Efficacy, Safety, and Fertility Outcomes of Loop Electrosurgical Excision Procedure Versus Cold-Knife Conization for Cervical Intraepithelial Neoplasia: A Systematic Review and Meta-Analysis

Background: Loop electrosurgical excision procedure (LEEP) and cold-knife conization (CKC) are both used for cervical intraepithelial neoplasia (CIN), yet their comparative efficacy and reproductive safety remain unclear. Methods: We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science through March 2025 for randomized controlled trials (RCTs) comparing LEEP with CKC in histologically confirmed CIN. 7 RCTs enrolling 1007 women (LEEP, n = 508; CKC, n = 499) from six countries were included. Primary endpoints were residual disease, perioperative morbidity, and obstetric outcomes; secondary endpoints included recurrence and re-intervention. Risk of bias was assessed with Cochrane tools, and data were pooled using RevMan. Results: CKC was associated with a lower rate of residual disease than LEEP (relative risk [RR] = 1.55; 95% confidence interval [CI]: 1.04–2.31; p = 0.03). Conversely, LEEP was associated with numerically lower rates of preterm births (RR = 0.54; 95% CI: 0.23–1.28; p = 0.16) and premature rupture of membranes (RR = 0.57; 95% CI: 0.29–1.14; p = 0.11), although CIs crossed unity. Excision dimensions, positive margins, postoperative bleeding, cervical stenosis, infection, spontaneous abortion, and reoperation rates did not differ significantly between groups. Recurrence showed a nonsignificant trend toward being higher after LEEP (RR = 2.25; 95% CI: 0.87–5.78; p = 0.09). Conclusions: CKC demonstrated superiority in reducing residual disease, whereas LEEP showed a nonsignificant trend toward lower risks of premature birth and premature rupture of membranes. Perioperative morbidity was comparable between procedures. Treatment decisions should integrate pathologic accuracy, surgical feasibility, and fertility considerations. Long-term, rigorously designed trials incorporating quality-of-life endpoints are warranted to validate these findings. Registration: The study has been registered on https://www.crd.york.ac.uk/PROSPERO/ (registration number: CRD420251009221; registration link: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251009221).