVF treatment. One hundred sixty one patients (69.7%) had at least one known and treated endocrine disorder (study group), and 70 patients were endocrine negative (control group). Endocrine disorders diagnosed were thyroid disorders (32.5%), diminished ovarian reserve (23.8%), insulin resistance (22.5%), PCOS (15.2%), hyperprolactinaemia (13.4%), obesity (12.1%), hypogonadotropic hypogonadism (0.8%) and congenital adrenal hyperplasia (0.2%). Before the IVF treatment, systematic endocrine laboratory examinations were performed in all patients. Higher age, BMI and FSH were found in the study group, while AMH level was lower. There were no differences in LH, E2, prolactin, TSH, FT3, FT4, TT, DHEAS, androstendione, 17-OHP and SHBG level between the study and control groups. The study group had higher baseline glucose, baseline insulin, 120-min glucose and 120-min insulin level after oral glucose tolerance test. With no difference in the IVF cycles performed, pregnancy rate was lower in the study group (61.43% vs. 34.16%; p = 0.003), and this difference (p = 0.0151) remained in age-corrected rates, as well. The analyses were also performed in individual endocrinology groups. The prevalence of endocrine disorders is high in females participating in IVF programs, and they are often accompanying each other. Even after proper correction, the presence of the endocrine disorder negatively influences the pregnancy rate in IVF treatment.
Perrotta M et al., 2022·Sociol Health Illn·
Open Access
With the increasing offer of fertility treatment by a largely privatised sector, which has involved the proliferation of treatment add-ons lacking evidence of effectiveness, In-Vitro Fertilisation (IVF) patients are expected to make informed choices on what to include in their treatment. Drawing on interviews with 51 individuals undergoing fertility treatment, this article explores patients' approaches to medical evidence interpretation and its role in their decisions to include add-ons. While most IVF patients share understandings of what counts as medical evidence, our findings show how their approaches also differ. Our analysis focuses on how patients negotiate the notion of medical evidence and its relation to other forms of experience or knowledge. We present four different approaches to evidence in (1) delegating evaluations of evidence to experts; (2) critically assessing available evidence; (3) acknowledging the process of making evidence; and (4) contextualising evidence in their lived experience of infertility. We suggest that patients' choice to include add-ons is not due to a lack of information on or understanding of evidence, but rather should be interpreted as part of the complexity of patients' experiences of infertility.
Chronic Endometritis · Endometritis and Reproductive Outcomes
Vitagliano A et al., 2022·Diagnostics (Basel)·
Open Access
This systematic review and meta-analysis aims to evaluate the impact of chronic endometritis (CE) and its therapy on in vitro fertilization (IVF) outcome. Additionally, we aim to investigate whether various degrees of CE severity may exert a different effect on IVF outcome. Ongoing-pregnancy rate/live-birth-rate (OPR/LBR), clinical-pregnancy rate (CPR), and miscarriage rate (MR) were calculated. A total number of 4145 patients (from ten studies) were included. Women with CE had lower OPR/LBR (OR 1.97, p = 0.02) and CPR (OR 2.28, p = 0.002) compared to those without CE. CE cure increased OPR/LBR (OR 5.33, p < 0.0001) and CPR (OR 3.64, p = 0.0001). IVF outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR and MR: p = ns). Women with severe CE had lower OPR/LBR (OR 0.43, p = 0.003) and CPR (OR 0.40, p = 0.0007) compared to those mild CE. Mild CE showed no influence on the IVF outcome as compared to women without CE (OPR/LBR, CPR and MR: p = ns). Based on this data analysis, CE significantly reduces OPR/LBR and CPR in women undergoing IVF. Importantly, CE resolution after antibiotic therapy may improves IVF outcome, leading to similar OPR/LBR and CPR as compared to unaffected patients. The negative effects of CE on IVF outcome may be restricted to severe disease, whereas mild CE may have no influence on IVF success.
Check JH et al., 2022·Gynecol Reprod Health·
Open Access
Many infertility specialists advise women with diminished oocyte reserve (DOR) that their remaining oocytes probably are of poor quality similar to women of advanced reproductive age. There have been studies, especially employing in vitro fertilization-embryo transfer (IVF-ET), showing very poor live delivered pregnancy rates despite the transfer of morphologically normal embryos in women even with mild DOR. However, other data suggests that the low pregnancy rates are related to the use of high dosages of follicle stimulating hormone (FSH) drugs which down-regulate some key FSH dependent enzymes, cytokines, or proteins required for proper embryo implantation. Some studies have shown that techniques that favor FSH receptor up-regulation, rather than down-regulation, can provide the chance of live delivery 80% as well in women ≤ 35 with DOR, 70% for women 36-39, and 50% for women 40-42. Though some infertility specialists will encourage women whose only infertility issue is DOR, who reject the initial suggestion to consider donor oocytes, to proceed immediately with IVF-ET to maximize success, pregnancies are quite possible with natural conception. Thus, it seems imprudent to make couples undergo the financial burden of IVF-ET in the absence of a significant tubal or male factor problem. Not only have live deliveries occurred in women with DOR, using the principle described to achieve a mature dominant follicle followed by proper luteal phase support, with serum FSH levels over 100 mIU/mL, but also serum Anti-Mullerian Hormone (AMH) levels that were undetectable. This even applies to women in overt menopause where FSH up-regulation was achieved by negative feedback to the pituitary using ethinyl estradiol inhibiting FSH release, or down-regulation of hypothalamic-pituitary stimulation of FSH production by using gonadotropin releasing hormone agonists or antagonists.
Gao Y et al., 2022·Frontiers in Endocrinology·
Open Access
Polycystic ovary syndrome (PCOS) is one of the most common reasons for infertility. The consensus of the treatment of infertile women with PCOS is ovulation induction (OI) for six to nine attempts beforein vitrofertilization (IVF)/intracytoplasmic sperm injection (ICSI). Nowadays, more attention was paid to a rising, noninvasive treatment, intrauterine insemination (IUI), as some experts claimed IUI could benefit PCOS patients with infertility. Our study means to investigate the outcomes of IUI for PCOS patients and if patients’ previous OI cycles can be a predictive factor for IUI outcomes. A total of 1,086 PCOS patients was included and 1,868 IUI cycles were performed between January 2007 and July 2021 in the department of assisted reproduction in Shanghai Ninth People’s Hospital. All included patients underwent IUI treatments with letrozole+human menopausal gonadotropin (LE+hMG) for ovarian stimulation. The pregnancy outcomes were not associated with the attempts of failed OI cycles previously. Specifically, the clinical pregnancy rate was 21.14% for PCOS patients without previous OI cycles, 21.95% for PCOS patients with 1-2 previous OI cycles and 23.64% for PCOS patients with 3 or more previous OI cycles (p=0.507). The corresponding live birth rate was 16.64%, 18.06%, and 18.68%, respectively, of which the difference was not statistically significant (p=0.627). The cumulative rate per patient was 38.59% for clinical pregnancy and 31.03% for live birth, and approximately 98% of the pregnancies occurred in the first 3 cycles of IUI. PCOS women with different attempts of OI cycles had similar pregnancy outcomes after IUI, thus a history of repeated failures of OI treatments was not a predictive factor for the pregnancy outcomes in IUI cycles. Most pregnancies occurred in the first three cycles of IUI, so we strongly recommended three attempts of IUI for PCOS women before they switched to IVF/ICSI. Generally, IUI might be an assist for infertile women with PCOS before IVF/ICSI and might accelerate pregnancy for target women without invasive manipulations.
Brodeur TY et al., 2022·Reproductive sciences (Thousand Oaks, Calif.)·
Open Access
Infertility has a prevalence of up to 16% worldwide and is on the rise in developed nations, largely due to pursuing childbearing at advanced reproductive ages. Advances in assisted reproductive technology have benefitted socioeconomically advantaged patients disproportionately. High costs of fertility care are largely responsible for this disparity; however, patients in rural areas also face barriers in accessing both gynecology and reproductive endocrinology subspecialty care. Here, focusing on the USA, we discuss fertility care in geographically underserved areas and low-resource settings, and the impact on reproductive outcomes. Increased innovation to improve patient access to fertility care such as assisted reproductive technology is critical for ensuring equity. Remote monitoring is frequently performed by fertility centers, but partnership with local gynecologists has also been demonstrated to be an effective assisted reproductive technology monitoring method. Telehealth is now in mainstream use and the continued application to reduce geographic barriers to infertility patients is imperative. Partnership between local gynecologists and reproductive endocrinology and infertility specialists may improve patient access to fertility care and provide the unique benefits of continuity and ongoing local social support.
Obrzut B et al., 2022·Journal of clinical medicine·
Open Access
Tubal diseases account for 25-40% of female factor infertility. Mainly, they involve the distal part of the fallopian tube, and hydrosalpinx is the most severe manifestation. Usually, the management decision is made between reconstructive surgery and ART, depending on the severity of the tubal damage, patient age, ovarian reserve, and seminogram, as well as financial, religious, ethical, and psychological factors. Estimated live-birth rates after corrective surgery range from 9% to 69%. The success rate of IVF is about 30% live-birth rate per cycle initiated in women across all ages with tubal factor infertility. Surgery offers a long-term cure and patients may attempt conception many times but are burdened with perioperative adverse events. IVF bypasses potential complications of operative treatment; however, this has its own unique risks. The effectiveness of reconstructive surgery versus ART has not been adequately evaluated. The success of fertility management depends on a thorough interpretation of existing data and careful patient selection. The presented review provides updates on the most recent progress in this area.
Coccia ME et al., 2022·Int J Environ Res Public Health·
Open Access
Laparoscopic surgery was originally considered the gold standard in the treatment of endometriosis-related infertility. Assisted reproductive technology (ART) was indicated as second-line treatment or in the case of male factor. The combined approach of surgery followed by ART proved to offer higher chances of pregnancy in infertile women with endometriosis. However, it was highlighted how pelvic surgery for endometriosis, especially in cases of ovarian endometriomas, could cause iatrogenic damage due to ovarian reserve loss, adhesion formation (scarring), and ischemic damage. Furthermore, in the last few years, the trend to delay the first childbirth, recent technological advances in ultrasound diagnosis, and technological progress in clinical and laboratory aspects of ART have certainly influenced the approach to infertility and endometriosis with, ART assuming a more relevant role. Management of endometriosis should take into account that the disease is chronic and involves the reproductive system. Consequently, treatment and counselling should aim to preserve the chances of pregnancy for the patient, even if it is not associated with infertility. This review will analyse the evolution of the management of infertility associated with endometriosis and propose an algorithm for treatment decision-making based on the most recent acquisitions.
Polygenic risk score analyses on embryos (PGT-P) are being marketed by some private testing companies to parents using in vitro fertilisation as being useful in selecting the embryos that carry the least risk of disease in later life. It appears that at least one child has been born after such a procedure. But the utility of a PRS in this respect is severely limited, and to date, no clinical research has been performed to assess its diagnostic effectiveness in embryos. Patients need to be properly informed on the limitations of this use of PRSs, and a societal debate, focused on what would be considered acceptable with regard to the selection of individual traits, should take place before any further implementation of the technique in this population.
Guidelines by Clinical Area · Obstetric Guidelines
Society for Maternal-Fetal Medicine et al., 2022·American Journal of Obstetrics and Gynecology·
Open Access
The use of assisted reproductive technology has increased in the United States in the past several decades. Although most of these pregnancies are uncomplicated, in vitro fertilization is associated with an increased risk for adverse perinatal outcomes primarily caused by the increased risks of prematurity and low birthweight associated with in vitro fertilization pregnancies. This Consult discusses the management of pregnancies achieved with in vitro fertilization and provides recommendations based on the available evidence. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we suggest that genetic counseling be offered to all patients undergoing or who have undergone in vitro fertilization with or without intracytoplasmic sperm injection (GRADE 2C); (2) regardless of whether preimplantation genetic testing has been performed, we recommend that all patients who have achieved pregnancy with in vitro fertilization be offered the options of prenatal genetic screening and diagnostic testing via chorionic villus sampling or amniocentesis (GRADE 1C); (3) we recommend that the accuracy of first-trimester screening tests, including cell-free DNA for aneuploidy, be discussed with patients undergoing or who have undergone in vitro fertilization (GRADE 1A); (4) when multifetal pregnancies do occur, we recommend that counseling be offered regarding the option of multifetal pregnancy reduction (GRADE 1C); (5) we recommend that a detailed obstetrical ultrasound examination (CPT 76811) be performed for pregnancies achieved with in vitro fertilization and intracytoplasmic sperm injection (GRADE 1B); (6) we suggest that fetal echocardiography be offered to patients with pregnancies achieved with in vitro fertilization and intracytoplasmic sperm injection (GRADE 2C); (7) we recommend that a careful examination of the placental location, placental shape, and cord insertion site be performed at the time of the detailed fetal anatomy ultrasound, including evaluation for vasa previa (GRADE 1B); (8) although visualization of the cervix at the 18 0/7 to 22 6/7 weeks of gestation anatomy assessment with either a transabdominal or endovaginal approach is recommended, we do not recommend serial cervical length assessment as a routine practice for pregnancies achieved with in vitro fertilization (GRADE 1C); (9) we suggest that an assessment of fetal growth be performed in the third trimester for pregnancies achieved with in vitro fertilization; however, serial growth ultrasounds are not recommended for the sole indication of in vitro fertilization (GRADE 2B); (10) we do not recommend low-dose aspirin for patients with pregnancies achieved with IVF as the sole indication for preeclampsia prophylaxis; however, if 1 or more additional risk factors are present, low-dose aspirin is recommended (GRADE 1B); (11) given the increased risk for stillbirth, we suggest weekly antenatal fetal surveillance beginning by 36 0/7 weeks of gestation for pregnancies achieved with in vitro fertilization (GRADE 2C); (12) in the absence of studies focused specifically on timing of delivery for pregnancies achieved with IVF, we recommend shared decision-making between patients and healthcare providers when considering induction of labor at 39 weeks of gestation (GRADE 1C).
