VANCOUVER, B.C. (FRONTLINE MEDICAL NEWS)Waiting a few days to see which way beta–human chorionic gonadotropin levels are headed spares women with unruptured ectopic pregnancies from unnecessary methotrexate treatment, according to an Israeli review of 1,703 ectopic pregnancies over the course of more than 11 years.

Although prompt administration of the drug is standard practice, investigators from Tel Aviv Sourasky Medical Center found that about 40% of ectopic pregnancies resolved on their own without any treatment.

“Our clinical message is that methotrexate is overused. It’s considered a relatively safe drug, but it has its side effects,” said Dr. Yaron Gil, a gynecologist who led the study at Sourasky.

In addition to abdominal cramping and other well-known issues, methotrexate might cause damage to the surrounding fallopian tube and may cause ectopic pregnancies to enlarge, Dr. Gil said at the meeting sponsored by AAGL.

Methotrexate doesn’t resolve the risk of rupture –the main concern with watchful waiting – since ectopic pregnancies can rupture even as the beta-hCG levels decline. A day or two of watchful waiting “doesn’t change the risk of rupture,” Dr. Gil said.

All 1,703 women with ectopic pregnancy were admitted to the hospital between January 2001 and June 2013; 620 (36%) required immediate surgery. The remaining 1,083 women – all hemodynamically stable with beta-hCG levels below 10,000 mIU/mL, no fetal heart activity, and an intervention nearby – were assigned to the watchful waiting protocol.

The investigators measured beta-hCG on admission and followed it daily. Patients who had a daily decline of 15% were considered self-resolving and sent home. Women with a daily increase of 15% or more were treated with methotrexate. Those with daily increases below 15% were followed for a maximum of 5 days, and then given methotrexate.

Among the 1,083 women assigned to the watchful waiting protocol, 674 (62%) had spontaneous resolutions, while 409 (38%) had stable or increasing beta-hCG levels and received methotrexate, 50 mg/m2 IM, usually once, but sometimes twice.

Methotrexate was effective in 356 (87%) of the women who received it. The remainder of the women underwent laparoscopic salpingectomies. Maternal age, parity, gestational age, endometrial thickness, and the size of the ectopic mass had no influence on whether the drug was effective.

In women with beta-hCG levels of 2,500-3,500 mIU/mL, methotrexate was effective 75% of the time. The drug was effective 65% of the time in women with beta-hCG levels greater than 4,500 mIU/mL ( Am. J. Obstet. Gynecol. 2014;211:128.e1-5 ).

As expected, watchful waiting led to a lower rate of methotrexate success than in other reported series because the Israeli team limited use to women who truly needed it, according to Dr. Gil.

“Early administration gives higher success rates, but at the cost of giving methotrexate unnecessarily to some women,” he said. “Longer intervals should be considered before administering the drug.”

Dr. Gil said he has no financial disclosures and didn’t receive outside funding for the study.


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