Protocol for a study comparing the efficacy of hysterectomy in patients with enlarged uterus via TU-LESS and vNOTES: a single-blind, prospective randomised clinical trial.

Uterine enlargement is a common clinical disorder with increasing incidence, often associated with constipation, urinary frequency and urgency due to compression of intestines and urethra, dysmenorrhoea, irregular menstruation and anaemia due to menorrhagia, significantly compromising the quality of life. It is mainly caused by adenomyosis 1 and uterine fibroids, 2 to which women in the perimenopausal and postmenopausal stages are particularly susceptible. 1 3 Consequently, compared with those of reproductive age, women in these stages are more likely to experience significant symptoms and complications related to enlarged uterus. Given that post-reproductive women represent the majority of patients affected by this condition, hysterectomy is often recommended as a definitive treatment, though the enlarged uterus is often regarded as a benign condition which may not necessitate treatment or be relieved only by hormonal treatments. Hysterectomy, widely applied in gynaecology, serves as a radical treatment for uterine disorders. The traditional laparotomy, first performed in 1809, 4 remains a critical surgical approach with its broad indications. However, laparotomy is associated with a high incidence of complications, coupled with a long recovery time due to the large incision in the abdominal wall. 5 This approach does not fully align with the principles of ERAS (enhanced recovery after surgery), promoting less invasive alternatives. As the laparoscopic technique matured over recent decades, providing a safer, more effective approach, there has been a notable shift from laparotomy to minimally invasive approaches. Conventional multiport laparoscopic hysterectomy and LAVH (laparoscopic-assisted vaginal hysterectomy) emerged in the 1980s, evidently decreasing the size of required incisions, allowing for better recovery and reducing the rate of complications. 6 8 Building on these advancements, newer innovations have further improved surgical approaches, focusing on minimising external incisions and optimising patient outcomes. Transumbilical Laparoendoscopic Single-Site Surgery (TU-LESS) has been introduced in recent years to further optimise recovery and cosmesis. Unlike conventional laparoscopy, which requires multiple incisions, TU-LESS use a single, concealed umbilical incision at the umbilicus. This technique provides excellent cosmetic benefits with little to no visible scarring. Additionally, innovations such as Zheng’s anchor suture technique improve the safety and aesthetic outcomes of TU-LESS, ensuring secure umbilical closure while minimising complications. 9 Another approach, the Transvaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES), eliminates abdominal incisions entirely by using the vaginal orifice for peritoneal access. Merging the benefits of laparoscopic and vaginal surgery, vNOTES offers reduced postoperative pain, faster recovery and improved cosmetic results. New access platforms have further enhanced its safety and feasibility, contributing to its growing adoption in hysterectomy, myomectomy and ovarian procedures. Studies have consistently demonstrated its advantages, including shorter hospital stays, minimal blood loss and high patient satisfaction. 10 12 Both vNOTES and TU-LESS represent significant advancements in minimally invasive gynaecological surgery, offering effective alternatives to traditional multi-port laparoscopic approaches. Both are noted for shortened recovery time, reduced pain, minimal scarring, fewer complications and quicker return to daily activities, especially vNOTES. 11 14 However, the prospective comparison in the real world of the safety and efficacy of these two methods, concentrating on enlarged uterus, remains lacking until now. Therefore, we aim to systematically assess and compare the results of vNOTES and TU-LESS in patients with large uteri undergoing hysterectomy. A prospective single-blinded randomised clinical trial (RCT) will be conducted to evaluate clinical outcomes of vNOTES and TU-LESS in hysterectomy to guide clinical decision-making. Participants will be randomly assigned, ensuring an unbiased comparison of the efficacy of the procedures in terms of healing status and recovery time.

