The Endometrial Microbiome and Fertility

Background: is the uterus really "sterile"?

Composition: "Lactobacillus-dominant" vs "dysbiotic"

• Eubiotic / Lactobacillus-dominant profile (generally >90% Lactobacillus spp., mirroring a healthy vaginal microbiome) is associated with better reproductive outcomes.
• Dysbiotic profile: a mix of non-Lactobacillus genera - Gardnerella, Streptococcus, Staphylococcus, Enterococcus, Prevotella, Atopobium, and others - is repeatedly linked to:
  • Lower implantation and pregnancy rates
  • Recurrent implantation failure (RIF) (Gao et al. 2025, PMID 40862108; Zhang et al. 2024, PMID 39469742)
  • Recurrent pregnancy loss
  • Chronic endometritis

Proposed mechanisms linking microbiome to fertility

1. Immune tolerance and receptivity: dysbiosis alters local cytokine profiles and immune cell populations (e.g., uterine NK cells, leukemia inhibitory factor signaling), impairing the immune tolerance needed for trophoblast invasion (Inversetti et al., Int J Mol Sci 2023, PMID 36769318; Zhang et al. 2024).
2. Chronic endometritis (CE): subclinical inflammation, often driven by Streptococcus, Enterococcus, E. coli, Mycoplasma/Ureaplasma, and Gardnerella, is strongly overrepresented in women with unexplained infertility and RIF. Antibiotic treatment of CE has been shown to restore spontaneous conception rates in several cohort studies (Cicinelli et al., cited in Berek & Novak's Gynecology).
3. Direct endometrial receptivity effects: dysbiotic microbiota has been correlated with altered expression of implantation markers in the secretory-phase endometrium.
4. Catheter contamination at embryo transfer: bacteria present on the transfer catheter tip have been shown to influence live birth rates after IVF (Moore et al., Fertil Steril 2000).

Clinical relevance / testing

Bottom line

• A Lactobacillus-dominated endometrial niche correlates with better implantation and pregnancy outcomes; dysbiosis (non-Lactobacillus overgrowth) correlates with implantation failure, RIF, and possibly pregnancy loss.
• Chronic endometritis, frequently identified through the same dysbiotic organisms, is a treatable contributor to unexplained infertility in some women.
• The field is still evolving: sampling contamination (from vaginal/cervical flora during biopsy), low biomass, and variable sequencing methods limit reproducibility across studies, so mechanistic causality (versus association) is not fully established.

Evidence currency check

Predominant Lactobacillus Species in the Endometrium

Key points

• L. crispatus is the species most reproducibility associated with a favorable, "protective" endometrial/vaginal environment - lower pH, hydrogen peroxide and bacteriocin production, and resistance to colonization by pathogens such as Gardnerella vaginalis (Goldman-Cecil Medicine).
• L. iners is paradoxical: it is the single most prevalent species in reproductive-age women, can persist through hormonal fluctuations and even mild dysbiosis, but a microbiota dominated by L. iners is less protective than one dominated by L. crispatus and is more often seen with bacterial vaginosis and, in some studies, with adverse reproductive outcomes.
• L. gasseri and L. jensenii-dominant profiles are less common but are also considered part of the "healthy," protective spectrum alongside L. crispatus.
• When any of these four Lactobacillus species collectively make up the community (a "Lactobacillus-dominant" state, generally defined as >90% relative abundance), outcomes are consistently better than a dysbiotic, polymicrobial state dominated by non-Lactobacillus genera (Gardnerella, Prevotella, Atopobium, Streptococcus, Enterococcus, Bacteroides), which is linked to implantation failure, chronic endometritis, and pregnancy loss.