ADNOLA trial: a study-protocol - a randomised controlled trial study comparing adnexal surgery by vNOTES or laparoscopy.

Adnexal surgery is one of the most common surgical procedures performed in women and can either be performed to treat pathology (ovarian cysts, hydrosalpinx) but also prophylactically for sterilisation or risk-reducing salpingo-oophorectomy in case of hereditary genetic alterations. 1 The laparoscopic technique is currently considered the gold standard for adnexal procedures reducing infections, postoperative complications, pain and cost compared with open adnexectomy. 2 The laparoscopic technique is used for 97% of adnexal cases in Sweden 3 and for 88.5% in the USA. 4 The latest advancement in minimally invasive surgery is vNOTES (vaginal natural orifice transluminal endoscopy), 5 in which the entrance to the abdomen is performed by an anterior or more commonly posterior colpotomy rather than via the abdominal wall. The technique offers the benefits of a vaginal, scarless entrance to the abdomen together with endoscopy through a GelPort via the vagina. 6 When feasible, a vaginal entrance to the abdomen is recommended in the case of hysterectomy due to fewer complications, quicker surgical time, and quicker postoperative recovery. 7 The NOTABLE trial comparing adnexectomy by laparoscopy versus vNOTES indicated equivalent results. The NOTABLE trial was an RCT showing that vNOTES adnexectomy was non-inferior to laparoscopy for the successful removal of benign adnexa without conversion. 8 vNOTES adnexectomy had shorter surgical time (39 min vs 24 min), less use of analgesics (11 units vs 6 units) and lower self-assessed VAS scores the first week postoperatively. The NOTABLE trial was a single-centre trial including only a small number of participants (n=67) performed by a single surgeon. The NOTABLE trial was a single-centre study with a limited sample size; consequently, its findings and conclusions are not generalisable. The aim of our study is to compare postoperative pain after vNOTES versus laparoscopic adnexal surgery.

The national Swedish ethical board at the main centre, Helsingborg Hospital, Sweden, has given ethical agreement (dated 20 March 2025). Before inclusion of patients, all centres must have an approved ethical agreement from their hospital or country. Results will be submitted for publication in a peer-reviewed journal.

