Methotrexate in Ectopic Pregnancy
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Direct answer
Methotrexate, a folate antagonist that kills rapidly dividing trophoblast, is the standard medical treatment of an unruptured ectopic pregnancy in a haemodynamically stable woman. The single-dose protocol gives 50 mg per square metre intramuscularly on day 1 with beta-hCG measured on days 4 and 7 — success is declared when hCG falls by at least 15 per cent between those two days, with weekly values followed until negative. Best results come with beta-hCG below about 5000 mIU/mL, a small adnexal mass, absent fetal cardiac activity and reliable follow-up; conception is avoided for three months after treatment.
What you must remember
- Selection criteria: haemodynamic stability, unruptured ectopic without significant haemoperitoneum, beta-hCG preferably below 5000 mIU/mL, adnexal mass below about 3.5-4 cm, absent fetal cardiac activity, no contraindication to methotrexate and guaranteed follow-up.
- Single-dose protocol: methotrexate 50 mg/m² intramuscularly on day 1; measure hCG on days 4 and 7 (a day-4 rise is expected, not failure); a fall of at least 15 per cent from day 4 to day 7 predicts resolution; repeat weekly doses (up to three or four) if inadequate, then weekly hCG until below 5 mIU/mL.
- Multidose protocol: methotrexate 1 mg/kg on days 1, 3, 5 and 7 with folinic acid rescue 0.1 mg/kg on days 2, 4, 6 and 8, continued until hCG falls by 15 per cent over 48 hours — higher success in less favourable cases at the cost of side effects.
- Contraindications: rupture or shock, significant haemoperitoneum, breastfeeding, active pulmonary disease, peptic ulcer, hepatic or renal dysfunction, blood dyscrasias, immunodeficiency and unreliable follow-up; fetal cardiac activity and high hCG are relative contraindications.
- Side effects and interactions: stomatitis, gastritis, transient transaminitis, bone marrow suppression and photosensitivity; avoid non-steroidal anti-inflammatory drugs (additive toxicity) and folate supplements during treatment; abdominal pain on day 2-3 ("separation pain") is common and benign if the patient is stable.
- Adjuncts and aftercare: give anti-D to Rh-negative women; contraception for at least three months after the last dose; subsequent fertility is broadly comparable to surgery.
- Persistent trophoblast after salpingostomy (hCG plateau or rise) is a recognised indication for single-dose methotrexate, avoiding reoperation.
Common confusion
Two protocol points trip candidates. First, the day-4 rise: hCG commonly rises before falling, and the verdict comes only from the day-4 to day-7 comparison. Second, separation pain: mild diffuse pain with stable vital signs on days 2-3 reflects tubal abortion or distension, whereas pain with tachycardia, hypotension, peritonism or a falling haematocrit means rupture and surgery.
Exam-focused takeaway
Stems quote a protocol day and an hCG value, asking the interpretation or next step; others test selection criteria against contraindications. Expect recall of 50 mg/m², the 15 per cent day-4-to-day-7 rule, folinic acid rescue, three-month contraception, NSAID avoidance and anti-D. Separation-pain versus rupture vignettes close the set.
Frequently asked questions
What is the single-dose methotrexate protocol?
Methotrexate 50 mg per square metre intramuscularly on day 1 with hCG on days 4 and 7; a 15 per cent or greater fall predicts success, then weekly hCG until negative.
Which patients are best suited to medical management?
Stable women with an unruptured ectopic, hCG below about 5000 mIU/mL, a small mass, no fetal cardiac activity and reliable follow-up.
Why is hCG measured on both day 4 and day 7?
Because hCG often peaks around day 4; only the day-4 to day-7 decline predicts resolution.
What are the major contraindications?
Rupture or haemodynamic instability, significant haemoperitoneum, hepatic, renal or haematological disease, active pulmonary disease, immunodeficiency and unreliable follow-up.
Is methotrexate compatible with concurrent NSAIDs or pregnancy?
Neither — NSAIDs increase its toxicity, and conception is avoided for three months after the last dose because of teratogenicity.