O-010 The ULTRA trial: transvaginal ULTRAsound-guided ovarian ablation using the novel May Health device in women with PCOS-related infertility: first–in-human feasibility clinical trial

Abstract

Abstract Study question Is transvaginal ULTRAsound (TVUS)-guided ovarian ablation using May Health device feasible, safe, and effective in inducing ovulation in Clomiphene citrate and/or Letrozole (CC/LTZ)-resistant PCOS women? Summary answer TVUS-guided ovarian ablation using the May Health device seems feasible, safe and effective in inducing ovulation in PCOS-related anovulatory infertility, with additional, larger studies needed. What is known already Laparoscopic ovarian drilling (LOD) is widely accepted and recommended as an effective second line treatment in PCOS-related infertility. However, it is an invasive procedure that requires general anaesthesia and carries significant risks. Furthermore, the off-the-shelf devices used for LOD are not specifically designed to precisely deliver the desired and effective amount of ablation. In contrast, the May Health device has been designed to induce a precisely calculated amount of ovarian ablation via a much less invasive route without general anaesthesia. May Health therefore transforms an invasive surgical procedure to an office-based technique similar in access to the well-established oocyte retrieval. Study design, size, duration This study included two phase-1 feasibility, single-arm clinical trials running in parallel in the US and EU assessing the May Health Device in performing TVUS-guided ovarian ablation in anovulatory PCOS women resistant to first-line ovulation induction drugs. Sample size was 35 participants with post-procedure follow-up (FU) of 24 months in EU and 12 months in US. Endpoints included procedure feasibility (successful ablation of at least one ovary), safety, and effectiveness (ovulation and pregnancy rates). Participants/materials, setting, methods Seven fertility centres (UK, France, Belgium, US) participated in the trials. Participants were CC/LTZ-resistant PCOS women aged 18-40 years. PCOS was diagnosed according to Rotterdam criteria. Participants underwent TVUS-guided ovarian ablation using May Health device. The initial five participants underwent laparoscopy concurrent with TVUS-ablation. Post-procedure, serum progesterone was measured weekly until confirmation of ovulation or up to 12 weeks. Women were evaluated at 3 and 6 months, then telephoned at 9, 12 and 24 months. Main results and the role of chance Twenty-three participants (mean±sd age, 31.8±3.1years; BMI, 29.8±5.0kg/m2) underwent May Health TVUS-guided ovarian ablation and completed at least three-months FU. Of those, 10 (43.5%) ovulated spontaneously during the first three months. Six more women ovulated between three- and nine-months FU, some with CC/LTZ, giving a total ovulation rate of 69.6% (16/23). Of the 11 participants who completed nine-months FU, five conceived. Two more participants conceived before 9-months giving a total pregnancy rate of 53.8% (7/13). In 19 cases (82.6%), ablation was achieved successfully in both ovaries, while in four cases (17.4%) one of the ovaries was not ablated either because it was too small (as per protocol) (n = 3) or inaccessible (n = 1). Overall, 14 participants experienced 29 adverse events (AEs), of which 25 were mild, two moderate and two severe. Nine mild/moderate AEs were deemed related to the device/ablation procedure. Examples of mild/moderate AEs included mild self-limiting vaginal bleeding (n = 5), pain (n = 5) and headache (n = 2). None of the severe AEs were deemed related to the device/ablation procedure. One participant in phase1a who underwent laparoscopy concurrent with the ablation, sustained a bowel injury involving the ilium near the ileocecal junction. Independent expert investigation concluded that the injury was likely caused by laparoscopic veress needle. Limitations, reasons for caution One possible limitation of this study is the lack of a comparator treatment / placebo arm. However, this was not necessary for this feasibility phase 1 trial. Furthermore, given the nature of TVUS-ovarian ablation, it would be difficult to compare it with other ovulation induction drugs or to a placebo. Wider implications of the findings These preliminary data suggest that the novel May Health device offers a promising office-based second line ovulation inducing procedure for CC/Letrozole-resistant anovulatory PCOS women. Trial registration number NCT03760926