A randomized controlled trial to compare the live birth rate of the first frozen embryo transfer following the progestin-primed ovarian stimulation protocol versus the antagonist protocol in women with an anticipated high ovarian response

Objective To compare the live birth rate of the first frozen embryo transfer following ovarian stimulation by the progestin-primed ovarian stimulation protocol versus the antagonist protocol in women with anticipated high ovarian response undergoing IVF Design Randomized controlled trial Settings A tertiary assisted reproduction center Patients Infertile women aged <43 years undergoing the first IVF cycle and having antral follicle count >15 Interventions Medroxyprogesterone 10 mg daily was given from the start of ovarian stimulation until the day of ovulation trigger in the progestin-primed ovarian stimulation protocol. In the antagonist protocol, an antagonist 0.25mg daily was given from 6th day of ovarian stimulation until the day of ovulation trigger. Blinding was not possible for women or physicians but the biostatistician was blinded to the group assignment. Main Outcome Measures Live birth rate of the first frozen embryo transfer cycle Results 784 women were recruited from June 2020 and October 2021 and randomly assigned in a 1:1 ratio into two groups: progestin-primed ovarian stimulation group (n=392) and antagonist group (n=392). Embryo transfer was either cancelled or postponed in 62 (62/392, 15.8%) women in the progestin-primed ovarian stimulation group and 65 (65/392, 16.6%) in the antagonist group because of no transferable embryos or no frozen embryo transfer within 6 months following randomizaion. The two groups were similar in demographic characteristics and number of oocytes obtained/fertilized, the number of cleaving embryos, number of good quality embryos at day 3, number of blastocysts developed and number of embryo/blastocyst frozen. There was no statistically significant difference in the live birth rate of the first frozen embryo transfer cycle between the progestin-primed ovarian stimulation and antagonist groups based on both intention to treat [37.5.0% (147/392) versus 32.7% (128/392), RR 1.148 (95% CI=0.949–1.390), P=0.16] and per protocol analysis [44.5% (147/330) versus 39.1.% (128/327), RR 1.138 (95%CI = 0.950–1.364), P=0.16]. Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and cumulative live birth rates. Conclusion The live birth rates of the first frozen embryo transfer following the progestin-primed ovarian stimulation and the antagonist protocol were comparable in women with an anticipated high ovarian response.