Alur-Gupta S, et al. - The efficacy of two-dose or multi-dose methotrexate protocols versus a single-dose protocol for the treatment of ectopic pregnancy are compared in this study. In light of these outcomes, all RCTs exhibited the increased efficacy of multi-dose or two-dose protocols when compared to the single dose. However, individually and when combined, the CIs cross 1. In this way, they can only conclude that there is a trend towards greater success with either two-dose and multi-dose methotrexate protocols. Larger prospective randomized controlled trials should be conducted to affirm superiority. The greater occurrence of side effects in the multi-dose protocol and the shorter follow-up time with the two-dose protocol can be incorporated into counseling patients.

Methods

• For this research, they designed a comprehensive systematic review and meta-analysis.
• They queried PubMed and Embase up to February 2017.
• In this research, all studies were prospective randomized controlled trials (RCTs) that compared two-dose or multi-dose methotrexate protocols to single-dose protocols for the treatment of patients with an ectopic pregnancy.
• Studies felt to be of poor quality by utilizing Cochrane Collaboration's bias evaluation tool were not included.
• Additional sub-group analyses were performed assessing treatment success in subjects with a high B-HCG (> 4000mIU/mL depending on the study) or a large ectopic pregnancy size (≥2cm).
• Fixed impacts meta-analysis was utilized to estimate the pooled risk ratio of treatment success, characterized by the individual studies and assess the incidence of side effects and need for surgery.
• Random effects meta-analysis using pooled mean differences was utilized to compare total length of follow-up between groups.

Results

• In the meta-analysis, a sum of 623 patients from 6 studies were incorporated.
• Out of these 6 studies, 3 studies assessed the two-dose vs. single methotrexate protocols and 3 assessed the multi-dose vs. single methotrexate protocols.
• There was a trend towards increased efficacy for both protocols when compared to the single-dose protocol (two vs. single: RR 1.09 95% CI [0.98, 1.20], multi vs. single: RR 1.08, 95% CI [0.99, 1.17]).
• For patients with high HCGs, the two-dose protocol was noted to be 42% more effective in achieving treatment success as compared to the single-dose (RR 1.42, 95% CI [1.00, 2.02]).
• The multi-dose protocol was significantly more likely to cause side effects compared to the single-dose protocol (RR 1.64 95% CI [1.15, 2.34]).
• Compared to the single-dose protocol, the two-dose protocol had a shorter time to resolution: -6.8 days (95% CI: -12.5, -1.0).