Lower Live Birth Rates Research Articles

P-705 Influence of ovulation induction strategy in oocyte meiotic maturation: hCG versus agonist

Abstract Study question What is the influence of the ovulation induction strategy on the meiotic status of collected oocytes? Summary answer Non-invasive imaging of meiotic spindles during ICSI showed that ovulation induction with a hCG improved meiotic maturation and subsequent blastocyst formation rate. What is known already Owing to the shorter half-life of GnRH, this strategy has gained attention by significantly reducing risk of ovarian hyperstimulation syndrome. Reduced exposure to LH often requires luteal support and has been associated with a lower live birth rate, a lower ongoing pregnancy rate (pregnancy beyond 12 weeks) and a higher rate of early miscarriage (less than 12 weeks) in fresh autologous cycles, nevertheless. Mid-cycle LH surge triggers molecular activity in follicle cells initiating resumption of meiosis I for competition of the first meiotic division and formation of a MII oocyte inferring competence for subsequent fertilization and further development. Study design, size, duration A retrospective observational study was carried in a cohort of 25 - > 36 years old women including 85 patients. Analysis was carried in two groups: 1: GnRHa trigger and 2: hCG trigger and later stratified for patient age. Participants/materials, setting, methods Women between 25 and > 36 years old, non PCOS, with an AMH > 1.2 ng/ml and stimulated under a short scheme GnRH-antagonist for downregulation, FSH and ovulation induction with GnRHa or hCG. Oocytes allocated to (intracytoplasmic sperm injection) ICSI treatment were cultured for 3-4 hours striped from cumulus cells 2 hours after retrieval and placed in G-MOPS PLUS in aglass bottom dish and with an Octax PolarAide system. Main results and the role of chance A spindle was present in 39.3% (218/554) of all morphologically mature (MII) oocytes alone. Group 1 (GnRHa trigger) and group 2 (hCG trigger) had 56% (309/554) and 44% (245/554) of oocytes at MII stage from which 38% (120/309) and 39% (96/245) showed spindles. A better meiotic maturation stage (scores 3, 4) at ICSI was found when ovulation induction was performed with hCG (group 2) (81% (98/120) versus 88% (85/96), p = 0,0031), nevertheless. Fertilization rate was no different between groups (60% and 58%, respectively), while significantly more blastocysts (at culture day 4 and 5) were generated from group 2 MII oocytes presenting a spindle and a good score (36% (35/98) versus 62% (53/85), p = 0.039). Good blastocyst quality (≥3BB) did not differ between groups. When stratifying for age, women between 25 – 30 presented no differences in presence or meiotic maturation (score 2, 3) in MII oocytes, while fertilization (42% versus 77%, p = 0.022) and blastocyst formation (32% versus 45%, p = 0.012) were better in group 2. Women between > 36 years old presented no differences in presence of meiotic maturation, however, fertilization (40% versus 54%, p = 0.042) and blastocyst formation (25% versus 57%, p = 0.007) were best in group 2. Limitations, reasons for caution Thorough multivariable analysis in a larger patient cohort is required to endorse these results, nevertheless. Wider implications of the findings Prediction of ovulation induction efficacy in different patient cohorts could help fine tuning cycle management. Trial registration number not applicable

P-748 Cesarean scar defect does not predict embryo transfer outcomes: A retrospective cohort study

Abstract Study question Is the presence of a cesarean scar defect associated with live birth outcomes at the time of embryo transfer? Summary answer The presence of a cesarean scar defect is not predictive of live birth rates at the time of embryo transfer. What is known already Cesarean delivery is associated with subsequent impaired fertility, with lower pregnancy and live birth rates and longer inter-pregnancy intervals, compared to patients who delivered vaginally. Studies exploring pregnancy rates after IVF and embryo transfer also suggest lower pregnancy rates among patients with prior cesarean delivery. A postulated mechanism by which a prior cesarean delivery may impact fertility is the cesarean scar defect, and prior studies have shown a possible association between a scar defect and suboptimal outcomes. Study design, size, duration We retrospectively identified a patient cohort based out of the Ottawa Fertility Centre in Ottawa, Ontario, Canada, between 2013 and 2019. Participants/materials, setting, methods This retrospective cohort study included 317 patients with a prior cesarean delivery. Embryo transfer outcomes compared between the two groups based on the finding of a cesarean scar defect. The primary outcome was live birth rate, secondary outcomes of positive hCG, clinical intrauterine pregnancy, miscarriage rate. We fit a multivariate log binomial regression model with a priori variables for the primary and secondary outcomes, adjusting for patient and cycle characteristics. Main results and the role of chance There was no statistically significant difference in live birth rate among patients with a cesarean scar defect compared to those without, 28.0% vs 29.5% respectively (adjusted RR 0.95, 95% CI 0.68-1.35). There was no statistically significant difference in any of the secondary outcomes. Area of the defect and subgroup analysis of fresh vs frozen embryo transfer did not demonstrate any difference. Secondary analysis of patients with retroverted uterus had significantly lower live birth rates compared to those with an anteverted uterus, 17.7% vs 32.4%, respectively (adjusted RR 0.56, 95% CI 0.34-0.91). Limitations, reasons for caution Although a multivariate log binomial model was used to adjust for clinically relevant confounders, there remains the possibility for residual confounding given the observational nature of our study. Wider implications of the findings The results of our study suggest that, after adjusting for patient and cycle characteristics, the presence of a cesarean scar defect may not impact live birth outcomes and secondary analysis of the impact of uterine retroversion requires more study. Trial registration number Not applicable

O-008 Low grade blastocysts result in healthy live births and should not be discarded

