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

Background: 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.