Vaginal microbiota and female infertility: systematic review and meta-analysis
Low-Lactobacillus vaginal microbiota (LL-VMB) is associated with increased risk of female infertility (OR 1.65; 95% CI 1.35–2.01), with effect direction favoring Lactobacillus-dominant microbiota.
| Population | Women of reproductive age, including patients from assisted reproduction centers and population cohorts |
|---|---|
| Intervention | LL-VMB (low-Lactobacillus vaginal microbiota), bacterial vaginosis (BV), or intermediate microbiota assessed by Nugent score, Amsel/Spiegel criteria, or 16S rRNA sequencing |
| Comparator | Lactobacillus-dominant vaginal microbiota |
| Outcome | Infertility associated with LL-VMB; Infertility associated with bacterial vaginosis; Infertility associated with intermediate microbiota; Infertility risk CST IV vs CST I (network meta-analysis); Tubal factor infertility associated with vaginal dysbiosis; Unexplained infertility associated with vaginal dysbiosis; Certainty of evidence (GRADE) for LL-VMB and infertility |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| Infertility associated with LL-VMB | OR 1.65, 95% CI 1.35-2.01 | — | Moderate | — | 31 studies |
| Infertility associated with bacterial vaginosis | OR 1.74, 95% CI 1.35-2.24 | — | Moderate | — | |
| Infertility associated with intermediate microbiota | OR 1.38, 95% CI 1.02-1.87 | — | Low | — | |
| Infertility risk CST IV vs CST I (network meta-analysis) | highest ranked CST for infertility risk vs CST I reference; exact OR not extractable from abstract | — | Low | — | |
| Tubal factor infertility associated with vaginal dysbiosis | subgroup data reported; exact OR not extractable from available text | — | Low | — | |
| Unexplained infertility associated with vaginal dysbiosis | subgroup data reported; exact OR not extractable from available text | — | Low | — | |
| Certainty of evidence (GRADE) for LL-VMB and infertility | GRADE assessment performed; rated low to very low due to observational design and heterogeneity | — | Low | — | 31 studies |
Context
Infertility affects approximately 1 in 6 adults globally; female factors account for 40–50% of cases. Lactobacillus-dominant vaginal microbiota is considered protective for conception, but quantitative evidence on the impact of distinct community state types (CSTs) remained fragmented.
What the study showed
LL-VMB was associated with OR 1.65 (95% CI 1.35–2.01) for infertility versus Lactobacillus-dominant microbiota. BV alone was associated with OR 1.74 (95% CI 1.35–2.24). Intermediate microbiota showed OR 1.38 (95% CI 1.02–1.87). In the network meta-analysis by CSTs, CST IV (anaerobic/non-Lactobacillus) showed the highest relative risk compared to CST I (L. crispatus-dominant).
How it was done
Systematic review and meta-analysis of observational studies (case-control, cohort, cross-sectional) identified in PubMed, Embase, Web of Science, Scopus, and Cochrane Library up to July 2025. Thirty-one studies met inclusion criteria; quality assessed by NOS and AHRQ; evidence certainty by GRADE; network meta-analysis for CSTs via MCMC (BUGSnet/JAGS).
Effect magnitude
OR 1.65 (95% CI 1.35–2.01) for LL-VMB versus Lactobacillus-dominant; moderate to high heterogeneity expected given the aggregated observational design. Clinical magnitude is modest to moderate.
Risk of bias
All included studies are observational; reverse causality cannot be excluded (infertility may alter microbiota). Risk of bias assessed by NOS and AHRQ — tools with recognized limitations for confounder control. Substantial clinical heterogeneity: different diagnostic criteria, populations, control definitions, and outcome definitions. Restriction to English-language publications excludes potentially relevant literature. CST data partially extracted from heatmaps, introducing imprecision risk.
What this study does NOT prove
This meta-analysis does not prove causality between vaginal dysbiosis and infertility — observational association does not establish cause and effect. Results are not generalizable to populations with high STI prevalence or low-income reproductive health settings where data are sparse.
In clinical practice
Presence of LL-VMB, BV, or intermediate microbiota identifies a subgroup of women with modestly elevated infertility risk; this information may be incorporated into initial evaluation. No RCT evidence demonstrates that restoring Lactobacillus-dominant microbiota improves conception rates — intervention should not be prescribed based on this meta-analysis alone.
Limitations
All included studies are observational; reverse causality cannot be excluded (infertility may alter microbiota). Risk of bias assessed by NOS and AHRQ — tools with recognized limitations for confounder control. Substantial clinical heterogeneity: different diagnostic criteria, populations, control definitions, and outcome definitions. Restriction to English-language publications excludes potentially relevant literature. CST data partially extracted from heatmaps, introducing imprecision risk.
What is still missing
RCTs evaluating whether restoration of Lactobacillus-dominant microbiota improves reproductive outcomes in infertile women are needed. Longitudinal studies with high-resolution sequencing and robust confounder adjustment (STIs, antibiotics, lifestyle) are a priority.
Technical appendix
Version history
- 1.0 · 2026-11-06 — Auto-generated under Evidence Standard v1.0