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Review
. 2025 Jun 5;15(6):916.
doi: 10.3390/life15060916.

Behind-the-Scenes Actors in Fertility: A Comprehensive Review of the Female Reproductive Tract Microbiome and Its Clinical Relevance

Anthi Papakonstantinou  1 , Efthalia Moustakli  2 , Anastasios Potiris  1 , Athanasios Zikopoulos  1 , Ermioni Tsarna  3 , Chrysi Christodoulaki  1 , Ioannis Tsakiridis  4 , Themistoklis Dagklis  4 , Periklis Panagopoulos  1 , Peter Drakakis  1 , Sofoklis Stavros  1
Affiliations
Review

Behind-the-Scenes Actors in Fertility: A Comprehensive Review of the Female Reproductive Tract Microbiome and Its Clinical Relevance

Anthi Papakonstantinou et al. Life (Basel). .

Abstract

The study of the microbiome has rapidly progressed over the past few decades, capturing the interest of both scientists and the general public. Nevertheless, there is still no widely agreed-upon definition for the term "microbiome" despite tremendous advances in our knowledge. The international scientific literature consistently underscores the difference between the human microbiome and human microbiota. Recent research has emphasized the importance of the female reproductive tract microbiome in fertility, impacting natural conception and assisted reproductive technologies (ARTs). This review explores the relationship between infertility and the microbiota of the female reproductive tract through a thorough evaluation of research papers and large-scale studies published up to 2024. The objective of this review is to critically assess current evidence on the role of the reproductive tract microbiome in female infertility and ART outcomes. Relevant papers were identified and analyzed through the electronic medical databases PubMed/MEDLINE and Scopus. A comprehensive synthesis of data from 36 original studies was performed, including observational, case-control, cohort, and randomized trials. By focusing on the vagina, cervix, and endometrium, this study offers a comprehensive overview of the microbiome throughout the female reproductive tract. RIF and poor reproductive outcomes are strongly linked to dysbiosis, which is characterized by a reduction in Lactobacillus species. Lactobacillus crispatus, in particular, plays a significant role in protecting against bacterial vaginosis and infertility. A thorough understanding of how the microbiome impacts fertility and the development of clinical strategies to improve reproductive outcomes requires standardized microbiome investigation techniques and larger, randomized trials that account for diverse patient characteristics.

Keywords: Lactobacillus; female infertility; female reproductive system; microbiome; microbiota.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Overview of the female reproductive tract microbiota.
Figure 2
Figure 2
Flow diagram illustrating the selection process of the review.
Figure 3
Figure 3
Microbial profiles associated with eubiotic and pathological endometrial conditions. The diagram illustrates key bacterial genera identified in the endometrium of women with normal (eubiotic) microbiota and those with endometriosis, hyperplasia, polyposis, myomatosis, and endometrial cancer, highlighting overlaps and condition-specific associations.
See this image and copyright information in PMC

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