Comparing ART outcomes in women with endometriosis after GnRH agonist versus GnRH antagonist ovarian hyperstimulation: A systematic review and meta-analysis

Background: Endometriosis can cause subfertility and women may require assisted reproductive technology (ART) to achieve their pregnancy goals. Objectives: To compare ART outcomes following the long GnRH-agonist and GnRH-antagonist controlled ovarian hyperstimulation (COH) protocols in patients with endometriosis. Search Strategy: MEDLINE, Embase, and Web of Science were systematically searched in February 2021. Selection Criteria: Randomised controlled trials (RCTs) and observational studies comparing GnRH-agonist versus GnRH-antagonist COH in women with all stages/subtypes of endometriosis. Data Collection and Analysis: Pooled weighted mean differences and relative risks were calculated using the random effects model. The Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-1) and ROB-2 tools (for RCT) were used for risk of bias assessment. Main Results: 7 studies (1 RCT, 6 observational) with 2,477 patients were included. Meta-analysis of the studies found no difference in the number of oocytes retrieved, clinical pregnancy rates, live birth rates, and gonadotrophin dose required for COH. Fertilization rates were significantly higher with the GnRH-agonist protocol (MD 4.3; 95% CI 0.30–8.29; P = 0.04). The GnRH-antagonist protocol required a significantly shorter COH duration (MD 0.44; 95% CI 0.11 – 0.78; P = 0.01). Studies were of moderate to high risk of bias. Conclusion: Both the long GnRH-agonist and GnRH-antagonist COH protocols generally yield similar ART outcomes. Clinicians should consider, treatment costs, stage/type of endometriosis, and pregnancy goals of their patients when selecting a GnRH-analogue for COH. A well-powered RCT is needed to minimise risk of bias and compare the risk for ovarian hyperstimulation syndrome.