#Grand Rounds

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

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

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

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

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

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