Chronic endometritis (CE) is a local inflammatory disease characterized by unusual plasmacyte infiltration in the endometrial stromal areas. CE has been neglected in gynecologic practice, as it is a less symptomatic benign disease that requires demanding and time-consuming histopathologic examinations for the definite diagnosis. Recent studies, however, suggest the association of CE with infertility and obstetric and neonatal complications. In this review article, we aimed to update the knowledge on epidemiology, etiology, and pathogenesis of CE as well as discuss its clinical management from diagnosis to treatment.
PMID 26478517 26478517 DOI 10.1111/aji.12438 10.1111/aji.12438
Cite this article
Kitaya, K., Matsubayashi, H., Yamaguchi, K., Nishiyama, R., Takaya, Y., Ishikawa, T., Yasuo, T., & Yamada, H. (2016). Chronic Endometritis: Potential Cause of Infertility and Obstetric and Neonatal Complications. American journal of reproductive immunology (New York, N.Y. : 1989), 75(1), 13-22. https://doi.org/10.1111/aji.12438
Kitaya K, Matsubayashi H, Yamaguchi K, Nishiyama R, Takaya Y, Ishikawa T, et al. Chronic Endometritis: Potential Cause of Infertility and Obstetric and Neonatal Complications. Am J Reprod Immunol. 2016;75(1):13-22. doi:10.1111/aji.12438
Kitaya, K., et al. "Chronic Endometritis: Potential Cause of Infertility and Obstetric and Neonatal Complications." American journal of reproductive immunology (New York, N.Y. : 1989), vol. 75, no. 1, 2016, pp. 13-22.
Chronic plasmacytic endometritis (CPE) is an infectious or reactive process with multiple etiologies. The lesion is reportedly often associated with pelvic inflammatory disease and intermenstrual bleeding. However, the clinical significance of the diagnosis when found incidentally and whether particular pathologic findings are associated with clinically important CPE have not been evaluated. We reviewed 105 chronic endometritis cases that had been diagnosed earlier and 130 controls to examine the pathologic and clinical associations in a diverse population.A pathology database was searched for endometrial biopsies diagnosed as CPE, and 105 cases were found. Systematic randomized sampling identified 130 control cases (biopsies not diagnosed as CPE). Slides were carefully reviewed to assess 10 histopathologic features. Clinical records were reviewed for 15 clinical parameters. Analysis was performed using chi tests and SAS software.Few patients (3%) received antibiotics or further clinical intervention after the diagnosis of CPE was rendered. The clinical data trended toward fewer menstrual abnormalities as plasma cells increased. The intensity of inflammation showed no association with patient age or symptom duration. Evaluation of controls revealed 17 cases with missed diagnosis of CPE, representing an overall 16% underdiagnosis rate.In CPE, there are no specific clinical features that correlate with the intensity of pathologic findings; the most specific histologic feature is the presence of plasma cells, and it is predominantly identified in weakly proliferative endometrium. There is a clinically insignificant 16% pathologic underdiagnosis rate. In contrast to the findings of past studies, only a small percentage of patients had pelvic inflammatory disease (4%).
