Impact of GnRH Agonist Pretreatment on Frozen-Thawed Embryo Transfer Outcomes of Overweight/Obese Women Undergoing Hormone Replacement Therapy

Zhihui Huang,1,* Yajie Liao,2,3,* Qiqi Xie,1,* Yanqing Deng,1 Hong Chen,1 Xinxia Wan,1 Lifeng Tian,1 Leizhen Xia,1 Yan Zhao,1 Jialyu Huang1 1Center for Reproductive Medicine, Jiangxi Key Laboratory of Reproductive Health, Jiangxi Maternal and Child Health Hospital, Jiangxi Branch of National Clinical Research Center for Obstetrics and Gynecology, Nanchang Medical College, Nanchang, People’s Republic of China; 2School of Queen Mary, Nanchang University, Nanchang, People’s Republic of China; 3Center for Research, Bright Prosperity Institute, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jialyu Huang; Leizhen Xia, Center for Reproductive Medicine, Jiangxi Maternal and Child Health Hospital, 318 Bayi Avenue, Donghu District, Nanchang, 330006, People’s Republic of China, Email [email protected]; [email protected]: Overweight and obesity are link to impaired endometrial receptivity and decreased pregnancy success in frozen-thawed embryo transfer (FET) cycles. Depot gonadotropin-releasing hormone agonist (GnRH-a) pretreatment before hormone replacement therapy (HRT) has been shown to improve endometrial function through multiple mechanisms. However, its efficacy in overweight and obese women remains unknown.Methods: This retrospective cohort study analyzed 1968 FET cycles from a large fertility center in Jiangxi Province between January 2016 and December 2021. Overweight and obese women were defined as those with body mass index ≥ 24.0 kg/m2 according to the Chinese criteria and categorized into HRT (n=946) and GnRH-a+HRT (n=1022) groups. The primary outcome measure was the live birth rate. Potential confounders were controlled by 1:1 propensity score matching (PSM) and multivariable logistic regression. Subgroup analysis was performed based on the status of dyslipidemia.Results: After PSM, 539 women remained in each group with balanced baseline characteristics. The GnRH-a+HRT group demonstrated a significantly higher live birth rate compared to the HRT group (55.84% vs 49.35%, P=0.033). Similarly, women with GnRH-a pretreatment had higher rates of positive hCG test (77.18% vs 68.65%, P=0.002), clinical pregnancy (68.09% vs 60.48%, P=0.009), and implantation (52.41% vs 47.47%, P=0.039), whereas the miscarriage rate was no statistical difference between groups (17.71% vs 16.87%, P=0.771). In the dyslipidemia subgroup, the increased likelihood of live birth remained for the GnRH-a+HRT protocol (adjusted odds ratio [OR]: 1.75, 95% confidence interval [CI]: 1.08– 2.85), but was not evident in the normolipidemia subgroup (aOR: 1.18, 95% CI: 0.87– 1.58).Conclusion: In summary, our study provides novel clinical evidence suggesting that GnRH-a pretreatment improves FET pregnancy outcomes in overweight and obese women compared to HRT alone, especially among those with dyslipidemia. The findings support a tailored approach for endometrial preparation in this population; however, further multicenter randomized controlled trials are needed for confirmation.Keywords: dyslipidemia, frozen-thawed embryo transfer, gonadotropin-releasing hormone agonist, obesity, pregnancy outcomes