Chronic Endometritis and Endometriosis: Two Sides of the Same Coin?

Both chronic endometritis and endometriosis are common entities in infertile patients. The association and the co-existence of these two entities are poorly evaluated. The aim of this systematic review and meta-analysis was to examine the association between chronic endometritis and endometriosis and to find the prevalence of chronic endometritis in women with endometriosis. A systematic electronic search was conducted using the MEDLINE, Scopus and Cochrane databases up to May 2022. Observational studies which examined the prevalence of chronic endometritis in women with endometriosis were included. Newcastle–Ottawa Scale was used for the quality assessment. Odds ratios (OR) with 95% confidence intervals (CIs) for dichotomous outcomes and pooled prevalences with 95% CIs were calculated. 855 studies were identified, of which six studies were included in the systematic review and five in the meta-analysis. The prevalence of chronic endometritis in women with endometriosis was 28%, with higher frequency observed in women with endometriosis rASRM stage III-IV (43%) in comparison to women with endometriosis rASRM stage I-II (25%). The meta-analysis showed a significantly higher chronic endometritis in women with endometriosis in comparison to the control group (five studies, 264 endometriosis vs. 435 control, OR = 2.07; 95% CI 1.11–3.84, I2 43%, p = 0.02). The present meta-analysis showed a significantly higher risk of chronic endometritis in women with endometriosis in comparison to the control group. These findings contribute to a better understanding of the causes and consequences of endometriosis and chronic endometritis and may help in the development of more efficient treatment strategies for women with associated infertility. Similar content being viewed by others Data Availability Not applicable. Code Availability Not applicable. Change history 30 January 2025 A Correction to this paper has been published: https://doi.org/10.1007/s43032-025-01805-x

Kitaya K, et al. Endometritis: new time, new concepts. Fertil Steril. 2018;110(3):344–50. Singh N, Sethi A. Endometritis - diagnosis, treatment and its impact on fertility - a scoping review. JBRA Assist Reprod. 2022;26(3):538–46. Molina NM, et al. New opportunities for endometrial health by modifying uterine microbial composition: present or future? Biomolecules. 2020;10(4):593. Murtinger M, et al. Diagnosing chronic endometritis: when simplification fails to clarify. Hum Reprod Open. 2022;2022:hoac023. Chen YQ, et al. Analysis of the diagnostic value of CD138 for chronic endometritis, the risk factors for the pathogenesis of chronic endometritis and the effect of chronic endometritis on pregnancy: a cohort study. BMC Womens Health. 2016;16(1):60. Johnston-MacAnanny EB, et al. Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertil Steril. 2010;93(2):437–41. McQueen DB, et al. Redefining chronic endometritis: the importance of endometrial stromal changes. Fertil Steril. 2021;116(3):855–61. Santoro A, et al. The role of plasma cells as a marker of chronic endometritis: a systematic review and meta-analysis. Biomedicines. 2023;11(6):1714. Bouet PE, et al. Chronic endometritis in women with recurrent pregnancy loss and recurrent implantation failure: prevalence and role of office hysteroscopy and immunohistochemistry in diagnosis. Fertil Steril. 2016;105(1):106–10. Liu Y, et al. Comparison of the prevalence of chronic endometritis as determined by means of different diagnostic methods in women with and without reproductive failure. Fertil Steril. 2018;109(5):832–9. Kushnir VA, et al. Systemic inflammation and autoimmunity in women with chronic endometritis. Am J Reprod Immunol. 2016;75(6):672–7. Cicinelli E, Cicinelli R, Vitagliano A. Consistent evidence on the detrimental role of severe chronic endometritis on in vitro fertilization outcome and the reproductive improvement after antibiotic therapy: on the other hand, mild chronic endometritis appears a more intricate matter. Fertil Steril. 2021;116(2):345–6. Mitter VR, et al. Treatment following hysteroscopy and endometrial diagnostic biopsy increases the chance for live birth in women with chronic endometritis. Am J Reprod Immunol. 