One versus two doses of methotrexate for the treatment of ectopic pregnancy: A retrospective cohort study at an urban US medical center

Objective: Ectopic pregnancy (EP) occurs in 2% of gestations. Medical management of stable EP relies on methotrexate (MTX) via intramuscular injection. Guidance is needed to define an optimal dosing regimen. Methods: A retrospective study from 2016 to 2022 evaluated treatment efficacy for one versus two doses of MTX. Treatment success was defined as ≥15% decline in quantitative serum beta human chorionic gonadotropin (b-hCG) days 4–7 after MTX administration. Multivariable logistic regression and Cox proportional hazard models were used to estimate differences in success rate. Results: A total of 472 cases were identified, 286 received one dose of MTX, and 186 received two doses. Average age was 31 years, parity 2.3, and body mass index (BMI) 29. Risk factors for EP included prior ectopic (16%) and prior infection (25%). B-hCG at the time of MTX initiation, presence and size of adnexal mass were similar across groups. Treatment success was similar between one dose (72%) and two doses (71%), and no statistically significant differences were observed between groups in adjusted models (odds ratio [OR] = 0.91, 95% confidence interval [CI]: 0.55–1.50). Odds of treatment success for one versus two doses was 0.96 (95% CI: 0.59, 1.57), and was unchanged after adjusting for cofounders. Initial b-hCG value and presence of adnexal mass >4 cm were not predictive of treatment response. The rate of laparoscopy was 17% and 11% for one and two doses, respectively. Median time to resolution was 27 days for both treatment groups. Conclusions: No significant difference was noted in treatment success, rate of laparoscopy, or total duration of treatment between one or two doses of MTX.