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Romualdi D et al., 2023 Hum Reprod
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).
Duffy JMN et al., 2020 Human Reproduction
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.
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.
Sanghera S et al., 2016 BMJ open Open Access
Conduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and 'no treatment' to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation. We developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported. On average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required. There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis.
Maheshwari A et al., 2015 Human Reproduction
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.
Lazaraviciute G et al., 2014 Hum Reprod Update
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.
Kamphuis EI et al., 2014 BMJ
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.
Whitelaw N et al., 2014 Human reproduction (Oxford, England)
Is DNA methylation in buccal cell DNA from children born following IVF (in vitro fertilization) and ICSI (intra-cytoplasmic sperm injection) different from that of spontaneously conceived children? DNA methylation in the imprinted gene, small nuclear ribonucleoprotein polypeptide N (SNRPN), was higher in children conceived by ICSI and in those born to women with the longest duration of infertility regardless of the method of conception. Fertility treatment is associated with a small but significant increase in the risk of a range of adverse obstetric outcomes, birth defects and longer term sequelae, but the biological basis for this is unknown. A growing evidence base suggests that epigenetics may play a role in subfertility and the link between fertility and health. In this retrospective cohort study of children born between 2002 and 2008, we measured DNA methylation in paternally expressed gene 3 (PEG3), insulin-like growth factor II (IGF2), SNRPN, long interspersed nuclear element 1 (LINE1) and the insulin gene (INS) in buccal cell DNA from children born following IVF (n = 49) and ICSI (n = 20) and compared them with a matched spontaneous conception group (n = 86). Participants were identified from the Aberdeen Maternity and Neonatal Databank and IVF and ICSI pregnancies were matched to spontaneous conception pregnancies on year of birth and maternal age at delivery. Only singleton pregnancies following fresh embryo transfer were included. DNA methylation was determined by pyrosequencing. Regression with adjustment for covariates was used to determine the effect of infertility on offspring DNA methylation. SNRPN methylation in the offspring was linked to fertility treatment in the parents. This effect was specific to children conceived using ICSI and was apparent in the comparison of ICSI versus spontaneous conception (1.03%; 95% CI 0.10, 1.97; P = 0.031), ICSI versus standard IVF (1.13%; 95% CI 0.04, 2.23; P = 0.043) and ICSI versus standard IVF and spontaneous conception (1.05; 95% CI 0.15, 1.94; P = 0.023). In all comparisons, the use of ICSI was associated with a higher level of SNRPN methylation in the offspring. A higher level of SNRPN methylation in the offspring was also associated with a longer duration of infertility in the parents. This was observed in all cases of infertility (0.18% per year of infertility; 95% CI 0.02, 0.33; P = 0.026) and after excluding ICSI cases (0.21% per year of infertility; 95% CI 0.04, 0.37; P = 0.017). There was a significant increase in the level of LINE1 methylation with age between birth and 7 years (0.77% per year; 95% CI 0.49, 1.05; P < 0.001). Methylation in the INS gene decreased significantly over the same period (-0.46% per year; 95% CI -0.89, -0.03; P = 0.035). There was no evidence from this cross-sectional data that methylation within the imprinted genes changed over the first 7 years of life. The ICSI sample size was limited but the groups were carefully selected and well matched and the SNRPN findings were consistent across different outcomes. The results of this study provide support for a role for epigenetics, and imprinting in particular, in fertility. The specific changes point to possible long-term consequences of fertility treatment for the health and fertility of future generations. The authors report no conflict of interest in relation to this work. Funding was provided by the University of Aberdeen and the Scottish Government. Not applicable.
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.
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.
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.
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.
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.
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.