Agence de la biomédecine, 2022·Agence de la biomédecine
Rapport annuel d'activité 2021 de l'Agence de la biomédecine. Annual activity report covering Agence de la biomédecine activities including AMP (Medically Assisted Reproduction) registry operations for 2021. Provides governance and operational context for the French national ART registry.
Progress in oncological treatment has led to an improved long-term survival of young male cancer patients over the last decades. However, standard cancer treatments frequently implicate fertility-damaging potential. Cryopreservation of sperm is the current standard option to preserve patient's fertility after treatment, yet long-term data on usage and reproductive experiences is still limited. Natural fertility after treatment and especially in relation to the type of treatment has been poorly analyzed so far. Therefore, we performed a retrospective survey including male patients with an indication for gonadotoxic treatment who cryopreserved reproductive material at our institution between 1994 and 2017. Study questionnaires regarding treatment, material usage, and reproductive outcomes were sent to eligible patients. Additionally, semen analyses of study participants from the time of cryopreservation were evaluated. A total of 99 patients were included in the study. Respondents' median age was 38.0 years. Most frequent diagnoses were testicular cancer (29.3%) and lymphoma (26.3%). A further 8.1% suffered from autoimmune diseases. Testicular cancer patients had a significantly lower pre-treatment median sperm concentration (18.0 million/ml) compared to non-testicular cancer patients (54.2 million/ml). Until November 2020, the determined sperm usage and cumulative live-birth rate per couple were 17.2% and 58.8%, respectively. Most sperm users received treatments with high (40.0%) or intermediate (33.3%) gonadotoxic potential. 20.7% of all patients reported to had fathered at least one naturally conceived child after treatment, this being the case especially if they had been treated with less or potentially gonadotoxic therapies. In conclusion, our findings emphasize the importance of sperm cryopreservation in the context of male fertility preservation. Furthermore, they indicate that the gonadotoxic potential of patients' treatments could represent a predictive factor for sperm usage.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org, 2021·Fertility and sterility
To provide evidence-based recommendations to practicing physicians and others regarding the efficacy of oocyte cryopreservation (OC) for donor oocyte in vitro fertilization and planned OC. The American Society for Reproductive Medicine conducted a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1986 to 2018. The American Society for Reproductive Medicine Practice Committee and a task force of experts used available evidence and through consensus developed evidence-based guideline recommendations. MAIN OUTCOME MEASURE(S): Outcomes of interest included live birth rate, clinical pregnancy rate, obstetrical and neonatal outcomes, and factors predicting reproductive outcomes. RESULT(S): The literature search identified 30 relevant studies to inform the evidence base for this guideline. RECOMMENDATION(S): Evidence-based recommendations were developed for predicting the likelihood of live births after planned OC, autologous OC in infertile women, and donor OC, as well as factors that may impact live birth rates. Recommendations were developed regarding neonatal outcomes after using fresh vs. cryopreserved oocytes in cases of autologous or donor oocytes. CONCLUSION(S): There is insufficient evidence to predict live birth rates after planned OC. On the basis of limited data, ongoing and live birth rates appear to be improved for women who undergo planned OC at a younger vs. older age. Although there are no significant differences in per transfer pregnancy rates with cryopreserved vs. fresh donor oocytes, there is insufficient evidence that the live birth rate is the same with vitrified vs. fresh donor oocytes. Neonatal outcomes appear similar with cryopreserved oocytes compared with fresh oocytes. Future studies that compare cumulative live birth rates are needed.
Companies have recently begun to sell a new service to patients considering in vitro fertilization: embryo selection based on polygenic scores (ESPS). These scores represent individualized predictions of health and other outcomes derived from genomewide association studies in adults to partially predict these outcomes. This article includes a discussion of many factors that lower the predictive power of polygenic scores in the context of embryo selection and quantifies these effects for a variety of clinical and nonclinical traits. Also discussed are potential unintended consequences of ESPS (including selecting for adverse traits, altering population demographics, exacerbating inequalities in society, and devaluing certain traits). Recommendations for the responsible communication about ESPS by practitioners are provided, and a call for a society-wide conversation about this technology is made. (Funded by the National Institute on Aging and others.).
A maternal Western-style diet (WSD) is associated with poor reproductive outcomes, but whether this is from the diet itself or underlying metabolic dysfunction is unknown. Here, we performed a longitudinal study using regularly cycling female rhesus macaques (n = 10) that underwent 2 consecutive in vitro fertilization (IVF) cycles, one while consuming a low-fat diet and another 6-8 months after consuming a high-fat WSD. Metabolic data were collected from the females prior to each IVF cycle. Follicular fluid (FF) and oocytes were assessed for cytokine/steroid levels and IVF potential, respectively. Although transition to a WSD led to weight gain and increased body fat, no difference in insulin levels was observed. A significant decrease in IL-1RA concentration and the ratio of cortisol/cortisone was detected in FF after WSD intake. Despite an increased probability of isolating mature oocytes, a 44% reduction in blastocyst number was observed with WSD consumption, and time-lapse imaging revealed delayed mitotic timing and multipolar divisions. RNA sequencing of blastocysts demonstrated dysregulation of genes involved in RNA binding, protein channel activity, mitochondrial function and pluripotency versus cell differentiation after WSD consumption. Thus, short-term WSD consumption promotes a proinflammatory intrafollicular microenvironment that is associated with impaired preimplantation development in the absence of large-scale metabolic changes.
Jiang Y et al., 2021·Oxidative medicine and cellular longevity
Oxidative stress has been recognized as one of the causal mediators of female infertility by affecting the oocyte quality and early embryo development. Improving oxidative stress is essential for reproductive health. Melatonin, a self-secreted antioxidant, has a wide range of effects by improving mitochondrial function and reducing the damage of reactive oxygen species (ROS). This minireview illustrates the applications of melatonin in reproduction from four aspects: physiological ovarian aging, vitrification freezing, in vitro maturation (IVM), and oxidative stress homeostasis imbalance associated with polycystic ovary syndrome (PCOS), emphasising the role of melatonin in improving the quality of oocytes in assisted reproduction and other adverse conditions.
Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). MAIN The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the SPIRIT statement, and over 80 specialty journals, including Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set.
While we agree with many of the points stated by Dyer et al. in their recent commentary inRBMO(Dyer et al., 2020), we believe their conclusions are focused too narrowly. Limiting the indicator of access to, and utilization of, fertility treatment to assisted reproductive technology (ART) excludes information that is of key importance for subfertile couples, populations, and policymakers. Even in countries where access to ART is widespread, there are more births in subfertile couples through non-ART treatment than through ART (Stanford et al., 2016).
While ART is necessary for some couples to have a child, it is not required for many subfertile couples, and overuse of ART may potentially be harmful (Annual Capri Workshop Group 2019). Focusing solely on ART as a metric may unnecessarily encourage overutilization (Boltz et al., 2017).
We believe the focus on ART and its outcomes for national and international registries of fertility treatment has stunted the scientific development of non-ART treatments, including those which seek to address underlying health conditions (Boyle et al., 2018). There is a pressing and critical need to develop robust registries of couples treated with non-ART treatments, for the improvement of outcomes and the promotion of robust consumer choice. (Spandorfer, 2020).
The ultimate measure of access to fertility care should be determined by the proportion of those with a desire for fertility who achieve a healthy live birth, whether or not ART is required to do so (Mascarenhas et al., 2012). Therefore, notwithstanding methodologic challenges, registry assessments should be developed and supported for all fertility treatments, not only ART.
Despite great advances in assisted reproductive technology, poor ovarian response (POR) is still considered as one of the most challenging tasks in reproductive medicine. The aim of this systemic review is to evaluate the role of different adjuvant treatment strategies on the probability of pregnancy achievement in poor responders undergoing IVF. Randomized controlled trials (RCTs) comparing 10 adjuvant treatments [testosterone, dehydroepiandrosterone (DHEA), letrozole, recombinant LH, recombinant hCG, oestradiol, clomiphene citrate, progesterone, growth hormone (GH) and coenzyme Q10 (CoQ10)] were included. Relevant studies published in the English language were comprehensively selected using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) until 11 July 2018. We included studies that investigated various adjuvant agents, including androgen and androgen-modulating agents, oestrogen, progesterone, clomiphene citrate, GH and CoQ10, during IVF treatment and reported subsequent pregnancy outcomes. The administration of GnRH analogs and gonadotrophins without adjuvant treatment was set as the control. We measured study quality based on the methodology and categories listed in the Cochrane Collaboration Handbook. This review protocol was registered with PROSPERO (CRD42018086217). Outcomes: Of the 1124 studies initially identified, 46 trials reporting on 6312 women were included in this systematic review, while 19 trials defining POR using the Bologna criteria reporting 2677 women were included in the network meta-analysis. Compared with controls, DHEA and CoQ10 treatments resulted in a significantly higher chance of clinical pregnancy [odds ratio (OR) 2.46, 95% CI 1.16 to 5.23; 2.22, 1.08-4.58, respectively]. With regard to the number of retrieved oocytes, HCG, oestradiol and GH treatments had the highest number of oocytes retrieved [weighted mean difference (WMD) 2.08, 0.72 to 3.44; 2.02, 0.23 to 3.81; 1.72, 0.98 to 2.46, compared with controls, respectively]. With regard to the number of embryos transferred, testosterone and GH treatment led to the highest number of embryos transferred (WMD 0.72, 0.11 to 1.33; 0.67, 0.43 to 0.92; compared with controls, respectively). Moreover, GH resulted in the highest oestradiol level on the HCG day (WMD 797.63, 466.45 to 1128.81, compared with controls). Clomiphene citrate, letrozole and GH groups used the lowest dosages of gonadotrophins for ovarian stimulation (WMD 1760.00, -2890.55 to -629.45; -1110.17, -1753.37 to -466.96; -875.91, -1433.29 to -282.52; compared with controls, respectively). CoQ10 led to the lowest global cancelation rate (OR 0.33, 0.15 to 0.74, compared with controls). For patients with POR, controlled ovarian stimulation protocols using adjuvant treatment with DHEA, CoQ10 and GH showed better clinical outcomes in terms of achieving pregnancy, and a lower dosage of gonadotrophin required for ovulation induction. Furthermore, high-level RCT studies using uniform standards for POR need to be incorporated into future meta-analyses.
Environmental Exposures · Radiation and Electromagnetic Exposure
Immersed in the world dominated by pragmatism, contemporary man seems to be thinking and functioning only according to the criteria of effective acting. However, life experience, philosophical reflection, and the truth of Revelation lead to the conclusion that the laws of nature must be respected in the name of care for man and for one’s genuine good, even though they may, in certain cases, limit the effectiveness of acting and the possibility to acquire current profit. This article justifies the necessity to respect natural law in the sphere of transmission of human life. The starting point of this scientific reflection is the theological vision of values and of the inviolability of human life on the basis of the description of creation from the Book of Genesis. The fundamental truths and moral norms are being neglected nowadays as—being so proud of modern technological achievements—man makes himself the creator and the master of human life. Although such activities seem impressive from the scientific point of view, they actually result in a number of serious contemporary and future threats. The second part of the article presents alarming aspects of artificial interventions in the sphere of life transmission. By exposing the threats and by trying to prevent them in the sphere of infertility treatment, the Church opposes the methods of artificial insemination and becomes engaged in promoting naprotechnology which is a method that expresses genuine humanism, and which gives hope not only to the parents who want to have a baby but also to the mankind that longs for propitious future.
Cancer and Fertility · Hormone Sensitive Cancer and Reproductive Care
D Farhud D et al., 2019·Iranian journal of public health
In-vitro fertilization (IVF) has been very popular since the birth of the first "test-tube" baby. This method is the last hope and the most serious solution for couples with infertility problems. Although childbearing is a concern of many couples, it must always be noted that any method can also have disadvantages. Thus, many studies have been done on the problems encountered by this method. We searched for relevant articles in Pub Med, Springer, Elsevier, and Google Scholar databases, and studied more than 70 papers. Keywords used included ovarian cancer, in vitro fertilization, gonadotropin hormone, clomiphene citrate, and infertility. Due to the large number of studies, high doses of the ovulation-stimulating drugs and their repeated use in this method can increase the risk of the ovarian hyper stimulation syndrome (OHSS), and ovarian cysts, which can lead to ovarian cancer. Also, an increase in the risk of developing ovarian cancer can be due to the increased duration of treatment for up to 12 months and the high doses of medications that are followed by defecation and failure of this treatment. Due to the increase in the rates of infertility treatments and the incidence of gynecological cancers, especially ovarian cancer, this method need to be used with caution. IVF clients and candidates should be informed about potential future risks. People should be evaluated genetically for their history of ovarian cancer and be more aware of the importance of "Personalized medicine".
