Preimplantation genetic testing for BReast CAncer gene 1 and risk-reducing surgery is more effective at age 35 than age 40

Objective: To compare the cost-effectiveness of in vitro fertilization (IVF) with preimplantation genetic testing for monogenic disorders (PGT-M) at age 35, followed by risk-reducing bilateral salpingo-oophorectomy, to delaying interventions to age 40 among BRCA1 (BReast CAncer gene 1) mutation carriers. Design: A cost-effectiveness analysis using a Markov mathematical model. Subjects: Probabilities, cost data, and utilities were derived from the literature to estimate the incremental cost-effectiveness ratios between the two strategies. Exposure: Age of interventions: age 35 or age 40. Main Outcomes Measures: Cost-effectiveness was the primary outcome, expressed as the ratio of differences in costs to the difference in quality-adjusted life years, and the willingness-to-pay threshold was set to $100,000 per quality-adjusted life year gained or lost. Results: In vitro fertilization with PGT-M at age 35 followed by immediate bilateral salpingo-oophorectomy demonstrated absolute dominance over treatment delay until 40, with an incremental cost-effectiveness ratio between the two strategies calculated as −153 when using a willingness-to-pay threshold of $100,000. Per 10,000 patients with BRCA1, interventions at age 35 are associated with an additional 950 live births, 726 fewer ovarian cancer cases, and 705 fewer ovarian cancer deaths. Interventions at age 40 increased costs by $3,721,823 and resulted in 24,379 fewer quality-adjusted life years. Probabilistic sensitivity analysis revealed absolute dominance for the age 35 cohort at all willingness-to-pay thresholds, modeled up to $200,000. Conclusions: Our model suggests that performing IVF with PGT-M is cost-effective at age 35 compared with age 40 in BRCA1 mutation carriers, with an increased number of live births and decreased ovarian cancer cases. Although this model informs counseling, shared decision-making should be undertaken with a multidisciplinary healthcare team for BRCA1 mutation carriers.