Emphasis on the off-label use of methotrexate for ectopic pregnancy

OBJECTIVE: To compare the treatment success and failure rates, as well as side effects and surgery rates between methotrexate protocols. DATA SOURCES: PubMed, Embase and the Cochrane library searched up till July 2018. STUDY ELIGIBILITY CRITERIA: RCTs that compared women with ectopic pregnancies receiving the single dose, two dose or multi-dose methotrexate protocols. STUDY APPRAISAL AND SYNTHESIS METHODS: Odds of treatment success, treatment failure, side effects and surgery for tubal rupture as well as length of follow-up until treatment success compared using random and fixed effects meta-analysis. Sensitivity analyses compared treatment success in high hCG and large adnexal mass groups, as defined by individual studies. Cochrane’s collaboration tool used to assess risk of bias. RESULTS: The two dose protocol was associated with higher treatment success compared to single dose protocol (OR: 1.84, 95% CI: 1.13, 3.00). The two dose protocol was more successful in women with high hCG (OR: 3.23, 95% CI: 1.53, 6.84) and in women with a large adnexal mass (OR: 2.93 95% CI: 1.23, 6.9). The odds of surgery for tubal rupture were lower in the two dose protocol (OR: 0.65, 95%CI: 0.26, 1.63), but not statistically significant. The length of follow up was 7.9 days shorter for the two dose protocol (95% CI: −12.2, −3.5). Odds of side effects were higher in the two dose protocol (OR: 1.53, 95% CI: 1.01, 2.30). Compared to the single dose protocol the multi-dose protocol is associated with a nonsignificant reduction in treatment failure (OR: 0.56, 95% CI: 0.28, 1.13) and a higher chance of side effects (OR: 2.10, 95% CI: 1.24, 3.54). Odds of surgery for tubal rupture (OR: 1.62, 95% CI: 0.41, 6.49) and time to follow-up (−1.3, 95% CI: −5.4, 2.7) were similar. CONCLUSION: The two dose methotrexate protocol is superior to the single dose protocol for the treatment of ectopic pregnancy in terms of treatment success and time to success. Importantly, these findings hold true in patients thought to be at a lower likelihood of responding to medical management, such as those with higher hCGs and large adnexal mass.