Endometrial Microbiome and Implantation: From Basic Knowledge to Clinical Medicine

Abstract

Background: Recurrent implantation failure (RIF) is an infertility condition in which uterine factors remain difficult to diagnose and treat. Recent studies implicate the endometrial microbiome in implantation. Methods: This clinically oriented narrative review summarizes female reproductive tract microbiota and evidence on endometrial microbiome testing and management in infertility. Main Findings (Results): Vaginal dysbiosis is linked to adverse reproductive outcomes and provides a reference for interpreting upper-tract findings. Endometrial microbial signals are detectable by sequencing, but interpretation is challenged by the low-biomass environment and vulnerability to carry-over, kitome effects, and contamination. Across ART studies, a Lactobacillus-enriched endometrial profile is more often associated with favorable pregnancy-related outcomes, whereas non–Lactobacillus-dominant patterns are more frequently reported in implantation failure, although effect sizes and statistical significance vary across cohorts and depend on sampling validity and cutoff definitions. Limited nonrandomized intervention studies suggest that testing-guided targeted management (typically antibiotics with or without vaginal Lactobacillus-containing probiotics) may benefit selected patients, but protocols are heterogeneous and results remain inconsistent. Conclusion: Evidence is rapidly evolving, yet observational designs and methodological variability limit causal inference. Future progress will require standardized sampling and contamination controls, outcome-anchored threshold validation, and pragmatic real-world evaluations of protocolized test-and-treat pathways using clinically meaningful endpoints.