FIRSTT study: randomized controlled trial of uterine artery embolization vs focused ultrasound surgery

Abstract

Background: Uterine leiomyomas (fibroid tumors) cause considerable symptoms in 30-50% of women and are the leading cause of hysterectomy in the United States. Women with uterine fibroid tumors often seek uterine-preserving treatments, but comparative effectiveness trials are lacking.

Objective: The purpose of this study was to report treatment effectiveness and ovarian function after uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery from the Fibroid Interventions: Reducing Symptoms Today and Tomorrow study.

Study design: The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study, which is a randomized controlled trial of uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery, enrolled premenopausal women with symptomatic uterine fibroid tumors; women who declined randomization were enrolled in a parallel observational cohort. A comprehensive cohort design was used for outcomes analysis. Our target enrollment was 220 women, of which we achieved 41% (n=91) in the randomized and parallel arms of the trial. Primary outcome was reintervention for uterine fibroid tumors within 36 months. Secondary outcomes were change in serum anti-Müllerian hormone levels and standardized measures of fibroid symptoms, quality of life, pain, and sexual function.

Results: From 2010-2014, 83 women (mean age, 44.4 years) were treated in the comprehensive cohort design (43 for magnetic resonance imaging-guided focused ultrasound surgery [27 randomized]; 40 for uterine artery embolization [22 randomized]); baseline clinical and uterine characteristics were similar between treatment arms, except for higher fibroid load in the uterine artery embolization arm. The risk of reintervention was higher with magnetic resonance imaging-guided focused ultrasound surgery than uterine artery embolization (hazard ratio, 2.81; 95% confidence interval, 1.01-7.79). Uterine artery embolization showed a significantly greater absolute decrease in anti-Müllerian hormone levels at 24 months compared with magnetic resonance imaging-guided focused ultrasound surgery. Quality of life and pain scores improved in both arms but to a greater extent in the uterine artery embolization arm. Higher pretreatment anti-Müllerian hormone level and younger age at treatment increased the overall risk of reintervention.

Conclusion: Our study demonstrates a lower reintervention rate and greater improvement in symptoms after uterine artery embolization, although some of the effectiveness may come through impairment of ovarian reserve. Both pretreatment anti-Müllerian hormone level and age are associated with risk of reintervention.

Clinical trial registration number: NCT00995878, clinicaltrials.gov.

Keywords: focused ultrasound surgery; leiomyoma; randomized controlled trial; uterine artery embolization; uterine fibroid tumor.

Figure 1.

Flow Diagram of Participants in Comprehensive Cohort Design. Solid lines and white boxes show disposition of randomized controlled trial participants. Dashed lines and shaded boxes indicate participants who were not randomized and entered the parallel cohort (PC1). GnRH indicates gonadotropin-releasing hormone; MRgFUS, magnetic resonance imaging–guided focused ultrasoun d surgery; MRI, magnetic resonance imaging; UAE, uterine artery embolization. ^a Eleven patients had 2 exclusion criteria. (From AbdElmagied et al. Used with permission).

Figure 2.

Cumulative Incidence of Second Uterine Fibroid Procedure and Menopause Accounting for Competing Risk Events. Cumulative incidence curves estimating the incidence of a second fibroid procedure (solid lines) or onset of menopause (dashed lines) for those in the magnetic resonance imaging–guided focused ultrasound surgery group (MRgFUS; black lines) or the uterine artery embolization group (UAE; red lines).

Figure 3.

Cumulative Incidence of Second Leiomyoma Procedure or Menopause Accounting for Competing Risk Events by Anti-Müllerian Hormone (AMH) Level. Patients were stratified into (A) high AMH (>0.3 ng/mL) and (B) low AMH (≤0.3 ng/mL) based on median AMH levels, among all comprehensive cohort design participants with baseline AMH levels. Cumulative incidence curves estimating the incidence of a second leiomyoma procedure (solid lines) or onset of menopause (dashed lines) for those in the magnetic resonance imaging–guided focused ultrasound surgery group (MRgFUS; black lines) or the uterine artery embolization group (UAE; red lines).