The role of microbiome in female fertility and reproductive health

The role of microbiome in female fertility and reproductive health | Image Credit: © MP - © MP - stock.adobe.com.

Influence of microbiome on female fertility and reproductive health

Female fertility and reproductive health may be influenced by a diverse microbiome, according to a recent study published in Reproductive and Developmental Medicine.¹

This data disproves the assumption held for decades that the uterus is a sterile environment. Alongside reduced odds of pregnancy in women with a non-Lactobacillus-dominated (LD) environment receiving in vitro fertilization (IVF), the research highlighted a link between microbiota composition with conditions such as endometriosis and recurrent implantation failure.

“A disturbed microbiome may create a hostile environment for embryo implantation” said Kai-Fai Lee, MD, corresponding author. “This could explain why some women struggle with unexplained infertility despite having no obvious reproductive issues.”

Lactobacillus dominance in reproductive health

According to investigators, Lactobacilli are the most abundant vaginal flora among reproductive-aged women, with a 60.7% implantation rate from LD endometrial microbiomes vs 23.1% from non-LD microbiomes.² For pregnancy, reported rates were 70.6% and 33.3%, respectively.

A key role of Lactobacilli is the production of lactic acid keeping pH low at 3.5 to 4.5, reducing the risk of harmful or pathogenic bacteria growing. This species is able to dominate during puberty when increased estrogenic glycogen levels lead to a decrease in pH.

Microbiota in the uterus, fallopian tubes, and cervix

The Lactobacillus species also dominates the vagina, with common samples including Acinetobacter, Pseudomonas, and Comamonadaceae. Data has also indicated 5326 transcriptionally active microorganisms in endometrial biopsy samples, 85% of which were bacteria, 10% fungi, 5% viruses, and 0.2% archaea.

A median relative abundance of 1.6% has been reported for Lactobacillus in the Falliopan tubes, but no Lactobacillus was identified in peritoneal fluid. Common cervical bacteria in reproductive-aged women include Lactobacillus, Pseudomonas, Acinetobacter, Vagococcus, Sphingobium, and others, with reported rates of 30.6%, 9%, 9%, 7.2%, 5%, and 11%, respectively.

Microbiota has also been evaluated in patients with infertility. Research found significantly reduced endometrial lactobacilli in IVF patients vs non-IVF patients, at 63.9% ± 41.4% vs 96.2% ± 34.6%, respectively. Lactobacillus was also reduced in the endometrium for these patients, at 38% and 73.9%, respectively.

Endometriosis and its connection to microbiota imbalance

Chronic endometriosis (CE) odds are increased by bacterial infections in the uterine cavity, highlighting additional roles of the microbiome. Twelve percent to 46% of infertility cases are linked to CE, and infertile patients are significantly more likely to present with CE than fertile patients.

Additionally, endometriosis has been identified in women with significantly varied uterine microbiota compositions. These include Pseudomonas, Acinetobacter, Vagococcus, and Sphingobium presentation in the uteri of women with infertility, alongside significantly decreased Lactobacillus in endometriotic samples.

The endometrial microbiome experiences changes during the proliferative and secretory phases of a healthy normal cycle. However, women with dysfunctional menstrual bleeding mainly experience anaerobes endometrial microbiota, potentially indicating dysbiosis that increases infection risks.

Endometrial polyps are also linked to CE, and women with this condition have presented with increased Lactobacillus, Bifidobacterium, Gardnerella, Streptococcus, Alteromonas, and Euryarchaeota. These women also had decreased Pseudomonas and Enterobacteriaceae.

Short-chain fatty acids and their role in fertility

Investigators also evaluated short-chain fatty acids (SCFAs) from the microbiota, as they lead to a reduction in bacterial phagocytosis. A 2000-fold increase in the presence of multiple pro-inflammatory cytokines, chemokines, and anti-inflammatory cytokine IL-10 was reported among bacterial-induced factors vs a control group without bacteria.

Conclusion

This data highlighted crucial roles of Lactobacillus and other abundant bacteria in the vaginal and uterine microbiota. Multiple positive effects were reported, including anti-inflammatory activities.

“Producing various molecules, including SCFAs, modulates human physiology and reproductive outcomes. Balanced microbiota in healthy individuals are crucial in pregnancy outcomes.,” investigators concluded.

References

1. How the microbiome influences female fertility? EurekAlert. February 24, 2025. Accessed March 7, 2025. https://www.eurekalert.org/news-releases/1074654
2. Manish K, Luhan J, Hoi-Lan L, et al. Impact of microbiota on female fertility and gynecological problems. Reproductive and Developmental Medicine, 2025;8(4):242-251. doi:10.1097/RD9.0000000000000082