Abstract Study question Does transfer of low grade blastocysts results in acceptable live birth rates the birth of healthy babies? Summary answer While BC/CB/CC blastocysts have a reduced chance of live birth compared with AA/AB/BA/BB blastocysts, the absolute chances are still reasonable. What is known already Transfer of poorer quality embryos and blastocysts result in lower live birth rates, though to what extent is unclear, nor if there is an absolute threshold below which live births are very rare or even do not occur. Further, the developmental competence of the inner cell mass (ICM) or trophectoderm (TE) could at least theoretically impact the pregnancy and/or the health of the baby. Many clinics do not transfer or freeze poor quality embryos and blastocysts, and prefer to submit the patient to a further stimulation cycle. Study design, size, duration We performed a retrospective analysis of 10,978 couples undergoing singleton blastocyst transfers between 2009 and March 2020. We included all single blastocyst transfers for which there was complete data on blastocyst quality, singleton or twin births, birthweight and gestation at delivery, irrespective of blastocyst grading, female age, cause of infertility, ovarian response or endometrial thickness. We recorded live birth rates, birth weight and gestational age. Participants/materials, setting, methods Data from 14 clinics in 3 countries, 8 from China, 5 from New Zealand, and 1 from Australia were included in the final dataset. We compared the impact of blastocyst grading using multiple logistic regression. Blastocyst grading was based on the Gardner classification, in which the first letter denotes the grade of the inner cell mass (A is best), and the second letter the grade of the trophectoderm. Main results and the role of chance Overall, 10,978 single blastocyst cycles resulted in 4,261 live births (38.8%) (4195 singletons and 132 twins). Live birth rates were 47% after transfer of AA blastocysts (n = 2306); 42% after AB/BA (n = 2088); 33% after BC (n = 1973); 25% after CB (n = 715) and 14% after CC (n = 117). There were too few AC (n = 27) or CA (n = 12) blastocysts to include in the analysis. The odds of live birth for BC/CB/CC blastocysts compared with AA/AB/BA blastocysts, vary between 0.8 and 0.9. The live birth rate appears to be more dependent on ICM quality (C grade, n = 844, 23.2%) rather than TE quality (C grade, n = 2117, 32.1%), with the odds of live birth 0.43 and 0.57 respectively compared to A grade ICM or TE. The average birth weight (singleton only) was 3336.9+/-570.3 g (range 3323 to 3386 g), and the average gestation at delivery (singleton only) was 38+6+/-2.0 weeks (range 38+2 to 39+1). There was no significant difference for birth weight or gestational age at delivery between blastocysts of different grades. Limitations, reasons for caution This was a retrospective study. Grading was based on inner cell mass and trophectoderm and not on degree of expansion, or on day of transfer. It is likely that higher quality blastocysts were transferred first, in a fresh cycle, and poorer quality blastocysts frozen for later transfer. Wider implications of the findings The most important finding is that reasonable live birth rates are obtained in CC-blastocysts. We therefore advocate that CC-blastocysts should be replaced or frozen for later transfer. It is reassuring that there was no impact of blastocyst quality on birth weights or gestational age at the time of delivery. Trial registration number Not applicable

O-255 Clinical and laboratory factors associated with pregnancy outcomes in patients undergoing frozen euploid blastocyst transfer

Abstract Study question Which variables do have an impact on the pregnancy and live birth rates (LBR) when euploid frozen embryo transfers (FET) are performed? Summary answer Day of trophectoderm biopsy, Body Mass Index (BMI) and endometrial preparation protocol have an impact on pregnancy rate (PR) and LBR in FET cycles. What is known already Preimplantation genetic testing for aneuploidy (PGT-A) and morphological grading of embryos are the two main criteria to select a blastocyst from a pool of embryos, having the highest implantation potential. However, other clinical and laboratory variables might play a crucial role for a successful outcome when top quality euploid embryos are transferred in a FET cycle. It has been described that higher BMI increases the odds for miscarriage when compared with non-obese women. Study design, size, duration This analysis includes 1660 FET cycles with data from of pregnancy rates, miscarriage rate and LBR. Embryos were obtained from 2564 IVF/ICSI cycles of couples with primary or secondary infertility at ART Fertility Clinics UAE, from November 2016 to December 2020. Participants/materials, setting, methods A total of 1660 FET cycles with 2439 euploid blastocysts were included. FET cycles with mosaic or segmental aneuploid embryos were excluded. PGT-A was performed on trophectoderm cells, using Next Generation Sequencing (NGS). Biopsy was performed on day 5, 6 or 7 blastocysts. Endometrial preparation included ovulatory natural cycles (NC) and hormone replacement therapy (HRT) cycles, chosen according to physician’s discretion. Ethical approval was obtained from the Research Ethics Committee (REFA023b). Main results and the role of chance Patients’ characteristics are described as mean±SD (min-max): age: 33.5±5.43(19-47), AMH: 3.30±3.05ng/mL(0.01-23.00), BMI: 27.1±4.87Kg/m2(13.1-43.90), mean number of blastocysts transferred: 1.4±0.49(1-3). Patients were categorized according to age (years) in 4 categories (<30,n=404; 30-34,n=487; 35-40,n=595; >40,n=174) and no association with pregnancy rate (PR, p = 0.856), biochemical miscarriage rate (BMR, p = 0.940), clinical miscarriage rate (CMR, p = 0.06) nor LBR (p = 0.154) was found. BMI (kg/m2) was divided into four groups according to World Health Organization: underweight (<18.5;n=32), normal weight (18.5–24.9;n=555), overweight (25–29.9;n=622), and obese (≥30;n=426). Although no differences were seen for PR or BMR between groups (p = 0.507 and p = 0.343, respectively), CMR was significantly lower for normal BMI group (p < 0.001) and LBR significantly higher when compared to the overweight and obese group (<18.5kg/m2=68.42%; 18.5–24.9kg/m2=68.35%; 25–29.9kg/m2=60.14%; ≥30kg/m2=53.29%; p < 0.001). No differences were observed on the outcomes when AMH was sub-divided as per Bologna Criteria (<1.3ng/mL,n=327; ≥1.3ng/mL,n=1090). Regarding endometrial preparation, NC protocol showed significantly lower BMR and CMR (7.93% vs 12.27%,p=0.026; 8.44% vs 17.97%,p<0.001), and higher LBR (70.33% vs 55.06%,p<0.001) compared to HRT. Day of trophectoderm biopsy had a significant higher PR for day 5 (day 5=75.58% vs day 6=61.1% and day 7=23.81%, p < 0.0001), yet no differences were observed for BMR, CMR nor LBR. Limitations, reasons for caution Although the large number of FET included, performed in the same centre with same methodology, the retrospective study design is a limitation. We could not discard other hypothetical variables contributing to miscarriage such as KIR-HLA discrepancies, or other obstetric factors affecting late miscarriage and live birth. Wider implications of the findings Evaluating the factors associated with pregnancy outcomes should be considered prior to euploid frozen embryo transfer for personalized treatment approach and adequate blastocyst selection. Women with higher BMI should be aware of higher risk of miscarriage and lower LBR although an euploid blastocyst is transferred. Trial registration number not applicable

