The quality of evidence is downgraded by imprecise results (few patients).
An individual participant data (IPD) meta-analysis «Solangon SA, Van Wely M, Van Mello N, et al. Methotrexate vs expectant management for treatment of tubal ectopic pregnancy: An individual participant data meta-analysis. Acta Obstet Gynecol Scand 2023»3 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 «Al Wattar BH, Solangon SA, de Braud LV, et al. Effectiveness of treatment options for tubal ectopic pregnancy: A systematic review and network meta-analysis. BJOG 2024;131(1):5-14. »4 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 «Xiao C, Shi Q, Cheng Q, et al. Non-surgical management of tubal ectopic pregnancy: A systematic review and meta-analysis. Medicine (Baltimore) 2021;100(50):e27851. »5 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 «van Mello NM, Mol F, Verhoeve HR et al. Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparis»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 «Interventions for tubal ectopic pregnancy»1 «Hajenius PJ, Mol F, Mol BW et al. Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev 2007;(1):CD000324. »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).