This is a two-arm, single-blind, parallel-group, randomised clinical trial. Patients with an enlarged uterus receiving hysterectomy and involved in our trial in West China Second University Hospital will be assigned to the vNOTES group and TU-LESS group at a 1:1 ratio. The total duration will be about 2 years from October 2025 to October 2027, including an approximately 1.5-year recruitment period followed by a 6-month follow-up. Participants who require conversion to conventional laparoscopy, as well as those lost to follow-up, will be excluded from the study, as outlined in the detailed study schedule in figure 1 . It will be in line with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. 15 Randomisation will be performed using age-stratified blocks for balanced allocation to treatment groups (1:1 ratio). Given 210 subjects, ‘blockrand’ automatically selects appropriate block sizes to ensure balanced random assignment of participants to treatment groups. A random code table is generated for the treatment assignments while keeping the block sizes confidential to maintain concealment and reduce bias. All of the data related to our protocol will be entered in an Excel table by an independent investigator and securely stored in the institutional computer. Anonymised data will be uploaded to a shared international database if necessary. Table 1 shows clinical characteristics and time points for data collection. 16 ERAS, enhanced recovery after surgery; FSFI, Female Sexual Function Index; POD1, postoperative day 1; POD2, postoperative day 2; POSAS, Patient and Observer Scar Assessment Scale; VAS, Visual Analogue Scale. The independent research assistant will inform the approach of hysterectomy to the surgeon after reviewing the random assignment of surgical approach for each patient in the computer. Patients will not get any information related to their surgery arrangement within 24 hours postoperatively. To enable the blinding, we will apply wound pads to all patients’ abdomens after the surgery is performed, no matter whether the incisions actually exist. The pads will not be adjusted unless they get soaked within 24 hours postoperatively. Participants will be notified of the specific surgical approach they underwent 24 hours after the procedure. All surgeons involved in the study must be qualified to perform both surgical pathways: vaginal endoscopic surgery and laparoscopy. They must have substantial experience with the relevant surgical approach, including at least 20 completed procedures and 5 in the past year. They also need to read the details of interventions in this study. These criteria confirm that participating surgeons have the necessary training and recent experience to maintain procedural competence. They also promote consistency throughout the study, guaranteeing that all surgeries are performed by qualified professionals. This strengthens the study’s validity and makes the findings more applicable to a broader surgical community. Women diagnosed with uterine enlargement (uterine size exceeding that of a 3-month pregnancy) due to benign uterine diseases or precancerous lesions, who are scheduled to undergo hysterectomy, will be recruited. Inclusion criteria are as follows (1) aged 18–70 years; (2) presence of enlarged uterus (uterine weight ≥280 g) planning to undergo hysterectomy with or without salpingectomy/adnexectomy; (3) willing to be randomly allocated to receive either vNOTES or TU-LESS and sign the informed consent form. Exclusion criteria include (1) virgins or having vaginal stenosis. (2) Patients requiring concurrent surgical intervention for conditions such as ovarian cysts or lesions on the vulva, vagina, appendix (3) presence of uterus exceeding approximately 20 gestational weeks in size (about 900–1000 g), which is beyond the limitations of a single-site laparoscopic approach due to concerns regarding technical feasibility and safety. (4) Active or suspected malignancy that contraindicates the planned surgical procedure; (5) prior pelvic surgeries (≥2) or suspected severe pelvic adhesions (eg, rectovaginal endometriosis or restricted uterine mobility); (6) medical history of peritoneal dialysis, pelvic radiation therapy or laparoscopic tuberculosis management; (7) patients with prolapse or pelvic inflammation; (8) poorly controlled diabetes mellitus; (9) obesity (body mass index greater than 30 kg/m²). Patients should avoid dairy products and starchy solid foods for at least 6 hours before anaesthesia and refrain from fried, fatty or meaty foods for 8 hours. Clear fluid intake (<300 mL) is restricted within 2 hours of anaesthesia. Bowel preparation is unnecessary. Preoperative prophylaxis includes administration of antibiotics according to standard guidelines and prevention of deep vein thrombosis as indicated. For pain management, patients receive 0.5 g of oral paracetamol 2 hours preoperatively for pre-emptive analgesia. General anaesthesia is used for the procedure, and an indwelling urinary catheter is placed preoperatively to monitor urine output and prevent bladder distension during surgery. Patients will be positioned in the lithotomy position, with a 30° rigid endoscope universally employed. 16 The access port specifications (manufacturer and model) will be documented for both vNOTES and TU-LESS groups. The procedure will begin with a posterior colpotomy via the vaginal fornix, followed by an anterior vaginal incision. These incisions will be connected, and blunt dissection with transection of the uterosacral ligaments will ensue. Subsequently, the vesicouterine peritoneum will be incised. Next, the retractor is inserted, and the vNOTES platform is attached to maintain access and establish CO ₂ pneumoperitoneum at 8 mm Hg. An assistant will maintain the laparoscope through one channel of the multiport device. The surgical steps include coagulation, transection of the utero-ovarian pedicles and mesosalpinx and division of broad ligaments adjacent to adnexa, minimising ureteral injury. 17 Bilateral adnexal excision (salpingectomy or adnexectomy) will be performed according to preoperative planning. The uterus is extracted transvaginally. Finally, the vaginal cuff will be closed with continuous sutures, and uterosacral ligaments will be reattached to the vaginal cuff. 18 The pneumoperitoneum is released, the platform and retractor are removed and haemostasis is confirmed. The procedure begins with a 1–2 cm longitudinal umbilical incision, through which the abdominal cavity is accessed layer-by-layer. Standard instrumentation includes a colpotomy cup and vaginal occluder balloon; a uterine manipulator may supplement these tools to enhance visualisation. 