MODERN APPROACHES TO THE DIAGNOSIS AND TREATMENT OF CHRONIC ENDOMETRITIS AND THEIR IMPACT ON FEMALE FERTILITY
(LITERATURE REVIEW)
DOI:
https://doi.org/10.11603/24116-4944.2025.2.15798Keywords:
chronic endometritis, endometrium, reproductive function, infertility, diagnosis, hysteroscopy, assisted reproductive technologies, embryo implantation, microbiomeAbstract
The aim of the study – to summarize current evidence regarding the pathogenesis, diagnostic tools, and therapeutic options for chronic endometritis (CE), as well as to evaluate its impact on female fertility.
Materials and Methods. A systematic review and comparative analysis of scientific publications indexed in PubMed, Google Scholar, and ResearchGate, as well as contemporary literature from the last five years, were conducted. The selection criteria included original research, review articles, and meta-analyses addressing chronic endometritis and its influence on women’s reproductive function.
Results and Discussion. This review presents an integrated analysis of up-to-date research on chronic endometritis, a clinically significant condition with increasing prevalence and a well-established negative impact on female reproductive health. CE is characterized by persistent inflammation of the endometrium, leading to structural alterations, impaired endometrial receptivity, and reduced implantation potential in both natural conception and assisted reproductive technology (ART) cycles. The review consolidates current knowledge regarding the involvement of the endometrial microbiome, local immune dysregulation, morphological changes, and fibrosis in the pathogenesis of CE. Recent studies highlight the importance of accurate and sensitive diagnostic approaches – particularly hysteroscopy, histopathological evaluation, immunohistochemical CD138 testing, and molecular microbiome profiling. The effectiveness of contemporary therapeutic strategies is also discussed, including antibiotic regimens, probiotics, immunomodulatory therapy, and emerging regenerative methods aimed at restoring endometrial receptivity.
Conclusions. Chronic endometritis plays a significant role in reproductive dysfunction, contributing to reduced endometrial receptivity, impaired implantation, and lower success rates in both spontaneous conception and ART. Early, sensitive, and comprehensive diagnostic strategies substantially improve the likelihood of timely detection. Personalized treatment aimed at restoring the endometrial microbiome, reducing inflammation, and improving functional endometrial capacity significantly increases the chances of achieving pregnancy.
References
1. Espinós, J.J., Fabregues, F., Fontes, J., García-Velasco, J.A., Llácer, J., Requena, A., ... & Spanish Infertility SWOT Group (SISG). (2021). Impact of chronic endometritis in infertility: A SWOT analysis. Reproductive Biomedicine Online, 42(5), 939–951. https://doi.org/10.1016/j.rbmo.2021.02.003
2. Buzzaccarini, G., Vitagliano, A., Andrisani, A., Santarsiero, C.M., Cicinelli, R., Nardelli, C., ... & Cicinelli, E. (2020). Chronic endometritis and altered embryo implantation: A unified pathophysiological theory from a literature systematic review. Journal of Assisted Reproduction and Genetics, 37(12), 2897–2911. https://doi.org/10.1007/s10815-020-01955-8
3. Gay, C., Hamdaoui, N., Pauly, V., Rojat Habib, M.C., & Djemli, A. (2021). Antibiotic therapy for chronic endometritis and reproductive outcomes. Fertility and Sterility, 115(4), 1541–1547. https://doi.org/10.1016/j.fertnstert.2021.01.048
4. Reig, A. (2025). Chronic endometritis, chronic questions: A narrative review of current practices. Current Opinion in Obstetrics & Gynecology, 37(5), 361–365. https://doi.org/10.1097/GCO.0000000000001053
