In an asymptomatic woman with ectopic pregnancy receiving single-dose methotrexate who shows a plateaued β‑hCG between day 4 and day 7, what is the next appropriate management step?

Administer a Second Dose of Methotrexate

In an asymptomatic woman with ectopic pregnancy showing plateaued β-hCG between day 4 and day 7 after single-dose methotrexate, the next appropriate step is to administer a second dose of methotrexate (Answer A). 1

Rationale for Second Dose

• The American College of Emergency Physicians explicitly states that a second dose of methotrexate is indicated when β-hCG levels fail to decrease appropriately or plateau after initial treatment, provided the patient remains hemodynamically stable with no signs of rupture 1

• Treatment failure with single-dose methotrexate occurs in 3-36% of cases, and a second dose successfully resolves most treatment failures 1

• The standard protocol requires β-hCG measurement on days 4 and 7, with a second dose administered if levels don't decrease by ≥15% between these timepoints 2

Expected β-hCG Pattern After Methotrexate

• After methotrexate administration, β-hCG levels typically plateau or even rise slightly in the first 1-4 days before declining 1

• All patients in one study experienced a continued rise in hCG for at least 3 days after methotrexate injection, though all levels began to decline by day 7 3

• A plateauing pattern between days 4 and 7 represents incomplete response requiring additional treatment, not treatment failure necessitating surgery 1

Why Not the Other Options

• Option C (Repeat in 48 hours): This deviates from established protocol and unnecessarily delays definitive management. The day 4 and day 7 measurements have already been obtained and show inadequate response 2

• Option D (Repeat in 1 week): Weekly monitoring is only appropriate after β-hCG levels clearly begin decreasing, not when they plateau 1

• Option B (Surgery): Surgical intervention is reserved for hemodynamic instability, signs of rupture (severe abdominal pain with peritoneal signs), or failure after a second methotrexate dose 1, 2

Critical Safety Monitoring

• Before administering the second dose, confirm the patient remains hemodynamically stable with no signs of rupture 1

• Warning signs requiring immediate surgical intervention include: severe abdominal pain with peritoneal signs, hemodynamic instability, heavy vaginal bleeding, or shoulder pain indicating diaphragmatic irritation 1

• After the second dose, measure β-hCG at least every 1-2 weeks until normalized 1

• If β-hCG plateaus over three consecutive measurements or increases over two consecutive measurements after the second dose, proceed to surgery 1

Common Pitfall to Avoid

• Do not confuse gastrointestinal side effects from methotrexate (nausea, abdominal pain) with acute ectopic rupture—rule out rupture before attributing symptoms to drug toxicity 1

• The asymptomatic status in this case strongly supports continuing medical management rather than proceeding directly to surgery 1