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Am Fam Physician. 2000;61(7):2228-2229

Many women with ectopic pregnancies are now being treated with methotrexate instead of conventional surgery. One or more intramuscular injections of the medication usually cause resorption or spontaneous tubal abortion of the ectopic conceptus. To date, the success of methotrexate has been thought to depend on the levels of human chorionic gonadotropin (hCG) and progesterone, and the absence of blood in the peritoneal cavity. However, the data on each of these factors are limited. Lipscomb and colleagues performed a large retrospective study to determine which specific pretreatment factors are related to the success of treatment with intramuscular methotrexate in patients with tubal ectopic pregnancies.

The authors conducted a retrospective chart review of 350 women with singleton ectopic pregnancies who were treated with intramuscular methotrexate at their institution. A diagnosis of ectopic pregnancy was established initially through the measurement of serum hCG and progesterone levels. Women with an hCG level of less than 50,000 mIU per mL (50,000 IU per L) or a serum progesterone level of less than 25 ng per mL (79.5 nmol per L) underwent further evaluation. If the initial hCG level was 2,000 mIU per mL (2,000 IU per L) or higher, a transvaginal ultrasound examination was performed. All of the other women were followed with serial hCG testing. If the level of hCG failed to rise appropriately, a dilation and curettage was performed. An ectopic pregnancy was diagnosed in these patients if no placental villi were found in the specimen or if the hCG level failed to decline by at least 15 percent within 12 to 24 hours after the procedure. In women whose hCG level reached 2,000 mUI per mL, transvaginal ultrasonography was performed. In these women, ectopic pregnancy was diagnosed if an intrauterine gestational sac was not seen and the serum hCG level continued to rise.

Women diagnosed with an ectopic pregnancy were considered candidates for treatment with intramuscular methotrexate (in a dosage of 50 mg per m2 of body-surface area) if they were hemodynamically stable, did not have free fluid outside the pelvic cavity on ultrasound examination, did not desire surgery and agreed to weekly follow-up visits until the level of serum hCG was 15 mIU per mL (15 IU per L) or lower. If the serum hCG did not decline by at least 15 percent between days four and seven, a second dose of methotrexate was given. Continued failure of the serum hCG to decline by at least 15 percent during any successive week mandated an additional dose of methotrexate. If after three doses the hCG level did not decline or cardiac activity was present, the ectopic pregnancy was treated surgically.

Of the 350 women included, 268 were found to have an ectopic tubal mass by transvaginal ultrasonography, 114 had free fluid in the peritoneal cavity and 46 had fetal cardiac activity. Treatment with methotrexate was successful in 320 (91 percent) of the women. Among these women, the mean hCG level was 4,019 mIU per mL (4,019 IU per L) compared with a mean level of 13,420 mIU per mL (13,420 IU per L) among the women whose treatment with methotrexate was not successful. Of note, 94 percent of women whose initial hCG level was less than 10,000 mIU per mL (10,000 IU per L) and 93 percent of those whose hCG level was less than 15,000 mIU per mL (15,000 IU per L) were successfully treated with methotrexate. Fetal cardiac activity was noted in 50 percent of women with an initial hCG level of 15,000 mIU per mL or more and was found in all women with an hCG level of more than 50,000 mIU per mL. Fetal cardiac activity was present in 12 percent of women who were successfully treated and in 30 percent of women in whom treatment was not successful. Of the 350 study participants, 283 women received only one dose of methotrexate, 60 received two doses and six received three doses. Among the 320 successfully treated women, 261 received only one dose.

The authors conclude that in women with an ectopic pregnancy, the level of serum hCG is the best predictor of successful treatment with intramuscular methotrexate. However, unlike previously published studies, in this study a high success rate was found in patients with hCG levels as high as 15,000 mIU per mL. In addition, the presence of free peritoneal fluid, which is considered by many physicians to be a contraindication to methotrexate therapy, was not associated with treatment failure in this study.

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