Metabolic and Endocrine Agents · Thyroid Replacement
Akhtar MA et al., 2019·Cochrane Database Syst Rev·
Thyroid disease is the second most common endocrine disorder affecting women of reproductive age. Subclinical hypothyroidism is diagnosed by an elevated thyroid-stimulating hormone concentration with a normal concentration of free thyroxine hormone. Autoimmune thyroid disease (ATD) is diagnosed by the presence of thyroid autoantibodies, regardless of thyroid hormone levels. Thyroxine may be a useful treatment for subfertile women with these two specific types of thyroid disease for improving pregnancy outcomes during assisted reproduction. To evaluate the efficacy and harms of levothyroxine replacement in subfertile women with subclinical hypothyroidism or with normal thyroid function and thyroid autoimmunity (euthyroid autoimmune thyroid disease, or euthyroid ATD) undergoing assisted reproduction. We searched the Cochrane Gynaecology and Fertility (CGF) Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers together with reference checking and contact with study authors and experts in the field to identify studies. We searched for all published and unpublished randomised controlled trials (RCTs) comparing thyroxine with no treatment or placebo, without language restrictions, from inception to 8 April 2019, and in consultation with the Cochrane CGF Information Specialist. We included women undergoing assisted reproduction treatment, meaning both in vitro fertilisation and intracytoplasmic sperm injection, with a history of subfertility and with subclinical hypothyroidism or with euthyroid ATD. We excluded women with a previously known clinical hypothyroidism or already taking thyroxine or tri-iodothyronine. RCTs compared thyroxine (levothyroxine) with either placebo or no treatment. We used standard methodological procedures expected by Cochrane. Our primary review outcomes were live birth and adverse events of thyroxine; our secondary outcomes were clinical pregnancy, multiple pregnancy and miscarriage. The review included four studies with 820 women. The included studies were of overall low risk of bias. Using GRADE methodology, we assessed the quality of evidence for the primary outcomes of this review to be very low- to low-quality evidence. Evidence was downgraded for imprecision as it was based on single, small trials with wide confidence intervals (CI). We were able to include data from three of the four included studies.In one study of women with both subclinical hypothyroidism and positive or negative anti-TPO antibodies (autoimmune disease), the evidence suggested that thyroxine replacement may have improved live birth rate (RR 2.13, 95% CI 1.07 to 4.21; 1 RCT, n = 64; low-quality evidence) and it may have led to similar miscarriage rates (RR 0.11, 95% CI 0.01 to 1.98; 1 RCT, n = 64; low-quality evidence). The evidence suggested that women with both subclinical hypothyroidism and positive or negative anti-TPO antibodies would have a 25% chance of a live birth with placebo or no treatment, and that the chance of a live birth in these women using thyroxine would be between 27% and 100%.In women with normal thyroid function and thyroid autoimmunity (euthyroid ATD), treatment with thyroxine replacement compared with placebo or no treatment may have led to similar live birth rates (risk ratio (RR) 1.04, 95% CI 0.83 to 1.29; 2 RCTs, number of participants (n) = 686; I(2) = 46%; low-quality evidence) and miscarriage rates (RR 0.83, 95% CI 0.47 to 1.46, 2 RCTs, n = 686, I(2) = 0%; low-quality evidence). The evidence suggested that women with normal thyroid function and thyroid autoimmunity would have a 31% chance of a live birth with placebo or no treatment, and that the chance of a live birth in these women using thyroxine would be between 26% and 40%.Adverse events were rarely reported. One RCT reported 0/32 in the thyroxine replacement group and 1/32 preterm births in the control group in women diagnosed with subclinical hypothyroidism and positive or negative anti-TPO antibodies. One RCT reported 21/300 preterm births in the thyroxine replacement group and 19/300 preterm births in the control group in women diagnosed with positive anti-TPO antibodies. None of the RCTs reported on other maternal pregnancy complications, foetal complications or adverse effects of thyroxine. AUTHORS' We could draw no clear conclusions in this systematic review due to the very low to low quality of the evidence reported.
Boyle PC et al., 2018·Front Med (Lausanne)·
Open Access
To determine the live birth rate for patients who chose to undergo treatment with Restorative Reproductive Medicine (RRM) after previous IVF (includes ICSI). To look at birth outcomes with RRM after IVF, particularly rates of twin and higher order pregnancies, premature birth, low birth weight, and potential cost savings achieved with RRM. Two outpatient clinics in Ireland providing advanced RRM treatment of infertility. All patients presenting between January 2004 and January 2010, with a history of infertility and previous IVF treatment were included if they proceeded beyond the initial consultation and began treatment. Main outcome is live birth per couple calculated using life table analysis. 403 patients met the study criteria, among which 74 had a subsequent live birth. These women had significant negative predictive characteristics for healthy live birth including: advanced reproductive age (average 37.2 years), an average of 5.8 years of infertility with 2.1 (range 1-9) previous IVF attempts, with only 5% having previously had a live birth from IVF. Despite these undesirable prognostic indicators, the overall RRM live birth rate was 32.1% (crude 18.4%). Women aged 35-38 had a live birth rate of 37.5% (crude 23.6%) and older women over 40 had a live birth rate of 27.4% (crude 16.0%). The average birth weight was 3374g (7lb 7oz) with 92% being born at 37+ weeks and no very low birth weight babies. There was only one twin pregnancy in the study population; the potential health care savings for avoidable multiple pregnancies in these patients was estimated at £205 672 (USD$284 915). Patients who have already tried IVF can achieve comparable live birth outcomes with RRM compared to another cycle of IVF. RRM has a low risk of twin or multiple births, and very good neonatal outcomes with a potential cost savings to the health care system.
Sharma S et al., 2018·J Hum Reprod Sci·
Open Access
Gonadotropin stimulation is used as the second line of treatment in patients with thin endometrium following clomiphene citrate (CC) administration, which is associated with higher cost, multiple births, and ovarian hyperstimulation syndrome. Tamoxifen (TMX), a selective estrogen receptor modulator, acts as an agonist on the endometrium. The objective of the present study was to compare the efficacy of low-dose CC, TMX, and gonadotropins in women with thin endometrium (<7 mm) following Clomiphene in intrauterine insemination (IUI) cycles. SETTINGS AND A prospective observational study between December 2011 and June 2013 was carried out in a tertiary infertility center. Women (n = 502) undergoing IUI with endometrium <7 mm after 100 mg CC were included in the study and divided into three treatment groups. Women in Group A (n = 182, cycles = 364) received clomiphene (50 mg/day from day 3 to 7), Group B (n = 179, cycles = 342) received TMX (40 mg/day from day 3 to 7), and Group C (n = 141, cycles = 226) received continuous urine-derived follicle-stimulating hormone 75-150 IU from day 3 onward until human chorionic gonadotropin injection. Endometrial thickness (ET), pregnancy rate, and live birth rate were considered as main outcome measures. Multiple comparisons using one-way ANOVA and Schiff's test were performed. Pregnancy and live birth rate were significantly higher (P < 0.004) in TMX and gonadotropin groups compared to clomiphene. A number of follicles in the TMX group were found to be lower (P < 0.001) compared to other two groups. In polycystic ovary syndrome patients, ovulation induction with TMX resulted in inadequate response in more than half of the cycles. TMX can improve ET and live birth rate in patients with thin endometrium after clomiphene.
Maxwell E et al., 2018·Journal of Obstetrics and Gynaecology Canada
The purpose of this study was to explore how barriers to accessing fertility services affect the treatment decisions made by fertility patients and service providers in Newfoundland and Labrador. Semistructured, in-depth interviews were conducted with 11 patients across Newfoundland and with eight service providers from Newfoundland and Labrador Fertility Services (located in St. John's) to gather the perspectives of both patients and providers. The interview transcripts were analyzed thematically. Patients' responses to fertility service access barriers included choosing cheaper drugs, substituting intrauterine insemination (IUI) for IVF or not using IVF, delaying IVF, choosing more accessible IVF clinics, transferring multiple embryos, and stopping treatment altogether. Some patients, however, noted that the barriers would not stop them from continuing with treatment. Providers' responses to the barriers patients faced included changing drug protocols, manipulating ovulation, providing teleconsultations, and minimizing patients' clinic visits for those living some distance away from St. John's. Both patients and providers make treatment-related decisions to maximize the likelihood of a successful pregnancy and to reduce costs, which can result in less effective care and at times increased risk to the patient. Unlike with other types of care, responses to barriers to fertility treatment largely result in changes to individual patient treatment plans rather than changing models of care. As a result, many patients must continue to seek fertility services in large urban centres and incur substantial personal costs.
Diagnostic Criteria and Classification · Terminology and Definitions
Can a consensus and evidence-driven set of terms and definitions be generated to be used globally in order to ensure consistency when reporting on infertility issues and fertility care interventions, as well as to harmonize communication among the medical and scientific communities, policy-makers, and lay public including individuals and couples experiencing fertility problems? A set of 283 consensus-based and evidence-driven terminologies used in infertility and fertility care has been generated through an inclusive consensus-based process with multiple stakeholders. In 2006 the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) published a first glossary of 53 terms and definitions. In 2009 ICMART together with WHO published a revised version expanded to 87 terms, which defined infertility as a disease of the reproductive system, and increased standardization of fertility treatment terminology. Since 2009, limitations were identified in several areas and enhancements were suggested for the glossary, especially concerning male factor, demography, epidemiology and public health issues. STUDY DESIGN, SIZE, Twenty-five professionals, from all parts of the world and representing their expertise in a variety of sub-specialties, were organized into five working groups: clinical definitions; outcome measurements; embryology laboratory; clinical and laboratory andrology; and epidemiology and public health. Assessment for revisions, as well as expansion on topics not covered by the previous glossary, were undertaken. A larger group of independent experts and representatives from collaborating organizations further discussed and assisted in refining all terms and definitions. PARTICIPANTS/MATERIALS, SETTING, Members of the working groups and glossary co-ordinators interacted through electronic mail and face-to-face in international/regional conferences. Two formal meetings were held in Geneva, Switzerland, with a final consensus meeting including independent experts as well as observers and representatives of international/regional scientific and patient organizations. MAIN A consensus-based and evidence-driven set of 283 terminologies used in infertility and fertility care was generated to harmonize communication among health professionals and scientists as well as the lay public, patients and policy makers. Definitions such as 'fertility care' and 'fertility awareness' together with terminologies used in embryology and andrology have been introduced in the glossary for the first time. Furthermore, the definition of 'infertility' has been expanded in order to cover a wider spectrum of conditions affecting the capacity of individuals and couples to reproduce. The definition of infertility remains as a disease characterized by the failure to establish a clinical pregnancy; however, it also acknowledges that the failure to become pregnant does not always result from a disease, and therefore introduces the concept of an impairment of function which can lead to a disability. Additionally, subfertility is now redundant, being replaced by the term infertility so as to standardize the definition and avoid confusion. LIMITATIONS, All stakeholders agreed to the vast majority of terminologies included in this glossary. In cases where disagreements were not resolved, the final decision was reached after a vote, defined before the meeting as consensus if passed with 75%. Over the following months, an external expert group, which included representatives from non-governmental organizations, reviewed and provided final feedback on the glossary. Some terminologies have different definitions, depending on the area of medicine, for example demographic or clinical as well as geographic differences. These differences were taken into account and this glossary represents a multinational effort to harmonize terminologies that should be used worldwide. None. N/A.
What is the optimal endometrial preparation protocol for a frozen embryo transfer (FET)?Summary answerAlthough the optimal endometrial preparation protocol for FET needs further research and is yet to be determined, we propose a standardized timing strategy based on the current available evidence which could assist in the harmonization and comparability of clinic practice and future trials. Amid a continuous increase in the number of FET cycles, determining the optimal endometrial preparation protocol has become paramount to maximize ART success. In current daily practice, different FET preparation methods and timing strategies are used.Study design, size, durationThis is a review of the current literature on FET preparation methods, with special attention to the timing of the embryo transfer.Participants/materials, setting, methodsLiterature on the topic was retrieved in PubMed and references from relevant articles were investigated until June 2017.Main results and the role of chanceThe number of high quality randomized controlled trials (RCTs) is scarce and, hence, the evidence for the best protocol for FET is poor. Future research should compare both the pregnancy and neonatal outcomes between HRT and true natural cycle (NC) FET. In terms of embryo transfer timing, we propose to start progesterone intake on the theoretical day of oocyte retrieval in HRT and to perform blastocyst transfer at hCG + 7 or LH + 6 in modified or true NC, respectively.Limitations reasons for cautionAs only a few high quality RCTs on the optimal preparation for FET are available in the existing literature, no definitive conclusion for benefit of one protocol over the other can be drawn so far.Wider implications of the findingsCaution when using HRT for FET is warranted since the rate of early pregnancy loss is alarmingly high in some reports.Study funding/competing interest(s)S.M. is funded by the Research Fund of Flanders (FWO). H.T. and C.B. report grants from Merck, Goodlife, Besins and Abbott during the conduct of the study.Trial registration numberNot applicable.
Ibrahim Y et al., 2017·Journal of assisted reproduction and genetics·
Open Access
The purpose of the study was to examine the association between serum progesterone levels on the day of hCG administration and birth weight among singleton live births after fresh embryo transfer. This study was conducted as a retrospective cohort database analysis on patients who underwent IVF treatment cycles from January 2004 to April 2012. The study was performed at a University affiliated private infertility practice. All cycles that had achieved a singleton live birth after fresh embryo transfer and for which progesterone was measured on the day of hCG administration were examined. Generalized linear models were used to calculate mean birth weight and z-scores. We analyzed 817 fresh IVF embryo transfers in which birth weight, gestational age, and progesterone (ng/mL) level on day of hCG administration were documented. While there was a decrease in birth weight as progesterone quartile [≤0.54; >0.54 to ≤0.81; >0.81 to ≤1.17; >1.17 ng/mL] increased, the difference in mean birth weights among the four quartiles was not statistically significant (p = 0.11) after adjusting for maternal age and peak estradiol levels. When dichotomizing based on a serum progesterone considered clinically elevated, cycles with progesterone >2.0 ng/mL had a significantly lower mean singleton birth weight (2860 g (95% CI 2642 g, 3079 g)) compared to cycles with progesterone ≤2.0 ng/mL (3167 g (95% CI 3122 g, 3211 g) p = 0.007)) after adjusting for maternal age and estradiol. We demonstrated that caution should be exercised when performing fresh embryo transfers with elevated progesterone levels and in particular with levels (>2.0 ng/mL) as this may lead to lower birth weight.
