Re-evaluating endometrial injury for IVF: was a promising approach abandoned prematurely? A critical review

Since the early 2000s, endometrial injury has been proposed to enhance receptivity and improve pregnancy outcomes, particularly in individuals with recurrent implantation failure (RIF). However, randomized controlled trials have yielded conflicting results, creating ongoing debate about their clinical utility. This review synthesizes over 20 years of research through to 31 January 2025, examining whether methodological variations explain conflicting outcomes and assessing the clinical significance of reported benefits. The most comprehensive individual participant data meta-analysis to date, including 4112 patients from 13 randomized controlled trials, demonstrated a modest but statistically significant improvement in live birth rate following endometrial injury (OR 1.29, 95% CI 1.02-1.64), with a number needed to treat of 26. Analysis revealed significant heterogeneity: studies using multiple biopsies, particularly in RIF patients, showed more pronounced benefits than single-biopsy protocols in unselected populations. The biological heterogeneity of implantation failure probably explains inconsistent outcomes, as different aetiologies require distinct therapeutic approaches. Current evidence suggests that endometrial injury may provide modest improvements using multiple-biopsy protocols in carefully selected patients, particularly those with RIF, while highlighting the need for appropriate counselling regarding the modest benefits. Future research should transition from empirical application to biomarker-guided patient selection to identify which molecular subtypes benefit from specific interventions.