Cost-effectiveness analysis of expectant versus active management for treatment of persistent pregnancies of unknown location

Background Persistent pregnancies of unknown location (PUL) are defined by abnormally trending serum human chorionic gonadotropin with nondiagnostic ultrasound. There is no consensus on optimal management. Objective This study was designed to assess the cost-effectiveness between three primary management strategies for persistent pregnancies of unknown location: (1) expectant management, (2) empirical two-dose methotrexate, (3) uterine evacuation followed by methotrexate, if indicated. Study Design We conducted a prospective economic evaluation performed concurrently with the Expectant versus Active Management for Treatment of Persistent Pregnancies of Unknown Location (ACT or NOT) multicenter randomized trial conducted from July 2014 to June 2019. Participants were randomized 1:1:1 to expectant management, two-dose methotrexate, or uterine evacuation. The analysis was from the healthcare sector perspective with a 6-week time horizon following randomization. Costs were expressed in 2018 U.S. dollars. Effectiveness was measured in quality-adjusted life-years (QALYs) and the rate of salpingectomy. Incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves were generated. Sensitivity analyses were performed to assess the robustness of the analysis. Results Methotrexate had the lowest mean cost, $875, followed by expectant management $1085, and uterine evacuation $1902 (p=0.001). Expectant management had the highest mean QALY (0.1043) followed by methotrexate (0.1031) and uterine evacuation (0.0992) (p=0.0001). Salpingectomy rate was higher for expectant management compared to methotrexate (9.4% vs 1.2%; p=0.02) and expectant management compared to uterine evacuation (9.4% vs 8.1%; p=0.04). Uterine evacuation, with highest costs and lowest QALYs, was dominated by both expectant management and methotrexate. In the base case analysis, expectant management was not cost-effective compared to methotrexate at a willingness-to-pay of $150,000/QALY given an ICER of $175,083/QALY gained (95% CI, -$1,666,825-2,676,375). Threshold analysis demonstrated methotrexate administration would have to cost $214 (an increase of $16 or 8%) to favor expectant management. Expectant management would also be favorable in lower risk patient populations with rates of laparoscopic surgical management for ectopic pregnancy not exceeding 4% of pregnancies of unknown location. Based on the cost-effectiveness acceptability curves, the probability expectant management was cost-effective compared to methotrexate at a willingness-to-pay of $150,000/QALY gained was 50%. Results were dependent on the cost of surgical intervention, and the expected rate of methotrexate failure. Conclusion Management of pregnancies of unknown location with a two-dose methotrexate protocol may be cost-effective compared to expectant management and uterine evacuation. While uterine evacuation was dominated, expectant management versus methotrexate results were sensitive to modest changes in treatment costs of both methotrexate and surgical management.