5. Veiga, E.C.A., Soares Junior, J.M., Samama, M., Ikeda, F., Francisco, L.S., Sartor, A., ... & Ueno, J. (2023). Chronic endometritis and assisted reproduction: A systematic review and meta-analysis. Revista da Associação Médica Brasileira, 69(10), e20230792. https://doi.org/10.1590/1806-9282.20230792
6. Kaku, S., Kubo, T., Kimura, F., Nakamura, A., Kitazawa, J., Morimune, A., ... & Murakami, T. (2020). Relationship of chronic endometritis with chronic deciduitis in cases of miscarriage. BMC Women's Health, 20, 114. https://doi.org/10.1186/s12905-020-00982-y
7. Xu, Y., Mei, J., Diao, L., Li, Y., & Ding, L. (2020). Chronic endometritis and reproductive failure: Role of syndecan-1. American Journal of Reproductive Immunology, 84(3), e13255. https://doi.org/10.1111/aji.13255
8. Smith, M., Hagerty, K.A., Skipper, B., & Bocklage, T. (2010). Chronic endometritis: A combined histopathologic and clinical review of cases from 2002 to 2007. International Journal of Gynecological Pathology, 29(1), 44–50. https://doi.org/10.1097/PGP.0b013e3181ae81bb
9. Ticconi, C., Inversetti, A., Marraffa, S., Campagnolo, L., Arthur, J., Zambella, E., & Di Simone, N. (2024). Chronic endometritis and recurrent reproductive failure: A systematic review and meta-analysis. Frontiers in Immunology, 15, 1427454. https://doi.org/10.3389/fimmu.2024.1427454
10. Kasius, J.C., Broekmans, F.J., Sie-Go, D.M., Bourgain, C., Eijkemans, M.J.C., Fauser, B.C., ... & Fatemi, H.M. (2012). The reliability of the histological diagnosis of endometritis in asymptomatic IVF cases: A multicenter observer study. Human Reproduction, 27(1), 153–158. https://doi.org/10.1093/humrep/der341
11. Moreno, I., Garcia-Grau, I., Perez-Villaroya, D., Gonzalez-Monfort, M., Bahçeci, M., Barrionuevo, M.J., ... & Simon, C. (2022). Endometrial microbiota composition is associated with reproductive outcome in infertile patients. Microbiome, 10(1), 1. https://doi.org/10.1186/s40168-021-01184-w
12. Kitaya, K., Takeuchi, T., Mizuta, S., Matsubayashi, H., & Ishikawa, T. (2018). Endometritis: New time, new concepts. Fertility and Sterility, 110(3), 344–350. https://doi.org/10.1016/j.fertnstert.2018.04.012
13. Yasuo, T., & Kitaya, K. (2022). Challenges in clinical diagnosis and management of chronic endometritis. Diagnostics, 12(11), 2711. https://doi.org/10.3390/diagnostics12112711
14. Halouani, A., Aloui, H., Hamdaoui, R., Masmoudi, Y., Triki, A., Ben Amor, A., & Halouani, L. (2025). Performance of hysteroscopy in diagnosing chronic endometritis and the role of intra- and inter-observer variability: A prospective study of 70 cases. AJOG Global Reports, 5, 100515. https://doi.org/10.1016/j.xagr.2025.100515
15. Yan, X., Jiao, J., & Wang, X. (2025). The pathogenesis, diagnosis, and treatment of chronic endometritis: A comprehensive review. Frontiers in Endocrinology, 16, 1603570. https://doi.org/10.3389/fendo.2025.1603570
16. Vitagliano, A., Sapia, F., Noventa, M., et al. (2021). Effect of chronic endometritis treatment on IVF outcomes: A systematic review and meta-analysis. Journal of Minimally Invasive Gynecology, 28(5), 1035–1044. https://doi.org/10.1016/j.jmig.2020.12.003
17. Herlihy, N.S., Klimczak, A.M., Titus, S., Scott, C., Hanson, B.M., Kim, J.K., Seli, E., & Scott, R.T. (2022). The role of endometrial staining for CD138 as a marker of chronic endometritis in predicting live birth. Journal of Assisted Reproduction and Genetics, 39(2), 473–479. https://doi.org/10.1007/s10815-021-02374-z
18. Ilic, J., Issa, J., Varinot, J., Bouaziz, J., Massin, N., Haddad, B., ... & Dabi, Y. (2025). Chronic endometritis diagnosis and fertility outcomes: An old unresolved question. Reproduction and Fertility. https://doi.org/10.1530/RAF-25-0016
