Efficacy of hormone pre‐treatment before ART to improve reproductive outcomes in infertile women with endometriosis: Network meta‐analysis of randomized controlled trials

Background: Hormone pre-treatment is still used before assisted reproductive technique (ART) in endometriotic women, but evidence supporting this recommendation is conflicting. Objectives: To evaluate whether hormone pre-treatment with gonadotropin-releasing hormone (GnRH) agonists or progestogens could improve fertility in women with endometriosis undergoing ART. Search Strategy: MEDLINE, LILACS, EMBASE, Scielo.br, PROSPERO, Cochrane at the CENTRAL Register of Controlled Trials, conference abstracts, and international controlled trials registries were searched without temporal, geographic, and language limitations. Selection Criteria: Randomized controlled trials that enrolled infertile women with endometriosis undergoing in vitro fertilization/intracytoplasmic sperm injection after the application of a stimulation protocol with hormone pre-treatment were selected and included. Data Collection and Analysis: We conducted a network meta-analysis based on the random-effects model for mixed multiple treatment comparisons to rank the available hormone pre-treatment by the surface under the cumulative ranking curve area (SUCRA) following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension statement for network meta-analyses. Quality assessment was carried out using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Egger test and funnel plot analysis were used for publication bias assessment. The primary outcome was clinical pregnancy rate (CPR). Secondary outcomes were live birth rate (LBR), pregnancy loss rate (PLR), and implantation rate (IR). Main Results: Nine studies with 2087 women were included. Ultralong (3 months GnRH agonist) (SUCRA 24.5%) and long protocols (1 month GnRH agonist) (SUCRA 24.9%) as well as progestins (SUCRA 28.8%) showed similar results to no treatment (SUCRA 21.8%) in terms of post-ART CPR. Regarding the LBR, no treatment (SUCRA 50.0%) showed highest rates relative to progestins (SUCRA 7.0%), and long (SUCRA 36.6%) and ultralong (SUCRA 6.4%) protocols. For PLR, no treatment (SUCRA 57.9%), followed by long protocol (SUCRA 18.4%), ultralong protocol (SUCRA 12.3%), and progestins (SUCRA 11.4%) showed the greatest degree of reduction. The long (SUCRA 45.0%) and ultralong (SUCRA 39.5%) protocols seemed more effective in increasing IR than did than progestins (SUCRA 15.5%). Conclusions: The increased number of implanted pregnancies using a GnRH agonist protocol does not lead to higher clinical pregnancies or live births. Currently, there is no indication for hormone pre-treatment before ART in women with endometriosis as it does not increase fertility chances.