Daniela Ruiz, Victoria Robinson, Mariam Doucoure, Amara R Cheema, Carolina Ramirez Cabal, Afrah Saleef Abdul Salam, Rimane Abi Younes, Weiai Song, Sarah Ayoub Ibrahim, Olushola Ariyo, Rajat Das Gupta
The female reproductive tract microbiome has emerged as a potential factor associated with reproductive health, infertility, and outcomes of assisted reproductive technologies (ARTs). Growing interest in host-microbiome interactions has highlighted the potential roles of microbial communities in implantation, immune regulation, and endometrial receptivity. This comprehensive narrative review summarizes current evidence on the reproductive tract microbiome and its relationship with infertility and ART outcomes. Relevant literature was identified from MEDLINE, Embase, and Web of Science from database inception through March 2026, with emphasis on observational, interventional, and mechanistic studies involving human participants or human-derived samples. The review examines microbial communities of the vagina, cervix, endometrium, and fallopian tubes and their associations with infertility, recurrent pregnancy loss, implantation failure, and ART outcomes. Proposed biological mechanisms, including alterations in epithelial barrier integrity, immune modulation, inflammatory signaling, and hormonal-microbial interactions, are also discussed. In addition, the review evaluates emerging microbiome-based diagnostic approaches and potential therapeutic strategies, including antibiotics, probiotics, micronutrient supplementation, and vaginal microbiota transplantation. Current evidence suggests that the reproductive tract microbiome may be associated with reproductive health and fertility outcomes and represents a promising area of translational research. However, substantial methodological heterogeneity, limited high-quality interventional evidence, and the lack of standardized diagnostic criteria currently restrict clinical implementation. Well-designed prospective studies and randomized clinical trials are needed to clarify causal relationships, evaluate microbiome-targeted interventions, and determine whether microbiome-based approaches can improve infertility and ART care.