Comparison of frozen embryo transfer outcomes in hormonal vs. mild stimulation protocols in polycystic ovary syndrome women: A randomized controlled trial.

BACKGROUND

Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility. In women undergoing frozen embryo transfer, the method of endometrial preparation (hormone replacement therapy [HRT] or mild ovarian stimulation [MOS]) can affect pregnancy outcomes. Letrozole-based MOS protocols may improve endometrial receptivity and reduce miscarriage rates by upregulating key implantation markers leukemia inhibitory factor, dickkopf-related protein 1, leukemia inhibitory factor receptor, fibroblast growth factor 22, integrin alpha V beta 3.

OBJECTIVE

This study aimed to compare the frozen embryo transfer outcomes in 2 endometrial preparation methods: HRT and MOS in infertile women with PCOS.

MATERIALS AND

METHODS

This double-blind randomized trial included 100 infertile women with PCOS and frozen embryos who referred to Al-Zahra hospital, Tabriz, Iran between October 2024 and 2025. Participants were assigned to HRT or MOS for endometrial preparation. In HRT, oral estradiol followed by injectable progesterone was used; in MOS, letrozole +  follicle-stimulating hormone stimulation continued until follicle   >  17 mm and endometrium   ≥   7.5 mm, then human chorionic gonadotropin was given. Cleavage-stage transfer was performed in both groups, and pregnancy outcomes (chemical, clinical, and final) were compared.

RESULTS

The number of transferred embryos (p = 0.771) and their quality (types 1 and 2) (p = 0.857) were similar between groups. The number of chemical pregnancies in the MOS group (25 cases) was non-significantly higher than in the HRT group (20 cases) (p = 0.078). However, the number of clinical pregnancies (p = 0.045) and the number of successful pregnancies (p = 0.049) were significantly higher in the MOS group compared to the HRT group.

CONCLUSION

This study showed that MOS achieved higher clinical and successful pregnancy rates than HRT in women with PCOS.