Reviewed clinical summary · Source-linked · Educational use only

PPOS vs GnRH Antagonist: Similar Euploidy Rates in PGT-A

Visual abstract summarising PPOS versus GnRH antagonist protocols in PGT-A cycles.

Clinical Bottom Line

A randomized controlled trial found progestin-primed ovarian stimulation and the GnRH antagonist protocol produced statistically similar euploidy rates in PGT-A cycles. PICO summary and expert commentary.

Summary: In 240 infertile women undergoing PGT-A, progestin-primed ovarian stimulation (PPOS, dydrogesterone 20 mg/day) was compared with a GnRH antagonist protocol in a randomized controlled trial. The euploidy rate (euploid blastocysts per injected oocyte) did not differ significantly between arms (12.5% PPOS vs 16.0% antagonist, P > 0.05), and pregnancy and live-birth outcomes were also comparable.

PICO Summary

ElementDetail
Population240 infertile women undergoing PGT-A with advanced maternal age (38-45 years), recurrent pregnancy loss, or repeated implantation failure; single-centre prospective randomized controlled trial, China (Aug 2021-Jul 2023).
InterventionProgestin-primed ovarian stimulation (PPOS): dydrogesterone 20 mg/day from the start of stimulation until trigger day (n = 120).
ComparisonGnRH antagonist protocol: antagonist 0.25 mg/day from the sixth day of stimulation until trigger day (n = 120).
OutcomePrimary outcome euploidy rate (euploid blastocysts per injected oocyte): 12.5% (PPOS) vs 16.0% (antagonist), P > 0.05 (no significant difference). No significant between-group differences in positive pregnancy test, clinical pregnancy, miscarriage, ectopic pregnancy, or live-birth rates per transfer in the first frozen embryo transfer cycles. Demographic and stimulation characteristics were similar. Effect estimates, 95% CIs, and absolute risk reduction were not reported.
RCT Reprod Biol Endocrinol · 2025

PPOS vs GnRH antagonist in PGT-A

RCT · PGT-A cycles · Aug 2021-Jul 2023

Trial design
Women in PGT-A cycles Enrolled & assessed RANDOMISED 1:1 PPOS Dydrogesterone 20 mg/d n = 120 GnRH antagonist Antagonist 0.25 mg/d n = 120 Euploidy rate (euploid blastocysts per oocyte)
Proportion reaching endpoint
P > 0.05 % euploid per injected oocyte 12.5% PPOS 16% GnRH antagonist ARR-3.5 pts (NS)
Euploidy (PPOS)
12.5%
per injected oocyte
Euploidy (antagonist)
16.0%
per injected oocyte
Difference
3.5 pts
P > 0.05, not significant
Live birth
Comparable
no significant difference
⬡ Bottom Line

Euploidy rate did not differ significantly between PPOS and the GnRH antagonist protocol (12.5% vs 16.0%, P > 0.05), with comparable pregnancy and live-birth outcomes. The trial is underpowered to confirm true equivalence.

Expert Commentary

This randomized controlled trial reports a null result: euploidy rates were not significantly different between PPOS and the GnRH antagonist protocol, and downstream pregnancy and live-birth outcomes were also comparable. The verdict is reassurance rather than superiority, since the numerically lower euploidy rate in the PPOS arm (12.5% vs 16.0%) was not statistically significant and should not be read as inferiority. The most important limitation is power: with 120 women per arm and no reported 95% confidence intervals or formal equivalence margin, the trial is underpowered to exclude a clinically meaningful difference, so an absence of significance is not proof of true equivalence. The single-centre design and enrichment for advanced maternal age, recurrent loss, and repeated implantation failure further limit generalisability. Can I use this with my patients? Cautiously yes, for women undergoing PGT-A in whom a freeze-all PPOS approach is already being considered, as the data suggest oral progestin priming is unlikely to compromise embryo ploidy relative to an antagonist cycle, though it is not yet grounds for a wholesale protocol switch. No industry sponsorship was evident, and the effect sizes are modest and plausible rather than implausibly strong. Larger multicentre randomized trials with pre-specified equivalence margins and cumulative live-birth endpoints are needed before firmer recommendations can be made.

References

Wang L, Wang JY, Zhang Y, Qian C, Wang XH, Ng EHY, et al. Comparison of the euploidy rate in preimplantation genetic testing for aneuploidy cycles following progestin-primed versus gonadotropin-releasing hormone antagonist protocol: a randomized controlled study. Reprod Biol Endocrinol. 2025;23(1):67. doi:10.1186/s12958-025-01404-0

Educational use: Hormone Insight is intended for healthcare professionals and learners. Interpret each summary alongside the primary source, local guidance, and patient-specific clinical judgement.

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