Chronic endometritis is a persistent inflammation of the endometrial mucosa caused by bacterial pathogens such as Enterobacteriaceae, Enterococcus, Streptococcus, Staphylococcus, Mycoplasma, and Ureaplasma. Although chronic endometritis can be asymptomatic, it is found in up to 40% of infertile patients and is responsible for repeated implantation failure and recurrent miscarriage. Diagnosis of chronic endometritis is based on hysteroscopy of the uterine cavity, endometrial biopsy with plasma cells being identified histologically, while specific treatment is determined based on microbial culture. However, not all microorganisms implicated are easily or readily culturable needing a turnaround time of up to 1 week. We sought to develop a molecular diagnostic tool for chronic endometritis based on real-time polymerase chain reaction equivalent to using the 3 classic methods together, overcoming the bias of using any of them alone. Endometrial samples from patients assessed for chronic endometritis (n = 113) using at least 1 or several conventional diagnostic methods namely histology, hysteroscopy, and/or microbial culture, were blindly evaluated by real-time polymerase chain reaction for the presence of 9 Chlamydia trachomatis, Enterococcus, Escherichia coli, Gardnerella vaginalis, Klebsiella pneumoniae, Mycoplasma hominis, Neisseria gonorrhoeae, Staphylococcus, and Streptococcus. The sensitivity and specificity of the molecular analysis vs the classic diagnostic techniques were compared in the 65 patients assessed by all 3 recognized classic methods. The molecular method showed concordant results with histological diagnosis in 30 samples (14 double positive and 16 double negative) with a matching accuracy of 46.15%. Concordance of molecular and hysteroscopic diagnosis was observed in 38 samples (37 double positive and 1 double negative), with an accuracy of 58.46%. When the molecular method was compared to microbial culture, concordance was present in 37 samples (22 double positive and 15 double negative), a matching rate of 56.92%. When cases of potential contamination and/or noncultivable bacteria were considered, the accuracy increased to 66.15%. Of these 65 patients, only 27 patients had consistent histological + hysteroscopic diagnosis, revealing 58.64% of nonconcordant results. Only 13 of 65 patients (20%) had consistent histology + hysteroscopy + microbial culture results. In these cases, the molecular microbiology matched in 10 cases showing a diagnostic accuracy of 76.92%. Interestingly, the molecular microbiology confirmed over half of the isolated pathogens and provided additional detection of nonculturable microorganisms. These results were confirmed by the microbiome assessed by next-generation sequencing. In the endometrial samples with concordant histology + hysteroscopy + microbial culture results, the molecular microbiology diagnosis demonstrates 75% sensitivity, 100% specificity, 100% positive and 25% negative predictive values, and 0% false-positive and 25% false-negative rates. The molecular microbiology method describe herein is a fast and inexpensive diagnostic tool that allows for the identification of culturable and nonculturable endometrial pathogens associated with chronic endometritis. The results obtained were similar to all 3 classic diagnostic methods together with a degree of concordance of 76.92% providing an opportunity to improve the clinical management of infertile patients with a risk of experiencing this ghost endometrial pathology.
Xu Y et al., 2020·American journal of reproductive immunology (New York, N.Y. : 1989)
Chronic endometritis (CE) is an unusual inflammatory condition characterized by endometrial plasmacyte infiltration. It has a high prevalence in women with reproductive failure. Because of its characteristic localization patterns and molecular functions, syndecan-1 has been identified as a biomarker of plasmacyte, and syndecan-1 immunohistochemistry (IHC) becomes the most dependable diagnostic method for CE. In this review, we discuss the association between CE and reproductive failure, the clinicopathological characterization of CE, the function and expression of syndecan-1, the progress of syndecan-1 IHC in the diagnosis of CE, and the prediction of reproductive outcome.
Jin LP et al., 2011·American journal of reproductive immunology (New York, N.Y. : 1989)
PROBLEM To evaluate whether the association of the costimulatory signal regulation with T helper 1/T helper 2 (Th1/Th2) bias at maternal-fetal interface in human pregnancy loss. METHOD OF STUDY The expression of CD80 and CD86 in decidual tissues and CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in the decidual T cells was compared between normal early pregnancy and miscarriage by qPCR and Western blot. The cytokine production in decidual T cells was performed by flow cytometry. The correlation of costimulatory molecule expression with Th1/Th2 cytokines was analyzed. RESULTS The CD80 mRNA and protein expression showed no significant difference between normal pregnancy and miscarriage. An increase in the expression of CD28 and CD86 was accompanied by a decrease in the expression of CTLA-4 in miscarriage in comparison with the early pregnancy. The higher expression of interleukin (IL)-2 and interferon-γ (IFN-γ), and lower expression of IL-4 and IL-10 in the decidual T cells were present in miscarriage. A correlation analysis showed a significant positive correlation of CD86 and CD28 expression with the Th1 cytokine production (IL-2 and IFN-γ), a significant negative correlation of CTLA-4 expression with the Th1 cytokine production. CONCLUSION The upregualtion of costimulatory signals on T cells might form an abnormal immune microenvironment, a shift to Th1 responses, at maternal-fetal interface, which leads to human miscarriage.