Reproductive Outcomes in Programmed Ovulatory versus Modified Natural Cycle FET: A Propensity Score–Matched Analysis of Prospective and Retrospective Cohorts

OBJECTIVE: To compare reproductive outcomes between a recently introduced programmed ovulatory frozen-thawed embryo transfer protocol (PO-FET), designed to avoid hCG trigger administration while providing additional progestin support, and the widely used modified natural cycle (mNC) FET. DESIGN: Single-center study with prospective enrollment for PO-FET cycles and retrospective data collection for mNC-FET cycles. Propensity score matching was applied to balance baseline characteristics between groups. SUBJECTS: A total of 662 normo-ovulatory women undergoing a single frozen-thawed blastocyst transfer between January 2021 and November 2023. After matching, 170 PO-FET cycles and 170 mNC-FET cycles were analyzed. EXPOSURE: The PO-FET protocol involved administration of oral dydrogesterone (30 mg daily) in the late follicular phase to induce endometrial receptivity, schedule embryo transfer, and provide luteal phase support, while allowing spontaneous ovulation without the use of recombinant human chorionic gonadotropin (hCG). In contrast, the mNC-FET protocol used recombinant hCG to trigger ovulation, followed by luteal phase support with progestin. MAIN OUTCOME MEASURES: The primary outcome was live birth rate. Secondary outcomes included clinical pregnancy, biochemical pregnancy, and miscarriage rates. Logistic regression models adjusting for maternal age, BMI, and embryo quality assessed the association between treatment protocol and outcomes. RESULTS: No significant differences were observed between the mNC-FET and PO-FET groups in live birth rates (35.29% vs 28.82%; OR 1.35, 95% CI 0.83-2.19, p=0.245). Clinical pregnancy rates were 41.18% following mNC-FET and 32.94% following PO-FET (OR 1.42, 95% CI 0.89-2.27, p=0.144), while biochemical pregnancy occurred in 18.84% vs 17.65% of cases, respectively (OR 0.92, 95% CI 0.37-2.30, p=1.000). Miscarriage rates were 14.29% in mNC-FET cycles compared to 12.50% in PO-FET cycles (OR 1.17, 95% CI 0.37-3.89, p=0.800). Logistic regression analysis confirmed that the endometrial preparation protocol (PO-FET vs mNC-FET) was not significantly associated with live birth (OR 1.38, 95% CI 0.86-2.23, p=0.179). CONCLUSIONS: Treatment outcomes did not differ significantly between PO-FET and mNC-FET regimens, suggesting that hCG may be unnecessary and that the protocol choice can align with patient and clinician preferences in a population of normo-ovulatory women.