To compare the treatment success and failure rates, as well as side
effects and surgery rates between methotrexate protocols. PubMed, Embase and the Cochrane
library searched up till July
2018. RCTs that compared women with ectopic pregnancies receiving the
single dose, two dose or multi-dose methotrexate protocols. 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. 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. 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.