Perioperative Inflammatory Biomarkers Predict Intrauterine Adhesion Development Following Hysteroscopic Submucosal Myomectomy: A Prospective Cohort Study

Background: Intrauterine adhesions (IUAs) pose a persistent challenge following hysteroscopic submucosal myomectomy, frequently compromising reproductive potential and menstrual health. While postoperative inflammation is implicated in endometrial fibrosis, the predictive capacity of inflammatory biomarkers for IUA formation is not well established. Methods: In this prospective cohort study, 200 women of reproductive age undergoing hysteroscopy resection of submucosal fibroids were enrolled. Serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were quantified preoperatively, 48 hours post-surgery, and at a 3-month follow-up. Adhesion development was assessed via follow-up hysteroscopy at 12 weeks and graded using the European Society for Gynecological Endoscopy (ESGE) criteria. Multivariate logistic regression and receiver operating characteristic (ROC) analyses evaluated biomarker-adhesion correlations. Results: Among the 180 participants who completed follow-up, 45 (25.00%) with mild-to-severity, which were included in predictive modeling. Median CRP and IL-6 levels were consistently elevated in the adhesion cohort at all intervals (p < 0.01), with IL-6 exhibiting the strongest correlation to adhesion severity (Spearman’s ρ = 0.51, p < 0.001). Adjusted regression identified IL-6 (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.08–1.29) and CRP (OR = 1.33, 95% CI: 1.07–1.65) as independent predictors. TNF-α levels were significantly higher at 48 hours and 3 months postoperatively and showed moderate predictive ability in univariate analysis (area under the curve [AUC] = 0.71). However, TNF-α did not remain an independent predictor after multivariable adjustment (OR = 1.12, 95% CI: 0.97–1.29, p = 0.112). ROC curves demonstrated robust discriminative accuracy for IL-6 (AUC = 0.82) and moderate predictive performance for CRP (AUC = 0.74). Conclusions: Sustained perioperative increases in IL-6 and CRP levels correlate strongly with IUA risk after hysteroscopic submucosal myomectomy, highlighting their potential as early, non-invasive indicators of adhesion development. TNF-α may serve as an auxiliary marker in univariate analyses but is not an independent predictor after adjustment. Integrating these biomarkers into postoperative surveillance may facilitate timely interventions to mitigate fibrosis, optimize endometrial healing, and safeguard fertility.