Pragmatic multicentre two-armed superiority randomised controlled trial. No blinding. SPIRIT reporting guidelines are used. 9 The recruitment started in Q4 2025 and is estimated to end in 2028. All women aged 18 years and above who planned for a unilateral or bilateral adnexectomy (ovaries and tubes) due to adnexal pathology or as a prophylactic procedure due to hereditary risk of cancer will be eligible for the study. The participant may not enter the trial if ANY of the following apply: Female participant who is pregnant or planning a pregnancy during the course of the trial. Scheduled elective surgery or other procedures requiring general anaesthesia during the trial. Any other significant disease or disorder which may either put the participant at risk because of participation in the trial or may influence the result of the trial or the participant’s ability to participate in the trial. Patients taking opioids or other painkillers routinely preoperatively. Patients with chronic pelvic pain. Patients with a surgical contraindication for vNOTES procedure: previous hysterectomy, history of rectal surgery, suspected or confirmed endometriosis, suspected malignancy, suspected obliteration of the pouch of Douglas following severe PID or other causes, active lower genital tract infection or pregnancy. Failure to provide written informed consent prior to surgery. Randomisation with random permuted blocks to achieve a 1:1 ratio of participants in the intervention (vNOTES) and control group (LSC) ( figure 1 ). We will stratify according to the preoperative ultrasound-assessed classification of the adnexal pathology, ie, if the cyst is solid/semisolid or not. We believe that a solid/semisolid cyst needs a larger extraction incision in the abdominal wall, which can give more pain. Potentially eligible women with a strong preference for a certain treatment or failing to provide written informed consent before surgery will not be subject to any formal non-randomised follow-up. These women will be recorded in the patient record but not in REDCAP. Permuted block randomisation via REDCap software will be used. Participants will sign an informed consent ( online supplemental material 1 ). To compare postoperative pain after adnexal surgery performed by vNOTES or laparoscopy. Postoperative pain is measured by VAS scale, days 1–7 postoperatively. Units of non-opioid analgesics, days 1–7 postoperatively. Units of postoperative opioids, days 1–7 postoperatively. The incidence of intraoperative complications, ie, any adverse event before the end of the surgical intervention including injury to the bladder, ureter, bowel or intrapelvic/intra-abdominal vessels, as a dichotomous outcome. Operation time, measured as the time in minutes from the insertion of the bladder catheter to the end of vaginal/abdominal wound closure, as a continuous outcome. Postoperative complications, for example but not restricted to major bleeding or pelvic hematoma requiring transfusion. Infections of the vaginal incision, abdominal wall or wound, urinary tract, chest or febrile episodes/unspecified infections. Thromboembolism. Postoperative ileus or wound dehiscence. Classified according to the Clavien-Dindo classification as a dichotomous outcome. Reported during the first 6 weeks after surgery. The rates of readmission requiring hospitalisation for at least 24 hours for any adverse event causally related to the gynaecological intervention during the first 6 weeks after surgery, as a dichotomous outcome. Conversion rates: the proportion of women treated by any other approach than the allocated technique as randomised, as a dichotomous outcome. vNOTES will most likely be converted to LSC and LSC to open surgery. Surgeon’s experience of comfort and flow measured by a 0 to 10 mm VAS scale. Surgeons that have performed at least 50 vNOTES adnexal cases will be invited to join the ADNOLA trial. Laparoscopic or vNOTES adnexal surgery is performed as previously described by Baekelandt et al . 8 The choice of suture material, size of trocars and laparoscopic camera differ between participating centres. The preoperative and perioperative anaesthesiologic protocols vary between hospitals, but the protocols are the same for vNOTES and laparoscopic procedures in each centre. All patients will have standardised postoperative pain regimen. Local anaesthetics Ropivacaine 7,5 mg/mL, 20 mL (given perioperatively) vaginally or in incisions in the abdominal wall Paracetamol 500 mg 2×4 Ibuprofen 400 mg 1×3 The aim of this study is to reproduce previously observed results in a larger sample. The sample size for this trial was based on the reported differences in VAS scores in the NOTABLE trial. We approximated that 50% would reach VAS 0 after 4 days in the vNOTES group and 7 days in the LSC group. We regarded a difference of 20% in VAS score to be clinically significant between the two groups. To detect statistically significant differences for the primary outcome between both comparison arms with an α=0.05 and a power of 80%, we calculated using a two-sided χ 2 test that 100 participants needed to be recruited per treatment arm. An intention to treat analysis will be performed. Sensitivity analysis will be performed assessing if the size of the laparoscopic trocar influences postoperative pain. Randomisation will be stratified for solid/semisolid cysts. If imbalance exists regarding cyst size between the vNOTES and laparoscopy arms, cyst size will be included as a covariate in the primary analysis and sensitivity analyses performed. Approximately 200 elective adnexal procedures are performed in Helsingborg Hospital per year. Based on a 30% willingness of women to participate in the study and the participation of four centres, we estimate that the duration of recruitment will be limited in time to between 12 and 18 months. The study period of the ADNOLA trial will be estimated at 2 years. First publication will be possible within 3 years after trial commencement. Our sample size calculation has allowed for a 5% loss to follow-up rate. The follow-up period of this multicentre pragmatic trial has been limited to 6 weeks postoperatively. Analysis will be performed on an ‘intention to treat’ basis in the first instance. A ‘per protocol’ analysis will also be performed to test the robustness of the results obtained. Baseline characteristics of the patients enrolled in the two comparison groups will be compared with ensure that randomisation has produced comparable groups of participants and will be covariates in the modelling procedure. The follow-up period of this multicentre pragmatic trial has been limited to 6 weeks postoperatively. No interim analysis is planned.