Perioperative inflammatory response as a determinant of post-myomectomy intrauterine adhesion formation

Intrauterine adhesions (IUAs), or Asherman's syndrome, are a common complication of intrauterine surgery (e.g. hysteroscopic myomectomy) that can lead to menstrual disturbances and infertility. Excessive postoperative inflammation is thought to drive adhesion formation, but the predictive value of specific inflammatory biomarkers remains unclear.

We performed a prospective observational study of 150 women (age 19-45) undergoing hysteroscopic submucosal fibroid resection. Serum C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured at three timepoints: preoperatively, 48 h postoperatively, and 3 months postoperatively. IUAs were assessed at 12 weeks via second-look hysteroscopy and graded by American Fertility Society criteria.

Of 135 patients who completed follow-up, 40 (30.8%) developed IUAs (20 mild, 12 moderate, 8 severe). Baseline characteristics were similar between those who developed IUAs and those who did not, except that FIGO type II fibroids were more frequent in the IUA group (20.0% vs. 8.4%, p = 0.04). IL-6 and CRP levels rose markedly after surgery in patients who developed adhesions, whereas increases in the no-IUA group were modest. By 48 h postoperatively, mean IL-6 was ~ 7 pg/mL higher in the IUA group than in no-IUA (23.0 vs. 15.8 pg/mL, p < 0.001), and CRP was ~ 2.4 mg/L higher (8.5 vs. 6.1 mg/L, p < 0.001). These differences persisted at 3 months (IL-6 18.2 vs. 14.2 pg/mL; CRP 6.4 vs. 5.1 mg/L; both p < 0.001), indicating a prolonged inflammatory response. TNF-α rose modestly postoperatively in both groups and was significantly higher in the IUA group at 48 h (13.0 vs. 10.0 pg/mL, p < 0.001) and 3 months (11.5 vs. 9.4 pg/mL, p = 0.01). IL-6 showed the strongest correlation with adhesion severity (Spearman ρ ≈ 0.5, p < 0.001) and was an independent predictor of moderate-to-severe IUA risk (adjusted odds ratio [OR] 1.25 per 1 pg/mL, 95% confidence interval [CI] 1.11-1.42). CRP was also an independent predictor (OR 1.32 per 1 mg/L, 95% CI 1.08-1.61, p = 0.006), whereas TNF-α did not retain significance in multivariate analysis. In a model adjusting for surgical factors (fibroid type, operative time), IL-6 and CRP remained significant predictors (adjusted OR 1.22, 95% CI 1.09-1.39 and OR 1.29, 95% CI 1.06-1.57, respectively). Women with type II fibroids had higher odds of developing moderate/severe adhesions (OR ~ 2.8, 95% CI 1.1-7.3). ROC analysis demonstrated that IL-6 had the highest discriminative ability for clinically significant IUAs (area under curve [AUC] ≈ 0.80), outperforming CRP (AUC ≈ 0.72) and TNF-α (AUC ≈ 0.65). At an optimal 48-hour IL-6 cutoff of ~ 20 pg/mL, sensitivity for predicting moderate/severe adhesions was ~ 81% and specificity ~ 74%, while a CRP cutoff of ~ 7 mg/L yielded ~ 75% sensitivity and 65% specificity.

Perioperative elevations in IL-6 and CRP are strongly associated with IUA formation after hysteroscopic myomectomy, and dynamic changes in these markers offer predictive value. Early post-surgical IL-6 and CRP measurements may help identify high-risk patients and support risk-stratified postoperative surveillance or prophylactic interventions.