Chronic endometritis in women undergoing in vitro fertilization: Diagnostic roles of hysteroscopy and endometrial biopsy and associations with reproductive outcomes - A systematic review and meta-analysis

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Abstract

STUDY QUESTION: What are the diagnostic roles of hysteroscopy and endometrial biopsy in the evaluation of chronic endometritis (CE), and how is CE associated with reproductive outcomes in women undergoing in vitro fertilization (IVF) or embryo transfer? SUMMARY ANSWER: Chronic endometritis was associated with lower clinical pregnancy rates and higher miscarriage risk following IVF or embryo transfer, whereas treated/resolved CE was associated with more favorable reproductive outcomes than persistent disease, based predominantly on observational evidence. Hysteroscopy demonstrated variable diagnostic performance and should be considered an adjunct to histopathological assessment rather than a standalone diagnostic test. WHAT IS KNOWN ALREADY: Chronic endometritis is increasingly recognized as a potential contributor to infertility, recurrent implantation failure, and recurrent pregnancy loss. Histopathological identification of endometrial stromal plasma cells, typically supported by CD138 immunohistochemistry, represents the principal tissue-based approach to CE diagnosis. Hysteroscopy may identify characteristic endometrial abnormalities, including micropolyps, stromal oedema, and focal hyperaemia, but its diagnostic performance as a standalone test remains uncertain. Interpretation of the available evidence is complicated by substantial heterogeneity in diagnostic criteria, plasma-cell thresholds, patient populations, and assisted reproductive technology protocols. STUDY DESIGN, SIZE, DURATION: This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 Statement and prospectively registered in PROSPERO (CRD420251130136). MEDLINE, Embase, Scopus, Web of Science Core Collection, and CENTRAL were searched from database inception to February 2026. Thirty-nine studies met the predefined eligibility criteria. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible studies included infertile women undergoing IVF or embryo transfer in whom CE was evaluated by hysteroscopy with or without endometrial biopsy. Histopathological assessment, with or without CD138 immunohistochemistry according to study-specific protocols, served as the reference standard, where applicable. Primary outcomes included live birth or ongoing pregnancy, clinical pregnancy, and miscarriage, whereas secondary outcomes included implantation rate and the diagnostic performance of hysteroscopy. Random-effects meta-analyses were performed to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Prespecified subgroup analyses evaluated treatment status and inflammatory burden according to CD138 plasma-cell thresholds. The certainty of evidence for all critical reproductive outcomes was assessed using the GRADE approach. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with women without CE, live birth or ongoing pregnancy tended to be lower (44.0% vs 50.6%; OR 0.77, 95% CI 0.53-1.11; I2 = 57%), although the pooled estimate did not reach statistical significance. Clinical pregnancy rates were lower (54.3% vs 60.1%; OR 0.55, 95% CI 0.42-0.74; I2 = 77%), whereas miscarriage rates were higher (16.4% vs 11.9%; OR 1.43, 95% CI 1.13-1.82; I2 = 48%). Compared with persistent chronic endometritis, treated or resolved disease was associated with higher live birth or ongoing pregnancy rates (OR 2.72, 95% CI 1.94-3.82; I2 = 62%), higher clinical pregnancy rates (OR 2.45, 95% CI 1.72-3.50; I2 = 75%), and lower miscarriage rates (OR 0.40, 95% CI 0.20-0.81; I2 = 35%). No statistically significant differences were observed according to higher versus lower CD138 plasma-cell thresholds. Across diagnostic studies, hysteroscopic sensitivity ranged from 22% to 86%, whereas specificity was generally moderate to high when compared with histopathological assessment. LIMITATIONS, REASONS FOR CAUTION: The available evidence was derived predominantly from observational studies and was affected by substantial clinical and methodological heterogeneity, including differences in patient populations, CE definitions, CD138 thresholds, hysteroscopic interpretation, antibiotic regimens, embryo-transfer protocols, and outcome definitions. These limitations preclude causal inference, and the certainty of evidence was low or very low across the principal reproductive outcomes, reflecting the predominantly observational evidence base together with outcome-specific concerns regarding risk of bias, inconsistency, imprecision, and potential small-study effects. WIDER IMPLICATIONS OF THE FINDINGS: Current evidence supports an association between CE and less favorable reproductive outcomes following IVF or embryo transfer but does not establish that treatment itself improves live birth. Hysteroscopy should be considered an adjunctive diagnostic tool interpreted together with histopathological assessment rather than a definitive diagnostic test. Routine CE screening before a first IVF cycle cannot currently be recommended on the basis of the available evidence. Instead, a targeted rather than universal approach to CE evaluation may be considered in selected women, particularly those with recurrent implantation failure, recurrent pregnancy loss, or otherwise unexplained infertility. Future adequately powered prospective studies and randomized controlled trials using standardized diagnostic criteria, uniform CD138-positive plasma-cell thresholds, and live birth as the primary patient-important outcome are required to clarify whether targeted diagnosis and treatment of CE improve reproductive outcomes. REGISTRATION NUMBER: PROSPERO CRD420251130136.

Abstract as published, via PubMed.