Effects of gonadotropin-releasing hormone agonist pretreatment on frozen embryo transfer outcomes in artificial cycles: a meta-analysis

Purpose: Gonadotropin-releasing hormone agonist (GnRHa) before artificial cycle (AC) is expected to improve pregnancy outcomes in frozen-thawed embryo transfer (FET). Many studies have explored the impact of GnRHa pretreatment of AC in FET, but the results were inconsistent. This meta-analysis was performed to systematically evaluate the effect of GnRHa pretreatment on AC in FET.

Methods: The last search was January 31, 2022. Randomized controlled trials and cohort studies aiming to assess the effect of GnRHa as the pretreatment of AC for endometrial preparation in FET were included. GnRHa was used before AC in the treatment group. In the control group, no pretreatment was used before AC. The eligible studies included at least one of the following outcomes: implantation, clinical pregnancy, and live birth. We calculated the odds ratio (OR) or mean difference (MD) and 95% confidence interval (CI) for each study and used a random-effects or fixed model to estimate the results.

Results: 27 articles (10 RCTs and 17 non-RCTs) and 14152 patients were included. AC + GnRHa improved the implantation rate (OR = 1.31, 95% CI 1.03-1.66, I² = 79%), clinical pregnancy rate (OR = 1.27, 95% CI 1.10-1.45, I² = 53%), and live birth rate (OR = 1.16, 95% CI 1.05-1.29, I² = 39%). We also found that AC + GnRHa increased the implantation rate (OR = 1.35, 95% CI 1.07-1.69, I² = 53%) and clinical pregnancy rate (OR = 1.50, 95% CI 1.12-2.01, I² = 50%) in repeated implantation failure. In addition, AC + GnRHa was positively associated with preterm birth (OR = 1.5, 95% CI 1.15-1.94, I² = 0%).

Conclusions: GnRHa pretreatment in FET can improve implantation, clinical pregnancy, and live birth rates, especially in patients with repeated implantation failure. GnRHa pretreatment seems to improve FET outcomes, though with a higher preterm birth rate.