19 The single-port trocar with a protective sleeve is inserted through the umbilical incision, secured and connected to the insufflation system to establish CO ₂ pneumoperitoneum (12–15 mm Hg). The patient is positioned to allow the surgical team (surgeon and assistant) to operate from the cephalad side. The laparoscope is inserted through one of the port channels by the assistant for visualisation 16 , while the surgeon uses the remaining channels to introduce instruments such as graspers, bipolar forceps, scissors, ultrasonic scalpel and a needle holder to perform an antegrade hysterectomy (cephalad-to-caudal dissection). BSO (bilateral salpingo-oophorectomy) will be selectively performed based on preoperative indications. Specimen retrieval will be performed via the umbilical incision. Cold knife morcellation will be performed to facilitate specimen removal. Intraoperative conversion to conventional laparoscopy is permitted if an auxiliary port is deemed necessary upon expert evaluation. Drainage tube placement is discouraged; however, if required, it will be documented and inserted vaginally. To maintain blinding, a wound pad will be applied to all patients’ umbilicus, retained for 24 hours, only replaced on saturation. On regaining consciousness from anaesthesia, patients may resume fluid intake and move. At 6 hours after operation, the urinary catheter should be removed unless contraindicated. Discharge will be determined based on hospital criteria, including normal body temperature, an uninfected incision, independent mobility, spontaneous urination and flatus passing. A follow-up will extend for 6 months after surgery. The proportion of patients able to consume a liquid diet post-surgery within 24 hours postoperatively. The proportion of patients able to pass flatus within 24 hours postoperatively. The proportion of patients regaining the ability to urinate without assistance after catheter removal within 24 hours postoperatively. The proportion of patients regaining mobility after catheter removal within 24 hours postoperatively. The percentage of patients discharged within 2 days postoperatively. 20 Postoperative pain at 24 hours assessed via Visual Analog Scale (0=no pain, 10=worst imaginable pain). Operative duration timed from initial skin/vaginal incision to final suture placement (minutes), excluding frozen biopsy intervals. Intraoperative blood loss volume. Intraoperative and 3-month postoperative complications graded via Clavien-Dindo Classification, which uses seven severity-based grades (I-V with ‘a/b’ subclasses). For example, Grade IIIa indicates a complication requiring surgical intervention without general anaesthesia, while IIIb requires intervention with anaesthesia. The subclasses (‘a/b’) can be excluded to streamline reporting into five grades (I-V). Scar evaluation at 3 and 6 months assessed by Patient and Observer Scar Assessment Scale composed of dual-component 10-point scale (1=normal skin, 10=worst scar): Observer: vascularisation, pigmentation, thickness, roughness, pliability, surface area. Patient: pain, pruritus, colour, thickness, relief, pliability. 21 Total dosage of 24-hour analgesic consumption, stratified by drug class. Sexual function will be evaluated via the Female Sexual Function Index preoperatively and 6 months postoperatively. Examination of pelvic function within 2 days postoperatively: it involves evaluating stress urinary incontinence, pelvic organ prolapse and sexual dysfunction. 20 Eligible patients will be enrolled before surgery by the designated surgeon. A detailed explanation of the trial will be provided to all participants, and an informed consent form must be signed. Data will be collected preoperatively, during the surgery, 24 and 48 hours after operation and at 3 and 6 months postoperatively. The size of the sample was determined on a pre-test-estimated 80% success rate of achieving the comprehensive ERAS index within 24 hours postoperatively. 16 Using a single-sided non-inferiority framework with α=0.025, power=1−β=80%, and a predefined non-inferiority margin (Δ=0.15) for pairwise comparative analyses, the required sample size per group was calculated as 88 patients. Allowing for a 15% attrition rate, each group will enrol 105 patients, totalling 210 participants. This ensures sufficient power to assess non-inferiority while maintaining statistical rigour. Analyses will be conducted in R V.4.3.2. The analysis will be intention-to-treat, excluding intraoperatively converted cases (laparoscopy/laparotomy) so as per-protocol. Continuous variables will be summarised as mean±SD (normally distributed) or median (IQR) (non-normal), with categorical variables reported as frequency (%). Comparisons between groups will be performed using independent t-tests, Mann-Whitney U tests or χ² tests for those three kinds of data, respectively. Statistical significance for all inferential analyses will be determined using a one-sided α level of 0.025, or a two-sided α level of 0.05. Since conventional laparoscopy or laparotomy could be introduced during operation if necessary, no additional risks beyond those of standard hysterectomy are expected. Adverse events will be documented from the time of informed consent through 12 months postoperatively. Serious adverse events will be immediately reported (≤24 hours) to the Ethics Committee. Study-related injuries will be compensated as in regulatory standards. All participants must adhere to the current approved protocol. Any post-approval protocol adjustments must be documented in a modification form signed by the principal investigator (PI), which must obtain Ethics Committee approval before implementation. The revised protocol must subsequently be reviewed by the principal investigator and reported during the presentation and publication of primary study outcomes. Approved by the Ethics Committee of West China Second University Hospital (2023 medical scientific research for ethical approval No.321). Written informed consent is mandatory for participation in online supplemental material . Findings will be published in peer-reviewed journals and presented at international conferences. The study started the recruitment in March 2025.