P-787 Factors associated with live birth rate (LBR) and multiple live birth rate (mLBR): UK vs France registries

Abstract Study question Do the associations between age, previous attempts, frozen and day-5 transfers relative to LBR and mLBR differ between national registries (UK vs France)? Summary answer Both registries agree age negatively correlates with LBR and mLBR; disagree on effects of frozen transfers, previous attempts and day-5 transfers on LBR and mLBR. What is known already Due to the high risks of multiple pregnancy, the focus of ART success was shifted from having a high number of live birth rate (LBR) to one full-term, healthy baby and a low multiple live birth rate (mLBR). Elective single embryo transfer (eSET) has been an effective strategy for reducing the risk of mLBR but in most guidelines, it is recommended for young patients (<35 years) only. There is extensive evidence from large-scale studies characterising how factors, seen in eSET policies, affect LBR. However, only a few studies focus on mLBR. Study design, size, duration A retrospective analysis of two national registry datasets, HFEA (UK) (N = 442042; 2014-2018) and ABM (France) (N = 305142; 2014-2018), evaluating how age (<35 yrs, 35-37 yrs, 38-40 yrs, >41 yrs), fresh/frozen embryo transfer (ET), previous attempts (0, 1, 2, 3, 4, 5 attempts), and embryo stage (day-5 or day-3 transfers) impact LBR and mLBR following eSET (control group) and multiple embryo transfer (MET) (treatment group). Participants/materials, setting, methods Statistical analyses of the datasets were conducted using adjusted two-sided odds ratios from chi-squared tests with 95% confidence intervals (α = 0.05) with Bonferroni correction. Main results and the role of chance Two registries agreed on the negative correlation between age and LBR (HFEA: eSET OR:1.00-0.79-0.73-0.57, p < 0.001; MET OR:1.00-0.85-0.74-0.55, p < 0.001; ABM: eSET OR:1.00-0.75-0.71-0.52, p < 0.001; MET OR:1.00-0.80-0.69-0.50, p < 0.001) and mLBR following MET (HFEA OR:1.00-0.79-0.70-0.71, p < 0.001; ABM OR:1.00-0.74-0.74-0.59, p < 0.001). mLBR following eSET remained constant with increasing age in both datasets (HFEA OR:1.00-0.91-0.92-1.34, NS; ABM OR:1.00-0.87-1.02-1.13, NS). LBR was significantly higher for fresh vs frozen eSET in both datasets (HFEA OR:1.36, p < 0.001; ABM OR:1.83, p < 0.001). However, HFEA showed no significant difference in LBR between fresh and frozen MET (OR:0.98, NS), whereas LBR in fresh MET was significantly higher in ABM (OR:1.28, p < 0.001). There was disagreement on fresh vs frozen ET mLBR (HFEA: eSET OR:1.10, NS; MET OR:0.97, NS; ABM: eSET OR:0.81, p < 0.05; MET OR:1.36, p < 0.001). Registry results differed regarding the impact of previous attempts on LBR and mLBR.Day-5 ETs had significantly higher LBR compared to day-3 (HFEA eSET OR:1.29, p < 0.001; MET OR:1.37, p < 0.001; ABM: eSET OR:1.50, p < 0.001; MET OR:1.35, p < 0.001). mLBR was significantly higher following day-5 MET (HFEA OR:1.59, p < 0.001; ABM OR:1.27, p < 0.001) but only significantly higher following eSET in the French registry (HFEA OR:0.64, NS; ABM OR:1.40, p < 0.01). Limitations, reasons for caution Limitations included selection bias due to the retrospective design of the study, as a result, the populations include predominantly caucasian, European populations. The conclusions drawn relate to the practices from particular countries, so it is important to evaluate multiple, more diverse datasets. Wider implications of the findings It is encouraging that both registries agreed on the effects of age, whilst remaining factors were not generalizable and require further assessment. This study demonstrated that even large, national registries contain inherent biases and policymakers should not draw policies based on one dataset, especially when prospective trial is not feasible. Trial registration number N/A

P-723 Lack of seasonal influence on fresh IVF/ICSI treatment outcomes. A population based nationwide registry study

Abstract Study question Is there a seasonal influence on fresh in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment outcomes? Summary answer Season does not seem to affect live birth rate, clinical pregnancy rate or miscarriage rate after fresh IVF/ICSI treatment. What is known already Seasonal variations in human natural conception and birth rates are well described. However, the impact of seasonal variation on IVF outcomes has not yet been clarified and conflicting reports have been published. Study design, size, duration Nationwide, register-based cohort study including all first time fresh IVF/ICSI treatments (n = 52 788) leading to oocyte pick up (OPU) in Sweden between 2009 and 2018. Participants/materials, setting, methods First time fresh IVF/ICSI cycles leading to OPU were identified in the National Quality Registry of Assisted Reproduction (Q-IVF). Data collected included patient characteristics, information about the treatment cycle and pregnancy outcome. The patients were divided into season subgroups based on the date for OPU. The primary outcomes of the study were live birth per OPU and per embryo transfer (ET), clinical pregnancy per ET and miscarriage per clinical pregnancy. Logistic regression was performed. Main results and the role of chance The impact of seasons on the outcome of first time fresh IVF/ICSI cycles leading to OPU was assessed. A statistically significant overall seasonal influence was seen on live birth rate per OPU in the unadjusted analysis (p =0.036), where cycles performed in summer showed lower live birth rate (OR 0.92, 95% CI 0.87-0.97, p =0.004) compared with the other seasons. After adjustment for relevant confounders the overall impact of seasons on live birth rate was no longer statistically significant (p =0.10). Although post-hoc analyses still showed lower live birth rate in summer compared with the other seasons (OR 0.93, 95% CI 0.88-0.99, p =0.019). The impact of seasons on clinical pregnancy rate, miscarriage rate and live birth rate was further assessed through the analysis of the first cycles where ET was performed. No overall statistically significant seasonal influence was seen on clinical pregnancy, miscarriage and live birth rates after adjustment for confounders. Limitations, reasons for caution Possible limitations are the retrospective design of the study and the lack of adjustment for other important confounders i.e. cause of infertility, not included in Q-IVF. Wider implications of the findings This large cohort study shows a lack of seasonal influence on live birth-, clinical pregnancy- and miscarriage rate after fresh IVF/ICSI treatment. In the clinical setting, season should not be taken into consideration when planning and performing fresh IVF/ICSI. Trial registration number non applicable

