What is the best protocol for treating ectopic pregnancy with Methotrexate (MTX)?

From the Guidelines

The best protocol for treating ectopic pregnancy with methotrexate is the single-dose regimen, which consists of administering methotrexate 50 mg/m² body surface area as a single intramuscular injection, as supported by the most recent and highest quality study 1. This approach should be followed by monitoring serum human chorionic gonadotropin (hCG) levels on days 4 and 7 after injection. A successful response is indicated by a decline of 15% or more in hCG levels between days 4 and 7. If the decline is less than 15%, a second dose of methotrexate should be administered. Some key points to consider when using methotrexate for ectopic pregnancy treatment include:

• Patients should have baseline laboratory tests including complete blood count, liver function tests, and renal function tests before treatment, as recommended by 1.
• Candidates for methotrexate therapy should be hemodynamically stable with an unruptured ectopic pregnancy, have a mass less than 3.5 cm in diameter, and no fetal cardiac activity, as stated in 1.
• During treatment, patients should avoid alcohol, non-steroidal anti-inflammatory drugs, folate supplements, and sun exposure, and abstain from sexual intercourse until hCG levels are undetectable, as advised in 1. Methotrexate works by inhibiting DNA synthesis in rapidly dividing cells, effectively terminating the developing embryo. This medical management approach avoids surgery and preserves fallopian tube function, which is important for future fertility. According to 1, the single-dose regimen has been shown to be effective in resolving ectopic pregnancies without surgery in a significant proportion of patients. It is essential to carefully select patients for methotrexate therapy and closely monitor them for potential complications, such as treatment failure or ruptured ectopic pregnancy, as highlighted in 1.

From the Research

Ectopic Pregnancy Treatment with Methotrexate

• The treatment of ectopic pregnancy with methotrexate has been studied in various protocols, including high-dose infusion with leucovorin rescue 2 and fixed-dose protocols 3.
• High-dose methotrexate infusion with leucovorin rescue has been shown to be highly effective, with a success rate of 96% in select patients with ectopic pregnancy 2.
• Fixed-dose methotrexate protocols have also been effective, with a success rate of 81.1% in patients with ectopic pregnancy 3.
• The effectiveness of methotrexate treatment is associated with baseline human chorionic gonadotropin (hCG) levels, with lower levels (<1000 mIU/ml) associated with higher success rates 3, 4.
• Methotrexate treatment is less effective in patients with high hCG levels (>5000 IU/L), and laparoscopic surgery may be a better option in these cases 4.

Protocol Considerations

• The choice of methotrexate protocol depends on various factors, including the patient's reproductive desire and the experience of the medical team 5.
• Single-dose treatment protocols are well-established, but there is still no uniformity in the parameters used to determine treatment success 5.
• Local methotrexate injection plus uterine artery embolization may be a viable option for high-risk interstitial ectopic pregnancy 6.

Predictive Factors

• Low hCG levels on days 0,4, and 7 are predictive of success with methotrexate treatment 4.
• The absence of pain, metrorrhagia, and hemoperitoneum are also predictive of success with methotrexate treatment 4.
• A cut-off value of 2439 IU/L for hCG has been suggested, with a sensitivity of 66.7% and a specificity of 93.9% for predicting treatment success 4.