BACKGROUND AND PURPOSE:

• ACOG and many other guidelines refer to single-dose, 2-dose, and multi-dose methotrexate (MTX) protocols for ectopic pregnancy treatment
• Alur-Gupta et al. (AJOG, 2019) compared the efficacy of MTX protocols, side effects and surgery rates

METHODS:

• Systematic review and meta-analysis
• Data sources
  • PubMed, Embase, and the Cochrane library searched up to July 2018
• Inclusion criteria
  • RCTs
  • Studies that compared the 3 MTX dosage protocols
• Primary outcomes
  • Treatment success and failure
  • Side effects
  • Surgery for tubal rupture
  • Length of follow-up until treatment success
• Data analysis
  • Outcomes were compared using random effect and fixed effect meta-analysis
  • Treatment success in the groups with high hCG values (range >3000 to 5500 mIU/mL) and a large adnexal mass range >2 to 3.5 cm) was compared using sensitivity analyses

RESULTS:

• 7 studies | 738 women received MTX
• 2-dose vs single-dose protocol
  • The 2-dose protocol was associated with higher treatment success compared to the single-dose protocol
    • Odds ratio [OR] 1.84 (95% CI, 1.13 to 3.00)
  • The 2-dose protocol was more successful in women with
    • High hCG: OR 3.23 (95% CI, 1.53 to 6.84)
    • Large adnexal mass: OR 2.93 (95% CI, 1.23 to 6.9)
  • The 2-dose protocol was not significantly associated with lower odds of surgery for tubal rupture
    • Tubal Rupture: OR 0.65 (95% CI 0.26 to 1.63)
  • Length of follow-up was 7.9 days shorter for the 2-dose protocol (95% CI, −12.2 to −3.5)
  • 2-dose protocol was associated with increased side effects (OR 1.53; 95% CI, 1.01 to 2.30), although mostly ‘mild and transient’
• Multi-dose vs single-dose protocol
  • Compared to the single-dose protocol, the multi-dose protocol was not significantly associated with a reduction in treatment failure
    • Treatment failure: OR 0.56 (95% CI, 0.28 to 1.13)
  • Multi-dose was associated with a higher chance of side effects
    • Side effects: OR 2.10 (95% CI, 1.24 to 3.54)
• Multi-dose vs 2-dose protocol
  • No statistical difference for the following
    • Odds of surgery for tubal rupture | Length of follow-up

CONCLUSION:

• The authors conclude that a 2-dose protocol improves the odds of treatment success and time to success
• These findings remain true in patients with higher hCGs and a large adnexal mass and based on the data state

Therefore, we would recommend the 2-dose protocol as the first-line protocol in patients being medically managed for ectopic pregnancies

Learn More – Primary Sources:

Two-dose versus single-dose methotrexate for treatment of ectopic pregnancy: a meta-analysis

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