P-632 Evaluation of low AMH levels in young women

Abstract Study question The primary objective was to evaluate impact of a low AMH level on the live birth rate in a population of young women IVF/ICSI . Summary answer Low AMH level in young women in FIV/ICSI is not expected to have an impact on the live birth. What is known already AMH is an important criterion for defining ovarian reserve. The majority of studies have shown that the AMH level in the general population is not correlated with the chances of spontaneous pregnancy. The management remains a challenge and must be individualized taking into account the new quantitative and qualitative criteria to be defined (POSEIDON classification). Finally, we know that the pregnancy rate is correlated to the rate of euploid embryos, and that the rate is higher before 35 years of age. Study design, size, duration In this single-center retrospective study from January 2015 to December 2020, 1824 IVF/ICSI attempts were analyzed. We analyzed the live birth rate according to 2 categories of young women matched by AMH level. Participants/materials, setting, methods We analyzed the live birth rate according to 2 categories of young women managed in IVF/ICSI protocol. A first group was ≤30 years old and a second group was between 31 and 35 years old. Then, we matched each of these groups to an AMH level, AMH<1ng/mL and AMH ≥1ng/mL. We analyzed the live birth rate of 4 groups of young women. Main results and the role of chance 1824 IVF/ICSI attempts were analyzed in this study. We have 539 women under 30 years of age and 1285 women between 31 and 35 years of age. For women aged ≤30 years, the group with AMH<1ng/mL had a non-statistically significant live birth rate compared to those with AMH≥1ng/mL (31% vs 32.7% p = 1). For women aged 31-35 years, the group with AMH<1ng/mL, has a statistically significant lower live birth rate compared to those with AMH≥1ng/mL (14.5% vs 29.3% p = 0.001). Limitations, reasons for caution The main limitation of our study is the few number of patients. Wider implications of the findings This study tries to demonstrate that low AMH levels in young women do not predict a poor IVF/ICSI success rate. Conclusions should not be drawn too quickly for low AMH in this population. However, the threshold AMH level is still debated in the studies and should be further adjusted. Trial registration number not applicable

P-282 Blastocyst transfer in advanced maternal age: Single versus double embryo transfer

Abstract Study question Is there a role for elective single blastocyst transfer (eSBT) in advanced maternal age? Summary answer Double blastocyst transfer (DBT) versus eSBT resulted in higher live birth rates except for those undergoing their first cycle. What is known already Women with advanced maternal age are generally considered poorer prognosis patients with lower live birth rates compared to their younger counterparts. This often results in a higher likelihood of double embryo transfer in this group. This is not without risk as multiple pregnancy is associated with significant maternal and neonatal morbidity especially with advancing maternal age. In older women with blastocysts available for transfer, it is unclear who should be recommended double versus elective single transfer. The concept of the “good-prognosis” older woman remains elusive. Study design, size, duration This was a retrospective observational study looking at 511 IVF/ICSI cycles between January 2010 and January 2020. Treatment cycle details and clinical outcomes were entered prospectively into a dedicated clinic database. Data was retrieved and analysed using SPSS V25. Participants/materials, setting, methods The study was conducted in a large London IVF centre. Data was collected on women aged 40 or above undergoing an IVF/ICSI cycle with eSBT (Group 1, n = 79) or DBT (Group 2, n = 430). Women with more than three previous IVF attempts were excluded. eSBT was defined as a single blastocyst transfer with at least one further blastocyst available for cryopreservation. Subgroup analysis was performed for those undergoing their first cycle. Main results and the role of chance Data from 511 cycles was analysed. The mean age was 40.6±1.2years. The live birth rate was 27%. Group 1 was marginally younger (40.2±0.6 v 40.8±1.2, p < 0.005) and was more likely to be undergoing their first IVF cycle (84% v 68%, p = 0.003). Those in Group 1 had more eggs collected (13.6±7.3 v 11.3±5.5, p = 0.009), more zygotes (8.9±4.7 v 7.3±3.6) formed and more blastocysts frozen (3.4±2.6 v 1.1±1.7, p < 0005). More women in Group 1 had a top quality blastocyst (expansion of > 2 and inner cell mass and trophectoderm of AA, AB, BA or BB) transfer (91% v 71%, p < 0.005). After logistic regression controlling for maternal age, number of previous IVF cycles and blastocyst quality, Group 1 had a lower likelihood of livebirth (aOR 0.550, 95%CI 0.306-0.988) but with a significantly lower multiple pregnancy rate (0% v 24%, p = 0.024). Importantly, for those undergoing their first IVF cycle (n = 359), there was no difference in live birth rate in the two groups (aOR 0.617, 95%CI 0.329-1.156) after controlling for age and blastocyst quality but Group 2 had a higher multiple pregnancy rate (24% v 0%, p = 0.020). Limitations, reasons for caution This study is limited by its retrospective nature putting it at risk of information bias as it relied on accurate documentation of studied variables into the patient database. The study did not examine cumulative birth rates of fresh and subsequent frozen cycles in Group 1. Wider implications of the findings Women should have individualised counseling about number of blastocysts to transfer taking into account their circumstances. Those undergoing their first IVF attempt and with a blastocyst available for transfer, should be counselled that DBT is associated with a higher multiple pregnancy rate with no increase in overall live birth rate. Trial registration number Not Applicable