19. Pérez-Cejuela, B.A., Vitale, S.G., Pérez-Medina, T., Rios-Vallejo, M., Della Corte, L., Vicente, A.R., Angioni, S., & Calles-Sastre, L. (2023). Hysteroscopic versus histopathological agreement in the diagnosis of chronic endometritis: Results from a retrospective observational study. Archives of Gynecology and Obstetrics, 308(6), 1817–1822. https://doi.org/10.1007/s00404-023-07163-w
20. Li, Y., Xu, S., Yu, S., Huang, C., Lin, S., Chen, W., ... & Zeng, Y. (2021). Diagnosis of chronic endometritis: How many CD138+ cells/HPF in endometrial stroma affect pregnancy outcome of infertile women? American Journal of Reproductive Immunology, 85(5), e13369. https://doi.org/10.1111/aji.13369
21. Shen, M., O'Donnell, E., Leon, G., Kisovar, A., Melo, P., Zondervan, K., ... & Southcombe, J. (2021). The role of endometrial B cells in normal endometrium and benign female reproductive pathologies: A systematic review. Human Reproduction Open, 2021(1), hoab043. https://doi.org/10.1093/hropen/hoab043
22. Gu, J., Sun, Q., Qi, Y., Hu, F., & Cao, Y. (2023). The effect of chronic endometritis and treatment on patients with unexplained infertility. BMC Women's Health, 23(1), 345. https://doi.org/10.1186/s12905-023-02499-6
23. Nandagopal, M., Rajan, N.R., Padhiar, C., et al. (2024). Revolutionizing chronic endometritis diagnosis: Real-time polymerase chain reaction unveils microbial pathogens in Indian women with abnormal bleeding and reproductive challenges. AJOG Global Reports, 4, 100377. https://doi.org/10.1016/j.ajoggr.2024.100377
24. Peric, A., Weiss, J., Vulliemoz, N., Baud, D., & Stojanov, M. (2019). Bacterial colonization of the female upper genital tract. International Journal of Molecular Sciences, 20(14), 3405. https://doi.org/10.3390/ijms20143405
25. Kaluanga Bwanga, P., Tremblay-Lemoine, P.L., Timmermans, M., Ravet, S., Munaut, C., Nisolle, M., & Henry, L. (2023). The endometrial microbiota: Challenges and prospects. Medicina, 59(9), 1540. https://doi.org/10.3390/medicina59091540
26. Balla, B., Illés, A., Tobiás, B., Pikó, H., Beke, A., Sipos, M., ... & Kósa, J.P. (2024). The role of the vaginal and endometrial microbiomes in infertility and their impact on pregnancy outcomes in light of recent literature. International Journal of Molecular Sciences, 25(23), 13227. https://doi.org/10.3390/ijms252313227
27. Hu, P., Chen, M., Zhu, L., Song, B., Wang, C., He, X., ... & Cao, Y. (2024). Antibiotics combined with vaginal probiotics in the embryo transfer cycle of infertile patients with chronic endometritis. Frontiers in Cellular and Infection Microbiology, 14, 1494931. https://doi.org/10.3389/fcimb.2024.1494931
28. Song, D., He, Y., Wang, Y., Liu, Z., Xia, E., Huang, X., ... & Li, T.C. (2021). Impact of antibiotic therapy on the rate of negative test results for chronic endometritis: A prospective randomized controlled trial. Fertility and Sterility, 115(6), 1549–1556. https://doi.org/10.1016/j.fertnstert.2020.12.019
29. Cheng, X., Huang, Z., Xiao, Z., & Bai, Y. (2022). Does antibiotic therapy for chronic endometritis improve clinical outcomes of patients with recurrent implantation failure in subsequent IVF cycles? A systematic review and meta-analysis. Journal of Assisted Reproduction and Genetics, 39(8), 1797–1813. https://doi.org/10.1007/s10815-022-02558-1
30. He, X., Chen, W., Zhou, X., Hu, G., Wei, J., Liu, Y., ... & Chen, T. (2025). The therapeutic potential of Lactobacillus crispatus for chronic endometritis: A comprehensive clinical trial and experimental investigation. Probiotics and Antimicrobial Proteins, 17(6), 4047–4065. https://doi.org/10.1007/s12602-024-10349-6
