Does an increased dosing of FSH improve the live birth rate as compared to standard FSH dosing in expected poor responders who undergo IVF? In this trial, women with an expected poor response allocated to increased FSH dosing did not have a statistically significant increase in cumulative live births as compared to a standard FSH dose. Poor ovarian reserve leads to worse IVF outcomes owing to the low number and quality of oocytes. Clinicians often individualize the FSH dose using ovarian reserve tests, including antral follicle count (AFC), and basal plasma FSH or anti-Müllerian hormone level. However, the evidence that increased FSH dosing improves fertility outcomes in women with an expected poor response is lacking. We performed a parallel, open-label randomized controlled trial between March 2019 and October 2021 in an assisted reproduction centre. Women <43 years of age with AFC <10 referred for their first IVF cycle were randomized for increased or standard FSH dosing. In participants allocated to increased FSH dosing, women with AFC 1–6 started with 300 IU/day, while women with AFC 7–9 started with 225 IU/day. In participants allocated to the standard care, women started with 150 IU/day. The primary outcome was cumulative live birth attributable to the first IVF cycle including fresh and subsequent frozen-thawed cycles within 18 months of randomization. Live birth was defined as the delivery of one or more living infants ≥24 weeks’ gestation. This trial was powered to detect an 11% difference in live birth attributable to the first IVF cycle. Outcomes were evaluated from an intention-to-treat perspective. We randomized 661 women to start FSH at increased dosing (n = 328) or standard dosing (n = 333). The primary outcome cumulative live birth occurred in 162/328 (49.4%) women in the increased group versus 141/333 (42.3%) women in the standard group [risk ratio (RR) 1.17 (95% CI, 0.99–1.38), risk difference 0.07 (95% CI, −0.005, 0.15), P = 0.070]. The live birth rate after the first embryo transfer in the increased versus standard group was 125/328 (38.1%) versus 117/333 (35.1%), respectively [RR 1.08 (95% CI, 0.83–1.33), P = 0.428]. Cumulative clinical pregnancy rates were 59.1% versus 57.1% [RR 1.04 (95% CI, 0.91–1.18), P = 0.586] with miscarriage rates of 9.8% versus 14.4% [RR 0.68 (95% CI, 0.44–1.03), P = 0.069] in the increased versus standard group, respectively. Other secondary outcomes, including biochemical pregnancy, ongoing pregnancy, multiple pregnancy and ectopic pregnancy, were not significantly different between the two groups both from the first and cumulative embryo transfer. As this study is open-label, potential selective cancelling and small dose adjustments could have influenced the results. In women with predicted poor response, we did not find evidence that increased FSH dosing improves live birth rates. A standard dose of 150 IU/day is recommended at the start of IVF in these women to reduce potential adverse effects and costs. This study was funded by the General Projects of Social Development in Shaanxi Province (No. 2022SF-565). B.W.M. is supported by NHMRC (GNT1176437). B.W.M. reports personal fees from ObsEva, and funding from Merck and Ferring outside the submitted work. Registered at Chinese clinical trial registry (www.chictr.org.cn). Registration number ChiCTR1900021944. 17 March 2019 20 March 2019

Background: Different endometrial preparation protocols are used prior to frozen-thawed embryo transfer (FET). Optimization of endometrial preparation protocols is mandatory to improve live birth rate and obstetric and perinatal outcomes. In the Comparison of Endometrial Preparation Protocols for Frozen Embryo Transfer (COMPETE) trial, our primary objective is to evaluate whether natural cycles (NCs) lead to a higher live birth rate after the first FET cycle compared to hormone replacement therapy (HRT) cycles in women with a regular ovulatory cycle. Methods and findings: We performed a single-center, parallel, open-label randomized controlled trial between December 2020 and December 2022 in a single assisted reproduction center in Xi’an, China. Women with a regular menstrual cycle undergoing in vitro fertilization (IVF) scheduled for FET were randomly assigned (1:1) to endometrial preparation in the NC or with HRT, using a web-based electronic data capture system. The primary outcome was live birth rate after the initial FET. The analysis was conducted based on the intention-to-treat principle. Obstetric and perinatal outcomes in all randomly assigned women were reported in this study. We randomly assigned 902 women to receive either NC ( n = 448) or HRT ( n = 454). In the NC group, 101 women received HRT because of no ovulation, while in the HRT group, 29 women received NC because of spontaneous ovulation. The number of live births was 242 (54.0%) in the NC group versus 195 (43.0%) in the HRT group (absolute difference, 11.1 percentage points, 95% CI 4.6 to 17.5; risk ratio (RR) 1.26, 95% CI 1.10 to 1.44). Miscarriage rates (RR 0.61, 95% CI 0.41 to 0.89) and the antepartum hemorrhage rates (RR 0.63, 95%CI 0.42 to 0.93) were lower in the NC group, with other obstetric and perinatal outcomes not significantly different. Conclusions: In women with a regular menstrual cycle undergoing FET, a strategy starting with NC endometrial preparation results in higher live birth rates than endometrial preparation with HRT. However, the permitted cross-over between arms limits certainty in directly assessing NC versus HRT efficacy. Trial registration: Chinese Clinical Trial Registry: ChiCTR2000040640.

Background: The evaluation of embryo morphology may be inaccurate. A euploid prediction model is needed to provide the best and individualized counseling about embryo selection based on patients and embryo characteristics. Methods: Our objective was to develop a euploid-prediction model for evaluating blastocyst embryos, based on data from a large cohort of patients undergoing pre-implantation genetic testing for aneuploidy (PGT-A). This retrospective, single-center cohort study included data from 1610 blastocysts which were performed PGT-A with known genetic outcomes. The study population was divided into the training and validation cohorts in a 3:1 ratio. The performance of the euploid-prediction model was quantified using the area under the receiver operating characteristic (ROC) curve (AUC). In addition, a nomogram was drawn to provide quantitative and convenient tools in predicting euploid. Results: We developed a reliable euploid-prediction model and can directly assess the probability of euploid with the AUC (95%CI) of 0.859 (0.834,0.872) in the training cohort, and 0.852 (0.831,0.879) in the validation cohort, respectively. The euploid-prediction model showed sensitivities of 0.903 and specificities of 0.578. Conclusions: The euploid-prediction model is a reliable prediction model and can directly assess the probability of euploid.