P-638 Racial Disparity of Anti Mullerian Hormone (AMH) & Antral Follicle Count (AFC) among the subfertile women: A Systematic Review and Meta-analysis

Abstract Study question Do racial disparities exist in AMH & AFC among the subfertile women ? Summary answer An insignificant disparity was noted in AMH&AFC among different races.Standard Mean Difference of AMH was in favour of non-whites & AFC in favour of whites. What is known already Evidence exposes racial disparity exists in clinical medicine. An emerging body of literature suggests that reproductive potential and function differ across different racial groups.Racial disparities permeate at every level of fertility care from access, baseline evaluation, care provision and treatment outcomes.AMH & AFC are important predictors of successful reproductive outcomes and their disparity amongst different races may be associated with poor reproductive outcomes.Evidence shows that non-white women have significantly lower live birth rates after fertility treatments when compared to white women. Study design, size, duration An electronic literature search of MEDLINE,EMBASE,CINAHL,Google Scholar, Scopus, Web of Science databases, Cochrane Library was done up to December 2021. The search used a combination of keywords like AMH, AFC, Ovarian reserve markers, Ethnicity, Race, Caucasian, Black, Hispanic, Asian. A total of 1178 abstracts were screened which reported on AMH & AFC in different races, 127 publications of them were reviewed and 20 were included for meta-analyses after detailed scrutiny done independently by authors. Participants/materials, setting, methods Studies that reported on AMH&AFC in subfertile women of different races (Whites, Blacks, Asians and Hispanics) were included in the meta-analysis. Comparison of AMH&AFC among different races was the main outcome. AMH and AFC’s were reported as means ± SD, standard mean differences (SMD) with 95% CI. p < 0.005 was considered as significant. NIH risk assessment tool was used to assess bias. The statistical analysis was done in STATA and Rev Man 5.4. Main results and the role of chance The mean AMH (ng/dl) among Asians, Hispanics, Blacks and Whites were 3.03,2.65,2.64and2.51 respectively. The mean AFC among Hispanics, Blacks, Whites and Asians were 16.48,5.76,3.63and11.53 respectively. The Standard Mean Difference (SMD) of AMH was in favour of non-whites in comparison to whites (0.32,95%CI 0.08-0.56,p=0.008) and subgroup analysis showed Asians fared better among all the races and there was no difference between Hispanics and Whites, Blacks and Whites. The Standard Mean Difference(SMD) of AFC was in favour of whites in comparison to non-whites (0.67,95%CI-0.38-1.71,p=0.21) and subgroup analysis showed Asians fared worse among all the races and there was no difference between Whites and Blacks, Hispanics and Blacks. Limitations, reasons for caution All Included studies were observational without age-specific fertility outcomes. The heterogeneity of the geography and the age groups included in different studies are not a global representation of the AMH & AFC in different races. The necessity of large multi-centre randomized controlled studies is needed to validate our findings. Wider implications of the findings The insignificant disparity in AMH & AFC in the background of skewed accessibility and availability of fertility services may explain the significant differences in the reproductive outcomes. The fertility societies may need to make race-specific fertility guidelines to counter the disparity of available resources and services to different races. Trial registration number not applicable

P-182 The impact of ethnic differences on embryo morphokinetics and clinical outcomes: the importance of racial admixture

Abstract Study question Can ethnic differences affect embryo morphokinetics and clinical outcomes in a time-lapse imaging (TLI) embryo culture system? Summary answer Embryos from Mestizos develop faster and have a higher implantation rate than those from Caucasian and Asian patients. What is known already Over the past decades, the use of assisted reproductive technology (ART) has made pregnancy possible for many infertile couples. However, certain infertile couples exhaust all forms of ART, without achieving success. Differences in treatment success have been described as varying by race and ethnicity. In fact, it has been reported that ethnicity is a major determinant of ART outcome as indicated by significantly lower live birth rates in some ethnic minority groups, however the precise reason for this fact remains unknown. TLI may allow the identification of morphokinetics events potentially affected by ethnicity, which may impact embryo development and implantation. Study design, size, duration This historical cohort study enrolled 3,304 embryos from 466 patients undergoing ICSI cycles from Feb/2019 to Ago/2021. Female patients were split into groups according to the patient’s ethnicity: (i) Caucasian (356 patients and 2556 embryos), Mestizo (82 patients and 592 embryos), and Asian (156 patients and 28 embryos). Embryos were cultured in a TLI incubation system and morphokinetics factors and clinical outcomes were compared between the groups using generalized linear models followed by Bonferroni post-hoc. Participants/materials, setting, methods Recorded kinetic markers were timing to pronuclei appearance and fading (tPNa and tPNf), timing to two (t2), three (t3), four (t4), five (t5), six (t6), seven (t7), and eight cells (t8), and timing to morulae (tM), start of blastulation (tSB) and blastulation (tB). Durations of second and third cell cycles (cc2 and cc3) and timing to complete synchronous divisions s1, s2, and s3 were calculated. Additionally, the known implantation data score (KIDScore) day-5 was recorded. Main results and the role of chance Embryos derived from Mestizo patients completed several key-point stages faster, followed by Caucasians, while Asiatic embryos were the slower ones. Mestizo presented shorter t6 (54.8 ± 0.92, 52.6 ± 0.20, 51.0 ± 0.42, for Asians, Caucasians, and Mestizos respectively, p < 0.001), t7 (58.4 ± 1.05, 55.4 ± 0.22, 54.1 ± 0.45, for Asians, Caucasians, and Mestizos respectively, p < 0.001), t8 (59.3 ± 1.2, 58.7 ± 0.24, 57.3 ± 0.49, for Asians, Caucasians, and Mestizos respectively, p = 0.019), tM (99.3 ± 2.1, 90.8 ± 0.37, 87.5 ± 0.79, for Asians, Caucasians, and Mestizos respectively, p < 0.001), tsB (106.4 ± 1.9, 101.4.0 ± 0.54, 98.0 ± 1.4, for Asians, Caucasians, and Mestizos respectively, p < 0.001), and tB (109.1 ± 0.31,116.2 ± 2.0, 106.0 ± 0.64, for Asians, Caucasians, and Mestizos respectively, p < 0.001). In addition, the KIDScore-D5 ranked significantly higher for Mestizos, followed by Caucasians, while Asian patients presented the lower KIDScore-D5 (2.9 ± 0.27, 5.3 ± 0.1, 6.3 ± 0.4, p < 0.001). Pregnancy (25.0 ± 4.9, 33.0 ± 13.2, 58.0 ± 11.5, p = 0.038) and implantation rates (30.0 ± 1.2, 16.3 ± 0.4, 50.0 ±1.5, p < 0.001) were also highest among Mestizos, followed by Caucasians, whereas the Asian patients had the lowest rates. Limitations, reasons for caution The retrospective nature of the study and the small sample size may have biased the results. Wider implications of the findings Despite the increasing number of studies investigating the effect of ethnicity on ART outcomes, most of the literature has focused on White, Black and Asians. However, racial admixture has markedly increased, making attempts at strict racial categorisation confusing and out-dated. Apparently, miscegenation benefits embryonic development, which may impact clinical outcomes. Trial registration number Not applicable

