Methotrexate for Tubal Ectopic Pregnancy

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),

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

Another systematic review 2 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).

References

• 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. [PubMed]
• 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. [PubMed][DARE]
• 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. [PubMed]
• 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. [PubMed]