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Grand Rounds

Ectopic Pregnancy Methotrexate Protocol: Single-Dose or 2-Dose?

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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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Related ObG Topics:

You’ve Diagnosed the Ectopic Pregnancy – When and How to Use the Medical Option
Disparities and the Management Patterns Over Time for Ectopic Pregnancy
Salpingectomy or Salpingostomy for the Management of Tubal Ectopic Pregnancy?

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