P-245 Cumulative live birth rates in egg donation regarding the origin of oocytes (fresh or cryopreserved oocytes) in unsynchronized cycles

Abstract Study question Is there a difference in cumulative live birth rates between the two groups of fresh or cryopreserved donor oocytes? Summary answer In egg donation cumulative live birth rates achieved with fresh donor oocytes are similar to those with cryopreserved donor oocytes. What is known already The improvement techniques of cryopreservation of gametes and embryos with vitrification has played an important role in ART and Oocyte Donation Programs. Oocyte donation is a worldwide established method for women with premature ovarian failure, those with repeated (IVF) failure, or those who have inherited genetic abnormalities. The increasing use of Oocyte cryopreservation has improved the outcomes and the success rates. However, cryopreserved-donated oocytes have been still achieved lower live birth rates in comparison to fresh donor oocytes. Study design, size, duration This study was carried out in Assisting Nature IVF Unit from January 2015 to December 2020. 191 recipient’s cycles were examined for the cumulative live birth outcomes according to the origin of oocytes. Group A include cycles with fresh donor oocytes from the retrieval day and Group B include cycles with cryopreserved donor oocytes. Participants/materials, setting, methods 191 recipient cycles participated in the study. Group A (n = 133) received fresh donor eggs in which the formed blastocysts were cryopreserved and then were thawed for the first embryotransfer (ET). Acceptors in Group B (n = 58) received cryopreserved donor eggs and carried out a fresh embryotransfer. The rest of formed blastocysts were cryopreserved and thawed in the next ET. All acceptors transferred at most two embryos and they occurred maximum 3 embryotransfers in egg donation. Main results and the role of chance In Group A 755 fresh donor oocytes were utilized when in Group B were 269 cryopreserved oocytes. Fertilization (87% Group A, 84% Group B) and blastulation rates (70% Group A and 65% Group B) were similar between two groups. Cumulatively the live birth rate in Group A was 61% (1st ET: 51,1%, 2nd ET: 9%, 3rd ET: 0,9%). Acceptors with a failure in the first ET carried out a second ET or in the third ET with cryopreserved blastocysts. In Group B acceptors achieved 59% live birth rates (1st ET: 50%, 2nd ET: 9%). Some acceptors after the failure of the first ET carried out a second ET and delivered a healthy baby. There was not observed significant difference in live birth rate between two groups. The vitrification and warming stages in oocyte cryopreservation has been dramatically improved in recent years and therefore in our study seems to have equal live birth rates as in the fresh oocytes in egg donation program. Limitations, reasons for caution Large scale studies are required with further investigation with more equal number of studied patients between groups. Moreover, information regarding sperm quality parameters, embryos quality or endometrium should be considered. Wider implications of the findings Acceptors should be reassured that the origin of oocytes does not have impact in the likelihood of becoming pregnant. Trial registration number NONE

Adenomyosis and fertility: does adenomyosis impact fertility and does treatment improve outcomes.

Adenomyosis has recently been associated with infertility. Relief of bleeding and pain has been demonstrated with medical and surgical therapy. Less is known about reproductive outcomes after treatment. Imaging findings during infertility evaluation can be suggestive of adenomyosis without pathologic evaluation. Among women with infertility undergoing assisted reproductive technologies (ART), adenomyosis is associated with lower live birth rates and clinical pregnancy rates. Treatment with gonadotropin releasing hormone (GnRH) modulators prior to frozen embryo transfer may increase the live birth rate and clinical pregnancy rate among women with adenomyosis. Pregnancy has been documented following image-guided adenomyosis ablation; however, the reproductive impact is not well established. Pregnancy following excisional procedures appears to be well tolerated, although may carry a higher risk of uterine rupture compared with pregnancy following myomectomy. It is not clear if ablative therapy or resection increases pregnancy rates. Adenomyosis is associated with lower embryo implantation rates and ongoing pregnancy rates. Adenomyotic changes in the uterus can be seen by ultrasound and MRI. GnRH modulators may be useful for women with adenomyosis undergoing ART. Additional prospective data is warranted to determine the optimal medical or surgical therapy for women with adenomyosis desiring conception.Video abstract Supplementary digital content, http://links.lww.com/COOG/A78.

