Abstract
Objective
How do numbers of oocytes retrieved per In vitro fertilisation (IVF) cycle impact on the live birth rate (LBR) and multiple gestation pregnancy (MGP) rates?
Design
Retrospective observational longitudinal study.
Setting
UK IVF clinics.
Population
Non-donor IVF patients.
Main Outcome Measures
LBR per IVF cycle and MGP levels against number of oocytes retrieved into subgroups: 0, 1-5, 6-15, 16-25, 26-49 oocytes and 50+ oocytes. Relative risk (RR) and 95% CIs were calculated for each group against the intermediate responder with '6-15 oocytes collected'.
Results
From 172 341 attempted fresh oocyte retrieval cycles, the oocyte retrieved was: 0 in 10 148 (5.9%) cycles from 9439 patients; 1-5 oocytes in 42 574 cycles (24.7%); 6-15 oocytes in 91 797 cycles (53.3%); 16-25 oocytes in 23 794 cycles (13.8%); 26-49 oocytes in 3970 cycles (2.3%); >=50 oocytes in 58 cycles (0.033%). The LBRs for the 1-5, 6-15, 16-25 and 26-49 subgroups of oocytes retrieved were 17.2%, 32.4%, 35.3% and 18.7%, respectively. The RR (95% CI) of live birth in comparison to the intermediate group (6-15) for 1-5, 16-25 and 26-49 groups was 0.53 (0.52 to 0.54), 1.09 (1.07 to 1.11) and 0.58 (0.54 to 0.62), respectively. The corresponding MGP rates and RR were 9.2%, 11.0%, 11.4% and 11.3%, respectively and 0.83 (0.77 to 0.90), 1.04 (0.97 to 1.11) and 1.03 (0.84 to 1.26), respectively.
Conclusion
There was only limited benefit in LBR beyond the 6-15 oocyte group going to the 16-25 oocytes group, after which there was significant decline in LBR. The MGP risk was lower in 1-5 group.
By this author
Evidence Synthesis · Systematic Reviews
The definition of unexplained infertility: A systematic review
Raperport C et al., 2024 · BJOG : an international journal of obstetrics and gynaecology · Free to read
There is no consensus on tests required to either diagnose unexplained infertility or use for research inclusion criteria. This leads to heterogeneity and bias affecting meta-analysis and best practice advice. This systematic review analyses the variability of inclusion criteria applied to couples with unexplained infertility. We propose standardised criteria for use both in future research studies and clinical diagnosis. CINAHL and MEDLINE online databases were searched up to November 2022 for all published studies recruiting couples with unexplained infertility, available in full text in the English language. Data were collected in an Excel spreadsheet. Results were analysed per category and methodology or reference range. Of 375 relevant studies, only 258 defined their inclusion criteria. The most commonly applied inclusion criteria were semen analysis, tubal patency and assessment of ovulation in 220 (85%), 232 (90%), 205 (79.5%) respectively. Only 87/220 (39.5%) studies reporting semen analysis used the World Health Organization (WHO) limits. Tubal patency was accepted if bilateral in 145/232 (62.5%) and if unilateral in 24/232 (10.3%). Ovulation was assessed using mid-luteal serum progesterone in 115/205 (56.1%) and by a history of regular cycles in 87/205 (42.4%). Other criteria, including uterine cavity assessment and hormone profile, were applied in less than 50% of included studies. This review highlights the heterogeneity among studied populations with unexplained infertility. Development and application of internationally accepted criteria will improve the quality of research and future clinical care.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Evidence-based guideline: unexplained infertility
Romualdi D et al., 2023 · Hum Reprod · Free full text on PubMed Central
Guideline Group on Unexplained Infertility; Romualdi D(1), Ata B(2)(3), Bhattacharya S(4), Bosch E(5), Costello M(6)(7), Gersak K(8), Homburg R(9), Mincheva M(10), Norman RJ(7)(11), Piltonen T(12), Dos Santos-Ribeiro S(13), Scicluna D(14), Somers S(15), Sunkara SK(16), Verhoeve HR(17), Le Clef N(18).
Acquired Uterine Conditions · Cesarean Scar Defect
Definition and Criteria for Diagnosing Cesarean Scar Disorder
Klein Meuleman SJM et al., 2023 · JAMA Netw Open · Free full text on PubMed Central
Approximately 60% of women develop a uterine niche after a cesarean delivery (CD). A niche is associated with various gynecological symptoms including abnormal uterine bleeding, pain, and infertility, but there is little consensus in the literature on the distinction between the sonographic finding of a niche and the constellation of associated symptoms. To achieve consensus on defining the clinical condition that constitutes a symptomatic uterine niche and agree upon diagnostic criteria and uniform nomenclature for this condition. Design, Setting, and A consensus based modified electronic Delphi (eDelphi) study, with a predefined Rate of Agreement (RoA) of 70% or higher. Experts were selected according to their expertise with niche-related consultations, publications, and participation in expert groups and received online questionnaires between November 2021 and May 2022. Definition, nomenclature, symptoms, conditions to exclude, and diagnostic criteria of an illness caused by a symptomatic uterine niche. In total, 31 of the 60 invited experts (51.7%) participated, of whom the majority worked in university-affiliated hospitals (28 of 31 [90.3%]), specialized in benign gynecology (20 of 31 [64.5%]), and worked in Europe (24 of 31 [77.4%]). Three rounds were required to achieve consensus on all items. All participants underlined the relevance of a new term for a condition caused by a symptomatic niche and its differentiation from a sonographic finding only. Experts agreed to name this condition cesarean scar disorder, defined as a uterine niche in combination with at least 1 primary or 2 secondary symptoms (RoA, 77.8%). Defined primary symptoms were postmenstrual spotting, pain during uterine bleeding, technical issues with catheter insertion during embryo transfer, and secondary unexplained infertility combined with intrauterine fluid. Secondary symptoms were dyspareunia, abnormal vaginal discharge, chronic pelvic pain, avoiding sexual intercourse, odor associated with abnormal blood loss, secondary unexplained infertility, secondary infertility despite assisted reproductive technology, negative self-image, and discomfort during participation in leisure activities. Consensus was also achieved on certain criteria that should be met and conditions that should be excluded before making the diagnosis. Conclusions and Relevance: In this modified Delphi study, a panel of 31 international niche experts reached consensus for the constellation of symptoms secondary to a uterine niche and named it cesarean scar disorder.
