Objective: To compare the in vitro fertilization (IVF) outcomes of the progestin-primed ovarian stimulation (PPOS) protocol using dydrogesterone and the GnRH antagonist (GnRH-ant) protocol in POSEIDON group 4 patients. Methods: This retrospective cohort study analyzed 447 POSEIDON group 4 patients who underwent IVF at a single center. Patients were categorized into GnRH-ant (n = 281) and PPOS (n = 166) groups. Propensity score matching was employed to balance baseline characteristics, yielding 165 patients in each group for comparison. The primary outcomes were the number and quality of cleavage and blastocysts embryos. Secondary outcomes included clinical pregnancy and ongoing pregnancy rates after the first frozen embryo transfer. Results: Baseline characteristics were balanced between groups after matching. The PPOS group had a significantly lower number of good quality cleavage embryos (adjusted mean ratio 0.80, 95% CI 0.66–0.97) and blastocysts (adjusted mean ratio 0.77, 95% CI 0.62–0.96) compared to the GnRH-ant group. The number of cleavage embryos and good quality blastocysts was comparable between groups. Although not statistically significant, the clinical pregnancy (31.4% vs 36.8%) and ongoing pregnancy rates (20.3% vs 29.9%) after the first embryo transfer tended to be lower in the PPOS group. Conclusion: In POSEIDON group 4 patients, the PPOS protocol using dydrogesterone may be associated with lower embryo quality and pregnancy outcomes compared to the GnRH-ant protocol. Further prospective randomized trials are needed to validate these findings.
