Medical Therapy for Ectopic Pregnancy

Gary H Lipscomb M.D.


Semin Reprod Med. 2007;25(2):93-98. 

In This Article

Single Versus Multidose Methotrexate

The most appropriate methotrexate treatment protocol remains controversial. The two most commonly used treatment protocols in the United States involve either a multidose or single-dose protocol. A recent well-conducted meta-analysis of single and multidose methotrexate protocols showed multidose to be significantly superior to single-dose methotrexate, with success rates of 241 of 260 (92.7%) versus 940 of 1067 (88.1%; p = 0.035).[11] This analysis was heavily weighted by patients from the University of Tennessee database, with 100 of the multidose patients (including four patients treated for persistent trophoblastic disease after surgery who were excluded in this study) and 350 of the single-dose patients involved in the meta-analysis. Due to the inherent weaknesses of meta-analysis, compiled data rather than individual raw data must be compared, making it impossible to compare patients directly.

However, a direct comparison of the single and multidose patients from the University of Tennessee showed no significant difference in success rates between multidose (92 of 97; 95%) and single-dose protocols (492 of 546; 90%; p = 0.18).[12] Both groups were comparable with regard to factors generally believed to increase failure except for the presence of ectopic cardiac activity, which was more common in the single-dose group. These factors would be expected to bias the study against the single-dose protocol.

Interestingly, the cure and failure rates are quite similar in both studies. It is possible that failure to find statistical significance in the latter study may have been because of its smaller sample size rather than a true lack of significance. One small prospective comparison of single-dose versus multidose methotrexate involving 108 patients showed no statistical difference between the two groups.[13] The failure rates of 92.6% for multidose and 88.9% for single-dose were also quite similar to both studies. Unfortunately, because of its relatively small size the study does not have the statistical power to prove there is no true difference.

Given the greater simplicity and low complication rate of single-dose methotrexate, the single-dose methotrexate protocol would seem to have an advantage over the multidose protocol if the success rates are indeed similar. Even if the ~4% difference in failure rates is true, the increased success rates may not offset the other disadvantages associated with multidose methotrexate protocols.


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