In vitro fertilization cycle and embryo transfer outcomes in oligoanovulatory patients with hypothalamic hypogonadism vs. polycystic ovary syndrome and compared with normo-ovulatory patients

ObjectiveTo study the difference in the live birth rates between anovulatory women with hypothalamic hypogonadism (HH) and those with polycystic ovary syndrome (PCOS) and normo-ovulatory women undergoing fresh embryo transfer or frozen embryo transfer (FET).DesignRetrospective cohort study.SettingAcademic medical center.Patient(s)Patients with oligoanovulation (HH, n = 47; PCOS, n = 533) and normo-ovulation (tubal factor infertility, n = 399) undergoing in vitro fertilization and intracytoplasmic sperm injection cycles from January 1, 2012, to June 30, 2019.Intervention(s)None.Main Outcome Measure(s)Live birth rate.Result(s)Patients with HH had longer stimulation durations than both patients with PCOS and tubal factor infertility. Patients with HH had fewer oocytes retrieved than patients with PCOS, but their numbers of blastocysts were similar. Patients with HH and tubal factor infertility had similar numbers of oocytes retrieved and blastocysts. In fresh embryo transfer cycles, the live birth rates were similar among patients with HH, PCOS, and tubal factor infertility (37.5% vs. 37.1% vs. 29.3%, respectively). When evaluating FET cycles, patients with HH had lower live birth rates than patients with PCOS (26.5% vs. 46.7%) and tubal factor infertility (42.6%).Conclusion(s)Live birth rates are similar among patients with HH, PCOS, and normo-ovulation undergoing fresh embryo transfer but are significantly lower in women with HH undergoing FET.

Pregnancy outcomes following maternal exposure to statins: A systematic review and meta-analysis.

The objective of this meta-analysis was to determine whether maternal exposure to statins is associated with increased rates of major congenital malformations and other adverse pregnancy outcomes. PubMed/Medline, Web of Science and Reprotox® databases were searched. Cohort and case control studies with prenatal exposure to statins were included. Analysis of five cohort studies and one case-control study showed no significant increase in rate of major congenital malformations when the exposed group was compared with the control ([OR 1.27; 95% CI 0.80-2.04], [aOR 1.05; 95% CI 0.84-1.31]). A significant increase in heart defect risk was detected in the statin-exposed group when unadjusted ORs were combined (OR 2.47; 95% CI 1.36-4.49). Further analysis of the same outcome by using adjusted ORs showed no significant increase in heart defect risk in the statin-exposed group compared with the controls (aOR 1.24; 95% CI 0.93-1.66). A significantly lower live birth rate (OR 0.60, 95% CI 0.49-0.75) and a higher spontaneous abortion rate (OR 1.36; 95% Cl 1.06-1.75) were detected in the statin-exposed group. Gestational statin exposure was not associated with a significant increase in risk of major congenital malformations, heart defects and other adverse pregnancy outcomes, except spontaneous abortion and live birth rate, which may be associated with maternal comorbidity and other unadjusted risk factors. Further research focusing on particular statins is needed to draw more definitive conclusions.

Intracervical insemination versus intrauterine insemination with cryopreserved donor sperm in the natural cycle: a randomized controlled trial.

Is intracervical insemination (ICI) non-inferior to IUI with cryopreserved donor sperm in the natural cycle in terms of live birth? ICI with cryopreserved donor sperm in the natural cycle was inferior to IUI in terms of live birth. Both ICI and IUI in the natural cycle are performed as first-line treatments in women who are eligible for donor sperm treatment. High-quality data on the effectiveness of ICI versus IUI with cryopreserved donor sperm in the natural cycle in terms of live birth is lacking. We performed an open-label multicentre randomized non-inferiority trial in the Netherlands and Belgium. We randomly allocated women who were eligible for donor sperm treatment with cryopreserved donor semen to six cycles of ICI in the natural cycle or six cycles of IUI in the natural cycle. The primary outcome was conception within 8 months after randomization leading to a live birth. Secondary outcomes were ongoing pregnancy, multiple pregnancy, clinical pregnancy, miscarriage and time to conception leading to live birth. We calculated relative risks (RRs) and risk differences (RDs) with 95% CI. Non-inferiority would be shown if the lower limit of the 95% RD CI was <-12%. Between June 2014 and February 2019, we included 421 women, of whom 211 women were randomly allocated to ICI and 210 to IUI. Of the 211 women allocated to ICI, 2 women were excluded, 126 women completed treatment according to protocol and 75 women did not complete 6 treatment cycles. Of the 210 women allocated to IUI, 3 women were excluded, 140 women completed treatment according to protocol and 62 women did not complete 6 treatment cycles. Mean female age was 34 years (SD ±4) in both interventions. Conception leading to live birth occurred in 51 women (24%) allocated to ICI and in 81 women (39%) allocated to IUI (RR 0.63, 95% CI: 0.47 to 0.84). This corresponds to an absolute RD of -15%; 95% CI: -24% to -6.9%, suggesting inferiority of ICI. ICI also resulted in a lower live birth rate over time (hazard ratio 0.58, 95% CI: 0.41-0.82). Our per-protocol analysis showed that, within the 8 months treatment horizon, 48 women (38%) had live births after ICI and 79 women (56%) had live births after IUI (RR 0.68, 95% CI: 0.52-0.88; RD -18%, 95% CI: -30% to -6%). The study was non-blinded owing to the nature of the interventions. We consider it unlikely that this has introduced performance bias, since pregnancy outcomes are objective outcome measures. Since ICI in the natural cycle was inferior to IUI in the natural cycle with cryopreserved donor sperm in terms of live birth rate, IUI is the preferred treatment. This trial received funding from the Dutch Organization for Health Research and Development (ZonMw project number 837002407). B.W.J.M. is supported by an NHMRC Investigator grant (GNT1176437), reports consultancy for ObsEva and has received research funding from Guerbet, Ferring and Merck. The other authors do not declare a COI. NTR4462. 11 March 2014. 03 June 2014.

Adenomyosis and infertility.