It has become increasingly apparent that the trophectoderm (TE) at blastocyst stage is much more mosaic than has been appreciated. Whether preimplantation genetic screening (PGS), utilizing a single TE biopsy (TEB), can reliably determine embryo ploidy has, therefore, increasingly been questioned in parallel. We for that reason here established 2 mathematical models to assess probabilities of false-negative and false-positive results of an on average 6-cell biopsy from an approximately 300-cell TE. This study was a collaborative effort between investigators at The Center for Human Reproduction in New York City and the Center for Studies in Physics and Biology and the Brivanlou Laboratory of Stem Cell Biology and Molecular Embryology, the latter two both at Rockefeller University in New York City. Both models revealed that even under best case scenario, assuming even distribution of mosaicism in TE (since mosaicism is usually clonal, a highly unlikely scenario), a biopsy of at least 27 TE cells would be required to reach minimal diagnostic predictability from a single TEB. As currently performed, a single TEB is, therefore, mathematically incapable of reliably determining whether an embryo can be transferred or should be discarded. Since a single TEB, as currently performed, apparently is not representative of the complete TE, this study, thus, raises additional concern about the clinical utilization of PGS.
Tamoxifen has played a vital role in endocrine therapy for the treatment of estrogen receptor-positive breast cancer. We examined the effect of tamoxifen in patients with a thin endometrium in frozen-thawed embryo transfer (FET) cycles and compared the improvement in endometrial thickness (EMT) and pregnancy outcomes stratified by different etiologies of thin endometrium. A total of 226 women were recruited for a new tamoxifen protocol; all had an EMT of less than 7.5 mm in previous cycles, including natural cycle (NC), hormone replacement treatment (HRT), and ovulation induction (OI) cycles. Compared with previous cycles, tamoxifen cycles showed a significantly increased EMT (from 6.11 ± 0.98 mm to 7.87 ± 1.48 mm in the NC group, from 6.24 ± 1.01 mm to 8.22 ± 1.67 mm in the HRT group, and from 6.34 ± 1.03 mm to 8.05 ± 1.58 mm in the OI group; all P < .001). Patients were further divided into 3 groups based on the causes of their thin endometrium: (1) history of intrauterine adhesion (n = 34), (2) history of uterine curettage (n = 141), and (3) polycystic ovary syndrome (PCOS; n = 51). Patients with PCOS obtained the thickest EMT (9.31 ± 1.55 mm), the lowest cycle cancellation rate (11.76%), and the highest rate of clinical pregnancy (60%) and live birth (55.56%) per transfer ( P < .001). Multivariable regression analysis showed that EMT was related to live birth (odds ratio: 1.487; 95% confidence interval: 1.172-1.887). A tamoxifen protocol improves EMT in patients after NC, HRT, and OI cycles during FET. Patients with PCOS show the most benefit from tamoxifen and achieve better pregnancy outcomes.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Assisted Reproductive Technology, 2017·Fertility and sterility
This document provides the latest recommendations for evaluation of gestational carriers and intended parents. It incorporates recent information from the US Centers for Disease Control and Prevention, the US Food and Drug Administration, and the American Association of Tissue Banks, with which all programs offering gestational carrier services must be thoroughly familiar. This document replaces the previous document of the same name, last published in 2015 (Fertil Steril® 2015; 103:e1-8).
Amoako AA et al., 2017·Advances in experimental medicine and biology
The periconception period starts 6 months before conception and lasts until the tenth week of gestation. In this chapter, we will focus on epigenetic modifications to DNA and gene expression within this period and during assisted reproduction. There are two critical times during the periconception window when significant epigenetic 'reprogramming' occur: one during gametogenesis and another during the pre-implantation embryonic stage. Furthermore, assisted conception treatments, laboratory protocols and culture media can affect the embryo development and birth weights in laboratory animals. There is, however, an ongoing debate as to whether epigenetic changes in humans, causing embryo mal-development, placenta dysfunction and birth defects, result from assisted reproductive technologies or are consequences of pre-existing medical and/or genetic conditions in the parents. The periconception period starts from ovarian folliculogenesis, through resumption of oogenesis, fertilisation, peri-implantation embryo development, embryogenesis until the end of organogenesis. In men, it is the period from spermatogenesis to epididymal sperm storage and fertilisation. Gametes and developing embryos are sensitive to environmental factors during this period, and epigenetic modifications can occur in response to adverse lifestyles and environmental factors. We now know that lifestyle factors such as advanced parentage age, obesity or undernutrition, smoking, excessive alcohol and caffeine intake and recreational drugs used during gamete production and embryogenesis could induce epigenetic alterations, which could impact adversely on pregnancy outcomes and health of the offspring. Furthermore, these can also result in a permanent and irreversible effect in a dose-dependent manner, which can be passed on to the future generations.
Which outcome measures are reported in RCTs for IVF? Many combinations of numerator and denominator are in use, and are often employed in a manner that compromises the validity of the study. The choice of numerator and denominator governs the meaning, relevance and statistical integrity of a studys results. RCTs only provide reliable evidence when outcomes are assessed in the cohort of randomised participants, rather than in the subgroup of patients who completed treatment. STUDY DESIGN, SIZE, Review of outcome measures reported in 142 IVF RCTs published in 2013 or 2014. PARTICIPANTS/MATERIALS, SETTING, Trials were identified by searching the Cochrane Gynaecology and Fertility Specialised Register. English-language publications of RCTs reporting clinical or preclinical outcomes in peer-reviewed journals in the period 1 January 2013 to 31 December 2014 were eligible. Reported numerators and denominators were extracted. Where they were reported, we checked to see if live birth rates were calculated correctly using the entire randomised cohort or a later denominator. MAIN Over 800 combinations of numerator and denominator were identified (613 in no more than one study). No single outcome measure appeared in the majority of trials. Only 22 (43%) studies reporting live birth presented a calculation including all randomised participants or only excluding protocol violators. A variety of definitions were used for key clinical numerators: for example, a consensus regarding what should constitute an ongoing pregnancy does not appear to exist at present. LIMITATIONS, Several of the included articles may have been secondary publications. Our categorisation scheme was essentially arbitrary, so the frequencies we present should be interpreted with this in mind. The analysis of live birth denominators was post hoc. There is massive diversity in numerator and denominator selection in IVF trials due to its multistage nature, and this causes methodological frailty in the evidence base. The twin spectres of outcome reporting bias and analysis of non-randomised comparisons do not appear to be widely recognised. Initiatives to standardise outcome reporting, such as requiring all effectiveness studies to report live birth or cumulative live birth, are welcome. However, there is a need to recognise that early outcomes of treatment, such as stimulation response or embryo quality, may be appropriate choices of primary outcome for early phase studies.
Infertility Distress · Anxiety and Depression in Infertility
Our study examined the psychological outcomes associated with failed ART treatment outcomes in men and women. A systematic search for studies published between January 1980 and August 2015 was performed across seven electronic databases. Studies were included if they contained data on psychosocial outcomes taken pre and post ART treatment. A standardised form was used to extract data and was verified by two independent reviewers. Studies were meta-analysed to determine the association of depression and anxiety with ART treatment outcomes. Narrative synthesis identified factors to explain variations in the size and directions of effects and relationships explored within and between the studies. Both depression and anxiety increased after a ART treatment failure with an overall pooled standardised mean difference (SMD) of 0.41 (95% CI: 0.27, 0.55) for depression and 0.21 (95% CI: 0.13, 0.29) for anxiety. In contrast, depression decreased after a successful treatment, SMD of -0.24 (95% CI: -0.37,-0.11). Both depression and anxiety decreased as time passed from ART procedure. Nonetheless, these remained higher than baseline measures in the group with the failed outcome even six months after the procedure. Studies included in the narrative synthesis also confirmed an association with negative psychological outcomes in relation to marital satisfaction and general well-being following treatment failure. Linking ART failure and psychosocial outcomes may elucidate the experience of treatment subgroups, influence deliberations around recommendations for resource allocation and health policy and guide patient and clinician decision making.
El Tokhy O et al., 2016·Women's Health·
Open Access
Ovarian hyperstimulation syndrome is a potentially life-threatening, but preventable iatrogenic complication of in vitro fertilisation treatment. In recent years, new strategies have been developed to minimise the risk of ovarian hyperstimulation syndrome after in vitro fertilisation, including better at-risk patient identification prior to starting treatment, the use of a lower human chorionic gonadotrophin dose or alternative medication instead of human chorionic gonadotrophin to induce final oocyte maturation such as gonadotrophin-releasing hormone agonist and kisspeptin in antagonist cycles, cryopreservation of all embryos and delayed embryo transfer, and the use of oral dopamine agonists after oocyte retrieval. In this article, the advantages and limitations of those new developments are discussed and future directions towards establishment of an ovarian hyperstimulation syndrome–free in vitro fertilisation clinic are explored.
American College of Obstetricians and Gynecologists, 2016·Obstetrics and Gynecology
Over the past decades, the use of assisted reproductive technology (ART) has increased dramatically worldwide and has made pregnancy possible for many infertile couples. Although the perinatal risks that may be associated with ART and ovulation induction are much higher in multifetal gestations, even singletons achieved with ART and ovulation induction may be at higher risk than singletons from naturally occurring pregnancies. However, it remains unclear to what extent these associations might be related to the underlying cause(s) of infertility. Before initiating ART or ovulation induction procedures, obstetrician-gynecologists and other health care providers should complete a thorough medical evaluation to ensure that patients are in good health and should counsel these women about the risks associated with treatment. Any maternal health problems or inherited conditions should be addressed. Couples at risk of passing genetic conditions on to their offspring, including those due to infertility-associated conditions, should be counseled appropriately. When a higher-order (triplet or more) multifetal pregnancy is encountered, the option of multifetal reduction should be discussed. In the case of a continuing higher-order multifetal pregnancy, ongoing obstetric care should be with an obstetrician-gynecologist or other obstetric care provider and at a facility capable of managing anticipated risks and outcomes.
Traditionally, IVF success rates have been reported in terms of live birth per fresh cycle or embryo transfer. With the increasing use of embryo freezing and thawing it is essential that we report not only outcomes following fresh but also those after frozen embryo transfer as a complete measure of success of an IVF treatment. Most people agree that an individual's chance of having a baby following fresh and frozen embryo transfer should be described as cumulative live birth rate. However, views on the most appropriate parameters required to calculate such an outcome have been inconsistent. There is an additional dimension - time for all frozen embryos to be used up by a couple, which can influence the outcome. Given that cumulative live birth rate is generally perceived to be the preferred reporting system in IVF, it is time to have an international consensus on how this statistic is calculated, reported and interpreted by stakeholders across the world.
Vettori D et al., 2015·Journal of Neonatal-Perinatal Medicine
Aplasia cutis congenita (ACC) is rare skin disorder of newborns that has been linked to both assisted reproductive technology (ART) and feto-reduction procedures. ACC is characterized by well-demarcated lesions that are devoid of all skin layers. Group-V ACC presents with a distinctive and symmetrical distribution pattern. It is thought to result from an insult to the fetus after concomitant twin demise and is almost exclusively reported in monochorionic gestations.A 41-year-old female with an in vitro fertilization (IVF) assisted tri-chorionic gestation subsequently underwent selective feto-reduction of Fetus C. The patient delivered two pre-term neonates secondary to pre-eclampsia. The initial exam of Twin B showed extensive, well-demarcated, symmetrical areas devoid of any skin over the anterior and lateral trunk, extending up the lateral thoracic walls. Chest and abdominal viscera were visible through a thin fibrous membrane. The skin defects were managed conservatively with twice-daily dressings of Aquaphor, and Vaseline gauze. The areas of aplasia slowly contracted, though residual scarring was noted. After four weeks in the NICU, most of the areas were healed.ACC in multi-fetal pregnancies is a rare, but well-described complication. This is, to our knowledge, the first reported case in a tri-chorionic IVF gestation after feto-reduction. With increased incidence of ART-associated pregnancies and the use of feto-reduction for higher order gestations, this may become more common. Neonates often require specialized intensive care. Conservative management usually will suffice, although surgical grafting may be required. Physicians should be aware of this condition and counsel their feto-reduction patients of the risk.
To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL). Decision analytic model comparing costs and clinical outcomes. Academic recurrent pregnancy loss programs. PATIENT(S): Women with unexplained RPL. INTERVENTION(S): IVF/PGS with 24-chromosome screening and expectant management. MAIN OUTCOMES MEASURE(S): Cost per live birth. RESULT(S): The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing $45,300 per live birth compared with $418 per live birth with expectant management. CONCLUSION(S): In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management.
Reproductive Aging · Mechanisms of Reproductive Aging
Babayev E et al., 2015·Current opinion in obstetrics & gynecology·
Open Access
Mitochondria are cellular organelles that are required for energy production. Emerging evidence demonstrates their role in oocyte development and reproduction. In this review, we examine recent animal and clinical studies on the role of mitochondria in fertility. We also analyse the impact of assisted reproductive techniques (ARTs) on mitochondrial function and discuss the future clinical implications of mitochondrial nutrients and mitochondrial replacement. Mitochondria affect all aspects of mammalian reproduction. They are essential for optimal oocyte maturation, fertilization and embryonic development. Mitochondrial dysfunction causes a decrease in oocyte quality and interferes with embryonic development. ART procedures affect mitochondrial function, while mitochondrial nutrients may increase mitochondrial performance in oocytes. New mitochondrial replacement procedures using mitochondria obtained from polar bodies or from the patient's own oogonial stem cells are promising and may address concerns related to the induction of high-levels of heteroplasmy, which could potentially result in negative long-term health effects. Optimal energy production is required for oocyte and embryo development, and mitochondrial abnormalities have devastating reproductive consequences. Improvement of oocyte mitochondrial function via intake of compounds that boost mitochondrial activity may have clinical benefits, and mitochondrial replacement could potentially be used for the prevention of mitochondrial diseases.
Bentov Y et al., 2014·Clin Med�Insights�Reprod�Health·
Open Access
The age-related reduction in live-birth rate is attributed to a high rate of aneuploidy and follicle depletion. We showed in an animal model that treatment with Coenzyme Q10 (CoQ10) markedly improved reproductive outcome. The aim of this study was to compare the post-meiotic oocyte aneuploidy rate in in vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI) patients treated with CoQ10 or placebo.
