Chronic endometritis: A prevalent yet poorly understood entity
Margulies SL,Flores V,Parkash V,Pal L
Published July 2022International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 158(1), 194-200
Margulies, S. L., Flores, V., Parkash, V., & Pal, L. (2022). Chronic endometritis: A prevalent yet poorly understood entity. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 158(1), 194-200. https://doi.org/10.1002/ijgo.13962
Margulies SL, Flores V, Parkash V, Pal L. Chronic endometritis: A prevalent yet poorly understood entity. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2022;158(1):194-200. doi:10.1002/ijgo.13962
Margulies, S. L., et al. "Chronic endometritis: A prevalent yet poorly understood entity." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, vol. 158, no. 1, 2022, pp. 194-200.
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Abstract
Objective
To examine the prevalent understanding of and management approaches to chronic endometritis among obstetricians/gynecologists.
Methods
In a cross-sectional observational study, 262 members of national and international professional obstetrician/gynecologist societies were surveyed via anonymous electronic survey that investigated knowledge of the pathophysiology, diagnostic criteria, clinical implications, and treatment strategies for chronic endometritis. Statistical analyses of results were performed using Fisher's exact tests, chi square tests and odds ratios with 95% confidence intervals. A two-sided P < 0.05 was deemed statistically significant.
Results
Responses identified a concerning spectrum of deficiencies in the understanding of the pathophysiology of chronic endometritis, in awareness of clinical presentation of chronic endometritis, and in the understanding of methodology/ies that allow diagnosis of chronic endometritis. Heterogeneities in management approaches to chronic endometritis were apparent.
Conclusion
Our findings underscore a need for targeted efforts to gain clarity on chronic endometritis and to establish evidence-based consensus for good clinical practice. In the absence of a clear understanding of chronic endometritis diagnosis, we posit that the prevalent inconsistencies are likely inflicting unquantified and underappreciated burdens on patients and healthcare systems. We propose consideration for a task force to examine existing literature and create standards for good practice for a prevalent condition.
Moustafa S et al., 2020·American journal of obstetrics and gynecology·Free to read
Endometriosis, a chronic disease that afflicts millions of women worldwide, has traditionally been diagnosed by laparoscopic surgery. This diagnostic barrier delays identification and treatment by years, resulting in prolonged pain and disease progression. Development of a noninvasive diagnostic test could significantly improve timely disease detection. We tested the feasibility of serum microRNAs as diagnostic biomarkers of endometriosis in women with gynecologic disease symptoms.
The objective of the study was to validate the use of a microRNA panel as a noninvasive diagnostic method for detecting endometriosis.
This was a prospective study evaluating subjects with a clinical indication for gynecological surgery in an academic medical center. Serum samples were collected prior to surgery from 100 subjects. Women were selected based on the presence of symptoms, and laparoscopy was performed to determine the presence or absence of endometriosis. The control group was categorized based on absence of visual disease at the time of surgery. Circulating miRNAs, miR-125b-5p, miR-150-5p, miR-342-3p, miR-451a, miR-3613-5p, and let-7b, were measured in serum by quantitative real-time polymerase chain reaction in a blinded fashion without knowledge of disease status. Receiver-operating characteristic analysis was performed on individual microRNAs as well as combinations of microRNAs. An algorithm combining the expression values of these microRNAs, built using machine learning with a random forest classifier, was generated to predict the presence or absence of endometriosis on operative findings. This algorithm was then tested in an independent data set of 48 previously identified subjects not included in the training set (24 endometriosis and 24 controls) to validate its diagnostic performance.
The mean age of women in the study population was 34.1 and 36.9 years for the endometriosis and control groups, respectively. Control group subjects displayed varying pathologies, with leiomyoma occurring the most often (n = 39). Subjects with endometriosis had significantly higher expression levels of 4 serum microRNAs: miR-125b-5p, miR-150-5p, miR-342-3p, and miR-451a. Two serum microRNAs showed significantly lower levels in the endometriosis group: miR-3613-5p and let-7b. Individual microRNAs had receiver-operating characteristic areas under the curve ranging from 0.68 to 0.92. A classifier combining these microRNAs yielded an area under the curve of 0.94 when validated in the independent set of subjects not included in the training set. Analysis of the expression levels of each microRNA based on revised American Society of Reproductive Medicine staging revealed that all microRNAs could distinguish stage I/II from control and stage III/IV from control but that the difference between stage I/II and stage III/IV was not significant. Subgroup analysis revealed that neither phase of the menstrual cycle or use of hormonal medication had a significant impact on the expression levels in the microRNAs used in our algorithm.
This is the first report showing that microRNA biomarkers can reliably differentiate between endometriosis and other gynecological pathologies with an area under the curve >0.9 across 2 independent studies. We validated the performance of an algorithm based on previously identified microRNA biomarkers, demonstrating their potential to detect endometriosis in a clinical setting, allowing earlier identification and treatment. The ability to diagnose endometriosis noninvasively could reduce the time to diagnosis, surgical risk, years of discomfort, disease progression, associated comorbidities, and health care costs.
