Evaluating progestin-primed and GnRH antagonist ovarian stimulation protocols in PGT-A cycles: implications for clinical practice

BACKGROUND: Progestin-primed ovarian stimulation (PPOS) has emerged as an alternative to GnRH-antagonist protocols in IVF, yet its impact on embryo chromosomal competence remains controversial. Evidence is particularly limited regarding whether PPOS influences blastocyst euploidy rates and key clinical outcomes in PGT-A cycles, and whether these effects vary according to maternal age and ovarian reserve status. METHODS: This retrospective cohort study included 1,843 PGT-A cycles (666 PPOS, 1,177 GnRH antagonist) performed at a single tertiary IVF center between January 2016 and January 2024. Controlled ovarian stimulation was performed with either oral medroxyprogesterone acetate or daily cetrorelix, followed by vitrification of all biopsied blastocysts and subsequent frozen embryo transfer. Primary outcomes were blastocyst euploidy and clinical pregnancy rates. Secondary outcomes included embryological parameters, miscarriage, live birth, and cumulative pregnancy rates. Subgroup analyses were performed according to maternal age and ovarian reserve. RESULTS: The mean age was 37.64±4.48 years in the PPOS group and 37.80±3.49 years in the GnRH-antagonist group; age and other baseline characteristics were comparable between groups. PPOS cycles had a shorter stimulation duration (median 8 vs. 9 days, p = 0.001), with comparable gonadotropin requirements and embryological outcomes. Euploidy (32.6% vs. 32.1%, p = 0.653), mosaicism, and aneuploidy rates did not differ significantly. Clinical pregnancy, live birth, and cumulative pregnancy rates were equivalent. CONCLUSION: PPOS and GnRH antagonist protocols yield comparable embryological and clinical outcomes in PGT-A cycles, including in advanced maternal age and diminished ovarian reserve subgroups. With its shorter stimulation duration and cost-effectiveness, PPOS is a valid alternative when fresh transfer is not planned.