Yiwu Cold Knife Technique Versus Electrocision for Multiple Endometrial Polyps

This section covers technical trial design, standardized surgical implementation, statistical methodology, data governance, adverse event oversight and multi-centre quality control measures, with no repetition of brief summary, eligibility criteria, outcome definitions or informed consent content.

1. Trial Design Technical Specifications This is a prospective, multi-centre, parallel-group, open-label non-inferiority randomised controlled trial (RCT). Randomisation allocation will be implemented via a centralised electronic randomisation system hosted independently from each study site to eliminate selection bias. The randomisation ratio is 1:1 between the cold knife hysteroscopy (Yiwu procedure) test group and conventional electroresection control group, with stratification planned across participating tertiary hospitals to balance baseline patient characteristics across centres. Open-label design is adopted due to the inherent visual difference between cold mechanical instruments and electric cutting loops; blinding of surgeons and participants is not technically feasible under routine clinical operation conditions. The non-inferiority framework is selected rather than superiority testing because the primary research hypothesis only requires demonstrating that cold knife resection does not produce an unacceptably higher 1-year polyp recurrence rate compared to the standard electroresection gold standard, rather than proving superior anti-recurrence performance.

2. Standardised Surgical Implementation Protocols A unified Standard Operating Procedure (SOP) manual will be distributed to all participating sites to standardise perioperative workflows and eliminate inter-centre technical heterogeneity. All operating surgeons must complete formal trial-specific training and pass a competency assessment before performing study procedures.

   • Unified perioperative management: Identical preoperative antiseptic preparation, anaesthesia regimens, intraoperative uterine distension fluid type and volume monitoring protocols, and routine postoperative anti-infection and uterotonic medication rules are enforced for both groups. Only the polyp excision hardware and cutting mechanism differ between arms.
   • Test group technical constraints: All polyp removal must rely solely on mechanical cutting via micro-scissors or hysteroscopic morcellators; no electrosurgical energy (cutting, coagulation current) is permitted at any stage of polyp resection or haemostasis. Bleeding control is limited to mechanical compression of the wound base.
   • Control group technical constraints: Resection and haemostasis must utilise standard high-frequency electrosurgical current as per daily clinical practice; thermal ablation of residual endometrial tissue outside polyp lesions is prohibited to avoid confounding anti-recurrence effects.
   • Intraoperative documentation mandates real-time recording of total operative duration, isolated polyp resection time, total inflow and outflow of distension medium, net fluid absorption, estimated intraoperative blood loss, and intra-operative adverse findings such as suspected perforation or fluid overload signs. Postoperative histopathological specimen labelling will link each specimen to the randomised treatment arm for centralised pathological review where required.
3. Sample Size Calculation Statistical Rationale Sample size derivation adheres strictly to two independent proportion non-inferiority statistical formulas for binary primary endpoints. The conservative statistical assumption assumes identical true 1-year recurrence rates (6.5%) across both groups to calculate the maximum required sample size for robust non-inferiority verification. A pre-specified clinically meaningful non-inferiority margin of 5 percentage points is agreed by a multidisciplinary gynaecology expert panel: the cold knife group will be deemed non-inferior if its upper bound of the 95% one-sided confidence interval for recurrence rate difference does not exceed +5%. Fixed statistical parameters include one-sided type I error α=0.025 and statistical power (1-β)=80%. Per-group calculated sample size before loss-to-follow-up adjustment is 382 subjects. A projected 10% overall loss-to-follow-up rate is incorporated to offset incomplete 12-month outcome data, resulting in a target enrolment of 425 participants per group and a total planned sample of 850 participants across all trial sites.

4. Centralised Data Management and Confidentiality Controls All clinical source data extracted into electronic Case Report Forms (eCRFs) is managed by an independent dedicated data management team separated from clinical investigators and statistical analysts. Double data entry logic and automated range/consistency validation rules are embedded within the eCRF platform to flag missing, contradictory or physiologically implausible entries for site clarification before database lock.

   Strict participant de-identification rules are applied throughout data storage and analysis: all direct identifiers (full name, ID number, contact information) are removed from analytical datasets, replaced with unique trial participant identification numbers only. Raw source medical records containing personal identifiers remain stored locally at each hospital's secure medical archive, restricted to site investigators only. All trial databases comply with domestic clinical research privacy regulations, with no external unauthorised data sharing permitted without formal ethical committee approval.

5. Adverse Event (AE) and Serious Adverse Event (SAE) Oversight Framework A site-level AE tracking log is mandated to record every untoward medical occurrence emerging intraoperatively, during hospitalisation, or across the 12-month follow-up window, regardless of presumed causal relationship to the assigned surgical procedure. Investigators perform structured causality assessment, severity grading and expectedness classification for each recorded AE.

   Standardised SAE reporting timelines are enforced: all events meeting SAE criteria (death, life-threatening complications, unplanned rehospitalisation, permanent organ dysfunction/disability, incident pregnancy during trial follow-up) require initial verbal notification to the central trial team and local Institutional Review Board (IRB) within 24 hours of investigator awareness, followed by a complete written SAE report within 7 calendar days. Incident pregnancy triggers immediate participant withdrawal from scheduled follow-up, with separate long-term pregnancy outcome tracking implemented under the SAE surveillance pathway. All AE/SAE source documentation is retained alongside hospital medical records for audit purposes.

6. Multi-Centre Quality Assurance and Monitoring A dedicated central trial monitor team will conduct regular on-site monitoring visits to all participating tertiary hospitals throughout enrolment and follow-up phases. Monitoring activities include verification of informed consent documentation completeness, cross-checking eCRF data against original medical charts, confirmation of adherence to surgical SOPs, validation of follow-up visit completion rates, and review of AE/SAE recording integrity. Any major protocol deviations identified during monitoring will trigger corrective and preventive action plans submitted to the ethics committee for review. A trial steering committee consisting of senior gynaecologists, biostatisticians and methodologists will hold periodic meetings to review overall trial progress, safety aggregate data and enrolment milestones, with authority to recommend protocol amendments if significant clinical or operational risks emerge mid-trial.