Birth Outcomes · Maternal Morbidity
Prevalence and main outcomes of placenta accreta spectrum: a systematic review and meta-analysis
Jauniaux E et al., 2019 · American Journal of Obstetrics and Gynecology · Free to read
The objective of this study was to evaluate the prevalence of placenta accreta spectrum in general population studies and the main maternal outcomes at delivery. We searched PubMed, Google Scholar, clinicalTrials.gov, and MEDLINE between 1982 and 2018. Articles that provided data on the number of cases of placenta accreta spectrum per pregnancies, births, or deliveries in a defined population were used. STUDY APPRAISAL Study characteristics were evaluated by 2 independent reviewers who used a predesigned protocol. Primary outcomes were the prevalence of placenta accreta spectrum and clinical diagnostic data at birth; the pathologic criteria were used to confirm the diagnosis. Secondary outcomes included cases that required transfusion, incidence of peripartum hysterectomy, and maternal mortality rates. Heterogeneity between studies was analyzed with the Cochran's Q-test and the I2 statistics. Of the 98 full-text studies that were identified, 29 articles met the defined criteria and included 22 retrospective and 7 prospective studies comprising 7001 cases of placenta accreta spectrum of 5,719,992 births. Prevalence rates ranged from 0.01-1.1% with an overall pooled prevalence of 0.17% (95% confidence interval, 0.14-0.19). Only 10 studies provided detailed histopathologic data. The pool prevalence for the adherent vs the invasive grades was 0.5 (95% confidence interval, 0.3-0.36) and 0.3 (95% confidence interval, 0.2-0.4) per 1000 births, respectively. The pooled incidence for peripartum hysterectomy was 52.2% (95% confidence interval, 38.3-66.4; I2=99.8%) and 46.9% (95 % confidence interval, 34-59.9; I2=98.8%) for hemorrhage that required transfusion. The pooled estimate of maternal death was 0.05% (95% confidence interval, 0.06-0.69; I2=73%). We found large amounts of heterogeneity between studies for all parameters and further quantification was limited because of methodologic inconsistencies between studies with regards to clinical criteria that were used for the diagnosis of the condition at birth and the histopathologic confirmation of the diagnosis and differential diagnosis between adherent and invasive accreta placentation. This meta-analysis indicated wide variation between studies for the prevalence rate of placenta accreta spectrum and for the different grades of accreta placentation that highlighted the need for consistency in definitions that are used to describe placenta accreta spectrum at birth and in the reporting of this increasing common obstetric complication.
Related research
Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles
Sunkara SK et al., 2011 · Human Reproduction
The aim of this study was to explore the association between egg number and live birth following IVF treatment and identify the number of eggs that would optimize the IVF outcome. Anonymized data on all IVF cycles performed in the UK between April 1991 and June 2008 were obtained from the Human Fertilisation and Embryology Authority (HFEA). The main outcome measure was the live birth rate (LBR) per cycle. A predictive model for LBR was constructed taking into account the number of eggs retrieved, the age of the woman and the year of treatment. A total of 400 135 IVF cycles were analyzed. The median number of eggs retrieved per cycle was 9 [inter-quartile range (IQR) 6-13] and the median number of embryos created was 5 (IQR 3-8), with an overall LBR of 21.3% per fresh IVF cycle. There was a strong association between the number of eggs and LBR; LBR rose with an increasing number of eggs up to \~15, plateaued between 15 and 20 eggs and steadily declined beyond 20 eggs. For a woman aged 18-34 years having her first cycle of IVF treatment during 2006-2007, the predicted LBR for 5 eggs was 17.4%, increasing to 26.0% and 40.0% for 10 and 15 eggs, respectively. The corresponding values for women aged 35-37 years were 12.4, 19.4 and 30.6%; for women aged 38-39 years were 9.4, 15.1 and 24.4%; and for women aged 40 years and over were 5.9, 9.7 and 16.0%. The number of eggs in IVF is a robust surrogate outcome for clinical success. We have produced a nomogram, depicting the predicted LBR with the number of eggs in different female age groups, which could be used in clinical counselling of couples undergoing IVF treatment.
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles
Smith ADAC et al., 2015 · JAMA · Free full text on PubMed Central
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.
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
Cumulative live-birth rates after in vitro fertilization
Malizia BA et al., 2009 · N Engl J Med
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.
Procedures and Protocols · Ovarian Stimulation
Observational retrospective study of US national utilisation patterns and live birth rates for various ovarian stimulation protocols for in vitro fertilisation
Kushnir VA et al., 2018 · BMJ Open · Free full text on PubMed Central
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.
Gulam Bahadur, Kanna Jayaprakasan, Judith A F Huirne, Santanu Acharya, Paul Racich, Ali Ahmed, Anil Gudi, Abha Govind
G Bahadur, K Jayaprakasan, J Huirne, S Acharya, P Racich, A Ahmed, A Gudi, A Govind
PMID 36592998 36592998 DOI 10.1136/bmjopen-2022-064711 10.1136/bmjopen-2022-064711 Bahadur et al. 2023, Bahadur 2023