P-698 The ULTRA trial: transvaginal ULTRAsound-guided ovarian ablation using May Health System in women with PCOS-related infertility: clinical and endocrine outcomes of first–in-human feasibility trial
Authors: Amer S , Hansen K , Wyns C , Autin C , Fakhreldin M , Fernandez H , Jegaden M , Jayaprakasan K , Metwally M 
Published: July 2024

Abstract

Study question
What is the feasibility of transvaginal ULTRAsound (TVUS)-guided ovarian ablation using the May Health System to improve ovulation, pregnancy, and hormonal abnormalities in PCOS-related infertility?

Summary answer
The feasibility of TVUS-guided ovarian ablation to improve ovulation, pregnancy, and hormonal abnormalities in PCOS-related anovulatory infertility was demonstrated. A pivotal study is underway.

What is known already
Laparoscopic ovarian drilling (LOD) is widely accepted as an effective second line treatment in PCOS-related infertility. However, laparoscopy is an invasive procedure that requires general anaesthesia and carries significant risks. Furthermore, there is no standardization of the LOD technique among surgeons. In contrast, the May Health System has been designed to deliver a precisely calculated amount of ovarian ablation via a less invasive route without general anaesthesia. This approach therefore transforms an invasive surgical procedure to an office-based technique similar in ovarian access to the well-established oocyte retrieval. Feasibility and safety results of this trial have previously been reported.

Study design, size, duration
This study included two feasibility, single-arm clinical trials running in parallel in the EU and US assessing the May Health System in performing TVUS-guided ovarian ablation in anovulatory PCOS women resistant to first-line ovulation induction drugs. Sample size was up to 35 participants with post-procedure follow-up (FU) of 24 months in EU and 12 months in US. Endpoints for this study were technical success, ovulation rates, pregnancy rates, and hormonal changes.

Participants/materials, setting, methods
Seven fertility centres participated in the trials. Participants were clomiphene/letrozole-resistant PCOS women aged 18-40 years. PCOS was diagnosed according to Rotterdam criteria. Participants underwent TVUS-guided ovarian ablation using the May Health System. 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 month, and then telephoned at 9- 12- and 24-month (EU sites only).

Main results and the role of chance
Thirty-one participants (mean±sd age, 31.9±3.3 years; BMI, 29.84.7kg/m2) underwent May Health TVUS-guided ovarian ablation and 25 completed at least six-months FU, with follow-up ongoing. Fourteen (45.2%) ovulated spontaneously within 3-months. Six more participants (19.3%) ovulated between three and nine months (after restarting CC/LTZ) giving a combined ovulation rate, with and without first-line medication restart, of 64.5% (20/31). Of the 31 participants who underwent the procedure, 10 (32%) have conceived to date, with seven live births, two ongoing, and one miscarriage.
In 30 cases (97%), the targeted ablation was achieved successfully, while in one case (3%) the procedure was abandoned for the second ovary due to pain (n = 1).
The median (IQR) serum AMH concentrations significantly decreased from baseline 76.1 (32.0, 210.7) to 62.5 (21.2, 253.6) pmol/l at 3-month (p = 0.001) and 56.7 (11.5, 126.8) pmol/l at 6-month (p = 0.001) post-procedure (Figure 2). The magnitude of post-ablation AMH decline was significantly (p = 0.047) greater in those who ovulated (responders) (-23.7% (-36.5, 17.7)) versus non-responders (-7.3% (-25.2, -1.6)). Ovarian volume significantly (p = 0.005) decreased from 13.6±5.1 ml at baseline to 10.1±3.7 ml at 6-month FU. There were no statistically significant changes in mean circulating testosterone, LH, or FAI at 3- or 6-month.

Limitations, reasons for caution
A limitation of this study is the lack of a comparator treatment / placebo arm. However, this was not necessary for this feasibility trial. It is possible to assume that the post-procedure ovulation and pregnancies could be compared for each participant with pre-procedure lack of ovulation and failure to conceive.

Wider implications of the findings
These data suggest that the investigational May Health System may offer an effective office-based second line ovulation inducing procedure for PCOS. The observed decline in circulating AMH, which was sustained for at least six months, could be the underlying mechanism of ovarian rebalancing that leads to subsequent resumption of ovulation.

Trial registration number
NCT03760926