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

Kobra Hamdi; Sahar Khakpour; Aliyeh Ghasemzadeh Darjani; Laya Farzadi; Behrouz Niknafs; Nazli Navali; Parvin Hakimi; Roghayeh Anvari Aliabad; Hamed Hajipour

doi:10.18502/ijrm.v23i12.20712

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

Int J Reprod Biomed. 2026 Feb 14;23(12):995-1006. doi: 10.18502/ijrm.v23i12.20712. eCollection 2025 Dec.

Authors

Kobra Hamdi¹, Sahar Khakpour¹, Aliyeh Ghasemzadeh Darjani¹, Laya Farzadi¹, Behrouz Niknafs², Nazli Navali¹, Parvin Hakimi¹, Roghayeh Anvari Aliabad¹, Hamed Hajipour³

Affiliations

¹ Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
² Department of Anatomical Sciences, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
³ School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

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 $\geq$ 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.

Keywords: Frozen embryo; Hormonal therapy; Mild ovarian stimulation protocol.; Endometrium; Polycystic ovary syndrome.