High Risk of Chronic Endometritis in Isthmocele-A Systematic Review and Meta-Analysis

Background: In recent decades, there has been a notable rise in the prevalence of caesarean sections, which has been accompanied by a concomitant increase in the incidence of long-term complications, including the occurrence of isthmocele. This anatomical alteration has been associated with symptoms such as abnormal uterine bleeding (AUB), chronic pelvic pain, and secondary infertility. On the other hand, chronic endometritis (CE), characterised by the infiltration of plasma cells into the endometrium, is also associated with infertility and repeated implantation failures. Given the coincidence of symptoms between these two conditions, the question arises as to whether there is an association between isthmocele and CE. Objective: This systematic review and meta-analysis aim to examine the association between isthmocele and CE and to assess its potential clinical implications. Methods: A systematic literature search was conducted in Medline, Embase, and Cochrane CENTRAL up to February 2025. The inclusion criteria were studies involving histopathological findings in isthmocele. The results of the meta-analysis incorporated observational studies and trials to evaluate the prevalence of CE in women with isthmocele, as well as the odds ratios (OR) for CE in isthmocele compared to women without isthmocele, and for CE in isthmocele with AUB compared to women without AUB. Results: A total of seven studies were included in the systematic review, comprising 976 women in the systematic review and 876 women in the meta-analysis. The pooled prevalence of CE in women with an isthmocele was 40% (95% CI: 24-58%). Here, the risk of CE was threefold higher in the presence of an isthmocele as compared to its absence (OR = 3.01; 95% CI: 1.02-9.03). Furthermore, the risk of CE was further increased in women with AUB and isthmocele compared to those without AUB (OR = 6.33, 95% CI: 1.94-20.67). Conclusions: CE and isthmocele are both under-diagnosed and poorly understood conditions. The high prevalence of CE in isthmocele indicates a substantial clinical burden. Specifically, women with AUB and isthmocele exhibit a six-fold higher risk of developing CE. These results underscore the importance of recognising isthmocele as a significant risk factor for CE, particularly in women presenting with isthmocele-associated AUB. Further research is warranted to elucidate the underlying mechanisms and to develop targeted interventions for the prevention and management of CE in this population.