A validation of the most commonly used protocol to predict the success of single-dose methotrexate in the treatment of ectopic pregnancy

BACKGROUND: Currently, the likely success of single-dose methotrexate (MTX) (50 mg/m(2)) for the treatment of ectopic pregnancy is indicated by a >15% decrease in hCG from days 4-7 after administration. The aim of this study was to assess this protocol and to develop new rules that could be used to predict the outcome at an earlier stage. METHODS: Data were collected prospectively. Women receiving MTX for an ectopic pregnancy had serum hCG and progesterone levels checked on days 1, 3, 4, 5 and 7. Other factors including age, gestational age, previous obstetric history and ultrasound findings were recorded. The women were followed up until the outcome of medical management was known. Univariate analysis was performed to determine the benefit of the '15% day 4-7 rule', as well as to develop new rules, which potentially could be used to predict the likelihood of success before 7 days. Historical and ultrasound variables were also analysed to identify the significant variables associated with successful conservative management. RESULTS: The success rate of single-dose MTX was 68.1% (47/69). A second dose was required in 18.8% (13/69) of cases, and it was successful in 84.6% (11/13). The 15% day 4-7 rule correctly predicted the outcome in 90.3% of cases [sensitivity 93.0%, specificity 84.2%, positive predictive value (PPV) 93.0% and negative predictive value (NPV) 84.2%, Fisher exact test P-value < 0.0001]. New rules were developed based on the percentage change day 4-5 and logistic regression models incorporating day 5 hCG levels and ultrasound findings. These new rules did not outperform the current 15% day 4-7 rule. CONCLUSIONS: We have confirmed that a 15% decrease in serum hCG between day 4 and day 7 is a very good indicator of the likely success of MTX. The development of new rules did not significantly improve our ability to predict a successful outcome at an earlier stage.