Ultrasound-guided high-intensity focused ultrasound is technically feasible and safe for occluding placental vessels in early-onset twin-twin transfusion syndrome.

Abstract

Twin-twin transfusion syndrome is a complication unique to monochorionic pregnancy, where shared placental vascular connections can lead to a circulatory imbalance, resulting in preterm delivery and attendant in utero or neonatal mortality. The only disease-modifying treatment is fetoscopic laser ablation of blood vessels, which has attendant risks of invasive intrauterine therapy. In this first-in-human technical feasibility and safety study, we investigated noninvasive, ultrasound-guided high-intensity focused ultrasound to occlude placental vascular targets as identified by color Doppler. The 2 outcomes were (1) safety: number/rate of patients experiencing significant iatrogenic harm, for first 14 days after high-intensity focused ultrasound and (2) efficacy: number/rate of targeted placental vessels which appear occluded at the end of a high-intensity focused ultrasound treatment cycle, assessed using comparison of color Doppler imaging of target anastomoses prehigh-intensity focused ultrasound and posthigh-intensity focused ultrasound exposure. Participants with anterior placenta and early-onset twin-twin transfusion syndrome were recruited to a Phase 1a clinical trial with co-primary endpoints of safety and efficacy of vessel occlusion at 12 to 17⁺⁶ weeks of gestational age. Ten participants underwent targeted ultrasound-guided high-intensity focused ultrasound occlusion of placental blood vessels that connected the 2 circulations, verified by color Doppler imaging, in whom 27 of 30 (90%) targeted placental vessels were successfully occluded by ultrasound-guided high-intensity focused ultrasound. No treatment-related significant maternal or fetal adverse events were recorded, and 18 of 20 fetuses were alive 14 days post-treatment. Participants expressed positive attitudes toward ultrasound-guided high-intensity focused ultrasound, valuing clear and consistent communication and sufficient time to consider participation in the study. In this Phase 1 study, ultrasound-guided high-intensity focused ultrasound showed a high rate of successful occlusion of placental vascular targets and no adverse side effects were observed within 14 days of treatment in women with early-onset twin-twin transfusion. While clinical efficacy of the technique could not be formally evaluated, 5 participants required fetoscopic laser and of the pregnancies treated, 12 of 20 neonates were alive at discharge.