Cicinelli, E., Trojano, G., Mastromauro, M., Vimercati, A., Marinaccio, M., Mitola, P. C., Resta, L., & de Ziegler, D. (2017). Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link. Fertility and sterility, 108(2), 289-295.e1. https://doi.org/10.1016/j.fertnstert.2017.05.016
Cicinelli E, Trojano G, Mastromauro M, Vimercati A, Marinaccio M, Mitola PC, Resta L, de Ziegler D. Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link. Fertility and sterility. 2017;108(2):289-295.e1. doi:10.1016/j.fertnstert.2017.05.016
Cicinelli, E., et al. "Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link." Fertility and sterility, vol. 108, no. 2, 2017, pp. 289-295.e1.
For EndNote, Zotero or Mendeley:
License
No open license is recorded for this paper. Reuse terms are set by the publisher.
Author affiliations
3 institutions
Unit of Obstetrics and Gynecology, Department of Biomedical and Human Oncologic Science, University of Bari, 70124 Bari, Italy027ynra39
Université de Versailles Saint-Quentin-en-Yvelines03mkjjy25
Linked to ROR, the Research Organization Registry
Abstract
Objective
To evaluate the association between endometriosis end chronic endometritis (CE) diagnosed by hysteroscopy, conventional histology, and immunohistochemistry.
Design
Case-control study.
Setting
University hospital.
Patients
Women with and without endometriosis who have undergone hysterectomy.
Interventions
Retrospective evaluation of 78 women who have undergone hysterectomy and were affected by endometriosis and 78 women without endometriosis.
Main Outcome Measures
CE diagnosed based on conventional histology and immunohistochemistry with anti-syndecan-1 antibodies to identify CD138 cells.
Results
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.
Conclusions
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.
Baldini GM et al., 2024·J Clin Med·Free full text on PubMed Central
Isthmocele is a gynecological condition characterized by a disruption in the uterine scar, often associated with prior cesarean sections. This anatomical anomaly can be attributed to inadequate or insufficient healing of the uterine wall following a cesarean incision. It appears that isthmocele may impact a woman's quality of life as well as her reproductive capacity. The incidence of isthmocele can range from 20% to 70% in women who have undergone a cesarean section. This review aims to sum up the current knowledge about the effect of isthmocele on fertility and the possible therapeutic strategies to achieve pregnancy. However, currently, there is not sufficiently robust evidence to indicate the need for surgical correction in all asymptomatic patients seeking fertility. In cases where surgical correction of isthmocele is deemed necessary, it is advisable to evaluate residual myometrial thickness (RMT). For patients with RMT >2.5-3 mm, hysteroscopy appears to be the technique of choice. In cases where the residual tissue is lower, recourse to laparotomic, laparoscopic, or vaginal approaches is warranted.
Chronic Endometritis · Endometritis and Reproductive Outcomes
Vitagliano A et al., 2022·Diagnostics (Basel)·Free full text on PubMed Central
This systematic review and meta-analysis aims to evaluate the impact of chronic endometritis (CE) and its therapy on in vitro fertilization (IVF) outcome. Additionally, we aim to investigate whether various degrees of CE severity may exert a different effect on IVF outcome. Ongoing-pregnancy rate/live-birth-rate (OPR/LBR), clinical-pregnancy rate (CPR), and miscarriage rate (MR) were calculated. A total number of 4145 patients (from ten studies) were included. Women with CE had lower OPR/LBR (OR 1.97, p = 0.02) and CPR (OR 2.28, p = 0.002) compared to those without CE. CE cure increased OPR/LBR (OR 5.33, p < 0.0001) and CPR (OR 3.64, p = 0.0001). IVF outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR and MR: p = ns). Women with severe CE had lower OPR/LBR (OR 0.43, p = 0.003) and CPR (OR 0.40, p = 0.0007) compared to those mild CE. Mild CE showed no influence on the IVF outcome as compared to women without CE (OPR/LBR, CPR and MR: p = ns). Based on this data analysis, CE significantly reduces OPR/LBR and CPR in women undergoing IVF. Importantly, CE resolution after antibiotic therapy may improves IVF outcome, leading to similar OPR/LBR and CPR as compared to unaffected patients. The negative effects of CE on IVF outcome may be restricted to severe disease, whereas mild CE may have no influence on IVF success.