We conducted a double blind placebo controlled randomized trial that included IVF-ICSI patients 35-43 years of age. The patients were treated with either 600 mg of CoQ10 or an equivalent number of placebo caps. We compared the post-meiotic aneuploidy rate using polar body biopsy (PBBX) and comparative genomic hybridization (CGH). According to the power calculation, 27 patients were needed for each arm.
Owing to safety concerns regarding the effects of polar body biopsy on embryo quality and implantation, the study was terminated before reaching the target number of participants. A total of 39 patients were evaluated and randomized (17 CoQ10, 22 placebo), 27 were given the study medication (12 CoQ10, 15 placebo), and 24 completed an IVF-ICSI cycle including PBBX and embryo transfer (10 CoQ10, 14 placebo). Average age, base line follicle stimulating hormone (FSH), peak estradiol and progesterone serum level, as well as the total number of human menopausal gonadotropin (hMG) units-did not differ between the groups. The rate of aneuploidy was 46.5% in the CoQ10 group compared to 62.8% in the control. Clinical pregnancy rate was 33% for the CoQ10 group and 26.7% for the control group.
No significant differences in outcome were detected between the CoQ10 and placebo groups. However, the final study was underpowered to detect a difference in the rate of aneuploidy.
The high costs of fertility care may deter couples from seeking care. Urologists often are asked about the costs of these treatments. To our knowledge previous studies have not addressed the direct out-of-pocket costs to couples. We characterized these expenses in patients seeking fertility care. Couples were prospectively recruited from 8 community and academic reproductive endocrinology clinics. Each participating couple completed face-to-face or telephone interviews and cost diaries at study enrollment, and 4, 10 and 18 months of care. We determined overall out-of-pocket costs, in addition to relationships between out-of-pocket costs and treatment type, clinical outcomes and socioeconomic characteristics on multivariate linear regression analysis. A total of 332 couples completed cost diaries and had data available on treatment and outcomes. Average age was 36.8 and 35.6 years in men and women, respectively. Of this cohort 19% received noncycle based therapy, 4% used ovulation induction medication only, 22% underwent intrauterine insemination and 55% underwent in vitro fertilization. The median overall out-of-pocket expense was $5,338 (IQR 1,197-19,840). Couples using medication only had the lowest median out-of-pocket expenses at $912 while those using in vitro fertilization had the highest at $19,234. After multivariate adjustment the out-of-pocket expense was not significantly associated with successful pregnancy. On multivariate analysis couples treated with in vitro fertilization spent an average of $15,435 more than those treated with intrauterine insemination. Couples spent about $6,955 for each additional in vitro fertilization cycle. These data provide real-world estimates of out-of-pocket costs, which can be used to help couples plan for expenses that they may incur with treatment.
Comment in Fertil Steril. 2014 Jan;101(1):47-8. doi: 10.1016/j.fertnstert.2013.09.043. To systematically quantify the impact of consumer cost on assisted reproduction technology (ART) utilization and numbers of embryos transferred. Ordinary least squared (OLS) regression models were constructed to measure the independent impact of ART affordability-measured as consumer cost relative to average disposable income-on ART utilization and embryo transfer practices. Not applicable. PATIENT(S): Women undergoing ART treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): OLS regression coefficient for ART affordability, which estimates the independent effect of consumer cost relative to income on utilization and number of embryos transferred. RESULT(S): ART affordability was independently and positively associated with ART utilization with a mean OLS coefficient of 0.032. This indicates that, on average, a decrease in the cost of a cycle of 1 percentage point of disposable income predicts a 3.2% increase in utilization. ART affordability was independently and negatively associated with the number of embryos transferred, indicating that a decrease in the cost of a cycle of 10 percentage points of disposable income predicts a 5.1% increase in single-embryo transfer cycles. CONCLUSION(S): The relative cost that consumers pay for ART treatment predicts the level of access and number of embryos transferred. Policies that affect ART funding should be informed by these findings to ensure equitable access to treatment and clinically responsible embryo transfer practices.
Fouany MR et al., 2013·Journal of assisted reproduction and genetics·
Open Access
Poor ovarian reserve and poor ovarian response presents a challenge to IVF centers. Dehydroepiandrosterone (DHEA) supplementation is increasingly being used by many IVF centers around the world in poor responders despite the lack of convincing data. We therefore examined the rationale for the use of DHEA in poor responders, address the relevant studies, present new data, and address its potential mechanisms of action. All published articles on the role of DHEA in infertile women from 1990 to April 2013 were reviewed. Several studies have suggested an improvement in pregnancy rates with the use of DHEA. Potential mechanisms include improved follicular steroidogenesis, increased IGF-1, acting as a pre-hormone for follicular testosterone, reducing aneuploidy, and increasing AMH and antral follicle count. While the role of DHEA is intriguing, evidence-based recommendations are lacking. While nearly 25 % of IVF programs use DHEA currently, large randomized prospective trials are sorely needed. Until (and if) such trials are conducted, DHEA may be of benefit in suitable, well informed, and consented women with diminished ovarian reserve.
Restorative Care and Assisted Reproduction · Outcome Comparisons
Dowbór-Dzwonka A et al., 2012·Zdr Publ·
Open Access
Infertility is a significant and constantly increasing individual and social problem. It is estimated that at present it affects approx. 15 to 20 percent of couples. Inability to conceive a child elicits a range of unfavourable implications in the scope of emotional experiences, in the partner’s relationship and in a broader social perspective. Making a decision on undergoing diagnostics and infertility treatment is a difficult and often postponed moment for many couples. This is an expression of the escape model of dealing with a situation that threatens with a fall of self-esteem. However, if a couple reacts in a task-oriented way and participates in the diagnostic and therapeutic procedure, new doubts appear connected with the medical, psychological, social and ethical sphere. Infertility treatment sometimes prompts fear connected with the stripping of intimacy, loss of control over one’s body, possible complications and unsuccessful therapy. This article is an analysis of the medical and the other aspects of struggling with infertility with reference to two extremely different methods of solving this NaProTechnology as a process of assisting natural procreation and assisted reproductive techniques with a special consideration of in vitro fertilization.
Reproductive Immunology · Autoimmune Conditions and Fertility
To investigate the impact of antithyroid antibody on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET). A total of 90 patients (156 cycles) positive for antithyroid antibody (ATA+ group) and 676 infertile women (1062 cycles) negative for antithyroid antibody (ATAgroup) undergoing IVF/ICSI from August 2009 to August 2010 were retrospectively analyzed. There was no significant difference in the days of ovarian stimulation, total gonadotropin dose, serum E2 level of HCG day and number of oocytes retrieved between the two groups. The fertilization rate, implantation rate and pregnancy rate following IVF-ET were significantly lower in women with antithyroid antibody than in control group (64.3% vs 74.6%, 17.8% vs 27.1% and 33.3% vs 46.7%, respectively), but the abortion rate was significantly higher in patients with antithyroid antibody (26.9% vs 11.8%). Patients with antithyroid antibody showed significantly lower fertilization rate, implantation rate and pregnancy rate and higher risk for abortion following IVF-ET when compared with those without antithyroid antibody. Thus, the presence of antithyroid antibody is detrimental for the pregnancy outcome following IVF-ET.
Boyle PC et al., 2011·Biomedicina (Sveikatos Mokslai/Health Sciences)·
Infertility is usually a consequence of multiple chronic conditions rather than a single acute condition. We propose that it is erroneous to apply acute medical interventions to a condition that is chronic in nature.
Retrospective analysis of 3 case studies which demonstrate the multifactorial and chronic nature of infertility that were previously managed unsuccessfully with acute intervention using IVF (in Vitro Fertilisation) or ART (Assisted Reproductive Technology).
Demonstration of the multifactorial approach and 3 successful singleton live births using NPT (Natural Procreative Technology or NaProTechnology). Infertility can be treated successfully with a multifactorial approach which takes into account the chronic nature of infertility and targets treatment to manage multiple factors responsible for the condition. Infertility is not a diagnosis but is often the expression of several underlying ill health conditions which if diagnosed and treated correctly will result in restoration of normal reproductive function. Physicians ought to consider broader diagnostic possibilities in their evaluation of infertile couples. A multifactorial treatment strategy for the chronic condition of infertility may be more effective than the widespread acute strategy employed by ART. Further study is required to investigate this possibility in more detail. Future studies looking at NPT and ART outcomes must be cohort studies comparing populations with similar patient characteristics.
To examine resource use (costs) by women presenting for infertility evaluation and treatment over 18 months, regardless of treatment pursued. Prospective cohort study in which women were followed for 18 months. eight infertility practices. 398 women recruited from infertility practices. Women completed interviews and questionnaires at baseline and after 4, 10, and 18 months of follow-up; medical records were abstracted after 18 months. per-person and per-successful-outcome costs. Treatment groups were defined as highest intensity treatment use. Twenty percent of women did not pursue cycle-based treatment; approximately half pursued IVF. Median per-person costs ranged from $1,182 for medications only to $24,373 and $38,015 for IVF and IVF-donor egg groups, respectively. Estimates of costs of successful outcomes (delivery or ongoing pregnancy by 18 months) were higher ($61,377 for IVF, for example), reflecting treatment success rates. Within the time frame of the study, costs were not significantly different for women whose outcomes were successful and women whose outcomes were not. Although individual patient costs vary, these cost estimates developed from actual patient treatment experiences may provide patients with realistic estimates to consider when initiating infertility treatment.
Infertility Distress · Anxiety and Depression in Infertility
To examine whether pretreatment emotional distress in women is associated with achievement of pregnancy after a cycle of assisted reproductive technology. Meta-analysis of prospective psychosocial studies. PubMed, Medline, Embase, PsycINFO, PsychNET, ISI Web of Knowledge, and ISI Web of Science were searched for articles published from 1985 to March 2010 (inclusive). We also undertook a hand search of reference lists and contacted 29 authors. Eligible studies were prospective studies reporting a test of the association between pretreatment emotional distress (anxiety or depression) and pregnancy in women undergoing a single cycle of assisted reproductive technology. Review methods Two authors independently assessed the studies for eligibility and quality (using criteria adapted from the Newcastle-Ottawa quality scale) and extracted data. Authors contributed additional data not included in original publication. Fourteen studies with 3583 infertile women undergoing a cycle of fertility treatment were included in the meta-analysis. The effect size used was the standardised mean difference (adjusted for small sample size) in pretreatment anxiety or depression (priority on anxiety where both measured) between women who achieved a pregnancy (defined as a positive pregnancy test, positive fetal heart scan, or live birth) and those who did not. Pretreatment emotional distress was not associated with treatment outcome after a cycle of assisted reproductive technology (standardised mean difference -0.04, 95% confidence interval -0.11 to 0.03 (fixed effects model); heterogeneity I2=14%, P=0.30). Subgroup analyses according to previous experience of assisted reproductive technology, composition of the not pregnant group, and timing of the emotional assessment were not significant. The effect size did not vary according to study quality, but a significant subgroup analysis on timing of the pregnancy test, a contour enhanced funnel plot, and Egger's test indicated the presence of moderate publication bias. The findings of this meta-analysis should reassure women and doctors that emotional distress caused by fertility problems or other life events co-occurring with treatment will not compromise the chance of becoming pregnant.
Reproductive Immunology · Autoimmune Conditions and Fertility
Pires ES et al., 2011·Journal of assisted reproduction and genetics·
Open Access
To establish importance of anti-ovarian antibodies (AOA) testing in infertile women. A clinical reproductive outcome comparative study between two groups of women undergoing IVF-ET. Group 1 consists of women tested positive for AOA, put on corticosteroid therapy, reverted to AOA negative and then taken up for IVF-ET. Group 2 were seronegative for AOA. Major urban infertility reference centre and National research institute. PATIENT(S): Five hundred seventy infertile women enrolled for IVF-ET. INTERVENTION(S): AOA testing, corticosteroid therapy and IVF-ET/ICSI. MAIN OUTCOME MEASURE(S): Comparable clinical outcome and significance of AOA testing established. AOA positive serum samples were sent periodically to re-investigate presence of AOA after corticosteroid therapy and women turned AOA negative were taken up for IVF-ET. Of the 70/138 women in group 1 who were treated with corticosteroids and turned seronegative for AOA, 22/70 were poor responders and needed donor oocyte-recipient cycles. Results demonstrated that fertilization and clinical pregnancy rates between both groups are comparable. Nevertheless, it is also observed that there is poor response to stimulation protocol, smaller number of oocytes retrieved and more spontaneous abortions in group 1 women. Hence not all outcomes following the treatment are comparable between the two groups. Usefulness of the test was established in two case studies. AOA testing could be included in the battery of tests investigating and treating infertility.
Gleicher N et al., 2010·Reproductive biology and endocrinology : RB&E·
Open Access
Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances in women with diminished ovarian reserve (DOR), and to reduce miscarriage rates by 50-80%. Such an effect is mathematically inconceivable without beneficial effects on embryo ploidy. This study, therefore, assesses effects of DHEA on embryo aneuploidy. In a 1:2, matched case control study 22 consecutive women with DOR, supplemented with DHEA, underwent preimplantation genetic screening (PGS) of embryos during in vitro fertilization (IVF) cycles. Each was matched by patient age and time period of IVF with two control IVF cycles without DHEA supplementation (n = 44). PGS was performed for chromosomes X, Y, 13, 16, 18, 21 and 22, and involved determination of numbers and percentages of aneuploid embryos. DHEA supplementation to a significant degree reduced number (P = 0.029) and percentages (P < 0.001) of aneuploid embryos, adjusted for relevant covariates. Short term supplementation (4-12 weeks) resulted in greatest reduction in aneuploidy (21.6%, 95% CI -2.871-46.031). Beneficial DHEA effects on DOR patients, at least partially, are the likely consequence of lower embryo aneuploidy. DHEA supplementation also deserves investigation in older fertile women, attempting to conceive, where a similar effect, potentially, could positively affect public health.
