Comparing the euploidy rate between the progestin-primed and gonadotrophin releasing hormone antagonist protocols in preimplantation genetic testing for aneuploidy: a randomized controlled trial

Abstract STUDY QUESTION In patients undergoing preimplantation genetic testing for aneuploidy (PGT-A), does the progestin-primed ovarian stimulation (PPOS) protocol result in a euploidy rate of blastocysts per patient comparable to that of the gonadotrophin-releasing hormone (GnRH) antagonist protocol? SUMMARY ANSWER The euploidy rate of blastocysts per patient is comparable for patients using PPOS and GnRH antagonist protocols. WHAT IS KNOWN ALREADY Progestin is effective in blocking the pituitary luteinising hormone (LH) surge during ovarian stimulation and the PPOS protocol is simpler and cheaper. However, published studies comparing euploidy rates between the two protocols have yielded contradictory results. STUDY DESIGN, SIZE, DURATION This was an open-label, randomized controlled trial of 400 women recruited between June 2020 and August 2024. Eligible women were randomly assigned in a ratio of 1:1 to the PPOS or GnRH antagonist group using an online randomisation program and sealed opaque envelopes. The primary outcome was the euploidy rate of blastocysts per patient. PARTICIPANTS/MATERIALS, SETTING, METHODS Women aged <43 years undergoing PGT-A cycles were randomly assigned to either the PPOS group (n = 200) or antagonist group (n = 200). PGT-A was indicated for advanced maternal age, recurrent pregnancy loss, repeated implantation failure, or history of foetal aneuploidy in previous pregnancies. PGT-A was performed using the next generation sequencing technology. MAIN RESULTS AND THE ROLE OF CHANCE The PPOS and antagonist groups were similar in demographic characteristics and the numbers of oocytes obtained/fertilized, cleavage stage embryos, and developed blastocysts. The PPOS group had significantly lower total gonadotrophin dose and significantly higher serum oestradiol level on the ovulation trigger day when compared to the GnRH antagonist group. No statistically significant difference was observed in the euploidy rate of blastocysts between the PPOS and antagonist groups (40.0 (0–66.7)% versus (44.4 (25.0–71.4)%, P = 0.192). The number of euploid blastocysts per patient was comparable for the PPOS and antagonist groups (1 (1–2) versus 1 (1–2.5), P = 0.47). There were 136 women in the PPOS group and 152 women in the antagonist group who had their first frozen embryo transfer after PGT-A. Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, ectopic pregnancy and live birth rates after the first frozen embryo transfer. LIMITATIONS, REASONS FOR CAUTION The participants and researchers were not blinded to the treatment allocation. The sample size was powered only to detect a 10% euploidy rate difference; smaller differences cannot be excluded. Not all women completed their first transfer cycle, and outcomes from a single cycle do not represent cumulative live birth rates. Results are based solely on euploid embryo transfers, limiting generalisability to mosaic embryos. Generalisation to other IVF populations or to the use of other progestins is also limited. WIDER IMPLICATION OF THE FINDINGS The findings of the study support the use of PPOS for patients undergoing a freeze-all IVF cycle, whether for PGT-A or oocyte preservation. FUNDING This study was supported by Shanghai Oriental Talent Award (QNWS2024045), the National Natural Science Foundation of China (82171644) and Shanghai Shen Kang Hospital Development Center Municipal Hospital New Frontier Technology Joint Project (SHDC12017105). DISCLOSURES The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER NCT04414748 TRIAL REGISTRATION DATE 4 June 2020. DATE OF FIRST PATIENT’S ENROLLMENT 10 June 2020.