Adenomyosis is a poorly understood entity with no unified treatment protocol. It has been thought to only affect the quality of life of older women, but growing evidence is highlighting the increased frequency of adenomyosis in younger patients and its possible effects on fertility outcomes. This can have a great impact on how clinicians screen, diagnose, and treat this condition. The aim of this review is to explore the relationship between adenomyosis and infertility. A literature search of the keywords "adenomyosis", "infertility", "pregnancy" and "fertility" was conducted using the PubMed and Medline search engines. The articles selected were observational, systematic reviews, meta-analyses, and randomized controlled trials. The search was limited to English, abstracts were screened, and articles were selected. The literature reports lower clinical pregnancy rates, lower live birth rates, higher miscarriage rates, and higher odds of adverse obstetric outcomes in patients with adenomyosis. Treatment seems to be associated with higher pregnancy rates and live births rates. An association between adenomyosis and infertility seems to exist, and treatment could lead to improved fertility outcomes.

Global DNA methylation profiles of\xa0buffalo (Bubalus bubalis)\xa0preimplantation embryos produced by handmade cloning and in vitro fertilization

Somatic cell nuclear transfer technique (SCNT) has proved to be an outstanding method of multiplication of elite animals but accompanied with low efficiency and live birth rate of cloned animals. Epigenetic alterations of DNA has been one of the culprits behind this issue. Cloned embryos are found to deviate slightly from regular pattern of demethylation and re-methylation at the time of nuclear reprogramming and embryonic development when compared with embryos produced by in vitro fertilization (IVF). Thus, the present study was aimed at evaluating global DNA methylation profiles of cloned embryos at 2-cell, 8-cell and blastocyst stages and compare it with corresponding stages of embryos produced by IVF by using MeDIP-Sequencing on Illumina-based platform. We found out that cloned embryos exhibited significantly different DNA methylation pattern as compared to IVF embryos with respect to distribution of differentially methylated regions in different components of genome, CpG islands distribution and methylation status, gene ontological profiles and pathways affected throughout the developmental stages. The data generated from MeDIP-Seq was validated at blastocyst stage cloned and IVF embryos by bisulfite-sequencing PCR on five randomly selected gene regions.

Single-administered GnRH agonist as luteal phase support in insemination cycles: a randomized controlled trial

Objective To find out whether a single-administered GnRH agonist improves the live birth rate in real-life patients undergoing intrauterine insemination (IUI) cycles. Study Design A prospective, randomized controlled trial in a public single tertiary center in Tampere University Hospital, Finland. Altogether 251 IUI cycles in 163 patients were randomized to triptorelin and a control group between January 2017 and April 2019. In the triptorelin group, the participants had a single administration of a subcutaneous GnRH agonist triptorelin 0.1 mg at the time of implantation. In the control group, there was no luteal phase support. The primary outcome measure was the live birth rate (LBR). The secondary outcome measures were clinical pregnancy rate (CPR) and miscarriage rate. Results Overall, the live birth rate was lower in the triptorelin group compared to the control group (7.9 vs. 12.1%; p = .297). The clinical pregnancy rates were 12.6 and 13.7%, respectively. There were 2.4% miscarriages in the triptorelin group and no miscarriages in the control group. Ovarian stimulation with letrozole was associated with lower LBR among the triptorelin group, in comparison to the control group (0 vs. 14.7%, p = .020). In contrast, when gonadotrophin was added to the letrozole, LBR was almost doubled compared to the control group (15.9 vs. 8.3%, p = .341). Conclusion A single administration of GnRH agonist in the luteal phase does not improve LBR in IUI cycles.

Protamines and DNA integrity as a biomarkers of sperm quality and assisted conception outcome.

Present research aim was to identify functional tests in semen associated with DNA damage and chromatin maturity (protamination) which predict the outcome in assisted reproduction. Couples were grouped according to male partner semen parameters, into normozoospermia (NZs), severe male factor (SMF) and mild male factor (MMF). DNA fragmentation index (DFI) in spermatozoa was analysed by sperms chromatin dispersion (SCD), sperm chromatin structure assay (SCSA) and acridine orange testing (AOT). Chromomycin A3 (CMA3) and toluidine blue (TB) staining to measure sperm chromatin maturity (CM). DFI and chromatin decondensation were significantly lower in N compared to male factor categories (MMF and SMF). Aneuploidy embryos were significantly higher in couples with male factor infertility (MMF and SMF). A positive correlation was observed between fertilization rate (FR) and live birth rate (LBR) with sperm concentration, motility, vitality, normal sperm morphology and negative correlation between sperm DFI and sperm CM. No correlation was observed between embryo aneuploidy and sperm DFI or CM. Lower percentage of spermatozoa chromatin integrity are associated with low fertilization and live birth rate. Male factor infertility, due to impaired semen parameters and chromatin defects could be regarded in future as an indication of IVF/ICSI, and predictor of assisted reproductive techniques outcome.

Pregnancy outcomes in papillary thyroid cancer survivors：A retrospective cohort study

ObjectiveThe purpose of this study was to evaluate the pregnancy outcomes among papillary thyroid cancer survivors. Methods65 cases singleton gravidas of papillary thyroid cancer survivors treated in the Department of Obstetrics, Peking University People's Hospital between January 2011 and January 2020 were selected retrospectively as the study group, and 130 cases of singleton pregnancy during the same time were randomly selected as the control group. The differences in general conditions, maternal and fetal complications between the two groups were analyzed. Risk factors of maternal complications and fetal malformation in patients with papillary thyroid cancer survivors were analyzed. Data was analyzed with t-test, χ2 test and logistic regression for statistical differences. ResultsTotally 65 cases of papillary thyroid cancer with 70 pregnancies were analyzed, which including 65 cases achieved live birth, 5 cases underwent induced labor because of fetal malformation. The study group showed higher incidence in gestational diabetes(20% vs 10%), cesarean section(39.1% vs 24.6%), postpartum hemorrhage(350 ​± ​193 ​ml vs 290 ​± ​181 ​ml) and fetal malformation(5.7% vs 1.5%), and lower live birth rate(91.4% vs 99.2%) (P ​< ​0.05). Multivariate analysis by logistic regression found that the patient's age, thyroid function, operation mode and postoperative I-131 treatment were not the risk factors which may affect the pregnancy outcomes or fetal malformation. ConclusionElevated maternal and fetal complications were observed among pregnancies in papillary thyroid cancer survivors. Management of these survivors may require a careful gestation monitoring, and further investigation is needed.