A systematic review and meta-analysis 5 assessed the efficacy of intramuscular methotrexate (MTX) in patients with recurrent compared with primary ectopic pregnancy. 15 observational studies with 3 944 patients (502 recurrent, 3 442 primary ectopic pregnancy) were included. Single dose MTX was significantly less successful in patients with recurrent compared with those with primary ectopic pregnancy (RR 0.79, 95% CI 0.63 to 1.00). However, there was no statistical difference in success for patients receiving multidose treatment (RR 1.14, 95% CI, 0.71 to 1.84).
A retrospective cohort study 6 included a total of 359 patients, with 268 (74.7%) succeeding with MTX and 91 (25.3%) required surgery. Specifically, 282 patients (78.6%) received 1-dose MTX, whereas 77 (21.4%) received 2-dose MTX. Gravidity, previous ectopic pregnancy, gestational age, pretreatment β-human chorionic gonadotropin (β-hCG) level, number of MTX treatments, and presence of a visible yolk sac in ultrasound were significant predictors. Higher gravidity (OR 1.25, 95% CI 1.01 to 1.54) and elevated pretreatment β-hCG levels (OR 1.00, 95% CI 1.0004 to 1.0008) were independent risk factors. Number of MTX treatments was a significant protective factor (OR 0.44, 95% CI 0.22 to 0.90).
A randomized controlled trial 4 assessed the efficacy of single-dose versus two-dose administration of methotrexate for ectopic pregnancy. 92 women were randomly assigned to follow either the single-dose or two-dose protocol. The success rates between the single-dose and two-dose groups did not show a significant difference (82.6 versus 87.0%; RR 0.95; 95% CI 0.80 to 1.13). However, the success rate in a subgroup of participants with a pretreatment hCG level over 5000 mIU/ml appeared to be higher in the two-dose group than in the single-dose group (80.0 versus 58.8%), although the difference was not statistically significant. No significant differences in methotrexate-associated side effects, cost or treatment satisfaction were observed between the groups.
A multicentre RCT 3 included 73 women who were assigned to systemic single dose methotrexate (MTX) treatment or expectant management. Serum hCG concentration was under 2000 IU/l. There was no difference in primary treatment success rate of single-dose MTX versus expectant management, 31/41 (76%) and 19/32 (59%), respectively (RR 1.3 95% CI 0.9 to 1.8). Nine women (22%) needed additional MTX injections, compared with 9 women (28%) in whom systemic MTX was administered after initial expectant management (RR 0.8; 95% CI 0.4 to 1.7). One woman (2%) from the MTX group underwent surgery compared with 4 women (13%) in the expectant management group (RR 0.2; 95% CI 0.02 to 1.7),
Comment: The quality of evidence is downgraded by study limitations, and partially by imprecise results (limited study size for each comparison).
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