The quality of evidence is downgraded by imprecise results (few patients).
An individual participant data (IPD) meta-analysis 4 included 2 RCTs suppliing IPD (n=153) comparing systemic methotrexate (MTX) and expectant management in women with tubal ectopic pregnancy and low hCG (< 2000 IU/L). Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (RR 1.16, 95% CI 0.95 to 1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23 to 1.14).
Another systematic review and network meta-analysis 5 included 31 randomised trials (n=2938) comparing the effectiveness of expectant, medical and surgical treatment (10 treatments evaluated). Direct meta-analysis showed no significant benefit for using methotrexate compared to expectant management. Network meta-analysis showed similar effect-size for most conservative treatment options compared to expectant management (methotrexate intra-sac instillation vs. expectant RR 0.91, 95% CI 0.75 to 1.10; multi-dose methotrexate vs. expectant RR 1.00, 95% CI 0.88 to 1.15; prostaglandin intra-sac instillation vs. expectant RR 0.75, 95% CI 0.53 to -1.07; salpingotomy vs. expectant RR 0.99, 95% CI 0.84 to -1.16; single dose methotrexate vs. expectant RR 0.97, 95% CI 0.85 to 1.10; single dose methotrexate + mifepristone vs. expectant RR 1.09, 95% CI 0.89 to 1.33). All treatment options showed a higher risk of failure compared to salpingectomy.
Another systematic review and network meta-analysis 6 compared single-dose MTX vs single-dose MTX plus mifepristone; single vs multiple doses of MTX; and single-dose versus placebo (expectant management). 15 studies with 1573 women were included. There was no significant difference in treatment success in the matched groups; however, single-dose MTX was associated with fewer side effects than multiple-dose and two-dose therapies.
A multicentre RCT 2 included 73 women who were assigned to systemic single dose methotrexate (MTX) treatment or expectant management, using a web-based randomization program, block randomization with stratification for hospital and serum hCG concentration (under 1000 versus 1000 - 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). In 9 women (22%), additional MTX injections were needed, 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), all after experiencing abdominal pain within the first week of follow-up. In the MTX group, 9 women reported side effects versus none in the expectant management group. No serious adverse events were reported. Single-dose systemic MTX does not have a larger treatment effect compared with expectant management in women with an ectopic pregnancy or a pregnancy of unknown location and low and plateauing serum hCG concentrations.
A Cochrane review [Abstract] 1 included 35 studies on the treatment of tubal ectopic pregnancy, describing 25 different comparisons. Systemic methotrexate in a fixed multiple dose intramuscular regimen has a non significant tendency to a higher treatment success than laparoscopic salpingostomy (1 RCT, n = 100, OR 1.8, 95% CI 0.73 to 4.6). No significant differences are found in long term follow up (n=74): intra uterine pregnancy (OR 0.82, 95% CI 0.32 to 2.1) and repeat ectopic pregnancy (OR 0.87, 95% CI 0.19 to 4.1). Expectant management was significantly less successful than prostaglandin therapy (1 RCT, n = 23, OR 0.08, 95% CI 0.02 to 0.39).
Date of latest search:2025-09-12
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