Managing interstitial ectopic pregnancies based on a standardized dual-site local methotrexate injection protocol and developing an equation to predict human chorionic gonadotropin decline Short running title: Dual-site MTX injection of interstitial EP

Objective: To evaluate the efficacy of dual-site local methotrexate injection guided by ultrasound in patients with interstitial ectopic pregnancies and to characterize the decline of hCG after injection. Design: A case series with retrospective data analysis. Setting: Tertiary academic Medical Center. Population: Patients who had interstitial (cornual) ectopic pregnancy referred for evaluation and management. Methods: Twelve patients, who were clinically stable and gave consents, received dual site local methotrexate injection, 50 mg each to the gestational sac and the placenta under transvaginal ultrasound guidance. We analyzed the time to negative hCG and the elimination half-life of hCG based on an exponential decay model. Using the above data, a formula was developed to estimate the time from injection to negative hCG. Main Outcome Measures: Negative serum hCG. Results: All 12 patients had negative serum hCG after the initial injection. None required surgery or additional injection. Serum hCG became negative (<5 mIU/mL) over a mean of 65.1 days (range 21–132 days). The elimination half-life of hCG was 5.08 ± 2.38 days (mean ± SD). Conclusions: Ultrasound-guided dual-site local methotrexate injection, 50 mg each to the gestational sac and the placenta, appears to be an effective alternative for patients who have stable, interstitial ectopic pregnancies.