Review
The medical management of ectopic pregnancy: a meta-analysis comparing “single dose” and “multidose” regimens

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Abstract

Objective

Medical management of an unruptured ectopic pregnancy with intramuscular methotrexate is common and cost-effective. Two treatment protocols, the “single dose” and the “multidose,” have been advocated and independently reported in the medical literature. This analysis systematically compares the success and prevalence of side effects of these two regimens.

Data sources

Published data on women with an ectopic pregnancy medically managed were identified using a MEDLINE search from 1966 to 2001 using key words and review of the references of each manuscript.

Methods of study selection

Studies were selected based on dosing regimen, number of subjects, and study quality. Data regarding outcome, number of doses administered, side effects, and baseline characteristics were extracted. Data were summarized, and the associations of failed management and the presence of side effects with treatment protocol were calculated. Baseline serum chorionic gonadotropin values and the presence of embryonic fetal actively were controlled for with multivariable logistic regression.

Tabulation, integration, and results

The overall success rate for women treated with methotrexate for an ectopic pregnancy was 89% (1181 of 1327). The single dose was much more commonly used. The use of single dose was associated with a significantly greater chance of failed medical management than the use of the multidose in both crude (odds ratio [OR] 1.71; 1.04, 2.82) and adjusted analyses (OR 4.74; 1.77, 12.62). The single-dose regimen was associated with fewer side effects (OR 0.44; 0.31, 0.63). Women who experienced side effects were more likely to have successful treatment regardless of regimen.

Conclusion

The multidose regimen is more effective than the single-dose regimen.

Section snippets

Sources

Using OVID, we conducted a MEDLINE search (January 1966 through January 2001) restricted to the English language and using the key words “methotrexate,” “ectopic pregnancy,” and “tubal pregnancy.” A manual search of references was then conducted for additional articles. Articles selected for review included only those that reported the outcome of patients treated with either of the two standard protocols for the medical management of ectopic pregnancy. The majority of reports were case series

Study selection

A summary data set was created in an electronic database. Each patient was entered into the datasheet individually with as much descriptive information as provided by the report. Patients were classified according to the protocol intended for treatment. Exposure was defined as use of the single-dose protocol; the referent group was defined as those subjects assigned to the multidose protocol. Subjects were not reclassified if they received two doses while managed with the single-dose protocol

Results

A total of 213 articles met the search criteria, of which 76 articles were reviewed. The data from 26 articles were included in the analysis (Table 2). Overall, we reviewed 1327 cases of women diagnosed with ectopic pregnancy treated with methotrexate. The overall success rate for women treated with methotrexate for an ectopic pregnancy (using either treatment regimen) was 89% (1181 of 1327). The mean hCG level reported was 33,120.75 ± 3715 mIU/mL, with a range of 2–59,000. An increasing hCG

Conclusion

Treatment guidelines exist for medical management; however, there is currently no consensus on dose and frequency of administration.36 The single dose is more commonly used because of its simplicity and convenience for both the clinician and the patient. This is a systematic analysis of the published literature comparing the two regimens. These data provide a precise estimate of outcome, actual dosing patterns, and side effects, and they illustrate a number of important clinical points.

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    Funding for this study was provided from the National Institutes of Health, grant RO1-HD-36455-01A1.

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