There are many causes of infertility, some of which are unknown, which bring difficulties to the diagnosis and treatment of infertility.With the further deepening of human understanding of microecology and the development of 16s rRNA gene sequencing and other technologies, it is gradually recognized that the endometrium is not a sterile environment, and there is a correlation between microecological imbalance and infertility. The endometrial microbiome may have a previously unrecognized role in uterine physiology and human reproduction. The analysis of endometrial microbiota is helpful to find the risk factors of reproductive tract diseases and provide guidance and help for the treatment of infertility. This article mainly reviews the research progress of female endometrial microecology in recent years, in order to improve the treatment methods and clinical outcomes of infertility.

Jiexia Qiu, Weiyan Huang, Jiahui He. Research progress of endometrial microecology in infertile women. Frontiers in Medical Science Research (2023) Vol. 5, Issue 1: 7-12. https://doi.org/10.25236/FMSR.2023.050102.

[1] Human Microbiome Project Consortium. (2012). Structure, function and diversity of the healthy human microbiome. Nature, 486(7402), 207–214.

[2] NIH HMP Working Group, Peterson, J., Garges, S., Giovanni, M., McInnes, P., Wang, L., Schloss, J. A., Bonazzi, V., McEwen, J. E., Wetterstrand, K. A., Deal, C., Baker, C. C., Di Francesco, V., Howcroft, T. K., Karp, R. W., Lunsford, R. D., Wellington, C. R., Belachew, T., Wright, M., Giblin, C., … Guyer, M. (2009). The NIH Human Microbiome Project. Genome research, 19(12), 2317–2323. 

[3] Ravel, J., Gajer, P., Abdo, Z., Schneider, G. M., Koenig, S. S., McCulle, S. L., Karlebach, S., Gorle, R., Russell, J., Tacket, C. O., Brotman, R. M., Davis, C. C., Ault, K., Peralta, L., & Forney, L. J. (2011). Vaginal microbiome of reproductive-age women. Proceedings of the National Academy of Sciences of the United States of America, 108 Suppl 1(Suppl 1), 4680–4687. 

[4] Hyman, R. W., Herndon, C. N., Jiang, H., Palm, C., Fukushima, M., Bernstein, D., Vo, K. C., Zelenko, Z., Davis, R. W., & Giudice, L. C. (2012). The dynamics of the vaginal microbiome during infertility therapy with in vitro fertilization-embryo transfer. Journal of assisted reproduction and genetics, 29(2), 105–115. 

[5] Zhu, N., Yang, X., Liu, Q., Chen, Y., Wang, X., Li, H., & Gao, H. (2022). "Iron triangle" of regulating the uterine microecology: Endometrial microbiota, immunity and endometrium. Frontiers in immunology, 13, 928475. 

[6] Franasiak, J. M., & Scott, R. T., Jr (2015). Reproductive tract microbiome in assisted reproductive technologies. Fertility and sterility, 104(6), 1364–1371.

[7] Mitchell, C. M., Haick, A., Nkwopara, E., Garcia, R., Rendi, M., Agnew, K., Fredricks, D. N., & Eschenbach, D. (2015). Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women. American journal of obstetrics and gynecology, 212(5), 611.e1–611.e6119. 

[8] Walther-António, M. R., Chen, J., Multinu, F., Hokenstad, A., Distad, T. J., Cheek, E. H., Keeney, G. L., Creedon, D. J., Nelson, H., Mariani, A., & Chia, N. (2016). Potential contribution of the uterine microbiome in the development of endometrial cancer. Genome medicine, 8(1), 122.

[9] Verstraelen, H., Vilchez-Vargas, R., Desimpel, F., Jauregui, R., Vankeirsbilck, N., Weyers, S., Verhelst, R., De Sutter, P., Pieper, D. H., & Van De Wiele, T. (2016). Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene. PeerJ, 4, e1602.

[10] Chen, C., Song, X., Wei, W., Zhong, H., Dai, J., Lan, Z., Li, F., Yu, X., Feng, Q., Wang, Z., Xie, H., Chen, X., Zeng, C., Wen, B., Zeng, L., Du, H., Tang, H., Xu, C., Xia, Y., Xia, H., … Jia, H. (2017). The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nature communications, 8(1), 875. 

[11] Babu, G., Singaravelu, B. G., Srikumar, R., Reddy, S. V., & Kokan, A. (2017). Comparative Study on the Vaginal Flora and Incidence of Asymptomatic Vaginosis among Healthy Women and in Women with Infertility Problems of Reproductive Age. Journal of clinical and diagnostic research: JCDR, 11(8), DC18–DC22. 

