The relationship between the microbiota type and immune resources of the endometrium among infertile women in the implantation window phase

   The features of the microbiota and the immune profile of the endometrium of women with infertility of different genesis during the "implantation window" period have been studied. Endometrial phenotypes different in immune profile and microbiota profile within each group were identified (with infertility of unclear genesis, tube-peritoneal genesis, chronic endometritis, "thin" endometrium): "normal," dysplastic, chronic inflammation. The phenotype of chronic endometritis is revealed a significant predominance of cytokines of the pro-inflammatory Th1/Th1 profile in the presence of a dysbiotic microbiota type. The features of the dysplastic endometrial phenotype consist in a "poor" immune response (cytokines, chemokines, growth factors) against the background of pronounced fibrotic transformation. Ideas about the endometrial phenotype (normal, dysplastic, chronic inflammation) are a criterion for readiness for blastocyst implantation.

1. Chen P., Yang M., Wang Y. et al. Aging endometrium in young women: Molecular classification of endometrial aging-based markers in women younger than 35 years with recurrent implantation failure // J Assist Reprod Genet. 2022. Vol. 39. N9. P.2143-2151. doi: 10.1007/s10815-022-02578-x

2. Chen W., Wei K., He X. et al. Identification of Uterine Microbiota in Infertile Women Receiving in vitro Fertilization with and Without Chronic Endometritis // Front. Cell Dev. Biol. 2021. Vol. 9. P. 693267. doi: 10.3389/fcell.2021.693267

3. Cicinelli E., Matteo M., Tinelli R. et al.: Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy // Hum Reprod. 2015. Vol. 30. P.323–330.

4. Drizi A., Djokovic D., Laganà A.S., van Herendael B. Impaired inflammatory state of the endometrium: a multifaceted approach to endometrial inflammation. Current insights and future directions // Prz Menopauz. 2020. Vol. 19. P. 90-100.

5. Franasiak J.M., Scott R.T. Reproductive tract microbiome in assisted reproductive technologies // Fertil. Steril. 2015. Vol. 104. P. 1364–1371. doi: 10.1016/j.fertnstert.2015.10.012

6. Gellersen B., Brosens J.J. Cyclic decidualization of the human endometrium in reproductive health and failure // Endocr Rev. 2014. Vol. 35. P. 851–905. doi: 10.1210/er.2014-1045

7. Haggerty C.L., Hillier S.L., Bass D.C. et al.: Bacterial Vaginosis and Anaerobic Bacteria Are Associated with Endometritis // Clinical Infectious Diseases. 2004. Vol. 39. P.990–995.

8. Hooper L.V., Littman D.R., Macpherson A.J. Interactions between the microbiota and the immune system // Science. 2012. Vol. 336. N 6086. P. 1268–1273. doi: 10.1126/science.1223490.

9. Huang J., Qin H., Yang Y. et al. A Comparison of Transcriptomic Profiles in Endometrium During Window of Implantation Between Women With Unexplained Recurrent Implantation Failure and Recurrent Miscarriage // Reproduction. 2017. Vol. 153. N 6. P. 749–58. doi: 10.1530/REP-16-0574

10. Katz S., Zsiros V., Doczi N., Kiss A.L. Inflammation-induced epithelialto-mesenchymal transition and GM-CSF treatment stimulate mesenteric mesothelial cells to transdifferentiate into macrophages // Inflammation. 2018. P. 825. doi: 10.1007/s10753-018-0825-4

11. Kitaya K., Matsubayashi H., Takaya Y. et al.: Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure // Am J Reprod Immunol. 2017. Vol. 78. P.5. doi: 10.1111/aji.12719.

12. Kyono K., Hashimoto T., Kikuchi S. et al. A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium // Reprod. Med. Biol. 2019. Vol. 18. P.72–82. doi: 10.1002/rmb2.12250.

13. Lédée N., Petitbarat M., Chevrier L. et al. The Uterine Immune Profile May Help Women With Repeated Unexplained Embryo Implantation Failure After In Vitro Fertilization // Am. J. Reprod. Immunol. 2016. Vol. 75. P. 388–401. doi: 10.1111/aji.12483

14. Lessey B.A., Young SL. What exactly is endometrial receptivity? // Fertil Steril. 2019. Vol. 111. P. 611–617.

15. Li X., Cannon A.R., Hammer A.M. et al. IL-23 restoration of Th17 effector function is independent of IL-6 and TGF-β in a mouse model of alcohol and burn injury // J Leukoc Biol. 2017. Vol.102. P.915–23. doi: 10.1189/jlb.3A1216-527R

16. Ohara Y., Matsubayashi H., Suzuki Y. et al. Clinical relevance of a newly developed endometrial receptivity test for patients with recurrent implantation failure in Japan // Reprod Med Biol. 2022. Vol.21. P.e12444. doi: 10.1002/rmb2.12444

17. Paul M.K, Bisht B., Darmawan D.O. et al. Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling // Cell Stem Cell. 2014. Vol. 15. P. 199–214.

18. Vannuccini S., Clifton V.L., Fraser I.S. et al. Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome // Hum Reprod Update. 2016. Vol. 22, N 1. P.104–115. doi: 10.1093/humupd/dmv044.

19. von Hundelshausen P., Agten S.M., Eckardt V. et al. Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation // Sci. Transl. Med. 2017. N 9. P.384. eaah6650. doi: 10.1126/scitranslmed.aah6650

20. Yen M., Donma O., Yildizfer F. et al. Association of fetuin A, adiponectin, interleukin 10 and total antioxidant capacity with IVF outcomes // Iran. J. Reprod. Med. 2014. V. 12. P. 747–754.