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Study question Is there any difference in developmental outcomes in children born after capacitation in vitro maturation (CAPA-IVM) compared with conventional in vitro fertilization (cIVF)? Summary answer Overall development up to 24 months of age was comparable in children born after CAPA-IVM compared with cIVF. What is known already IVM has been shown to be a feasible alternative to conventional IVF in women with a high antral follicle count (AFC). Data from a randomized clinical trial did not show non-inferiority of CAPA-IVM compared with cIVF with respect to live birth rate, although the findings did approach inferiority for IVM versus IVF when cumulative outcomes were considered (cumulative ongoing pregnancy rates of 44% versus 63%). In addition to live birth rate, childhood development is also a relevant metric to compare between the two approaches to assisted reproductive technology (ART) and there are currently no data on this. Study design, size, duration This study was a follow-up of babies born to women who participated in a randomized controlled trial comparing CAPA-IVM with cIVF (Vuong LN et al, Hum Reprod 2020;35:2537-2547). Developmental assessments were performed on children over 24 months of follow-up. Participants/materials, setting, methods Randomized trial participants had an indication for ART and a high AFC (≥24 follicles in both ovaries) were randomized to undergo one cycle of either CAPA-IVM (n = 273) or IVF (n = 273). Of these, 96 women and 118 women, respectively, had live births. Seventy-six women (94 children, 79.2%) and 104 women (137 children, 88.1%), respectively, completed Ages & Stages Third Edition (ASQ-3) Questionnaires, and assessment of Developmental Red Flags at 6, 12 and 24 months of age. Main results and the role of chance Baseline characteristics of follow-up study participants in the CAPA-IVM and IVF groups were comparable. Overall, there were no significant differences in ASQ-3 scores at 6, 12 and 24 months between children born after CAPA-IVM or IVF. The proportion of children with developmental red flags was low and did not differ between groups. The only significant difference between the CAPA-IVM and IVF groups was for ASQ-3 scores in problem solving and personal-social in twins only at 6 months. These scores were slightly lower in the CAPA-IVM versus IVF group but were still within the normal range and had caught up to the IVF group in the 12- and 24-month assessments. Twenty-eight babies in the IVM group and 26 in the IVF group had an abnormal ASQ-3 on at least one occasion (36% versus 25%, relative risk [RR] 1.6, 95% confidence interval [CI] 0.99–2.5, p = 0.08). All babies with abnormal ASQ-3 were referred to a specialist. Four babies in the IVM and two in the IVF group were confirmed to have abnormal mental and/or motor development (RR 2.9, 95% CI 0.54–15.6, p = 0.23). Children in both groups showed normal and comparable growth with respect to body weight over the first 24 months. Limitations, reasons for caution This study is an open-label follow-up of participants in a randomized controlled trial, and not all original trial subjects took part in the follow-up. Wider implications of the findings These data add to the evidence available to physicians when considering different approaches to fertility treatment and justify further surveillance. Trial registration number NCT04296357

Study question Does the presence of FSHR variants influence the clinical pregnancy rate (CPR), live birth rate (LBR) and cumulative live birth rate (CLBR) in predicted normoresponders? Summary answer The presence of at least one G allele in FSHR variant rs6165 is associated with higher CPR and LBR when compared to genotype AA. What is known already FSHR protein expression has been found in the placenta, umbilical cord, amnion and decidua, suggesting a role in the promotion of a healthy pregnancy. Previous reports have analysed the impact of FSHR SNP rs6166 in pregnancy outcomes with conflicting results, mainly due to the heterogeneity in the inclusion criteria and limited sample size. Moreover, the literature is scarce regarding the association between FSHR SNPs rs6165 and rs1394205 and reproductive outcomes. Our aim is to determine whether FSHR SNPs rs6166, rs6166 and rs1394205 influence the reproductive prognosis following IVF. Study design, size, duration We performed a secondary analysis of a multicenter multinational prospective study, including 368 patients from Vietnam, Belgium and Spain (168 from Europe and 200 from Asia) from 11/2016-06/2019. All patients underwent ovarian stimulation with fixed-dose 150IU rFSH in an antagonist protocol. Participants/materials, setting, methods Patients aged <38 years, undergoing their first or second IVF cycle with a predicted normal response (antral follicle count >9 and/or antimullerian hormone >1.1ng/ml) were included. CPR, LBR and miscarriage rate (MR) in the first embryo transfer, as well as CLBR, were compared between the different genotypes of FSHR SNPs rs6166, rs6165 and rs1394205. Main results and the role of chance A total of 351 patients performed at least one embryo transfer (ET). Enrolled patients had a mean age of 30.5 ± 3.63 years. Mean CPR and LBR in the first ET were 56.1% and 48.4%, respectively. Univariate genetic model analysis revealed a significantly higher CPR in the dominant model for variant rs6165 (46.3% (38/82) for genotype AA vs 59.1% (159/269) for genotypes AG/GG, p = 0.04). No statistically significant difference was found regarding the CPR for variants rs6166 nor rs1394205. Also, no statistically significant difference was found in univariate analysis regarding LBR nor MR for the different FSHR variants. However, multivariable logistic regression analysis adjusted for patient age, BMI, ethnicity, type of embryo transfer, embryo stage and number of top quality embryos transferred revealed a statistically significant higher CPR and LBR for FSHR variant rs6165 genotype GG (adjOR 2.50, 95% CI 1.30-4.81, and adjOR 1.96, 95%CI 1.02-3.78, respectively). No statistically significant differences were found regarding CLBR for FSHR variants rs6166, rs6165 nor rs1394205. Limitations, reasons for caution The young age of the included patients precludes the generalization of the results to older patients. Also, the results should be confirmed in larger cohorts before being extrapolated to the general population. Wider implications of the findings Our results demonstrate a previously unreported association between variant FSHR SNPs rs6165 genotype GG and higher CPR and LBR and reinforce a potential role for the genetic background in the prediction of a favorable prognosis following IVF. Trial registration number not-applicable