Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment
Ettore Cicinelli, Maria Matteo, Raffaele Tinelli
Vincenzo Pinto, Marco Marinaccio, Ugo Indraccolo, Dominique De Ziegler, Leonardo Resta
Author affiliations (5)
Unit of Obstetrics and Gynecology, Department of Biomedical and Human Oncologic Science, University of Bari, 70124 Bari, ItalyROR
Recurrent miscarriage (RM) is defined as 3 or more miscarriages before 20 weeks' pregnancy. In recent years, interest has been focused on chronic endometritis (CE), a subtle inflammation thought to be associated with RM. We aimed to evaluate the relationships between CE and RM. The records of 360 women with unexplained RM were retrospectively analyzed. Data from hysteroscopy, endometrial histology, endometrial culture, and polymerase chain reaction for chlamydia, performed before and after antibiotic treatment for CE, were analyzed. The occurrence of successful pregnancies within 1 year after treatment was also evaluated. Results showed that 208 (57.8%) women with RM showed CE at hysteroscopy; 190 (91.3%), positive at hysteroscopy, were also positive at histology, and 142 (68.3%) had positive cultures. Common bacteria were found in 110 (77.5%) patients. Mycoplasma and Ureaplasma were found in 36 (25.3%) patients and Chlamydia in 18 patients (12.7%). In 102 (71%) women, antibiogram-based antibiotic treatment normalized hysteroscopy, histology, and cultures (group 1); while in 40 (28.2%) patients, CE was still present at hysteroscopy (group 2). In 16 of the 66 patients positive at hysteroscopy, but not at cultures, the hysteroscopy becomes normal (group 3) after a Centers for Disease Control and Prevention-based therapy; while in 50 women, CE was still present (group 4). One year after treatment, group 1 showed a significantly higher number of pregnancies (78.4%) compared to group 2 (17.5%; P < .001) and group 4 (15.3%; P = .005). The CE is frequent in women with RM. Antibiotic treatment seems to be associated with an improved reproductive outcome.
PMID 24177713 24177713 DOI 10.1177/1933719113508817 10.1177/1933719113508817 Cicinelli et al. 2013, Cicinelli 2013
Cite this article
Cicinelli, E., Matteo, M., Tinelli, R., Pinto, V., Marinaccio, M., Indraccolo, U., De Ziegler, D., & Resta, L. (2014). Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment. Reproductive sciences (Thousand Oaks, Calif.), 21(5), 640-647. https://doi.org/10.1177/1933719113508817
Cicinelli E, Matteo M, Tinelli R, Pinto V, Marinaccio M, Indraccolo U, et al. Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment. Reprod Sci. 2014;21(5):640-647. doi:10.1177/1933719113508817
Cicinelli, E., et al. "Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment." Reproductive sciences (Thousand Oaks, Calif.), vol. 21, no. 5, 2014, pp. 640-647.
Cicinelli E et al., 2015·Human reproduction (Oxford, England)
What is the prevalence of chronic endometritis (CE) in women with repeated unexplained implantation failure (RIF) at IVF, and how does antibiotic treatment affect the reproductive outcome? Chronic endometritis, associated with infection with common bacteria or mycoplasma, is common in women complaining of RIF and antibiotic treatment significantly improves the reproductive outcome at a subsequent IVF cycle. We have reported that CE is a frequent finding in women with repeated pregnancy loss and a significantly higher rate of successful pregnancies was achieved after adequate antibiotic treatment. Moreover, CE was identified in 30.3% of patients with repeated implantation failure at IVF and women diagnosed with CE had lower implantation rates (11.5%) after IVF cycles. In contrast, other authors reported that the clinical implication of CE should be considered minimal and that the reproductive outcome at IVF/ICSI cycles was not negatively affected by CE. STUDY DESIGN, SIZE, A retrospective study was performed from January 2009 through June 2012 on 106 women with unexplained infertility and a history of RIF. PARTICIPANTS/MATERIALS, SETTING, All patients underwent hysteroscopy and endometrial sampling for histology and microbiological investigations. Women diagnosed with CE underwent antibiotic treatment and the effect of treatment was confirmed by hysteroscopy with biopsy. Within 6 months after treatment all women had a further IVF attempt. The IVF outcomes were compared in women without signs of CE (Group 1) and persistent CE (Group 2) after antibiotic treatment. Clinical pregnancy rate (PR), and live birth rate (LBR) were compared at post-treatment IVF attempt. MAIN Seventy (66.0%) women were diagnosed with CE at hysteroscopy. In 61 (57.5%) CE was confirmed by histology and 48 (45.0%) by cultures. Common bacteria and mycoplasma were the most prevalent agents. In 46 (75.4%) out of 61 women, with diagnosis of CE at hysteroscopy and histology, examinations were normal after appropriate antibiotic treatment control (Group 1) while in 15 (24.6%) cases signs of CE were still present (Group 2). At IVF attempt after treatment, a significantly higher PR and LBR was reported in women from Group 1 compared with women from Group 2 (65.2 versus 33.0% P = 0.039; 60.8 versus 13.3%, P = 0.02, respectively). LIMITATIONS, Possible biases related to retrospective studies and to preferential referral of patients with CE, and limited number of cases. A prospective randomized clinical trial is needed to confirm our findings but in women with RIF a hysteroscopic evaluation of the uterine cavity to exclude CE should be considered and appropriate antibiotic treatment should be given before submitting the patient to a further IVF attempt.
