What is the usage of methotrexate (MTX) in obstetrics and gynaecology, particularly in pregnant women or those of childbearing age?

Methotrexate Usage in Obstetrics and Gynaecology

Primary Indication: Ectopic Pregnancy Treatment

Methotrexate is FDA-approved and guideline-supported exclusively for treating ectopic pregnancy in obstetrics and gynaecology, NOT for elective termination of intrauterine pregnancy. 1, 2

Eligibility Criteria for Ectopic Pregnancy Treatment

Methotrexate is appropriate for hemodynamically stable patients meeting ALL of the following criteria: 1, 3, 4

• Ectopic mass ≤3.5 cm in greatest dimension 1, 4
• β-hCG levels ≤5,000 mIU/mL (preferably) 1
• No embryonic cardiac activity on ultrasound 1
• Hemodynamically stable patient 1, 5

Dosing Protocol

Standard dosing: 50 mg/m² intramuscular injection 1

• Single-dose regimen successful in 73% of tubal ectopic pregnancies 5
• Repeated doses required in 14% of cases 5
• Overall success rate: 88-96% for unruptured ectopic pregnancy 5, 4

Treatment Outcomes and Complications

Treatment failure occurs in 3-36% of cases, with tubal rupture in 0.5-19% 1

• Emergency surgery required in only 8% of tubal ectopic pregnancies 5
• Tubal patency preserved in 84.5% on the involved side 4
• Subsequent intrauterine pregnancy rate: 89.2% 4

Absolute Contraindication: Pregnancy Planning and Exposure

Pre-Conception Requirements

Women must discontinue methotrexate at least 3 months before attempting to conceive. 6, 7

This recommendation is based on: 6, 7

• Median half-life for elimination of methotrexate polyglutamate from red blood cells: 1.2-4.3 weeks 6
• Median time to undetectable levels: up to 10 weeks 6
• Complete hepatic and tissue clearance requires 3 months 7

Men must also wait at least 3 months after their last methotrexate dose before attempting to conceive 7, as one complete cycle of spermatogenesis requires 74 days 7.

Contraception Requirements

• Women of childbearing potential must use two methods of effective contraception throughout the 3-month waiting period 7
• Pregnancy testing required prior to initiating methotrexate therapy 7, 2
• Males with female partners of reproductive potential must use effective contraception during treatment and for 3 months after the final dose 2

Critical Risk: Inadvertent Exposure During Pregnancy

Teratogenic Effects

Methotrexate is FDA Pregnancy Category X and causes catastrophic embryo-fetal toxicity. 7, 2

Documented risks include: 6, 1, 2

• 23% miscarriage rate 6, 1
• 42% spontaneous abortion rate when exposed after conception 2
• 3.4-fold increased risk of cardiovascular defects 6, 1
• 2.6-fold increased risk of oral clefts 6, 1
• Multiple congenital anomalies: skull anomalies, facial dysmorphism, central nervous system abnormalities, limb abnormalities, cardiac defects, intellectual impairment 1, 2, 8

Highest Risk Period

The teratogenic risk is highest within the first 6-8 weeks of pregnancy 7, though exposure during second and third trimesters causes intrauterine growth restriction and functional abnormalities 2.

Immediate Management if Pregnancy Occurs

If a woman becomes pregnant while taking methotrexate, implement the following immediately: 6, 1, 7

1. Discontinue methotrexate immediately 6, 1, 7
2. Initiate or continue high-dose folic acid supplementation 6, 1
3. Urgent referral for obstetric counseling, preferably to a high-risk obstetrics program 6, 1, 7
4. Termination is NOT mandatory—counsel patient on teratogenic risks and management options 6

Special Obstetric Applications

Caesarean Scar Pregnancy

Methotrexate can be used for caesarean scar pregnancy in combination with uterine evacuation 5, though careful consideration is required 5.

Pregnancy of Unknown Location (PUL)

Methotrexate should NOT be used for PUL when the intent is termination of a potentially viable intrauterine pregnancy. 1

• Treatment successful in 93% of persistent PUL cases 5
• The location of pregnancy must be established definitively before treatment if the pregnancy is undesirable 1
• If intrauterine pregnancy is confirmed, methotrexate is absolutely contraindicated for elective termination 1

Gestational Trophoblastic Disease

Methotrexate is used to treat gestational trophoblastic neoplasia 9, 3, representing another established obstetric indication beyond ectopic pregnancy.

Critical Pitfalls to Avoid

Never use methotrexate for elective termination of intrauterine pregnancy—this is absolutely contraindicated and carries catastrophic teratogenic risks. 1, 2

Never treat PUL with methotrexate without definitively excluding intrauterine pregnancy if the pregnancy is undesirable, as misdiagnosis can result in severe fetal malformations. 1, 8

Never allow conception within 3 months of methotrexate discontinuation for either partner, as tissue stores persist and teratogenic risk remains. 6, 7

Fertility Considerations

Methotrexate can cause impairment of fertility and menstrual dysfunction in women during and after treatment 2, though it is unknown if infertility may be reversed in all affected females 2.

Methotrexate can cause oligospermia or infertility in males during and after treatment 2, with reversibility uncertain 2.

Despite these risks, methotrexate preserves tubal patency and future fertility better than surgical management of ectopic pregnancy. 3, 4