Methotrexate for tubal ectopic pregnancy

Systemic methotrexate appears to be effective for ectopic pregnancy.

A randomized controlled trial 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 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),

A Cochrane review 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 is significantly less successful than prostaglandin therapy (1 RCT, n = 23, OR 0.08, 95% CI 0.02 to 0.39).

Another systematic review on the efficacy of intramuscular methotrexate in ectopic pregnancy including 9 studies with a total of 408 subjects (and 10 case reports of adverse effects) was abstracted in DARE. No randomised trials were identified. Percentage of patients successfully treated with 1 dose was 71% (95% CI 58% to 81%), and with 1 or 2 dose it was 84% (95% CI 77% to 90%). 24% of the patients had adverse effects, 40% had exacerbation of pain and 10% had ruptured ectopic pregnancy. Serious complications have occurred.

Comment: The quality of evidence is downgraded by study limitations, and partially by imprecise results (limited study size for each comparison).

Ədəbiyyat

1. Hajenius PJ, Mol F, Mol BW, Bossuyt PM, Ankum WM, van der Veen F. Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev 2007 Jan 24;(1):CD000324.
2. Parker J, Bisits A, Proietto AM. A systematic review of single-dose intramuscular methotrexate for the treatment of ectopic pregnancy. Aust N Z J Obstet Gynaecol 1998 May;38(2):145-50.
3. 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 comparison. Hum Reprod 2013;28(1):60-7.
4. Song T, Kim MK, Kim ML et al. Single-dose versus two-dose administration of methotrexate for the treatment of ectopic pregnancy: a randomized controlled trial. Hum Reprod 2016;31(2):332-8.