31. Ma, N., Li, J., Zhang, J., Jin, Y., Wang, J., Qin, W., ... & Qin, A. (2023). Combined oral antibiotics and intrauterine perfusion can improve in vitro fertilization and embryo transfer pregnancy outcomes in patients with chronic endometritis and repeated embryo implantation failure. BMC Women's Health, 23(1), 344. https://doi.org/10.1186/s12905-023-02443-8
32. Liu, J., Liu, Z.A., Liu, Y., Cheng, L., & Yan, L. (2022). Impact of antibiotic treatment for chronic endometritis on pregnancy outcomes in women with reproductive failures (RIF and RPL): A systematic review and meta-analysis. Frontiers in Medicine, 9, 980511. https://doi.org/10.3389/fmed.2022.980511
33. Liu, J., Liu, Z.A., Liu, Y., Cheng, L., & Yan, L. (2022). Impact of antibiotic treatment for chronic endometritis on pregnancy outcomes in women with reproductive failures (RIF and RPL): A systematic review and meta-analysis. Frontiers in Medicine, 9, 980511. https://doi.org/10.3389/fmed.2022.980511
34. Ticconi, C., Inversetti, A., Marraffa, S., et al. (2024). Chronic endometritis and recurrent reproductive failure: A systematic review and meta-analysis. Frontiers in Immunology, 15, 1427454. https://doi.org/10.3389/fimmu.2024.1427454
35. Pandey, C., Maunder, A., Liu, J., Vaddiparthi, V., Costello, M.F., Bahri-Khomami, M., ... & Ee, C. (2024). The role of nutrient supplements in female infertility: An umbrella review and hierarchical evidence synthesis. Nutrients, 17(1), 57. https://doi.org/10.3390/nu17010057
36. Lozano, F.M., Bernabeu, A., Lledo, B., Morales, R., Diaz, M., Aranda, F.I., ... & Bernabeu, R. (2021). Characterization of the vaginal and endometrial microbiome in patients with chronic endometritis. European Journal of Obstetrics & Gynecology and Reproductive Biology, 263, 25–32. https://doi.org/10.1016/j.ejogrb.2021.05.045
37. Takimoto, K., Yamada, H., Shimada, S., Fukushi, Y., & Wada, S. (2023). Chronic endometritis and uterine endometrium microbiota in recurrent implantation failure and recurrent pregnancy loss. Biomedicines, 11(9), 2391. https://doi.org/10.3390/biomedicines11092391
38. Alonso-Frías, P., Francés-Herrero, E., Bueno-Fernandez, C., Gómez-Álvarez, M., Agustina-Hernández, M., Cervelló, I., & Cozzolino, M. (2025). Beneficial effects of infiltration of platelet-rich plasma in the endometrium. Biology, 14(4), 319. https://doi.org/10.3390/biology14040319
39. Pantos, K., Simopoulou, M., Maziotis, E., Rapani, A., Grigoriadis, S., Tsioulou, P., ... & Sfakianoudis, K. (2021). Introducing intrauterine antibiotic infusion as a novel approach in effectively treating chronic endometritis and restoring reproductive dynamics: A randomized pilot study. Scientific Reports, 11(1), 15581. https://doi.org/10.1038/s41598-021-95072-w
40. Ban, Y., Yang, X., Xing, Y., Que, W., Yu, Z., Gui, W., ... & Liu, X. (2023). Intrauterine infusion of leukocyte-poor platelet-rich plasma is an effective therapeutic protocol for patients with recurrent implantation failure: A retrospective cohort study. Journal of Clinical Medicine, 12(8), 2823. https://doi.org/10.3390/jcm12082823
41. Zeng, S., Liu, X., Liu, D., & Song, W. (2022). Research update for the immune microenvironment of chronic endometritis. Journal of Reproductive Immunology, 152, 103637. https://doi.org/10.1016/j.jri.2022.103637
42. Santoro, A., Travaglino, A., Inzani, F., Angelico, G., Raffone, A., Maruotti, G.M., ... & Zannoni, G.F. (2023). The role of plasma cells as a marker of chronic endometritis: A systematic review and meta-analysis. Biomedicines, 11(6), 1714. https://doi.org/10.3390/biomedicines11061714
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