Association of GnRH Agonist Pretreatment with Reproductive Outcomes in Women ≥35 years with Diminished Ovarian Reserve Undergoing Frozen Embryo Transfer: A Large Retrospective Cohort Study

Yueping Zhou, Zhiqi Liao, Yaxin Guo Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Yaxin Guo, Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei, 430030, People’s Republic of China, Tel +86 13297966986, Email guoyaxin610@163.comPurpose: This study aimed to assess whether different endometrial preparation regimens—natural cycle (NC), hormone replacement therapy (HRT), and gonadotropin-releasing hormone agonist pretreatment followed by HRT (GnRH-a + HRT)—are associated with differences in reproductive and perinatal outcomes among women with diminished ovarian reserve undergoing frozen embryo transfer (FET), and to evaluate whether age (< 35 vs ≥ 35 years) modifies these associations.Patients and Methods: A total of 4629 women with DOR, defined as anti-Müllerian hormone (AMH) < 1.2 ng/mL and/or antral follicle count (AFC) < 5, undergoing their first autologous FET between 2016 and 2024. Endometrial preparation protocols included natural cycle (NC), hormone replacement therapy (HRT), or gonadotropin-releasing hormone agonist (GnRH-a) pretreatment followed by HRT. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to adjust for baseline differences.Results: GnRH-a pretreatment before HRT was associated with improved live birth and clinical pregnancy compared with HRT alone, particularly among older women. No significant differences were observed between natural cycle and HRT. Perinatal outcomes among singleton live births were generally comparable across protocols.Conclusion: GnRH-a pretreatment before HRT may be beneficial for women with diminished ovarian reserve undergoing FET, particularly in those of advanced maternal age.Keywords: diminished ovarian reserve, frozen embryo transfer, endometrial preparation, GnRH agonist, pregnancy outcomes