Distinctive reproductive tract microbial characteristics associated with infertility in women: a systematic review and meta-analysis.

OBJECTIVE

To evaluate α-diversity alterations, summarize microbial taxa reported to be associated with infertility, and examine site-specific differences in reproductive tract microbiota between infertile and fertile women via systematic review and meta-analysis.

DATA SOURCES: Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were searched from inception to December 30, 2025, supplemented by clinical trial registries, conference proceedings, and manual reference screening.

STUDY ELIGIBILITY CRITERIA: Observational studies (cross-sectional, case-control, cohort) including women 18-45 years with infertility versus healthy fertile controls, using high-throughput sequencing of reproductive tract microbiota, reporting α-diversity or taxa abundance. Excluded randomized controlled trials (RCTs), animals, reviews.

STUDY APPRAISAL AND SYNTHESIS

METHODS

PRISMA-compliant review. The Newcastle-Ottawa Scale (NOS) for quality, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for evidence. Random-effects meta-analysis with standardized mean differences (SMD) and 95% credible interval (CrI); I² for heterogeneity; subgroup and sensitivity analyses by site.

RESULTS

Twenty-seven studies with 2174 participants were included. Infertile women had higher α-diversity (Shannon SMD 0.27 [0.10 to 0.44; I² = 40%], Simpson SMD 0.24 [0.01 to 0.47; I² = 52%], ACE SMD 0.43 [0.15 to 0.71; I² = 33%]). Lactobacillus abundance was lower (SMD -0.40 [-0.55 to -0.25; I² = 0%]), while Prevotella (SMD 0.48 [0.27 to 0.70; I² = 12%]) and Burkholderia (SMD 0.55 [0.33 to 0.77; I² = 0%]) were higher. Changes were prominent in vaginal samples, and β-diversity differed in 81% of studies.

CONCLUSIONS

Infertile women show site-specific microbiota patterns, including reduced Lactobacillus and elevated opportunistic pathogens in the reproductive tract, especially vaginally. Given the low to very low certainty of largely observational evidence, high-quality prospective studies are needed to validate these associations and clarify causality.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251275219.