To assess the prevalence of chronic endometritis in women with a history of recurrent early pregnancy loss (REPL) and/or fetal demise (FD). Observational cohort study using prospectively collected data. Recurrent pregnancy loss program in an academic medical center. PATIENT(S): Three hundred ninety-five women with a history of two or more pregnancy losses of less than 10 weeks' size or a fetal demise of 10 or more weeks' size. INTERVENTION(S): All women had an endometrial biopsy. Chronic endometritis was treated with antibiotics, and a second endometrial biopsy was recommended as a "test of cure." MAIN OUTCOME MEASURE(S): Subsequent live-birth rate (LBR). RESULT(S): The overall prevalence of chronic endometritis was 9% (35/395) in this cohort; 7% (21/285) in the REPL group, 14% (8/57) in the FD group, and 11% (6/53) in the combined REPL/FD group. The cure rate was 100% after a course(s) of antibiotics. The subsequent cumulative LBR was 88% (21/24) for the treated chronic endometritis group versus 74% (180/244) for the group without chronic endometritis. The per-pregnancy LBR for the treated chronic endometritis group was 7% (7/98) before treatment versus 56% (28/50) after treatment. CONCLUSION(S): There was a high prevalence of chronic endometritis in this cohort. The test of cure was 100% with antibiotics. Subsequent LBRs after treatment were encouraging.
Chen L et al., 2025·Frontiers in reproductive health
[OBJECTIVE] To analyze the effect of autologous platelet-rich plasma (PRP) intrauterine perfusion on the clinical outcomes of frozen-thawed embryo transfer in patients with chronic endometritis. [METHODS] A retrospective continuous cohort of 219 patients diagnosed with chronic endometritis at the Reproductive Medicine Center of Affiliated Hospital of Putian University between January 2020 and December 2022, undergoing their first frozen-thawed embryo transfer cycle, was included. All patients received standardized oral doxycycline treatment after diagnosis. Based on whether they received PRP intrauterine perfusion prior to embryo transfer, patients were divided into an observation group (PRP group, n=103) and a control group (non-PRP group, n = 116). Outcome measures included live birth rate per transfer cycle, clinical pregnancy rate per transfer cycle, and early miscarriage rate per clinical pregnancy. [RESULTS] All patients underwent endometrial preparation using a hormone replacement therapy (HRT) protocol. Endometrial thickness on the day before transformation was significantly higher in the PRP group compared to the control group (10.58 ± 1.78 mm vs. 9.79 ± 1.58 mm, P = 0.001). The PRP group exhibited significantly higher clinical pregnancy rate per transfer cycle and live birth rate per transfer cycle than the control group (58.25% vs. 40.52%, P = 0.038; 52.43% vs. 34.48%, P = 0.007). The difference in early miscarriage rate per clinical pregnancy between the PRP group and the control group was not statistically significant (8.33% vs. 14.89%, P = 0.86). The live birth rate per transfer cycle in the single-PRP subgroup was significantly lower than in the multiple-PRP subgroup (44.62% vs. 65.79%, P = 0.038). There were no statistically significant differences in clinical pregnancy rate per transfer cycle or early miscarriage rate per clinical pregnancy between the single-PRP and multiple-PRP subgroups (52.31% vs. 68.42%, P = 0.110; 11.76% vs. 3.85%, P = 0.377). [CONCLUSION] For patients diagnosed with chronic endometritis undergoing their first frozen-thawed blastocyst transfer after standardized antibiotic treatment, adjunctive PRP intrauterine perfusion therapy improves pregnancy outcomes.
infections-and-microbiome/chronic-endometritis/endometritis-and-reproductive-outcomesgynecology/infections/pelvic-inflammatory-diseaseinfertility/uterine-factor/endometrial-receptivity
Open Access
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.