To characterize the demographic correlates of IVF availability and utilization.
Demographic analysis of public data.
Each of the 50 states in the United States was used as a unit of analysis. PATIENT(S): Patients undergoing IVF, as demographically estimated. INTERVENTION(S): Publicly available data were collected through the Society for Assisted Reproductive Technology and the Centers for Disease Control. The US Census Bureau data were collected by using software available from the Centers for Disease Control. MAIN OUTCOME MEASURE(S): The number of physicians performing IVF and the number of IVF cycles per 100,000 reproductive-age women were used to estimate IVF availability and utilization. RESULT(S): In 2005, 1,031 providers performed 98,242 fresh IVF cycles in 430 centers. Overall availability was 2.5 IVF physicians per 100,000, and utilization was 236 IVF cycles per 100,000. Availability and utilization of IVF were highly correlated. Mean IVF availability and utilization were significantly higher in states with IVF insurance coverage. In adjusted analyses, IVF availability correlated positively with mandated insurance coverage, percentage of single persons, and median income. Utilization of IVF correlated with IVF availability, percentage urbanization, and percentage of individuals >or=25 years of age who had a bachelor's degree. CONCLUSION(S): Lower rates of IVF utilization in some states are correlated with a lack of insurance coverage and decreased availability of physicians providing this service.
van Casteren NJ et al., 2008·Fertility and sterility
To assess the use rate and assisted reproductive technologies (ART) outcome of the cryopreserved semen of cancer patients with an average follow-up of 7 years (range, 2-23 years). Retrospective data analysis. University-affiliated andrology and reproduction center. Six hundred twenty-nine male cancer patients who were referred for semen cryopreservation between 1983 and 2004. Review of patient characteristics and ART outcome. Use rate and live births using cryopreserved semen. A total of 749 semen samples from 557 men were preserved. Ninety-one patients died during follow-up, and another 29 requested disposal. Forty-two patients requested the use of their banked semen. ART data were available for 37 patients. A total of 101 ART cycles (32 IVF, 53 intracytoplasmic sperm injection [ICSIs], nine cryo-ET, and seven intrauterine inseminations [IUIs]) were performed, resulting in, respectively, 8, 16, 2, and 1 pregnancies. Pregnancies rates for IVF and ICSI were significantly higher than those for IUI. So far, 7.5% of the cancer survivors have used their banked semen, which led to live births in 49% of the couples. Semen cryopreservation is a reliable method to preserve fertility potential and gives couples a reasonable chance of achieving parenthood.
An Act to amend the Human Fertilisation and Embryology Act 1990 and the Surrogacy Arrangements Act 1985; to make provision about the persons who in certain circumstances are to be treated in law as the parents of a child; and for connected purposes. The 2008 Act updated the regulatory framework established in 1990 to reflect scientific and social developments. Key changes included: explicit provision for human admixed embryos (cytoplasmic hybrids) for research purposes; recognition of same-sex couples as legal parents following licensed treatment; replacement of the previous 'need for a father' welfare clause with 'supportive parenting'; tightened consent and withdrawal-of-consent provisions following the Evans judgment; expanded scope of pre-implantation genetic testing including saviour-sibling testing; statutory regulation of mitochondrial replacement (later activated via 2015 regulations); and enhanced parental order provisions for surrogacy. The 2008 Act maintained the HFEA's role as licensing authority and registry steward but reorganised offence definitions and licence conditions.
To analyze IVF outcomes in patients with a history of one or more elevations in basal FSH who have a normal basal FSH at the start of their IVF cycle, compared with the general IVF population.
Retrospective clinical study.
University hospital. PATIENT(S): General IVF patient population. INTERVENTION(S): Patients received standard IVF gonadotropin protocols, oocyte retrieval, and embryo transfer. MAIN OUTCOME MEASURE(S): Oocyte yield, fertilization, implantation, clinical pregnancy, and cancellation rate. RESULT(S): Oocyte yields were lower in patients with a history of elevated basal FSH, for all age groups, and showed an age-dependent decline in all patients. Over the age of 40 years, both implantation and clinical pregnancy rates were lower in these patients, with no significant difference observed in patients under the age of 40 years. No pregnancies were observed in patients with a history of three or more elevated FSH levels, regardless of age. CONCLUSION(S): A history of elevated basal FSH levels in patients under the age of 40 years predicts a lower oocyte yield in IVF cycles with normal basal FSH levels but does not translate to either lower pregnancy or implantation rates. Patients aged >40 years with prior elevations in basal FSH levels have both compromised ovarian response and compromised embryo quality relative to those with normal FSH levels, as illustrated by lower oocyte yield, higher cancellation rates, and lower implantation and pregnancy rates.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY·
An economic analysis of NaProTECHNOLOGY compares the total treatment costs and cost-per-live-birth outcomes against assisted reproductive technologies, including IVF, drawing on outcome data from the Pope Paul VI Institute to demonstrate that NaPro's higher per-cycle success rates yield a favorable cost-effectiveness ratio despite comparable or lower upfront expenditures. Because NaProTECHNOLOGY identifies and corrects underlying pathology rather than bypassing it, its resource utilization model supports long-term gynecological health benefits that IVF cannot provide, making the economic case inseparable from the clinical one.
To investigate the effects of letrozole in patients undergoing superovulation with gonadotropins and IUI. Retrospective analysis. Academic teaching hospital. PATIENT(S): Women younger than 40 years of age with patent fallopian tubes and infertility of more than 1 year in duration who were undergoing IUI and gonadotropin therapy. INTERVENTION(S): Gonadotropins alone administered from day 3 or a combination of letrozole, 5 mg/d on day 3 to 7, and gonadotropins starting on day 5 of the menstrual cycle. Ultrasonography was performed before initiation of treatment, on day 9 of menstrual cycle, and as required thereafter until the dominant follicle reached 18 mm in diameter. Ovulation was triggered with 10,000 IU of hCG, and IUI was performed 24 and 48 hours later. MAIN OUTCOME MEASURE(S): Gonadotropin requirements, endometrial thickness, number of follicles, and pregnancy rate. RESULT(S): All 205 IUI treatment cycles conducted from March 2001 to March 2002 were included. Gonadotropins alone were used in 145 cycles and combination therapy was used in 60 cycles. Patients cotreated with letrozole required fewer gonadotropin administrations (median difference, 300 IU [95% confidence interval (CI), 225-375 IU]), developed more follicles larger than 14 mm (median difference, 1 follicle [95% CI, 1-2 follicles), and had a thinner endometrium (median difference, 1 mm [95% CI, 0.4-1.6 mm]). The pregnancy rate did not differ between patients using gonadotropin alone and those using gonadotropin plus letrozole (20.9% vs. 21.6%). CONCLUSION(S): The addition of letrozole to gonadotropins decreases gonadotropin requirements, increases the number of pre-ovulatory follicles and decreases endometrial thickness, without a negative effect on pregnancy rates.
To confirm that hCG levels in follicular fluid and serum would be comparable between i.m. and s.c. administration of purified hCG. In a prospective study, serum and follicular fluid levels of hCG after an i.m. or s.c. injection of 10,000 IU of hCG were evaluated 36 hours after injection, that is, at the time of oocyte retrieval. This study was carried out in a university-affiliated IVF program. PATIENT(S): Forty women undergoing oocyte retrieval were entered into the study at the time of egg retrieval, that is, 36 hours after hCG administration. INTERVENTION(S): S.c. or i.m. injection of hCG. MAIN OUTCOME MEASURE(S): Serum and follicular fluid concentrations of hCG were evaluated 36 hours after injection at the time of oocyte retrieval. RESULT(S): There was a significantly higher serum hCG level in the s.c. group (348.6 +/- 98 IU/L) vs. the i.m. group (259.0 +/- 115 IU/L) and a significantly higher follicular fluid hCG level in the s.c. vs. the i.m. group (233.5 +/- 85 vs. 143.4 +/- 134 IU/L). CONCLUSION(S): After purified hCG administration via the s.c. route, both serum and follicular fluid levels are greater compared with the i.m. route.
To review the use of hCG and to describe the clinical benefit of recombinant hCG (r-hCG) based on the published results of prospective, randomized studies. Review of published articles. Tertiary infertility care center.None.None. Oocyte number and quality, luteal phase progesterone, pregnancy and OHSS rate, and local tolerability. The published data consistently show that single doses of 250 microg r-hCG and 5,000 IU urinary (u)-hCG produce similar clinical outcomes when used in infertility treatment cycles for timed intercourse, IUI, and IVF in terms of the number of oocytes retrieved, number of mature oocytes harvested, and fertilization and pregnancy rates attained. Single doses of 10,000 IU u-hCG also gave results comparable to single doses of 250 microg r-hCG. P levels in the midluteal phase were significantly higher with the use of r-hCG compared with u-hCG, and local injection site adverse effects were significantly less frequent, demonstrating the higher purity of the recombinant product. A single 500-microg dose of r-hCG led to a higher rate of ovarian hyperstimulation syndrome compared with a 250-microg dose, with no significant improvement in pregnancy rates.A single dose of 250 microg r-hCG was at least as effective as single doses of 5,000 or 10,000 IU u-hCG but offered the advantages associated with use of a recombinant product: local injection site adverse effects were significantly less frequent with r-hCG than with u-hCG.
As a result of oocyte donation, women in their sixth decade of life are now able to conceive and carry pregnancies to term. However, little is known about pregnancy outcomes in this population. To describe pregnancy outcomes in women aged 50 years or older who conceived after in vitro fertilization with donor oocytes. Retrospective analysis of cycles conducted at a US university assisted reproduction program during calendar years 1991-2001. Seventy-seven postmenopausal women with no chronic medical conditions (mean [SD] age, 52.8 [2.9] years; range, 50-63 years) who underwent 121 embryo transfer procedures (89 fresh and 32 frozen). Pregnancy outcomes were ascertained by chart review and telephone follow-up. Maternal and neonatal outcomes. There were 55 clinical pregnancies for a total pregnancy rate of 45.5%. The live birth rate was 37.2%. Of the 45 live births, 31 were singletons, 12 were twins, and 2 were triplets, for which the mean (SD) gestational ages at delivery were 38.4 (2.1) weeks, 35.8 (2.8) weeks, and 32.2 weeks, respectively. Mean (SD) birth weights were 3039 g (703 g), 2254 g (581 g), and 1913 g, respectively. Apgar scores at 1 and 5 minutes were 8.2 (0.9) and 9.1 (0.5), respectively. Of singletons, 68% were delivered by cesarean, and all multiples were delivered by cesarean. Mild preeclampsia was noted in 25% of patients and severe preeclampsia in 10%. Gestational diabetes required diet modification in 17.5%, and 2.5% required insulin. Appropriately screened women aged 50 years or older can successfully conceive via oocyte donation and experience similar pregnancy rates, multiple gestation rates, and spontaneous abortion rates as younger recipients. During pregnancy, they appear at increased risk of preeclampsia and gestational diabetes. A majority can expect to deliver via cesarean. However, there does not appear to be any definitive medical reason for excluding these women from attempting pregnancy on the basis of age alone.
To evaluate the effect of an antifibrotic treatment by a combination of pentoxifylline (PTX) and tocopherol (vitamin E) in patients with a thin endometrium who were enrolled in an oocyte donation programme. Eighteen oocyte recipients who failed to develop a pre-ovulatory endometrial thickness of at least 6 mm after receiving vaginal micronized estradiol were enrolled in the study. The patients received a combination of PTX (800 mg/day) and vitamin E (1000 IU/day) for 6 months. The main outcome measurements were the change in endometrial thickness and the pregnancy and delivery rates after treatment. Endometrial thickness increased significantly (P <0.001), with a mean of (+/-SD) 4.9 +/-0.6 mm before and 6.2 +/- 1.4 mm after treatment, with 72% (13/18) of patients being good responders. Five patients either did not respond to the treatment or responded only slightly. Three patients, of which two had received previous radiotherapy, became spontaneously pregnant, and two became pregnant after embryo transfer. Three patients did not have embryo transfer. A total of four babies were delivered. The pregnancy rate was thus 33% and the delivery rate 27%. Treatment by combination of PTX and vitamin E appears to improve the pregnancy rate in patients with a thin endometrium by increasing the endometrial thickness and improving ovarian function. This was especially noticeable in patients who had previously received total body irradiation.
To examine the use of the aromatase inhibitor letrozole with FSH for ovarian stimulation in poor responders undergoing ovarian superovulation and IUI. Observational cohort study as a prospective clinical trial in patients with unexplained infertility and a low response to ovarian stimulation with FSH. Two tertiary referral infertility clinics associated with the Reproductive Sciences Division, University of Toronto. PATIENT(S): Twelve patients with unexplained infertility undergoing IUI who received FSH alone in 25 prior cycles with poor response (less than three dominant follicles). INTERVENTION(S): Patients were offered letrozole, 2.5 mg/day from day 3-7 of the menstrual cycle with FSH (50-225 IU/day) starting on day 5-7. hCG (10,000 IU) was given when two leading follicles were >/=2 cm followed by IUI. MAIN OUTCOME MEASURE(S): Number of mature follicles (>1.8 cm), FSH dose, endometrial thickness, and pregnancy rate. RESULT(S): Improved response to FSH stimulation with letrozole co-treatment was evidenced by the significantly lower FSH dose associated with significantly higher number of mature follicles. During letrozole plus FSH stimulation cycles, clinical pregnancy was achieved in three cycles (21%). CONCLUSION(S): In this preliminary report, we demonstrate a potential benefit of aromatase inhibition for improving ovarian response to FSH in poor responders.
