Effect of Postoperative Hormonal Suppression on Fertility in Patients With Endometriosis After Conservative Surgery

Abstract

To evaluate the effect of hormonal suppression on fertility when administered to infertile patients or patient wishing to conceive after surgery for endometriosis. A systematic search of MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov was performed by two independent reviewers from the databases' inception until December 2020. We included randomized controlled trials comparing any suppressive hormonal therapy to an inactive control (placebo or absence of treatment) after conservative surgery for endometriosis. Studies that did not report fertility outcomes after surgery were excluded. This systematic review and meta-analysis was registered in PROSPERO. Two reviewers extracted data and assessed the risk of bias as well as the strength of evidence using GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed. Relative risks (RRs) were pooled by quantitative random effect meta-analysis. From 3,138 citations, 19 trials (2,028 patients) were included. Overall, no difference was observed between the treatment and the control group for pregnancy (RR 1.15; 95% CI 1.00-1.32) and live births (RR 1.05; 95% CI 0.84-1.32). When pooling all hormonal therapies, the duration of administration of postoperative therapy was identified as a substantial source of heterogeneity between studies (I2 difference=74%) with increased chances of pregnancy compared with control when administered for at least 3 months (RR 1.22; 95% CI 1.04-1.43). Gonadotropin-releasing hormone (GnRH) agonists (14 trials, 1,721 patients) were associated with increased chances of pregnancy compared with placebo or no treatment (RR 1.20; 95% CI 1.03-1.41; I2=25%). Data were limited for other hormonal treatments with no significant difference between groups. Subgroup analyses taking into account the use of fertility treatments (insemination or in vitro fertilization), stages of the disease and risk of bias of included trials did not modify the results. Postoperative hormonal suppression should be considered on a case-by-case basis to enhance fertility while balancing this benefit with the risks of delaying conception. If chosen, GnRH agonists would be the treatment of choice, and a duration of at least 3 months should be favored. PROSPERO, CRD42021224424.