THE ROLE OF THE ENDOMETRIAL MICROBIOME IN INFERTILITY AND REPRODUCTIVE HEALTH: CURRENT EVIDENCE AND FUTURE DIRECTIONS
DOI:
https://doi.org/10.31435/ijitss.4(48).2025.4242Keywords:
Uterine Microbiome, Vaginal Microbiota, Implantation, InfertilityAbstract
Infertility affects 10–12% of couples and growing evidence implicates the reproductive tract microbiome in implantation success. This narrative review synthesizes human studies on the vaginal and uterine (endometrial) microbiota in relation to fertility outcomes and mechanistic markers. We searched PubMed/MEDLINE, Embase, and Scopus (2000–30 Oct 2025) for randomized and observational studies reporting implantation, clinical pregnancy, live birth, or relevant biomarkers (e.g., α/β-diversity, inflammatory cytokines, LIF). Data were summarized descriptively due to heterogeneity in sampling, sequencing pipelines, and outcome definitions. Across studies, the uterine cavity is no longer viewed as sterile and typically shows low-biomass, often Lactobacillus-lean communities distinct from the vagina. Dysbiosis—frequently characterized by reduced Lactobacillus dominance and increased anaerobes—has been associated with lower implantation and clinical pregnancy rates and with inflammatory profiles that may suppress LIF. Limited interventional data suggest that targeted therapies (e.g., probiotics or antibiotics followed by probiotics) can restore eubiosis in some patients and may improve implantation, but evidence remains preliminary and at risk of bias. We conclude that microbiome composition is plausibly linked to implantation and early pregnancy outcomes, yet clinical adoption is premature. Standardized sampling, rigorous contamination control, multi-omic profiling, and well-powered randomized trials are needed to define actionable thresholds and therapeutic strategies.
References
World Health Organization. (2020). Infertility: Definitions and terminology. Geneva: WHO.
Zegers-Hochschild, F., Adamson, G. D., Dyer, S., et al. (2017). The International Glossary on Infertility and Fertility Care, 2017. Human Reproduction, 32(9), 1786–1801. https://doi.org/10.1093/humrep/dex234
Chavarro, J. E., Rich-Edwards, J. W., Rosner, B. A., & Willett, W. C. (2007). Diet and lifestyle in the prevention of ovulatory disorder infertility. Obstetrics & Gynecology, 110(5), 1050–1058. https://doi.org/10.1097/01.AOG.0000287293.25465.e1
Bashiri, A., Halper, K. I., & Orvieto, R. (2018). Recurrent implantation failure: Update overview on etiology, diagnosis, treatment and future directions. Reproductive Biology and Endocrinology, 16(1), 121. https://doi.org/10.1186/s12958-018-0414-2
Macklon, N. S., Stouffer, R. L., Giudice, L. C., & Fauser, B. C. J. M. (2006). The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocrine Reviews, 27(2), 170–207. https://doi.org/10.1210/er.2005-0015
Practice Committee of the American Society for Reproductive Medicine. (2021). Fertility evaluation of infertile women: A committee opinion. Fertility and Sterility, 116(6), 1255–1265. https://doi.org/10.1016/j.fertnstert.2021.08.038
Human Microbiome Project Consortium. (2012). Structure, function and diversity of the healthy human microbiome. Nature, 486(7402), 207–214. https://doi.org/10.1038/nature11234
Chen, C., Song, X., Wei, W., et al. (2017). The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nature Communications, 8(1), 875. https://doi.org/10.1038/s41467-017-00901-0
Verstraelen, H., Vilchez-Vargas, R., Desimpel, F., et al. (2016). Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1–V2 region of the 16S rRNA gene. PeerJ, 4, e1602. https://doi.org/10.7717/peerj.1602
Moreno, I., Codoñer, F. M., Vilella, F., et al. (2018). Relevance of assessing the uterine microbiota in infertility. Reproductive Biomedicine Online, 36(3), 247–254. https://doi.org/10.1016/j.fertnstert.2018.04.041
Moreno, I., & Simon, C. (2019). Deciphering the effect of reproductive tract microbiota on human reproduction. Reproductive Medicine and Biology, 18(1), 40–50. https://doi.org/10.1002/rmb2.12249
Polifke, A., Haid, D., & Schuppe-Koistinen, I. (2024). Differential characteristics of vaginal versus endometrial microbiota in IVF patients. Human Reproduction, 39(2), 345–356. doi: 10.1038/s41598-024-82466-9
