Impact of definitive uterine artery occlusion on ovarian reserve markers in laparoscopic myomectomy: a randomized controlled trial with 2-year follow-up.

study questionDoes definitive occlusion of uterine arteries have a short- or long-term impact on ovarian reserve markers in reproductive-age women undergoing laparoscopic myomectomy? SUMMARY ANSWER: Preventive definitive uterine artery occlusion (UAO) during laparoscopic myomectomy reduces intraoperative blood loss but does not impact serum AMH levels after short- and long-term follow-up in reproductive-age women. WHAT IS KNOWN ALREADY: Uterine leiomyomas are the most common benign tumours in women of reproductive age. For symptomatic women willing to retain their uterus, especially for a future pregnancy, the current gold standard is surgical myomectomy for subserous/intramural leiomyoma. Temporary or definitive occlusion of uterine arteries can be performed to control bleeding during surgery but its impact on ovarian reserve markers is still unclear. A single randomized trial with a 1-year follow-up demonstrated that temporary bilateral UAO during laparoscopic myomectomy slightly decreased AMH levels at postoperative day 2 but has no significant impact at 3, 6, and 12 months after surgery. STUDY DESIGN, SIZE, DURATION: We conducted a randomized controlled trial with a 2-year follow-up evaluating the effect of definitive occlusion of uterine arteries on ovarian reserve markers via sequential measures of AMH levels and AFC by ultrasound assessment. The study included 58 women with symptomatic leiomyoma type FIGO 3 to 6 scheduled for laparoscopic myomectomy between July 2015 and October 2021. Patient allocation was disclosed to the surgeon just before starting the procedure; women were blinded to group allocation throughout the study. PARTICIPANTS/MATERIALS, SETTING,

methodsPatients were randomized in two groups: the UAO group (laparoscopic myomectomy with preventive occlusion of uterine arteries) (n = 29 women) and the no-UAO group (laparoscopic myomectomy without occlusion of uterine arteries but with intra-myometrial injection of vasoconstrictive agents) (N = 29 women). Serum AMH levels and AFC were evaluated at baseline (T0) and followed at 1 month (T1), 3 months (T3), 6 months (T6), 12 months (T12), and 24 months (T24) after surgery. Intraoperative blood loss, evolution of uterine bleeding and pain symptoms, and leiomyoma recurrence were also evaluated as secondary outcomes. Pregnancies and live births were monitored. MAIN RESULTS AND THE ROLE OF CHANCE: Women in both groups did not differ in their baseline characteristics in terms of age, body mass index, ethnicity, parity, wish to become pregnant, hormonal treatment, leiomyoma number and size, baseline haemoglobin levels, uterine bleeding symptoms, baseline serum AMH levels, and AFC. The mean operative time was similar between both groups. Mean blood loss during surgery was on average 138 (±104) ml in the UAO group versus 436 (±498) ml in controls (P < 0.001). In the UAO group, 0% had an intraoperative blood loss >500 ml versus 32.1% in the no-UAO group (P < 0.01). Regarding clinical symptoms, most patients in both groups had decreased menstrual flow at the last follow-up visit (24 months) compared to baseline and improvement of dysmenorrhea followed the same trend with a reduction in pain levels in both groups. The risk of leiomyoma recurrence was similar between both groups. Serum AMH levels did not differ between the groups at any time (T1, T3, T6, T12, and T24) and non-inferiority of preventive occlusion was demonstrated with a non-inferiority margin of [-3.5 pmol/l]. Differences between means and 95% CI (in parentheses) were as follows: at T1 -0.11 (-2.14 to 2.40), at T3 -0.25 (-2.36 to 2.21), at T6 0.81 (-2.69 to 3.84), at T12 -0.95 (-3.15 to 1.33), and at T24 1.18 (-1.95 to 3.82). AFC did not differ between the groups at any time, however, non-inferiority of preventive occlusion could not be demonstrated, presumably due to a large variability in this measurement. LIMITATIONS, REASONS FOR CAUTION: Our sample size was calculated to detect a clinically relevant difference of at least two-thirds of the SD in serum AMH levels, but we cannot exclude that a larger sample size might have revealed a smaller impact on serum AMH. WIDER IMPLICATIONS OF THE

findingsPreventive UAO during laparoscopic myomectomy does not compromise ovarian reserve markers and can be used safely to improve perioperative bleeding control in women of reproductive age. Incorporating UAO as a preventive measure during laparoscopic myomectomy may enhance the safety of the procedure. STUDY FUNDING/COMPETING INTEREST(S): Funded by the Department of Paediatrics, Gynecology and Obstetrics of the Geneva University Hospitals. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: NCT02563392. TRIAL REGISTRATION DATE: 9 July 2015. DATE OF FIRST PATIENT’S ENROLMENT: July 2015.