Methotrexate Dosing for Molar Pregnancy Treatment
The standard dose of methotrexate for treating molar pregnancy is 50 mg/m² intramuscular injection, which may be repeated as needed based on β-hCG level monitoring. 1, 2
Treatment Protocols Based on Risk Stratification
Low-Risk Molar Pregnancy
- Methotrexate 50 mg/m² intramuscular injection, repeated every 48 hours for a total of four doses 1
- Calcium folinate (folinic acid) 15 mg orally 30 hours after each methotrexate injection 1
- Treatment courses are repeated every 2 weeks (days 1,15,29, etc.) 1
- Therapy should be continued for 6 weeks after the hCG normalizes (becomes <5 IU/L) 1
High-Risk Molar Pregnancy
- For high-risk cases, more intensive regimens such as EMA/CO (Etoposide, Methotrexate, Actinomycin D alternating with Cyclophosphamide and Vincristine) are recommended 1
- In patients with very advanced disease, starting with low-dose chemotherapy (etoposide 100 mg/m² and cisplatin 20 mg/m² on days 1 and 2, repeated weekly for 1-3 weeks) may reduce early mortality 1
Monitoring and Follow-up
- Serial β-hCG monitoring is essential until levels are undetectable 3
- Treatment should continue until β-hCG levels normalize and then for an additional 6 weeks 1
Efficacy and Treatment Considerations
- Success rates for methotrexate treatment range from 65-96%, with higher success rates when β-hCG levels are lower 2
- A recent study suggests that a single-dose MTX as prophylactic chemotherapy may not be effective for preventing post-molar gestational trophoblastic neoplasia in high-risk molar pregnancy 4
- Some studies have investigated methotrexate infusion therapy (100 mg/m² IV bolus followed by 200 mg/m² as a 12-hour infusion) as an alternative approach with high efficacy (91.5% complete response rate) 5
Side Effects and Complications
- Common side effects include nausea/vomiting (30%), gastritis, stomatitis (7%), and reversible alopecia (3%) 1
- More severe complications are rare but can include bone marrow suppression, hepatotoxicity, and pulmonary toxicity 2
Important Considerations
- Pre-treatment laboratory testing is required, including complete blood count with differential and platelet counts, liver enzyme levels, and renal function tests 2
- Drug interactions should be avoided: folic acid supplements counteract methotrexate's action, and aspirin/NSAIDs should be avoided due to potentially lethal interactions 2
- For Rh-negative women, anti-D immunoglobulin should be administered due to the risk of alloimmunization 2
- Breastfeeding should be discontinued immediately upon methotrexate administration and not resumed until at least 3 months after the last dose 2
Warning Signs Requiring Immediate Medical Attention
- Severe abdominal pain 2, 6
- Signs of hemodynamic instability 2, 6
- Heavy vaginal bleeding 2, 6
- Shoulder pain (may indicate diaphragmatic irritation from blood) 2
Methotrexate has been the mainstay of medical treatment for gestational trophoblastic disease for decades, with established efficacy and safety when administered according to standardized protocols and with appropriate monitoring.