Twenty-six case series (1,327 women: 1,067 given the single- and 260 the multidose regimen) were included.
The overall success rate for any methotrexate regimen was 89% (1,181 out of 1,327 women).
Single-dose regimens significantly increased the failure rate compared with multidose regimens; the crude OR was 1.71 (95% CI: 1.04, 2.82). The difference was still statistically significant when only high-quality studies were included.
Increasing hCG value and the presence of foetal cardiac activity were found to be significantly associated with treatment failure (P<0.001). The difference between regimens was greater after adjusting for these variables; the adjusted OR was 4.74 (95% CI: 1.77, 12.62).
The use of single-dose regimens significantly reduced side-effects compared with multidose regimens (OR 0.44, 95% CI: 0.31, 0.63). Women reporting side-effects were more likely to have successful treatment using either regimen than women without side-effects. Overall, 36.2% of women reported side-effects such as nausea, diarrhoea, mouth sores, or elevated liver transaminases; 28.3% reported abdominal pain; and 8.8% were admitted to hospital for reasons other than treatment failure.
The results were also reported for each treatment protocol according to the actual number of doses administered.