Endometrial microbiota-targeted therapies for chronic endometritis-associated recurrent implantation failure and their impact on IVF outcomes: A systematic review and methodological quality assessment.

Abstract

<h4>Introduction</h4>Recurrent implantation failure (RIF) is a multifactorial reproductive disorder, often associated with chronic endometritis (CE) and alterations of the intrauterine microbiota.<h4>Material and methods</h4>This systematic review evaluated whether microbiota-targeted therapeutic interventions improve pregnancy outcomes in women with CE-associated RIF undergoing in vitro fertilization (IVF)-embryo transfer (ET). Study quality and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) and the Revised Cochrane Risk of Bias in Non-Randomized Studies - of Interventions (ROBINS-I).<h4>Results</h4>Four studies met the inclusion criteria, encompassing antibiotic, probiotic, and nutraceutical interventions. Considerable heterogeneity was observed in study design, diagnostic criteria, and microbiota assessment methods. Across studies, the reproductive outcomes revealed a clinical pregnancy rate of 50.5% (187/370), ongoing pregnancy rate of 40.1% (107/267), and live birth rate of 41.2% (105/255). Other reported outcomes included seven multiple pregnancies (8.3%), 39 miscarriages (20.0%), 35 biochemical pregnancies (17.9%), and one stillbirth (1.17%).<h4>Conclusions</h4>Microbiota-targeted treatments may improve reproductive outcomes in women with CE-associated RIF; however, the limited number of available studies, small sample sizes, and methodological variability reduce the strength of current evidence. High-quality, prospective, confounder-adjusted trials with rigorous participant selection processes and standardized, validated diagnostic and implementation criteria are needed to confirm these findings and inform clinical practice.