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The Medical Management of Ectopic Pregnancy: A Meta-analysis Comparing “Single Dose” and “Multidose” Regimens

Barnhart, Kurt T. MD, MSCE; Gosman, Gabriella MD; Ashby, Rachel MD; Sammel, Mary ScD


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.

The “single dose” protocol is associated with a two- to five-fold increase in failure compared with the “multidose” protocol for the medical management of ectopic pregnancy.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania; Magee Women's Hospital, Pittsburgh, Pennsylvania; and Division of Reproductive Endocrinology and Infertility, Brigham & Women's Hospital, Boston, Massachusetts.

Address reprint requests to: Kurt T. Barnhart, MD, MSCE, Assistant Professor Obstetrics and Gynecology, Senior Scholar Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Medical Center, 3400 Spruce Street, 106 Dulles, Philadelphia, PA 19104; E-mail:

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

Received August 26, 2002. Received in revised form October 28, 2002. Accepted November 7, 2002.

© 2003 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.