Microbiota and infertility: a translational review of mechanisms and clinical applications in assisted reproduction.

Infertility constitutes a major global health concern, affecting approximately 17.5% of couples of reproductive age. Although advances in assisted reproductive technologies (ART) have expanded treatment options, success rates remain highly variable due to host-specific and biological determinants. This review synthesizes current evidence on the reproductive impact of the human microbiota and its translational relevance to ART outcomes. Vaginal microbial communities dominated by Lactobacillus, particularly L. crispatus, are associated with improved conception and implantation, whereas genital or intestinal dysbiosis correlates with infertility and suboptimal treatment responses. The microbiota modulates reproductive competence through intertwined immune, endocrine-metabolic, and mucosal barrier pathways that regulate inflammation, hormonal balance, and epithelial integrity. Emerging findings indicate that gut microbial alterations linked to polycystic ovary syndrome (PCOS) and endometriosis are accompanied by insulin resistance and chronic inflammation, impairing ovulation, endometrial receptivity, and embryo viability. Interventions such as probiotics and synbiotics yield heterogeneous efficacy; individualized antimicrobial strategies, metabolic modulation, and lifestyle optimization may offer complementary benefit, while microbiota reconstruction remains experimental. Methodological limitations, including contamination in low biomass samples, variations in sequencing workflows, and population heterogeneity, still hinder data comparability and mechanistic interpretation. Future research should prioritize adequately powered randomized controlled trials using standardized microbiome metrics and live birth as a primary endpoint. Integrating microbiome profiling into ART workflows may refine patient stratification and inform precision adjuvant therapies. However, clinical implementation requires stronger causal evidence, validated biomarkers, and harmonized methodological frameworks to translate microbiome discoveries into reproducible reproductive gains.