Infertile women show higher microbial diversity and lower Lactobacillus abundance in their reproductive tracts compared to fertile women, with stronger shifts in vaginal samples. The evidence is observational and low-to-very-low certainty, so causality remains unclear.
A systematic review and meta-analysis of 27 studies involving 2,174 women identified consistent microbial differences between infertile and fertile women. The analysis, published in Frontiers in Cellular and Infection Microbiology, quantified alpha-diversity changes (species richness within samples) and catalogued bacterial taxa linked to reduced fertility.
The most striking finding: infertile women had higher overall microbial diversity in the reproductive tract. This seems counterintuitive since diversity is often considered beneficial for health, but in the vaginal microbiota, it may indicate dysbiosis, a state of microbial imbalance. Across three diversity measures, the increases were consistent. Shannon diversity increased by a standardized mean difference of 0.27, Simpson diversity by 0.24, and ACE diversity by 0.43 in infertile women. These differences, while statistically significant, had moderate heterogeneity in some measures (up to 52% for Simpson), meaning variation across studies was substantial.
Lactobacillus abundance was substantially lower in infertile women (SMD -0.40), with minimal variation across studies (I² = 0%), suggesting this finding is robust. Lactobacillus species, particularly Lactobacillus crispatus and Lactobacillus gasseri, dominate healthy vaginal microbiota and produce lactic acid, maintaining an acidic environment that suppresses pathogenic bacteria. By contrast, Prevotella and Burkholderia bacteria were elevated in infertile women (SMD 0.48 and 0.55, respectively). These organisms are classified as opportunistic pathogens and their overgrowth has been associated with inflammation and altered immune function in the reproductive tract.
The microbiota shifts were most pronounced in vaginal samples. The analysis also noted that beta-diversity, which measures differences in microbial composition between individuals, differed significantly between infertile and fertile women in 81% of included studies, pointing to highly variable dysbiosis patterns even within the infertile group.
This research identifies an association between reproductive tract microbiota composition and infertility, but does not establish causation. The studies reviewed were observational, comparing microbiota profiles between existing groups rather than testing interventions. This means we cannot conclude that dysbiosis causes infertility, only that the two are correlated.
For those investigating infertility, this suggests reproductive tract microbiota may warrant clinical attention, though no validated microbiota-targeting treatments for infertility are yet standard of care. Vaginal microbiota testing is commercially available but utility for infertility management is not established by high-quality evidence. If microbiota dysbiosis is confirmed in a given individual, therapeutic approaches under investigation include targeted probiotics or vaginal microbiota transplantation, but efficacy data remain limited.
General reproductive health practices remain foundational: smoking-cessation, stress management, sleep-duration, nutritional status, and treatment of underlying gynecological conditions. The role of vaginal microbiota optimization as a fertility intervention requires prospective, randomized controlled trial data to clarify.
The authors explicitly note that very low certainty of evidence warrants caution in interpretation. High-quality prospective studies tracking microbiota changes over time and testing microbiota-directed interventions are needed before clinical recommendations can be made.
| Parameter | Details |
|---|---|
| Study Type | Systematic review and meta-analysis |
| Sample Size | 2,174 women across 27 studies |
| Study Design | Observational (cross-sectional, case-control, cohort) |
| Evidence Certainty | Low to very low (per GRADE assessment) |
| Primary Outcomes | Alpha-diversity, Lactobacillus abundance, opportunistic pathogen abundance |
| Key Finding | Infertile women: higher diversity, lower Lactobacillus, elevated Prevotella and Burkholderia |
| Heterogeneity | Moderate to high variation across studies; most pronounced for Simpson diversity (I² = 52%) |
| Site-Specific Patterns | Changes most prominent in vaginal samples; 81% of studies showed significant beta-diversity differences |
| Journal | Frontiers in Cellular and Infection Microbiology |
| Registration | PROSPERO CRD420251275219 |
Frontiers in Cellular and Infection Microbiology. "Distinctive reproductive tract microbial characteristics associated with infertility in women: a systematic review and meta-analysis." 2025. PubMed. Available at: https://pubmed.ncbi.nlm.nih.gov/42394823/
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