[12] Wee, B. A., Thomas, M., Sweeney, E. L., Frentiu, F. D., Samios, M., Ravel, J., Gajer, P., Myers, G., Timms, P., Allan, J. A., & Huston, W. M. (2018). A retrospective pilot study to determine whether the reproductive tract microbiota differs between women with a history of infertility and fertile women. The Australian & New Zealand journal of obstetrics & gynaecology, 58(3), 341–348. 

[13] Fanchin, R., Harmas, A., Benaoudia, F., Lundkvist, U., Olivennes, F., & Frydman, R. (1998). Microbial flora of the cervix assessed at the time of embryo transfer adversely affects in vitro fertilization outcome. Fertility and sterility, 70(5), 866–870. 

[14] Selman, H., Mariani, M., Barnocchi, N., Mencacci, A., Bistoni, F., Arena, S., Pizzasegale, S., Brusco, G. F., & Angelini, A. (2007). Examination of bacterial contamination at the time of embryo transfer, and its impact on the IVF/pregnancy outcome. Journal of assisted reproduction and genetics, 24(9), 395–399. 

[15] Inzunza, J., Midtvedt, T., Fartoo, M., Norin, E., Osterlund, E., Persson, A. K., & Ahrlund-Richter, L. (2005). Germfree status of mice obtained by embryo transfer in an isolator environment. Laboratory animals, 39(4), 421–427. 

[16] Franasiak, J. M., Werner, M. D., Juneau, C. R., Tao, X., Landis, J., Zhan, Y., Treff, N. R., & Scott, R. T. (2016). Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit. Journal of assisted reproduction and genetics, 33(1), 129–136.

[17] Moreno, I., Codoñer, F. M., Vilella, F., Valbuena, D., Martinez-Blanch, J. F., Jimenez-Almazán, J., Alonso, R., Alamá, P., Remohí, J., Pellicer, A., Ramon, D., & Simon, C. (2016). Evidence that the endometrial microbiota has an effect on implantation success or failure. American journal of obstetrics and gynecology, 215(6), 684–703. 

[18] Benner, M., Ferwerda, G., Joosten, I., & van der Molen, R. G. (2018). How uterine microbiota might be responsible for a receptive, fertile endometrium. Human reproduction update, 24(4), 393–415. 

[19] McQueen, D. B., Bernardi, L. A., & Stephenson, M. D. (2014). Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertility and sterility, 101(4), 1026–1030. 

[20] Kasius, J. C., Fatemi, H. M., Bourgain, C., Sie-Go, D. M., Eijkemans, R. J., Fauser, B. C., Devroey, P., & Broekmans, F. J. (2011). The impact of chronic endometritis on reproductive outcome. Fertility and sterility, 96(6), 1451–1456. 

[21] Dimitriadis, E., White, C. A., Jones, R. L., & Salamonsen, L. A. (2005). Cytokines, chemokines and growth factors in endometrium related to implantation. Human reproduction update, 11(6), 613–630. 

[22] Di Pietro, C., Cicinelli, E., Guglielmino, M. R., Ragusa, M., Farina, M., Palumbo, M. A., & Cianci, A. (2013). Altered transcriptional regulation of cytokines, growth factors, and apoptotic proteins in the endometrium of infertile women with chronic endometritis. American journal of reproductive immunology (New York, N.Y.: 1989), 69(5), 509–517. 

[23] Cicinelli, E., Matteo, M., Tinelli, R., Lepera, A., Alfonso, R., Indraccolo, U., Marrocchella, S., Greco, P., & Resta, L. (2015). Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Human reproduction (Oxford, England), 30(2), 323–330. 

[24] Kitaya, K., Matsubayashi, H., Takaya, Y., Nishiyama, R., Yamaguchi, K., Takeuchi, T., & Ishikawa, T. (2017). Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure. American journal of reproductive immunology (New York, N.Y. : 1989), 78(5), 10.1111/aji.12719. 

[25] Verhelst, R., Verstraelen, H., Claeys, G., Verschraegen, G., Delanghe, J., Van Simaey, L., De Ganck, C., Temmerman, M., & Vaneechoutte, M. (2004). Cloning of 16S rRNA genes amplified from normal and disturbed vaginal microflora suggests a strong association between Atopobium vaginae, Gardnerella vaginalis and bacterial vaginosis. BMC microbiology, 4, 16.