To compare the efficacy of Crinone 8% intravaginal progesterone gel vs. IM progesterone for luteal phase and early pregnancy support after IVF-ET. Randomized, open-label study. Academic medical center. PATIENT(S): Two hundred and one women undergoing IVF-ET. INTERVENTION(S): Women were randomized to supplementation with Crinone 8% (90 mg once daily) or IM progesterone (50 mg once daily) beginning the day after oocyte retrieval. MAIN OUTCOME MEASURE(S): Pregnancy, embryo implantation, and live birth rates. RESULT(S): The women randomized to luteal phase supplementation with IM progesterone had significantly higher clinical pregnancy (48.5% vs. 30.4%; odds ratio [OR], 2.16; 95% confidence interval [CI], 1.21, 3.87), embryo implantation (24.1% vs. 17.5%; OR, 1.89; 95% CI, 1.08, 3.30), and live birth rates (39.4% vs. 24.5%; OR, 2.00; 95% CI, 1.10, 3.70) than women randomized to Crinone 8%. CONCLUSION(S): In women undergoing IVF-ET, once-a-day progesterone supplementation with Crinone 8%, beginning the day after oocyte retrieval, resulted in significantly lower embryo implantation, clinical pregnancy, and live birth rates compared with women supplemented with IM progesterone.
Assisted reproductive technologies (ART) pregnancy rates improve with the replacement of multiple embryos. The specific number of embryos to be transferred (typically between two and four) is based on a patient's age and past history and a morphologic assessment of embryo quality. Superovulation, with the goal of multifollicular recruitment and the harvest of multiple preovulatory oocytes, is therefore an integral aspect of in vitro fertilization and related techniques. Given the considerable interindividual variability in response to superovulation, the selection of an appropriate ovarian stimulation protocol is critical both for the safety and success of ART. Specific superovulation strategies have therefore been developed for treatment of abnormal response patients as well as for patients expected to manifest a "normal" response to ovulation inducing agents.
To evaluate the effect of supernumerary preovulatory follicular reduction as an approach to avoid multiple pregnancies in ovulation induction or superovulation cycles. Retrospective study. Tertiary referral center. PATIENT(S): In 26 cycles, 24 patients underwent ovulation induction or superovulation with either clomiphene citrate or hMG. INTERVENTION(S): Selective follicle aspiration was performed before hCG administration. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate and numbers of multiple pregnancies. RESULT(S): A mean number of 4.5 follicles with a diameter > or =15 mm and a mean number of 4.5 follicles with a diameter < or =14 mm were observed before hCG administration. A mean number of 2.3 follicles with a diameter > or =15 mm and a mean number of 1.8 follicles with a diameter < or =14 mm were aspirated before the hCG administration. Seven singleton pregnancies (26.9% per cycle) ensued from the treatment. CONCLUSION(S): Aspiration of supernumerary follicles after ovulation induction or superovulation seems to be a valid approach to avoid multiple pregnancies without affecting pregnancy rate.
To investigate whether uterine contractility at the time of embryo transfer (ET) can be reduced by early onset of luteal support with progesterone administered vaginally. Prospective analysis. Assisted reproduction unit. PATIENT(S): Eighty-four women undergoing 84 GnRH-a and FSH/hCG cycles for IVF-ET were studied. INTERVENTION(S): Vaginal progesterone was randomly started on the day of oocyte retrieval (group A, n = 43) or on the evening of ET (group B, n = 41). On the day of hCG administration and just before ET, 2-minute sagittal uterine scans were obtained by ultrasound and digitized with an image analysis system for assessing uterine contraction frequency. MAIN OUTCOME MEASURE(S): Uterine contraction frequency. RESULT(S): Whereas uterine contraction frequency was similar in both groups on the day of hCG (4.6 +/- 0.3 and 4.5 +/- 0.3 contractions per minute, respectively), only women in group A showed decreased uterine contraction frequency on the day of ET (2.8 +/- 0.2 vs. 4.2 +/- 0.3 contractions per minute). CONCLUSION(S): Vaginal progesterone administration starting on the day of oocyte retrieval induced a decrease in uterine contraction frequency on the day of ET as compared with preovulatory values. Uterine relaxation before ET is likely to improve IVF-ET outcome by avoiding the displacement of embryos from the uterine cavity.
To compare the incidence of pregnancy-induced hypertension in patients with and without polycystic ovary disease (PCOD). We conducted a retrospective, case-control analysis of patients who achieved singleton pregnancies with human menopausal gonadotropin (hMG) therapy. Twenty-two PCOD patients were compared to 27 infertility patients without PCOD who were pregnant after hMG therapy. Non-PCOD patients received hMG for superovulation as part of superovulation/intrauterine insemination or in vitro fertilization/embryo transfer. PCOD patients were receiving hMG for simple ovulation induction. Pregnancy-induced hypertension was defined as late pregnancy blood pressure > 140/90 mm Hg on two readings six hours apart and return to normal blood pressure by four to six weeks postpartum. There were no differences between PCOD and non-PCOD patients with reference to age, body mass index, parity or other pregnancy-induced hypertension risk factors (i.e., chronic hypertension, diabetes or chronic renal disease). Pregnant PCOD patients had a much higher incidence of pregnancy-induced hypertension, 31.8% (7/22), versus non-PCOD patients, who only had a pregnancy-induced hypertension incidence of 3.7% (1/27) (P = .016, OR = 12.1, 95% CI = 1.3-566.8). PCOD patients are at very high risk of pregnancy-induced hypertension when pregnant after ovulation induction.
A large part of infertility treatment involves the use of exogenous gonadotropins. The last decade has seen a progressive switch from human menopausal gonadotropin (hMG), the original gonadotropin product, to progressively more costly products, primarily or exclusively containing follicle-stimulating hormone (FSH). Though obviously at least in part driven by marketing efforts of pharmaceutical companies, this switch has received relatively little scrutiny despite its obvious cost implications. We therefore investigated whether a switch back to a generic or less costly hMG-driven ovulation induction protocol would affect patient outcome after ovulation induction and, by implications, with other assisted reproductive technologies. We prospectively studied clinical pregnancy rates in a large number of consecutive ovulation induction cycles in a well-defined patient population (group 1) which, after October of 1997, had been switched from a predominantly FSH to an hMG-driven protocol, based on an institutional formulary change. Until a transition period (between July and September 1997), this patient population had been on a primarily FSH-driven protocol (between July 1996 and June 1997). In parallel, we evaluated a second patient population (group 2), which was managed by the same physicians outside of formulary requirements and remained almost exclusively on principally FSH-driven ovulation induction cycles. FSHand hMG-driven ovulation induction protocols did not differ in pregnancy outcome during the prospective study period. Group 1 patients, however, demonstrated a significant increase in pregnancy rates after the switch from FSH to hMG stimulation had taken place (P = 0.02), while group 2 patients demonstrated no change in pregnancy rate during the same time period. Generic hMG products do not adversely affect pregnancy rates in comparison to more costly FSH products in routine ovulation induction cycles and should be considered an appropriate alternative to more expensive FSH products.
To assess the total costs of infertility coverage, determine the proportion of healthcare costs related to infertility, compare infertility costs to those of other diseases, and calculate a per member per month cost of an infertility benefit. Historical prospective analysis. A university-based, self-insured, fee-for-service healthcare plan. PATIENT(S): Healthcare policy members from January 1993 through December 1995. INTERVENTION(S): General and infertility-specific healthcare that included diagnostic tests for infertility, induction of ovulation, artificial insemination, donor gametes, in vitro fertilization, gamete intrafallopian transfer, zygote intrafallopian transfer, microsurgical epididymal sperm aspiration, embryo cryopreservation, and frozen embryo transfer. MAIN OUTCOME MEASURE(S): Healthcare costs, as calculated from the International Classification of Diseases, Volume 9 codes. RESULT(S): Total healthcare and infertility-specific costs of the university healthcare plan over a 3-year period were $86,445,642 and $680,921, respectively. Therefore, infertility accounted for 0.79% of the total university healthcare costs. The mean total and infertility-specific per member per month healthcare costs were $86.15 and $0.67, respectively. CONCLUSION(S): These data reveal that infertility costs account for only a small fraction of the total healthcare costs and can be attained at a nominal monthly fee.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
The objective of the present study was prospectively and randomly to evaluate the role of L-arginine in improving uterine and follicular Doppler flow and in improving ovarian response to gonadotrophin in poor responder women. A total of 34 patients undergoing assisted reproduction was divided in two groups according to different ovarian stimulation protocols: (i) flare-up gonadotrophin-releasing hormone analogue (GnRHa) plus elevated pure follicle stimulating hormone (pFSH) (n = 17); and (ii) flare-up GnRHa plus elevated pFSH plus oral L-arginine (n = 17). During the ovarian stimulation regimen, the patients were submitted to hormonal (oestradiol and growth hormone), ultrasonographic (follicular number and diameter, endometrial thickness) and Doppler (uterine and perifollicular arteries) evaluations. Furthermore, the plasma and follicular fluid concentrations of arginine, citrulline, nitrite/nitrate (NO2-/NO3-), and insulin-like growth factor-1 (IGF-1) were assayed. All 34 patients completed the study. In the L-arginine treated group a lower cancellation rate, an increased number of oocytes collected, and embryos transferred were observed. In the same group, increased plasma and follicular fluid concentrations of arginine, citrulline, NO2-/NO3-, and IGF-1 was observed. Significant Doppler flow improvement was obtained in the L-arginine supplemented group. Three pregnancies were registered in these patients. No pregnancies were observed in the other group. It was concluded that oral L-arginine supplementation in poor responder patients may improve ovarian response, endometrial receptivity and pregnancy rate.
Cancer and Fertility · Hormone Sensitive Cancer and Reproductive Care
To investigate a possible linkage between the use of fertility drugs for infertility and the risk of breast and ovarian cancers. Long-term, historic-prospective study. Fertility clinic in a university hospital. PATIENT(S): Files of 1,197 infertile women with a mean (+/- SD) follow-up of 17.9+/-5 years (21,407 person-years) were reviewed. Diagnoses, number of courses, and dosage of fertility drugs were extracted from the files. INTERVENTION(S): Cancers were identified by record linkage to the National Cancer Registry. Histopathologic reports and data on estrogen and progesterone receptors in breast cancer tissue were also reviewed. MAIN OUTCOME MEASURE(S): Standardized incidence ratio with 95% confidence interval (CI) were used for risk assessment. RESULT(S): Of 20 breast cancers (standardized incidence ratio, 1.40 [95% CI, 0.83-2.10]), 16 were detected among 780 women who had been exposed to 3,978 cycles of clomiphene citrate (CC) and/or hMG (standardized incidence ratio, 1.65 [95% CI, 0.94-2.68]). The standardized incidence ratio for this cancer was significantly increased only in patients with one or two CC treatments and a dose of < or =1,000 mg (2.6 [1.19-5.0] and 2.52 [1.21-4.64], respectively). Two cases of ovarian cancer (1 patient unexposed) were observed with no evidence of excessive risk. Six of the eight patients with data on estrogen and progesterone receptors were exposed to CC, and all tested positive for these receptors. CONCLUSION(S): An association between the use of fertility drugs and an increased risk of breast and ovarian cancers has not been confirmed.
Hull MG et al., 1999·Endocrinol Metab Clin North Am·
This article has provided outcome-based evidence using easily understood graphic representation of cumulative pregnancy rates whenever possible for the methods used to investigate and treat female infertility. A scheme of basic routine investigations in specialist practice is developed and clear guidance provided on the choice of treatment for each couple.
The birth of the McCaughey septuplets in Iowa in November 1997 brought issues of fertility assistance and their potential outcomes to worldwide attention. This Pergonal-stimulated multiple pregnancy ended successfully, but not without health hurdles and economic consequences for the new siblings and their family. This article reviews the general situation surrounding infertility services and, within the current debate of epidemiological, economic, legal and social issues, posits that managed care may be able to make greater strides than the present fee-for-service system in providing more accessible and comprehensive care to the 5.3 million US citizens at risk for infertility. Our conclusions suggest that managed care plans for infertility can aid in assuring quality and decreasing unnecessary costs. Managed care organizations should take the lead in providing infertile couples with an organized, humanistic approach that is mindful of the attending social issues. On May 5, 1997, a US District court in Chicago ruled that infertility fits the definition of a disability, and thus is subject to the antidiscrimination enforcement under the Americans with Disabilities Act.
To determine whether singleton IVF pregnancies carry adverse maternal or fetal outcome when compared with naturally conceived gestations. An analysis of the obstetric outcome of singleton IVF pregnancies in comparison with matched, naturally conceived singleton controls. In vitro fertilization unit and obstetric service at a tertiary medical center. PATIENT(S): Two hundred sixty consecutive singleton IVF pregnancies and 260 naturally conceived singleton controls matched 1:1 for maternal age, parity, ethnic origin, and location and date of delivery. INTERVENTION(S): In vitro fertilization-ET. MAIN OUTCOME MEASURE(S): The rate of antenatal obstetric complications, nonvertex presentation, cesarean section, preterm labor, low birth weight, small and very small for gestational age, neonatal intensive care unit admissions, and perinatal mortality. RESULT(S): The rates of most antenatal complications were similar in both groups. Urinary tract infection was the only complication diagnosed significantly more frequently after IVF (7.3% versus 1.2%); however, the rates of severe urinary tract infection necessitating hospitalization were similar. The incidence of nonvertex presentation was also similar. The cesarean section rate was significantly higher among IVF patients (41.9% versus 15.5%). The rates of preterm labor, low birth weight, small and very small for gestational age, neonatal intensive care unit admissions, and perinatal mortality were comparable. CONCLUSION(S): When controlling for maternal age, parity, ethnic origin, and location and date of delivery, singleton IVF pregnancies do not carry an increased risk for prematurity, low birth weight, or maternal or fetal complications. Still, these pregnancies are associated with a high rate of cesarean sections.
