Research Finds No Advantage Between PPOS and Antagonist Protocols in IVF

When selecting an ovarian stimulation protocol for IVF, clinicians must balance efficacy, patient convenience, and safety. But do protocol choices—specifically between progestin-primed ovarian stimulation (PPOS) and GnRH antagonist strategies—impact oocyte yield or pregnancy rates when a GnRH agonist trigger is used? A newly published study in the Archives of Gynecology and Obstetrics addresses this pressing question, providing much-needed clarity for reproductive specialists.

Study Design at a Glance

This large, retrospective cohort study analyzed 802 patients at a single high-volume IVF center from 2022 to 2024. All patients underwent ovarian stimulation with a starting dose of 300 IU gonadotropins and received either a GnRH antagonist protocol or PPOS (oral progestin) for pituitary suppression. Each cycle concluded with a GnRH agonist (GnRHa) trigger for final oocyte maturation, followed by frozen embryo transfer (FET). The primary outcome was oocyte yield; secondary outcomes included pregnancy and live birth rates.

Key Findings: Oocyte Yield and Embryo Outcomes

Both PPOS and antagonist groups had comparable baseline characteristics, including age, BMI, and infertility duration.

Duration of ovarian stimulation was slightly shorter and LH levels higher on the trigger day in the PPOS group, but these differences did not affect oocyte yield or embryological outcomes.

Oocyte yield, mature oocyte count, fertilization rate, blastulation rate, and number of frozen blastocysts were statistically similar between protocols.

Pregnancy and Live Birth Rates: No Clinically Significant Gaps

Clinical pregnancy rates were nearly identical: 63.6% (PPOS) vs. 63.8% (antagonist).

Live birth rates also matched closely: 51.7% (PPOS) vs. 52.2% (antagonist), with no significant difference in miscarriage or multiple pregnancy rates.

Regression analysis identified embryo quality—not protocol choice—as the key predictor of live birth.

Clinical Implications for IVF Practice

These findings suggest that PPOS is a clinically effective and flexible alternative to the GnRH antagonist protocol for ovarian stimulation cycles using a GnRH agonist trigger. Oral progestins offer practical advantages, including lower cost and easier administration, without compromising patient outcomes. While the exact mechanism of pituitary suppression by progestins remains unclear, the data support the use of PPOS, especially when scheduling flexibility is desired or when antagonist use is less feasible.

Limitations and Areas for Future Research

This was a retrospective, single-center study, which may limit external validity. The study did not address outcomes in specific subgroups, such as poor responders, nor did it evaluate cumulative live birth rates across multiple FET cycles. Prospective, multicenter trials are needed to confirm these results and further clarify the optimal use of PPOS in diverse IVF populations.

Conclusion

For clinicians seeking both effectiveness and flexibility in IVF stimulation protocols, this study provides reassurance: PPOS and GnRH antagonist approaches yield comparable outcomes when paired with a GnRH agonist trigger. As always, individual patient factors and preferences should guide protocol selection, but the evidence supports PPOS as a strong option in modern IVF practice.

Key Points

Both PPOS and GnRH antagonist protocols yield similar oocyte numbers and live birth rates when using a GnRH agonist trigger.

Embryo quality, not protocol choice, is the strongest predictor of live birth.

PPOS offers scheduling flexibility and avoids daily injections, making it a practical alternative in appropriate patients.

No increase in adverse outcomes, including miscarriage or multiple pregnancy rates, was observed with PPOS.

Further research is needed to assess cumulative live birth rates and the use of PPOS in varied patient subgroups.

Citation:

Tohma YA, Boynukalın FK, Gültomruk M, Bahçeci M, Bozdağ G. GnRH agonist trigger in focus: does protocol choice between PPOS and antagonist strategies affect outcomes? Archives of Gynecology and Obstetrics. 2025;312:2303–2309. doi:10.1007/s00404-025-08229-7