Comparison of Two-dose and Single-dose Methotrexate Protocol for Ectopic Pregnancy: a Randomized Controlled Trial

Ectopic pregnancy is an important cause of maternal morbidity and occasionally mortality. Deaths associated with ectopic pregnancy have declined, though approximately 75% of deaths in the first trimester and 9-13% of all pregnancy-related deaths are associated ectopic pregnancy. The main stays of management for ectopic pregnancy were surgery and medical treatment. Medical management with systemic methotrexate administration avoids the inherent morbidity of anesthesia and surgery is cost-effective, and also offers success rates comparable to surgical management, with no loss in future potential fertility.

However, although medical management using methotrexate is used commonly, there is no solid consensus regarding dose protocol. Currently, there are three methotrexate protocols for the treatment of an ectopic pregnancy, "multi-dose", "single-dose", or "two-dose". Among them, the multi-dose protocol includes the administration of 4 methotrexate doses alternating with leucovorin (rescue regimen). As a result of the multiple dosing of methotrexate, side effects are more common. In contrast, the advantages of the single-dose protocol include elimination of a rescue regimen, lower incidence of adverse effects, and better compliance. However, the single-dose protocol was found to be associated with a considerably lower success rate as compared with the multi-dose protocol (88% versus 93%) in a recent meta-analysis. The two-dose protocol, which it balances efficacy and safety/convenience, was described as a cross between the multi-dose and single-dose protocols.

However, there were a few studies comparing between single-dose and two-dose protocol. The purpose of this prospective randomized trial was to compared the success rates of single-dose and two-dose methotrexate protocol for the treatment of tubal ectopic pregnancy.