Two progesterone presentations, a vaginal application of 90 mg progesterone per day (Crinone) or 300 mg progesterone administered orally (Utrogestan), were compared for luteal phase support of patients undergoing an in-vitro fertilization (IVF) procedure. A total of 283 patients were randomly allocated to either treatment. The treatment started within 24 h after the embryo transfer procedure and continued until day 30 in cases of implantation. Efficacy was assessed using the pregnancy and delivery rates. Safety was assessed through specific symptoms and usual safety monitoring. The pregnancy rates per transfer were not significantly different in the Crinone and Utrogestan groups at days 12 (Crinone 35.3%, Utrogestan 29.9%, P = 0.55), 30 (Crinone 28.5%, Utrogestan 25.0%, P = 0.61) and 90 (Crinone 25.9%, Utrogestan 22.9%, P = 0.69). No differences in the spontaneous abortion rates were seen thereafter. The delivery rates (number of deliveries per patient; Crinone 23.0%, Utrogestan 22.2%, P = 1.00), as well as the ratio of newborn babies per embryo transferred (Crinone 11.7%, Utrogestan 11.1%, P = 0.91), were not significantly different. Safety parameters were similar in both groups, except for drowsiness, which was more significantly frequent in the oral progesterone group than in the Crinone group at all time points. No serious adverse events were recorded in this study. The fact that Crinone matches the efficacy of the larger doses of progesterone used orally reflects an advantage of the transvaginal route of administration which avoids the metabolic inactivation of progesterone during its first liver pass.
To evaluate the influence of female age on clomiphene citrate (CC) with IUI therapy and to compare the efficacy of this therapy between patients with ovulatory and anovulatory infertility. A university fertility clinic. Six hundred sixty-four CC with IUI cycles from 290 women aged 22 to 48 years. Cumulative and clinical pregnancy rates (PRs). Both cumulative and clinical PRs declined substantially in women > 35 years when compared with those < or = 35 years. In addition, no difference in these parameters was noted between patients with ovulatory and anovulatory infertility diagnoses. The vast majority of pregnancies occurred within the first four treatment cycles, irrespective of age or ovulatory versus anovulatory infertility diagnoses. The age-related decline in clinical PR is most rapid beginning at the age of 35 years. For any given age group, CC with IUI therapy has similar cumulative and clinical PRs for both ovulatory and anovulatory infertility diagnoses. This therapy usually should not extend beyond four cycles. Couples should be counseled about the dramatic fall in PRs occurring beyond the age of 35 years.
To assess the efficacy of IVP-ET in infertile women with the polycystic ovary syndrome (PCOS) and to provide a comprehensive review of contemporary therapeutic options and their complications as reflected in the current literature. Pertinent studies in medical literature identified through computerized bibliographic search and via manual review of relevant scientific publications. In vitro fertilization and ET is an effective therapy for PCOS patients who are refractory to ovulation induction in vivo or who have coexisting infertility factors. The use of GnRH agonist (GnRH-a) is associated with significant reductions in the incidence of pregnancy loss and may improve fertilization and cleavage rates. In the PCOS patient, the use of purified FSH preparations does not appear to improve pregnancy rates nor other clinical parameters when compared with hMG. Severe ovarian hyperstimulation syndrome (OHSS) is an important consideration when PCOS patients undergo superovulation protocols. Strategies for OHSS prevention include the use of intravenous albumin immediately after oocyte retrieval, triggering of ovulation with a GnRH-a, or withholding menotropin therapy for several days before hCG administration. Cryopreservation of all embryos for future transfer in an artificial cycle has also proven to be an effective alternative in PCOS patients at high risk for severe OHSS. Pregnancy rates for PCOS patients undergoing IVF-ET are comparable with those for women with tubal factor infertility. Therefore, IVF-ET should be offered to patients with PCOS who are refractory to conventional infertility modalities.
Cancer and Fertility · Hormone Sensitive Cancer and Reproductive Care
Concern has been expressed that exposure to fertility drugs might be associated with a risk of ovarian cancer. We have examined the incidence of breast and ovarian cancer in a cohort of 10,358 women referred for in-vitro fertilisation (IVF) treatment in Victoria, Australia, between 1978 and 1992. The "exposed" group (n = 5564) had had ovarian stimulation to induce multiple folliculogenesis and the "unexposed" group (n = 4794) had been referred for IVF but were untreated or had had "natural cycle" treatment without ovarian stimulation. Duration of follow-up ranged from 1 to 15 years. Cases of cancer were determined by record linkage with data from population-based cancer registries. 34 cases of invasive breast cancer and 6 of invasive ovarian cancer were observed. A comparison with the expected numbers, derived by applying age-standardised general population rates to the cohort gave standardised incidence ratios (SIR) for breast cancer of 0.89 (95% CI 0.55-1.46) in the exposed group and 0.98 (0.62-1.56) in the unexposed group, and for ovarian cancer SIRs were 1.70 (0.55-5.27) and 1.62 (0.52-5.02), respectively. Rates of all cancers were not significantly different from general population rates. The relative risk (RR) of cancer, adjusted for age and infertility type, was, in the treated group compared with the untreated group, 1.11 (95% CI 0.56-2.20) for breast cancer and 1.45 (0.28-7.55) for ovarian cancer. The risk of body of uterus cancer was increased in the exposed and unexposed groups combined (SIR 2.84 [1.18-6.81]). Women with unexplained infertility, independent of IVF exposure, had significantly increased risks of ovarian cancer (RR = 19.19 [2.23-165.0]) and body of uterus cancer (RR = 6.34 [1.06-38.0]) compared with women with known causes of infertility. This relatively short-term follow-up suggests that ovarian stimulation with IVF is not associated with an increased risk of breast cancer. Although there was no significantly increased risk of ovarian cancer after ovarian stimulation with IVF the small number of cases limits the conclusions that can be drawn. Longer-term follow-up of large cohorts of women who have been in IVF programmes will be necessary.
To determine whether the use of luteal phase support improves pregnancy rate (PR) in infertility. A meta-analysis of randomized trials of luteal phase support. Search of the National Library of Medicine MEDLINE data base from 1971 using the words luteal, pregnancy, human, and comparative. Bibliography of relevant articles, reviews, and abstracts of scientific meetings were hand searched. All randomized controlled trials of luteal phase support in infertility were included. Luteal phase support for recurrent abortion and nonrandomized trials were excluded. The common odds ratio was calculated for each intervention using the Mantel-Haentzel test. Homogeneity of treatment effect was evaluated using the Breslow-Day test. Pregnancy per cycle, rate of spontaneous abortion, and ovarian hyperstimulation syndrome rate. Eighteen trials met the above criteria. Human chorionic gonadotropin improved PRs in IVF when GnRH agonist (GnRH-a) was used (n = 151) and was superior to P (n = 352). Its benefit in all IVF cycles, however, was not established because of significant heterogeneity of treatment effect. Progesterone improved the PR in all IVF cycles (n = 457). No significant reduction in spontaneous abortion was noted with luteal support (n = 200). Ovarian hyperstimulation syndrome occurred in 5% of patients with hCG. Combination of data from trials of luteal support with other infertility therapies was not possible because of the differences in patient populations. The meta-analysis supports the routine use of hCG in IVF cycles using a GnRH-a. Progesterone was also beneficial for luteal phase support in IVF. For other infertility therapy, however, further research is needed to evaluate the role of luteal phase support.
An Act to make provision in connection with human embryos and any subsequent development of such embryos; to prohibit certain practices in connection with embryos and gametes; to establish a Human Fertilisation and Embryology Authority; to make provision about the persons who in certain circumstances are to be treated in law as the parents of a child; and to amend the Surrogacy Arrangements Act 1985. The 1990 Act established the HFEA as the UK's statutory regulator of fertility treatment and human embryo research. It introduced licensing requirements for any clinic offering in vitro fertilisation, donor insemination, embryo storage, or human embryo research. The Act created criminal offences for unlicensed activity and prohibited certain practices including placing a non-human embryo in a woman, keeping or using an embryo after the appearance of the primitive streak (interpreted as 14 days post-fertilisation), and replacing an embryo's nucleus. The HFEA was empowered to keep a register of identifying information about donors, recipients, and people born from licensed treatments, and to issue a Code of Practice. Sections 13 and 14 set out treatment licence conditions including welfare-of-the-child considerations and consent requirements.
It has been reported that the pregnancy rate after in vitro fertilization (IVF) after pituitary desensitization with luteinizing hormone-releasing hormone agonist (LH-RH-a) is twice as low if the luteal phase is not supported. We therefore tested the respective advantages of luteal support using human chorionic gonadotropin (hCG, 1,500 IU three times) and progesterone (P, micronized, oral administration, 400 mg/d) after 171 embryo transfers (ET) in which the cycle was stimulated with the LH-RH-a triptoreline. The type of luteal phase support was randomly selected except when the estradiol level exceeded 2,700 pg/mL. The clinical pregnancy rate and the ongoing pregnancy rate were significantly higher using hCG (after the transfer of 3 embryos, 45% and 43% with hCG versus 23% and 17% with P). The same results were noted for the embryo implantation rate per ET (19% of embryos are viable after 6 months of pregnancy after hCG versus 7.5% after P). Adequate luteal support, therefore, significantly improves the results of IVF when LH-RH-a are used. The poor results obtained with P in this study might be related to its poor bioavailability after oral administration.
Selective fetal reduction was performed in the first trimester of pregnancy in 20 women with multifetal gestations after ovulation induction with human menopausal gonadotropin (hMG). In 10 women (group A) reduction was performed transabdominally, and in 10 women (group B) the transvaginal approach was used. The transvaginal technique achieved penetration of several gestational sacs without withdrawing the needle from the uterus. Fetal termination using either procedure occurred with intrafetal injection of potassium chloride. Six (60%, group A) and eight (80%, group B) patients delivered healthy newborns. One patient (group B) is at 30 weeks' gestation. Four (40%, group A) and one (10%, group B) aborted 1 day to 8 weeks after the procedure (1 septic abortion, each group). Our results suggest that transvaginal fetal reduction offers a better outcome, with minimal complications, to patients referred for selective continuation of pregnancy.
We studied 500 women who conceived after investigation and treatment for different infertility problems and compared the outcome of the 5 infertility groups (Group 1 to 5), the ovulatory dysfunction (Group 1), male infertility (Group 2), A.I.D. (Group 3), tubal surgery and IVF (Group 4) and no treatment (Group 5) with the outcome in the hospital group during a period of 3 years. The incidence of abortion in Group 3 is significantly higher (13.8%), the incidence of ectopic pregnancy is significantly higher in Group 4 (21.7%) as compared with the incidence in the hospital group (P less than 0.01). The rate of pre-existing hypertension and gestational diabetes is significantly higher in all the 5 infertility groups as compared with the incidence in the hospital group (P less than 0.05). The incidence of preterm labor in general is less in the infertility group as compared with the incidence in the hospital group (P greater than 0.05). The incidence of older women, multiple pregnancy, induction of labor, operative deliveries, fetal distress, low Apgar score, babies with birth weight below the tenth centile were higher in the infertility groups (P less than 0.05). But the perinatal mortality or major or minor fetal anomalies were not significantly different in the infertility groups as compared with the rate in the hospital groups (P greater than 0.05).
In a consecutive series of 167 patients reaching the stage of embryo transfer after in vitro fertilization and embryo transfer, 19 clinical pregnancies ensued. The serum progesterone (P) levels were significantly greater on the first and second (P less than 0.01) and third (P less than 0.05) postaspiration days for those who conceived. Higher circulating levels of P were achieved on days 1, 2, and 3 (P less than 0.05) by the daily injection of P, 50 mg in oil, given for 5 consecutive days, beginning immediately after follicle aspiration. Both pregnancy and nonpregnancy cycles demonstrated high circulating P levels, but the study implies that relatively higher levels are required for conception, and such levels can be achieved by the use of intramuscular P.
Yovich JL et al., 1984·Aust N Z J Obstet Gynaecol·
Luteal phase lengths and hormonal profiles (progesterone, oestradiol-17 beta, beta HCG and prolactin) have been documented in 77 cases derived from a series of patients undergoing IVF. Nineteen pregnancies were generated during this series and 12 healthy infants have already been delivered. Luteal phase lengths were 14.5 +/- 0.5 days with 14.3% demonstrating mid-luteal progesterone levels of less than 31 nmols/l, considered to be low for successful conception. A random study of luteal support regimens comparing HCG or medroxyprogesterone acetate (MPA) with nil therapy was studied in a series of 44 consecutive embryo transfers during which 10 pregnancies were achieved. No difference was noted in the pregnancy rates for the 3 groups but the pregnancy outcome was better in those who had HCG support and this was more apparent in the overall series of 19 pregnancies. A significant luteotrophic effect was noted with HCG support regimens whilst MPA appeared to have a luteal suppressant action. Six pregnancies which aborted with blighted ova were derived from cycles in which the luteal phase progesterone levels were low raising the possibility that a poor hormonal environment may predispose to blighted ova.
The experience of the gynecologic endocrinology and infertility clinic at The Johns Hopkins Hospital has been subjected to a nonconcurrent prospective analysis in an attempt to evaluate the gestational fate of clomiphene-related conceptions (study series, n = 86). This latter series was contrasted with a series of pregnancies following bilateral ovarian wedge resection (BOWR) (n = 51) in a comparative analysis of gestational outcome event rates. Post-therapy follow-up was available for varying time spans of up to 15 years. A 12.8% twinning rate constituted the single most important complication of clomiphene therapy, resulting in measurable increments in perinatal morbidity and mortality rates. The observation of a 26.5% spontaneous abortion rate would seem to suggest that clomiphene-related conceptions are at little or more risk for spontaneous abortion than would have been expected from the infertile population under discussion. A 3.1% incidence of post-clomiphene birth defects was not increased as compared with commonly quoted rates for the population at large. The corresponding incidence rates of twinning, spontaneous abortion, and birth defects for the BOWR series were 0%, 21.6%, and 0%, respectively.