Fertility Outcomes After Antibiotic Treatment In Women With Chronic Endometritis (MORE)

Chronic endometritis (CE) is a chronic inflammatory condition of the endometrium characterized by plasma cell infiltration of the endometrial stroma. The condition is frequently asymptomatic or associated with nonspecific symptoms, which may contribute to underdiagnosis in women with infertility. Increasing evidence suggests that CE may negatively affect endometrial receptivity, embryo implantation, and reproductive outcomes, including recurrent implantation failure and pregnancy loss.

The MORE study is a prospective cohort study designed to evaluate the prevalence, diagnosis, treatment response, and reproductive impact of CE in women undergoing infertility evaluation. The study will enroll women aged 18 to 40 years with diagnosed infertility who are scheduled for diagnostic hysteroscopy with endometrial biopsy. Approximately 100 participants are expected to be enrolled between January 2026 and December 2029.

The study will assess the prevalence of histologically confirmed CE using histopathological evaluation combined with immunohistochemical detection of plasma cells (CD138 staining). Hysteroscopic findings suggestive of CE, including endometrial hyperemia, stromal edema, micropolyps, and abnormal vascular patterns, will be systematically documented and correlated with histopathological results in order to evaluate the diagnostic value of hysteroscopic markers in routine clinical practice.

Participants diagnosed with CE will receive standardized antibiotic treatment according to institutional protocols. Following treatment, reproductive outcomes will be prospectively monitored for up to 12 months. Outcomes of interest include spontaneous conception, assisted reproductive technology (ART) outcomes, implantation rates, clinical pregnancy, ongoing pregnancy, live birth, and miscarriage rates. Pregnancy-related complications, including preeclampsia, placental disorders, premature rupture of membranes, preterm birth, and delivery complications, will also be evaluated in participants who achieve pregnancy.

The study will additionally investigate the relationship between the endometrial microbial environment and reproductive outcomes. Endometrial samples obtained during hysteroscopy may be analyzed to characterize microbial profiles associated with CE and treatment response. Particular attention will be paid to microorganisms previously associated with CE, including Escherichia coli, Enterococcus faecalis, Corynebacterium species, Klebsiella pneumoniae, Mycoplasma species, and sexually transmitted pathogens.

A retrospective control cohort will include infertile women who previously underwent hysteroscopy with endometrial biopsy. Archived endometrial tissue samples from these participants will undergo additional immunohistochemical evaluation for CE in order to compare reproductive outcomes between participants with and without histological evidence of CE.

Clinical, demographic, reproductive, laboratory, imaging, and treatment-related data will be collected from electronic medical records and entered into a secure REDCap database using structured electronic case report forms. Collected variables will include demographic characteristics, infertility history, prior ART treatment, hysteroscopic findings, histopathological and immunohistochemical results, antibiotic treatment details, reproductive outcomes, pregnancy complications, and neonatal outcomes.

Data quality assurance procedures will include structured data entry forms, predefined variable definitions, range and consistency checks, and periodic review of entered data by authorized study investigators. Source data verification will be performed using electronic medical records and pathology reports. All study data will be pseudonymized using unique study identification codes. Direct participant identifiers will be stored separately from study data in accordance with institutional data protection procedures and General Data Protection Regulation (GDPR) requirements. Access to the REDCap database will be restricted to authorized study personnel only.

The planned statistical analysis will primarily be descriptive. Results will be reported as absolute numbers, percentages, and 95% confidence intervals. Comparisons between subgroups will be performed using chi-square or Fisher exact tests for categorical variables and t-tests or Mann-Whitney U tests for continuous variables, depending on data distribution. A p-value below 0.05 will be considered statistically significant. Missing or incomplete data will be documented and analyzed according to predefined statistical procedures.

The study will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP) principles, and GDPR requirements. The protocol and related study documents will be submitted for approval to the Ethics Committee of University Hospital Královské Vinohrady (FNKV), Prague, Czech Republic.