Reproductive Tract Microbiome, Infertility, and ART: Comprehensive Narrative Review
This narrative review associates non-Lactobacillus-dominant endometrial profiles with worse implantation and ART outcomes, but establishes no causality and provides no quantified effect estimates.
| Population | Adults with infertility or undergoing ART (IVF, ICSI, embryo transfer) |
|---|---|
| Intervention | Characterization of the female reproductive tract microbiome (vagina, cervix, endometrium, fallopian tubes) by 16S rRNA sequencing and NGS |
| Comparator | Lactobacillus-dominant vs. non-Lactobacillus-dominant (NLD) profiles; fertile vs. infertile populations (when applicable) |
| Outcome | Implantation rate (Lactobacillus-dominant vs. NLD endometrium); Clinical pregnancy in ART cycles; Live birth rate in ART cycles; Recurrent implantation failure associated with NLD profile; Chronic endometritis associated with NLD microbiome; Vaginal CST I profile (L. crispatus) and reproductive environment; Efficacy of microbiome-based interventions (probiotics, antibiotics) in ART |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| Implantation rate (Lactobacillus-dominant vs. NLD endometrium) | not reported (narrative review; in the pooled estimate) | — | Low | — | |
| Clinical pregnancy in ART cycles | not reported (narrative review; in the pooled estimate) | — | Low | — | |
| Live birth rate in ART cycles | not reported (narrative review; in the pooled estimate) | — | Low | — | |
| Recurrent implantation failure associated with NLD profile | not reported (narrative review; in the pooled estimate) | — | Low | — | |
| Chronic endometritis associated with NLD microbiome | not reported (narrative review; in the pooled estimate) | — | Low | — | |
| Vaginal CST I profile (L. crispatus) and reproductive environment | not reported (narrative review; in the pooled estimate) | — | Low | — | |
| Efficacy of microbiome-based interventions (probiotics, antibiotics) in ART | not reported (narrative review; in the pooled estimate) | — | Very low | — |
Context
Infertility affects approximately one in six adults globally and imposes substantial psychological, social, and financial burdens. The female reproductive tract microbiome has emerged as a potential modulator of endometrial receptivity and ART outcomes. The absence of quantitative synthesis and formal risk-of-bias assessment limits the practical conclusions of this review.
What the study showed
Included observational studies associate Lactobacillus-dominant endometrial profiles with higher implantation, clinical pregnancy, and live-birth rates in ART cycles; NLD profiles (enriched with Gardnerella, Prevotella, Atopobium) were associated with worse outcomes and chronic endometritis. No absolute numbers, relative risks, or confidence intervals were reported in the review for any outcome. Vaginal CST I (L. crispatus) is associated with a more favorable reproductive environment; CST IV is associated with bacterial vaginosis and, in some studies, implantation failure. The review acknowledges substantial heterogeneity among primary studies and lack of methodological standardization.
How it was done
Comprehensive narrative review; structured search of MEDLINE, Embase, and Web of Science from inception to March 2026. No protocol registration, no independent duplicate screening, no PRISMA, no formal risk-of-bias assessment (RoB 2, ROBINS-I, or AMSTAR-2), and no quantitative meta-analysis. Observational, interventional, and mechanistic human studies were included, along with systematic reviews and meta-analyses to identify primary literature.
Effect magnitude
No quantitative effect size estimates (RR, OR, SMD, MD) or confidence intervals were derived or synthesized in this review; the magnitude of effects described in primary studies cannot be extracted from this publication.
Risk of bias
Narrative design without a registered protocol, without risk-of-bias assessment (RoB 2/ROBINS-I/AMSTAR-2 not applied), and without quantitative synthesis precludes causal conclusions. Marked heterogeneity in primary studies — populations, sequencing platforms, microbial classifications, and outcome definitions — is acknowledged by the authors themselves. Selection bias in study inclusion and contamination in low-biomass samples (endometrium, fallopian tubes) are additional unquantified limitations.
What this study does NOT prove
This review does not prove causality between reproductive microbiome composition and infertility or ART failure. Findings are not generalizable to unstudied populations and do not support individualized therapeutic recommendations based on microbial profiles.
In clinical practice
Evidence is insufficient to recommend routine endometrial or vaginal microbiome screening before ART. Microbiome-based therapeutic approaches (probiotics, microbiota transplantation, targeted antibiotics) remain experimental and should not be incorporated into standard clinical protocols without support from RCTs with live-birth outcomes. Clinicians should treat established infections (bacterial vaginosis, chronic endometritis) according to current guidelines.
Limitations
Narrative design without a registered protocol, without risk-of-bias assessment (RoB 2/ROBINS-I/AMSTAR-2 not applied), and without quantitative synthesis precludes causal conclusions. Marked heterogeneity in primary studies — populations, sequencing platforms, microbial classifications, and outcome definitions — is acknowledged by the authors themselves. Selection bias in study inclusion and contamination in low-biomass samples (endometrium, fallopian tubes) are additional unquantified limitations.
What is still missing
Well-designed RCTs evaluating microbiome-directed interventions (probiotics, selective antibiotics) with live birth as the primary outcome in ART populations are needed. Standardization of sequencing methods, diagnostic thresholds, and dysbiosis criteria is a prerequisite for cross-study comparability.
Technical appendix
Version history
- 1.0 · 2026-10-29 — Auto-generated under Evidence Standard v1.0