**Purpose:**To perform a cost-effectiveness analysis of hysterectomy (HYST), uterine artery embolization (UAE), and Magnetic Resonance guided Focused Ultrasound (MRgFUS) for treatment of uterine fibroids while taking into account long and short term utilities associated with different treatment modalities.

**Method: **Cost-effectiveness analysis was performed from a societal perspective to compare MRgFUS with hysterectomy (HYST) and uterine artery embolization (UAE). We developed a microsimulation model with a 6-month cycle length to evaluate the treatment options for premenopausal women with symptomatic uterine fibroids at age 40. Lifetime costs and utilities were calculated after modeling three scenarios in which each treatment strategy was the first-line strategy. Long and short term utilities specific to each treatment modality were incorporated to weigh the effectiveness values. We included hospital, physician, and treatment related costs incurred, as well as lost-productivity costs. Incremental cost-effectiveness ratios (ICER) below willingness-to-pay (WTP) threshold of $50,000 per quality adjusted life-year (QALYs) were considered cost-effective. Extensive sensitivity analysis was performed on costs and probability estimates to determine the robustness of our results.

**Result: **In base case analysis, UAE was the most effective and highest costing strategy (22.75 QALYs, $22,968) followed by MRgFUS (22.73 QALYs, $20,252) and then HYST (22.54 QALYs, $11,253). MRgFUS was cost-effective relative to HYST, with an associated incremental cost-effectiveness ratio (ICER) of $47,891/QALY, while UAE was not; an ICER of $234,565/QALY is much higher than the WTP threshold. Cost-effectiveness of MRgFUS improved as the starting age approached the age of menopause. At post-MRgFUS symptom relief rates below 80% (base case 93%), UAE became the more cost-effective strategy. For most instances, MRgFUS remained the most cost-effective strategy. However, HYST became the most cost-effective with post-UAE recurrence rates above 4.7% (base case 3.2%) and at pre-symptom relief utility values below 0.67 (base case 0.815). UAE only became cost-effective only if the WTP is increased to $75,000 and the probability of fibroid recurrence of UAE below 2.0%.

**Conclusion: **Taking into account lifetime costs and utilities, MRgFUS was a cost-effective starting strategy for treatment of uterine fibroids beginning at age 40. Results were stable to changes in most parameters, except for post-UAE recurrence rates and pre-symptom relief utility values.

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