Chen, W., Zhang, Y., Wang, X., et al. (2021). Identification of uterine microbiota in infertile women and its association with IVF outcomes. Frontiers in Cellular and Infection Microbiology, 11, 672611 doi: 10.3389/fcell.2021.693267
Bui, B. N., Ha, J., Cho, S., et al. (2023). The endometrial microbiota of women with or without a live birth following IVF. Reproductive Biology and Endocrinology, 21(1), 1–10. doi: 10.1038/s41598-023-30591-2
Foteinidou, P., et al. (2024). Endometrial microbiome and its correlation to female infertility. Journal of Assisted Reproduction and Genetics, 41(3), 567–580
doi: 10.3390/amh69010004, DOI:10.3390/amh69010004
Koedooder, R., Singer, M., Schoenmakers, S., et al. (2019). The vaginal microbiome as a predictor for outcome of in vitro fertilization: A prospective study. Human Reproduction, 34(6), 1042–1054. https://doi.org/10.1093/humrep/dez065
Amirchaghmaghi, E., Taghavi, S. A., Shapouri, F., Saeidi, S., Rezaei, A., & Aflatoonian, R. (2013). The role of Toll-like receptors in pregnancy. International Journal of Fertility & Sterility, 7(3)
Kyono, K., Hashimoto, T., Kikuchi, S., et al. (2018). Analysis of endometrial microbiota by 16S rRNA gene sequencing in infertile women. American Journal of Reproductive Immunology, 80(3), e12979, DOI: 10.1002/rmb2.12105
Odendaal, J., et al. (2024). The endometrial microbiota and early pregnancy loss: A scoping review. Fertility and Sterility, 121(2), 123–134, DOI: 10.1093/humrep/dead274
Vomstein, K., et al. (2024). The microbiome in recurrent pregnancy loss: A scoping review. Reproductive Sciences, 31(4), 879–892, DOI: 10.1016/j.jri.2024.104251
Elnashar, A. M., & Fahmy, A. A. (2021). The impact of endometrial microbiome modulation by antibiotics on fertility outcomes. Middle East Fertility Society Journal, 26(1), 8, DOI:10.1186/s43043-020-00050-3
Karadbhajne, P., More, A., & Dzoagbe, H. Y. (2023). The role of endometrial microbiota in fertility and reproductive health: A narrative review. International Journal of Reproductive Medicine, 2023, Article ID 6694321, DOI: 10.7759/cureus.78982
Toson, B., et al. (2022). The endometrial microbiome and its impact on human reproduction. International Journal of Molecular Sciences, 23(12), 6789, DOI: 10.3390/ijms23010485
Lev-Sagie, A., Goldman-Wohl, D., Cohen, Y., et al. (2019). Vaginal microbiome transplantation in women with intractable bacterial vaginosis. Nature Medicine, 25(10), 1500–1504. https://doi.org/10.1038/s41591-019-0600-6
Franasiak, J. M., & Scott, R. T. (2017). Endometrial microbiome at the time of embryo transfer: Implications for implantation and pregnancy outcomes. Fertility and Sterility, 108(1), 29–36 doi: 10.1007/s10815-015-0614-z
Kitazawa, J., & Kimura, F. (2020). Endometrial immunity for embryo implantation and pregnancy establishment. Reproductive Medicine and Biology, 19(1), 6–13, DOI: 10.1620/tjem.250.49
Robertson, S. A., Moldenhauer, L. M., Green, E. S., Care, A. S., & Hull, M. L. (2023). Immune determinants of endometrial receptivity: A biological perspective. Reproductive Biology and Endocrinology, 21(1), 22, DOI: 10.1016/j.fertnstert.2022.04.023
Robertson, S. A., Care, A. S., & Moldenhauer, L. M. (2018). Immune determinants of implantation success. International Journal of Developmental Biology, 62(3–5), 217–227, DOI: 10.1387/ijdb.140096sr
Xiao, L., et al. (2024). Microbiome in female reproductive health: A comprehensive review. Frontiers in Reproductive Health, 2(1), 56–74,
Eisenhofer, R., Minich, J. J., Marotz, C., Cooper, A., Knight, R., & Weyrich, L. S. (2019). Contamination in low microbial biomass microbiome studies: Issues and recommendations. Trends in Microbiology, 27(2), 105–117 DOI: 10.1016/j.tim.2018.11.003
Ranjan, R., Rani, A., Metwally, A., McGee, H. S., & Perlman, D. H. (2016). Analysis of the microbiome: Advantages of whole genome shotgun versus 16S rRNA amplicon sequencing. Briefings in Bioinformatics, 17(4), 858–866, DOI: 10.1016/j.bbrc.2015.12.083
Published
Issue
Section
License
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.

