How Best to Medically Manage Ectopic Pregnancy?

Abstract & Commentary

by Frank W. Ling, MD, Clinical Professor, Dept. of Obstetrics, University of Colorado Health Services, Denver, is Associate Editor for OB/GYN Clinical Alert.

Dr. Ling reports no financial relationship to this field of study.

Synopsis: Single dose and multi-dose regimens for methotrexate treatment of ectopic pregnancy are equally efficacious.

Source: Alleyassin A, et al. Fertil Steril. 2006;85:1661-1666.

These Iranian investigators randomized treatment of 108 patients with unruptured ectopic pregnancy to either a single dose protocol or a multiple dose protocol. The single dose regimen was successful in 48/54 cases (88.9%), while 92.6% (50/54) patients responded to the multiple-dose regimen. The 6 failures in the single-dose protocol all responded to a second course of treatment. In the multi-dose group, 2 required surgery while the other 2 responded to a second course of therapy. Fifteen patients in the single-dose and 20 patients in the multi-dose group had side effects (dermatitis, pruritis, abdominal pain, stomatitis, diarrhea, and elevated liver enzymes).


The two protocols used are very familiar to this feeble old mind. I was fortunate enough to have participated with Dr. Thomas Stovall and others in the development of the early multi-dose and single-dose methotrexate protocols.

In the multi-dose protocol used in this study, the patient received 1 mg/kg methotrexate on days 1, 3, 5 and 7 with leucovorin 0.1 mg/kg on days 2, 4, 6, and 8. These injections were continued until the hCG levels decreased 15% in 48 hours or 4 doses of methotrexate had been given. In the single-dose regimen, which was developed after the multi-dose protocol, the patient received methotrexate 50 mg/m2. If measurement of hCG on days 4 and 7 did not show a decrease of 15%, a second course of therapy was given.

This is by no means the last word on the medical treatment of ectopic pregnancy, but it goes a long way to answer some of the questions. Advantages of the single-dose regimen are obvious: less medicine, fewer injections, less laboratory testing, and less surveillance. If the outcomes are similar, why not use the simpler treatment protocol? This is the first randomized study, but it appears to support the other case series.

The astute reader should recognize that the medical treatment of ectopic pregnancy may not be for every practice. For example, if you cannot reliably diagnose an unruptured ectopic pregnancy without surgery, medical treatment is an illogical option. You might as well treat the ectopic surgically while you're already in there making the diagnosis. Certainly, ruptured ectopic pregnancies that result in a patient being hemodynamically unstable should be treated surgically, not medically. Also, the patient needs to be reliable enough to follow up with you as prescribed. Otherwise, you don't have the opportunity to follow through with the needed treatments and laboratory tests.

Should you treat an ectopic medically if you're not comfortable doing so? I think the answer to that is the same as anything else in the practice of medicine, ie, you can become comfortable if you gain experience under controlled circumstances. For many years, we would field questions over the phone from people who wanted to be reassured that what they were doing was correct. We co-managed patients with clinicians in town. We tried to share as much of our experience as possible. As a result, today, medical treatment for the unruptured ectopic pregnancy is considered mainstream.

So the teaching point of the article is that the 2 regimen are comparable based on the best type of study design, randomized. The unspoken teaching point is that medical treatment of the unruptured ectopic pregnancy is a service that can be incorporated into a women's health practice.


  1. Alleyassin A, et al. Comparison of success rates in the medical management of ectopic pregnancy with single-dose and multiple-dose administration of methotrexate: a prospective, randomized clinical trail. Fertil Steril. 2006;85:1661-1666.