2021;86(5):e13482. Vitagliano A, et al. Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure: a systematic review and meta-analysis. Fertil Steril. 2018;110(1):103-112.e1. Shafrir AL, et al. Risk for and consequences of endometriosis: a critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol. 2018;51:1–15. Kalaitzopoulos DR, et al. Treatment of endometriosis: a review with comparison of 8 guidelines. BMC Womens Health. 2021;21(1):397. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382(13):1244–56. Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39(4):535–49. Kohl Schwartz AS, et al. Endometriosis, especially mild disease: a risk factor for miscarriages. Fertil Steril. 2017;108(5):806-814.e2. Tanbo T, Fedorcsak P. Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options. Acta Obstet Gynecol Scand. 2017;96(6):659–67. Pirtea P, de Ziegler D, Ayoubi JM. Endometrial receptivity in adenomyosis and/or endometriosis. Fertil Steril. 2023;120:928. Paffoni A, et al. Live birth after oocyte donation in vitro fertilization cycles in women with endometriosis: a systematic review and meta-analysis. JAMA Netw Open. 2024;7(1):e2354249. Moher D, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. Freitag N, et al. Are uterine natural killer and plasma cells in infertility patients associated with endometriosis, repeated implantation failure, or recurrent pregnancy loss? Arch Gynecol Obstet. 2020;302(6):1487–94. Khan KN, et al. Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis†. Hum Reprod. 2014;29(11):2446–56. Wells G, et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analysis. 2000. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Takebayashi A, et al. The association between endometriosis and chronic endometritis. PLoS ONE. 2014;9(2):e88354. Cicinelli E, et al. Chronic endometritis in patients with unexplained infertility: Prevalence and effects of antibiotic treatment on spontaneous conception. Am J Reprod Immunol. 2018;79(1):e12782. Qiao X, et al. Existence of chronic endometritis and its influence on pregnancy outcomes in infertile women with minimal/mild endometriosis. Int J Gynaecol Obstet. 2023;160(2):628–34. Kitaya K, Yasuo T. Immunohistochemistrical and clinicopathological characterization of chronic endometritis. Am J Reprod Immunol. 2011;66(5):410–5. Khan KN, et al. Occurrence of chronic endometritis in different types of human adenomyosis. Reprod Med Biol. 2022;21(1):e12421. Margulies SL, et al. The diagnostic criteria for chronic endometritis: a survey of pathologists. Int J Gynecol Pathol. 2021;40(6):556–62. Puente E, et al. Chronic endometritis: old problem, novel insights and future challenges. Int J Fertil Steril. 2020;13(4):250–6. Ejzenberg D, et al. Blind aspiration biopsy versus a guided hysteroscopic technique for investigation of the endometrium in infertile women. Histol Histopathol. 2016;31(9):981–6. Kim MR, et al. High frequency of endometrial polyps in endometriosis. J Am Assoc Gynecol Laparosc. 2003;10(1):46–8. Vitagliano A, et al. Association between endometrial polyps and chronic endometritis: is it time for a paradigm shift in the pathophysiology of endometrial polyps in pre-menopausal women? Results of a systematic review and meta-analysis. Diagnostics (Basel). 2021;11(12):2182. Bender Atik R, et al. (2023) ESHRE guideline: recurrent pregnancy loss: an update in 2022. Hum Reprod Open. 2023;1:hoad002. Straub RH. The complex role of estrogens in inflammation. Endocr Rev. 2007;28(5):521–74. Gajbhiye R, et al. Multiple endometrial antigens are targeted in autoimmune endometriosis. Reprod Biomed Online. 2008;16(6):817–24. Greenbaum H, et al. Endometriosis and autoimmunity: Can autoantibodies be used as a non-invasive early diagnostic tool? Autoimmun Rev. 2021;20(5):102795. Sarapik A, et al. Serum anti-endometrial antibodies in infertile women - potential risk factor for implantation failure. Am J Reprod Immunol. 2010;63(5):349–57. Leonardi M, et al. Endometriosis and the microbiome: a systematic review. BJOG. 2020;127(2):239–49. Jiang I, et al. Intricate Connections between the Microbiota and Endometriosis. Int J Mol Sci. 2021;22(11):5644. Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas. 2017;103:45–53. Cicinelli E, et al. Chronic endometritis: correlation among hysteroscopic, histologic, and bacteriologic findings in a prospective trial with 2190 consecutive office hysteroscopies. Fertil Steril. 2008;89(3):677–84. Kitaya K, Yasuo T. Aberrant expression of selectin E, CXCL1, and CXCL13 in chronic endometritis. Mod Pathol. 2010;23(8):1136–46. Di Pietro C, et al. Altered transcriptional regulation of cytokines, growth factors, and apoptotic proteins in the endometrium of infertile women with chronic endometritis. Am J Reprod Immunol. 2013;69(5):509–17. Wu D, et al. Chronic endometritis modifies decidualization in human endometrial stromal cells. Reprod Biol Endocrinol. 2017;15(1):16. Mirakhor Samani S, et al. Expression of p53, Bcl-2 and Bax in endometrial carcinoma, endometrial hyperplasia and normal endometrium: a histopathological study. J Obstet Gynaecol. 2018;38(7):999–1004. Fatima N, et al. Structural equation modelling analysis determining causal role among methyltransferases, methylation, and apoptosis during human pregnancy and abortion. Sci Rep. 2020;10(1):12408. Yilmaz BD, Bulun SE. Endometriosis and nuclear receptors. Hum Reprod Update. 2019;25(4):473–85. Samartzis N, et al. The immunohistochemical expression of GPER and classical sex hormone receptors differs in adenomyosis and eutopic endometrium. J Reprod Immunol. 2023;156:103795. Monsivais D, et al. ERβ- and prostaglandin E2-regulated pathways integrate cell proliferation via Ras-like and estrogen-regulated growth inhibitor in endometriosis. Mol Endocrinol. 2014;28(8):1304–15. Ryan E, et al. The menstrual cycle phase impacts the detection of plasma cells and the diagnosis of chronic endometritis in endometrial biopsy specimens. Fertil Steril. 2022;118(4):787–94. Liu Y, et al. Additional dydrogesterone for the treatment of chronic endometritis treated with antibiotic in premenopausal women with endometrial polyps: a retrospective cohort study. BMC Womens Health. 2022;22(1):435. Qu D, et al. Combination of dydrogesterone and antibiotic versus antibiotic alone for chronic endometritis: a randomized controlled trial study. Reprod Sci. 2021;28(11):3073–80. Pinto V, et al. Altered uterine contractility in women with chronic endometritis. Fertil Steril. 2015;103(4):1049–52. Leyendecker G, et al. Archimetrosis: the evolution of a disease and its extant presentation : Pathogenesis and pathophysiology of archimetrosis (uterine adenomyosis and endometriosis). Arch Gynecol Obstet. 2023;307(1):93–112. Tortorella C, et al. Interleukin-6, interleukin-1β, and tumor necrosis factor α in menstrual effluents as biomarkers of chronic endometritis. Fertil Steril. 2014;101(1):242–7. Espinós JJ, et al. Impact of chronic endometritis in infertility: a SWOT analysis. Reprod Biomed Online. 2021;42(5):939–51. Darici E, Blockeel C, Mackens S. Should we stop screening for chronic endometritis? Reprod Biomed Online. 2023;46(1):3–5. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author information Authors and Affiliations Contributions DRK and NS were involved in the conception and design of the study. UC, PD and GS were involved in the acquisition of data, analysis and interpretation of data, and drafting of the article. BL, AKS, DRK, NS, PD and UC were involved in revising the manuscript critically for important intellectual content. DRK was responsible for final approval of the version to be submitted. Corresponding author Ethics declarations Ethics Approval Not applicable. Consent to Participate Not applicable. Consent for Publication Not applicable. Conflicts of Interest DRK has nothing to disclose related to this study, UC has nothing to disclose related to this study, AKS has nothing to disclose related to this study, GS has nothing to disclose related to this study, BL has nothing to disclose related to this study, PD has nothing to disclose related to this study, NS has nothing to disclose related to this study. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Kalaitzopoulos, D.R., Catena, U., Schwartz, A.K. et al. Chronic Endometritis and Endometriosis: Two Sides of the Same Coin?. Reprod. Sci. 32, 474–487 (2025). https://doi.org/10.1007/s43032-025-01785-y Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-025-01785-y