Loop electrosurgical excision procedure with or without intraoperative iodine: A randomized controlled trial

Intraoperative Lugol's iodine staining of the cervix (IOS) during loop electrosurgical excision procedure (LEEP) is commonly used to better define surgical resection margins. No randomized head-to-head comparison of LEEP with vs without IOS is available to inform clinical practice.

To compare LEEP with versus without IOS regarding rates of involved resection margins, patient satisfaction and procedure-related outcomes.

Consecutive women referred to a university colposcopy unit were recruited and randomized 1:1 to LEEP with intraoperative application of Lugol's iodine or LEEP without intraoperative Lugol's iodine (control). The primary endpoint was the histopathological rate of involved resection margins. Secondary endpoints included patient satisfaction assessed on the day of surgery and 14 days thereafter using numerical rating scales (0-10) and procedure-related complications, pain, blood loss, and surgeon preference. Results were compared using nonparametric, chi-square, and t tests. Multivariable logistic regression was used to assess the influence of covariates on the primary outcome.

Between January 2022 and September 2025, we randomized 229 women, 114 in the IOS arm and 115 in the control arm. In an intention-to-treat analysis, rates of involved resection margins were 20/114 (17.5%) vs 8/115 (7.0%) (risk difference, 10.6 percentage points; 95% confidence interval [CI] 2.1-19.3; risk ratio, 2.52; 95% CI 1.16-5.49; P=.014). Post hoc analysis of 215 women showed lower main-cone depth after fixation with IOS (transformation-zone-adjusted mean difference, -1.47 mm; 95% CI, -2.61 to -0.34; P=.011). There were no differences in operative metrics including cone weight, cone fragmentation, procedure time, and time to complete hemostasis. Intraoperative complications were similar in both groups as were surgeons' ratings. Immediate postoperative pain and satisfaction did not differ significantly between groups. At 14-day follow-up, bleeding outcomes favored the iodine group. Bleeding intensity during the first 24 postoperative hours was lower (median 1 [interquartile range 0-3] vs 2 [1-4]; P=.008) and bleeding duration was shorter (median 3 [1-9] vs 5 [2-14] days; P=.047). There were no differences in pain intensity, pain duration, analgesic use, or overall satisfaction at follow-up. In multivariable logistic regression adjusting for age, body mass index, ever smoking, and transformation zone, randomization to IOS remained associated with higher odds of involved resection margins (adjusted odds ratio 3.46, 95% CI 1.38-8.70; P=.008).

LEEP with IOS is associated with a higher rate of involved resection margins and should therefore not be used routinely in clinical practice.