Outcomes of GnRH agonist trigger in Dydrogesterone-based PPOS versus GnRH antagonist cycles: a retrospective parallel cohort in freeze-all IVF treatment

Abstract

To compare laboratory and embryological outcomes between dydrogesterone-based progesterone-primed ovarian stimulation (PPOS) and GnRH antagonist cycles when a GnRH agonist is used for final oocyte maturation in freeze-all IVF treatment. Methods This retrospective parallel cohort study included 795 stimulation cycles (718 antagonist, 77 PPOS) performed between May 2015 and September 2024 at ART Fertility Clinics UAE. All cycles used a GnRH agonist trigger (triptorelin 0.3 mg) for final oocyte maturation. The primary outcome was the number of mature (MII) oocytes retrieved. Secondary outcomes included fertilization rate, blastulation rate, blastocyst count, euploidy rate, oocyte retrieval rate (ORR), and follicular output index (FOI). Multivariable mixed-effects models adjusted for age, BMI, ovarian reserve parameters, stimulation medication, cycle type, and treatment center. Results Patients in the PPOS and antagonist groups differed in age and BMI, while ovarian reserve markers were comparable. After adjustment for confounders, no statistically significant differences were observed between protocols in mature oocyte yield (IRR 1.00, p = 0.962), maturation rate (OR 0.94, p = 0.680), fertilization rate (OR 0.88, p = 0.384), blastocyst count (IRR 0.97, p = 0.773), blastulation rate (OR 1.10, p = 0.639), or euploidy rate (OR 1.06, p = 0.734). Maternal age remained the strongest predictor of euploidy. Conclusions Dydrogesterone-based PPOS demonstrated no statistically significant differences in oocyte, embryo, or genetic outcomes compared with GnRH antagonist cycles when a GnRH agonist trigger was used. These findings indicate that PPOS is a feasible alternative for freeze-all cycles requiring an agonist trigger, although larger prospective studies are needed to confirm equivalence.