Vitagliano A et al., 2021·Diagnostics (Basel)·Free full text on PubMed Central
Chronic endometritis (CE) and endometrial polyps (EPs) are common conditions in reproductive age women. CE is an infectious disorder of the endometrium characterized by signs of chronic inflammation at hysteroscopic and histological analyses. EPs are abnormal endometrial growths containing glands, stroma and blood vessels projecting from the lining of the uterus. During the last years, different authors have investigated the correlation between CE and EPs, with controversial results. The aim of this study was to summarize available evidence on the potential correlation between CE and EPs.
Systematic literature review and meta-analysis. Observational-studies were identified by searching electronic databases from their inception to September 2021. Only studies on pre-menopausal women were included. Statistical analysis was performed using MedCalc 16.4.3 (Ostend, Belgium) and Review Manager version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration). The summary measures were reported as pooled proportion or odds ratio (OR) with 95% confidence interval (CI). The primary outcome was to evaluate the prevalence of CE in women with EPs. The secondary outcome was to determine the prevalence of CD-138-positive EPs among EPs. Tertiary outcomes were to compare the prevalence of CE in women with EPs versus women with a non-polypoid endometrium and to compare the prevalence of CE in women with a single EP versus women with multiple EPs. Eight observational studies (n = 3225 patients) were included in quantitative synthesis. Pooled prevalence of CE among women with EPs was 51.35% (95% CI, 27.24-75.13%). Pooled proportion of CD-138-positive EPs among EPs was 70.73% (95% CI, 55.73-83.68%). Women with EPs showed higher prevalence of CE compared to women without EPs (OR 3.07, 95% CI 1.59-5.95). Women with ≥3 EPs had higher prevalence of CE then women with a single EP (OR 3.43, 95% CI 1.83-6.46). In pre-menopausal women, CE and EPs may have a dependent relationship and may represent two consequent steps of a common pathological process.
Chronic Endometritis · Diagnosis of Chronic Endometritis
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 chronic endometritis pathogens: 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.
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 · 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
Puente E et al., 2019·Int J Fertil Steril·Free full text on PubMed Central
Chronic endometritis (CE) is a poorly investigated pathology which has been related to adverse reproductive outcomes, such as implantation failure and recurrent miscarriage. In this paper, we aim to provide an overview of diagnosis, etiology, pathophysiology and treatment of CE, its impact on endometrial microenvironment and its association with infertility. We present a narrative review of the current literatures, synthesizing the findings retrieved from searches of computerized databases. CE is more prevalent in infertile patients. Effective antibiotic treatment of CE seems to improve the pregnancy and live birth rate in patients with unexplained recurrent pregnancy loss (RPL), and increase ongoing pregnancy rate in patients with recurrent implantation failure. In order to increase the diagnostic accuracy, immunohistochemistry is recommended besides the conventional histology. In addition, hysteroscopy could be considered as gold standard tool for diagnosis, considering its high correlation with histological findings. CE, as the chronic inflammation of endometrium, is usually asymptomatic and probably underestimated. Interaction of bacteria with endometrial microenvironment promotes changes in leukocyte population, cytokine production and growth factors which support its negative impact on endometrial receptivity. Nevertheless, standardization of the criteria for histopathological diagnosis and immunohistochemistry technique needs to be defined.
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.
Infections and the Reproductive Microbiome › Chronic Endometritis › Diagnosis of Chronic Endometritis · Diagnostics › Endometrial Assessment › Endometrial Infection · Endometriosis › Associated Conditions › Comorbid Conditions
Ettore Cicinelli, Giuseppe Trojano, Marco Marinaccio, Leonardo Resta, Dominique De Ziegler
E Cicinelli, G Trojano, M Marinaccio, L Resta, D Ziegler
PMID 28624114 28624114 DOI 10.1016/j.fertnstert.2017.05.016 10.1016/j.fertnstert.2017.05.016 Cicinelli et al. 2017, Cicinelli 2017
Cite this article
Cicinelli, E., Trojano, G., Mastromauro, M., Vimercati, A., Marinaccio, M., Mitola, P. C., Resta, L., & de Ziegler, D. (2017). Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link. Fertility and sterility, 108(2), 289-295.e1. https://doi.org/10.1016/j.fertnstert.2017.05.016
Cicinelli E, Trojano G, Mastromauro M, Vimercati A, Marinaccio M, Mitola PC, Resta L, de Ziegler D. Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link. Fertility and sterility. 2017;108(2):289-295.e1. doi:10.1016/j.fertnstert.2017.05.016
Cicinelli, E., et al. "Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link." Fertility and sterility, vol. 108, no. 2, 2017, pp. 289-295.e1.
027ynra39