Cesarean Scar Defect (Isthmocele) and Secondary Infertility: A Systematic Review of Reproductive Significance.

Cesarean scar defect (CSD), also termed isthmocele or uterine niche, is an indentation or pouch-like defect in the myometrium at the site of a previous cesarean scar and may be associated with secondary infertility and adverse reproductive outcomes. This systematic review evaluated the reproductive significance of CSD across diagnostic, assisted-reproduction, surgical, and mechanistic evidence. PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online) and Scopus were searched from database inception through the final search date, supplemented by Google Scholar, PubMed Central, publisher webpages, DOI records, citation tracking, and manual reference-list screening. Original human studies examining the reproductive significance of CSD were eligible. Substantial clinical and methodological heterogeneity precluded meta-analysis; therefore, the findings were synthesized narratively. A total of 36 studies were included. Across the evidence base, the reproductive significance of CSD appeared greater when the defect was accompanied by adverse anatomical or functional features rather than by niche presence alone. These features included thin residual myometrium, intrauterine or intracavitary fluid, chronic endometrial inflammation, and altered uterine contractility. Some assisted reproductive technology (ART) cohorts reported lower implantation, clinical pregnancy, or live-birth outcomes among women with uterine niches. Surgical studies reported anatomical improvement and subsequent pregnancies or live births in selected patients. However, findings varied across patient populations, treatment approaches, and outcome definitions. CSD may be associated with secondary infertility and adverse reproductive outcomes, particularly when accompanied by adverse anatomical or functional features. The available evidence remains observational and heterogeneous, which limits causal inference and direct comparisons between treatment approaches. No single surgical approach was shown to be superior, and treatment selection should remain individualized and anatomy-guided. Future studies should use standardized CSD definitions and clearly defined fertility outcomes.