Background: In women with polycystic ovary syndrome (PCOS), the optimal endometrial preparation strategy for frozen embryo transfer (FET) remains unclear. This clinical trial aimed to compare a long-term protocol with a stimulated cycle protocol in FET cycles of PCOS women, with clinical pregnancy rate per embryo transfer as the primary outcome.
Methods: This non-randomized, open-label, two-arm clinical trial was conducted at Fatemieh Hamedan Hospital, Iran, involving 340 women with PCOS. Participants were allocated to the long-term or stimulated cycle protocols based on clinical scheduling and physician decision. The long-term protocol included low-dose combined oral contraceptives for 14 days, GnRH agonist downregulation, estradiol valerate (4–6 mg/day for ≥10 days), and progesterone before embryo transfer. The stimulated cycle protocol involved recombinant FSH with ultrasound monitoring, hCG trigger for oocyte maturation, and intramuscular progesterone (50 mg/day) for luteal phase support. For each participant one FET cycle was analyzed.
Results: Baseline characteristics were similar between groups (n=170 each). The long-term protocol showed higher clinical pregnancy rates (35.9%) compared to the stimulated cycle (22.9%) (OR=1.92; 95%CI: 1.15–3.19; p=0.011). Chemical pregnancy rates also favored the long-term protocol (34.7% vs. 21.8%) (OR=1.91; 95%CI: 1.17–3.09; p=0.008). Endometrial thickness was significantly greater in the long-term protocol (8.7±0.9 mm vs. 8.4±0.8 mm; p=0.004).
Conclusion: Although the long-term protocol showed higher clinical pregnancy rates in unadjusted analyses, after adjusting for confounders, protocol type was not independently associated with clinical pregnancy. Larger randomized trials are needed to confirm these findings, and adverse outcomes should be assessed in future studies.