Second dose methotrexate in ectopic pregnancies The role of beta human chorionic gonadotropin

Day-1 b-hCG should be used as a predictor for methotrexate treatment success, both in the first and the second injection of methotrexate.


Aviad Cohen, M.D., Guy Bibi, M.D., Benny Almog, M.D., Ziv Tsafrir, M.D., Ishai Levin, M.D.

Volume 102, Issue 6, Pages 1646-1649



To evaluate the role of β-hCG levels on days 1, 4, and 7 after methotrexate as predictors for second-dose requirement and success.


Retrospective cohort study.


Tertiary university-affiliated hospital.


A total of 1,703 patients were admitted because of ectopic pregnancy. Four hundred nine received methotrexate, of whom 73 women required a second dose.


The “single-dose” methotrexate protocol with 50 mg/m2 was administered to patients with progressing ectopic pregnancy. Surgical intervention was performed in cases of methotrexate second-dose treatment failure.

Main Outcome Measure(s):

Methotrexate second-dose requirement and success according to β-hCG levels on days 1, 4 and 7.


Second-dose methotrexate was successful in 58 patients (79.4%, success group), whereas 15 patients (20.6%) failed treatment and required surgical intervention (failure group). The medians of β-hCG levels on days 1, 4, and 7 were significantly higher in the “failure group” (1,601 vs. 2,844, 2,164 vs. 3,225, and 1,915 vs. 3,745 mIU/mL, respectively). Logistic regression analysis demonstrated that day-1 β-hCG levels were the only significant independent variable for second-dose treatment outcome. The receiver operating characteristic curve for β-hCG levels on day 1 was 0.727, and at a cutoff value of 2,234 mIU/mL the sensitivity and specificity reached the optimum for treatment success (77.5% and 73.3%, respectively).


Day-1 β-hCG levels were the only predictors for methotrexate second-dose requirement and treatment success. The cutoff value of β-hCG on day 1 with the optimal treatment results was found to be 2,234 mIU/mL.

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