Related research
Chronic Endometritis · Diagnosis of Chronic Endometritis
To evaluate the type and etiopathogenic role of infectious agents detected in endometrial cultures obtained from women with chronic endometritis (CE). Prospective controlled study. University hospital. PATIENT(S): 2190 women undergoing hysteroscopy for different indications. INTERVENTION(S): Vaginal and endometrial samples were collected from 438 women with a CE diagnosis at hysteroscopy and 100 women with no signs of CE (controls). MAIN OUTCOME MEASURE(S): Histology and cultures for common bacteria, Neisseria gonorrhoeae and Mycoplasma, and molecular biology testing for Chlamydia were performed. RESULT(S): We compared results of vaginal and intrauterine cultures obtained from women with and without CE. Histologic results were positive in 388 of these cases (88.6%), and at least one microorganism was found in 320 endometrial samples (73.1%). In the control group, histologic results and endometrial culture were positive in only 6% and 5% of cases, respectively. The most frequent infectious agents detected at the endometrial level were common bacteria (58% of cases). Ureaplasma urealyticum was detected in 10% and Chlamydia in only 2.7% of positive endometrial cultures. In only 143 (32.6%) cases were the same infectious agent isolated in endometrial and vaginal cultures. CONCLUSION(S): More than 70% of CE cases resulted from nongonococcal, nonchlamydial infections. Common bacteria and Mycoplasma were the most frequent etiologic agents. Vaginal cultures have low concordance with endometrial cultures.
Chronic Endometritis · Diagnosis of Chronic Endometritis
To evaluate the association between endometriosis end chronic endometritis (CE) diagnosed by hysteroscopy, conventional histology, and immunohistochemistry. Case-control study. University hospital. PATIENT(S): Women with and without endometriosis who have undergone hysterectomy. INTERVENTION(S): Retrospective evaluation of 78 women who have undergone hysterectomy and were affected by endometriosis and 78 women without endometriosis. MAIN OUTCOME MEASURE(S): CE diagnosed based on conventional histology and immunohistochemistry with anti-syndecan-1 antibodies to identify CD138 cells. RESULT(S): The prevalence of CE was statistically significantly higher in the women with endometriosis as compared with the women who did not have endometriosis (33 of 78, 42.3% vs. 12 of 78, 15.4% according to hysteroscopy; and 30 of 78, 38.5% vs. 11 of 78, 14.1% according to histology). The women were divided into two groups, 115 patients without CE and 41 patients with CE. With univariate analysis, parity was associated with a lower risk for CE, and endometriosis was associated with a statistically significantly elevated risk of CE. Using multivariate analysis, parity continued to be associated with a lower incidence of CE, whereas endometriosis was associated with a 2.7 fold higher risk. CONCLUSION(S): The diagnosis of CE is more frequent in women with endometriosis. Although no etiologic relationships between CE and endometriosis can be established, this study suggests that CE should be considered and if necessary ruled out in women with endometriosis, particularly if they have abnormal uterine bleeding. Identification and appropriate treatment of CE may avoid unnecessary surgery.
Chronic Endometritis · Endometritis and Reproductive Outcomes
Park HJ et al., 2017·Clin Exp Reprod Med·Free full text on PubMed Central
Chronic endometritis (CE) is a condition involving the breakdown of the peaceful co-existence between microorganisms and the host immune system in the endometrium. A majority of CE cases produce no noticeable signs or mild symptoms, and the prevalence rate of CE has been found to be approximately 10%. Gynecologists and pathologists often do not focus much clinical attention on CE due to the time-consuming microscopic examinations necessary to diagnose CE, its mild clinical manifestations, and the benign nature of the disease. However, the relationship between CE and infertility-related conditions such as repeated implantation failure and recurrent miscarriage has recently emerged as an area of inquiry. In this study, we reviewed the literature on the pathophysiology of CE and how it may be associated with infertility, as well as the literature regarding the diagnosis and treatment of CE. In addition, we discuss the value of hysteroscopic procedures in the diagnosis and treatment of CE.
Chronic Endometritis · Endometritis and Reproductive Outcomes
Yan X et al., 2025·Frontiers in endocrinology·Free full text on PubMed Central
Chronic endometritis (CE) is a subtle but persistent inflammatory disorder of the endometrium that is often underdiagnosed due to its asymptomatic or non-specific presentation. The etiology of CE primarily involves microbial infections and immune dysregulation, often accompanied by microbial dysbiosis. Diagnosis relies on histopathological examination, especially the identification of stromal plasma cells, alongside hysteroscopic findings and microbiological testing, though standardization remains lacking. Mechanistically, CE-induced infertility stems from altered immune cell profiles, impaired endometrial receptivity, aberrant decidualization, dysbiosis of the endometrial microbiota, and abnormal uterine peristalsis. Aberrant gene expression and hormone receptor dysregulation further disrupt the implantation window. This review summarizes current understanding of the diagnostic criteria, pathogenic mechanisms, and therapeutic strategies for CE, emphasizing its crucial role in infertility and the need for standardized clinical management.
General Gynecology › Clinical Practice › Practice Patterns · Infections and the Reproductive Microbiome › Chronic Endometritis › Diagnosis of Chronic Endometritis · Diagnostics › Endometrial Assessment › Endometrial Infection
PMID 34605024 34605024 DOI 10.1002/ijgo.13962 10.1002/ijgo.13962 Margulies et al. 2022, Margulies 2022
Cite this article
Margulies, S. L., Flores, V., Parkash, V., & Pal, L. (2022). Chronic endometritis: A prevalent yet poorly understood entity. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 158(1), 194-200. https://doi.org/10.1002/ijgo.13962
Margulies SL, Flores V, Parkash V, Pal L. Chronic endometritis: A prevalent yet poorly understood entity. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2022;158(1):194-200. doi:10.1002/ijgo.13962
Margulies, S. L., et al. "Chronic endometritis: A prevalent yet poorly understood entity." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, vol. 158, no. 1, 2022, pp. 194-200.