Isthmocele, not cesarean section per se, reduces IVF success: a systematic review and meta-analysis of over 10,000 embryo transfer cycles.

Previous reviews have shown that a history of cesarean section (CS) is associated with a worse in vitro fertilization (IVF) prognosis. To date, whether the decline in IVF chances of success should be attributed to the CS procedure itself or to the presence of isthmocele is still to be clarified.To summarize the available evidence regarding the impact of isthmocele on IVF outcomes.Electronic databases and clinical registers were searched until 30th May 2023.Observational studies were included if they assessed the effect of isthmocele on IVF outcomes. Comparators were women with isthmocele and women without isthmocele with a previous CS or vaginal delivery. Study quality was assessed using the modified Newcastle-Ottawa Scale.Primary outcome was Live Birth Rate (LBR). The effect measures were expressed as adjusted Odds Ratios (aORs) and unadjusted Odds Ratios (uORs) with a 95% confidence interval (95% CI). The body of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group methodology.Eight studies (n=10,873 patients) were included in the analysis. Women with isthmocele showed a lower LBR compared to both women with a previous CS without isthmocele (aOR 0.62 [95% CI 0.53-0.72]) and those with a history of vaginal delivery (aOR 0.55 [95% CI 0.42, 0.71]). The LBR in women with a previous CS without isthmocele and in those with a history of vaginal delivery was similar (aOR 0.74 [95% CI 0.47, 1.15]). Subgroup analysis suggested a negative effect of the intra-cavitary fluid (ICF) in women with isthmocele on LBR (uOR 0.36, 95% CI 0.18, 0.75), while those without ICF had a similar LBR compared to women without isthmocele (uOR 0.94, 95% CI 0.61, 1.45).AND RELEVANCE: We found moderate quality evidence (GRADE 3/4) supporting a negative impact of isthmocele, but not of CS per se, on LBR in women undergoing IVF. The adverse effect of isthmocele on IVF outcomes seems to be worsened by ICF accumulation before embryo transfer.CRD42023418266.