What is the best course of action for a female patient of reproductive age with an ectopic pregnancy, who has been treated with methotrexate (methotrexate) and has rising beta-human chorionic gonadotropin (beta-hCG) levels from 1000 at baseline to 2100 on the 7th day?

Administer a Second Dose of Methotrexate

The patient should receive a second dose of methotrexate (50 mg/m² IM) as she remains hemodynamically stable and the rising β-hCG pattern (baseline 1000 → day 4: 1200 → day 7: 2100) represents expected treatment failure requiring additional dosing rather than rupture. 1

Understanding β-hCG Dynamics After Methotrexate

• β-hCG levels commonly increase during the first 1-4 days after methotrexate administration before declining, which is a normal pharmacologic response 1, 2
• The critical assessment point is between day 4 and day 7: a failure to achieve at least 15% decline in β-hCG between these timepoints indicates treatment failure requiring intervention 1, 3
• In this case, β-hCG rose from 1200 (day 4) to 2100 (day 7), representing a 75% increase rather than the required 15% decrease, confirming single-dose methotrexate failure 3

Why Second Dose Rather Than Surgery

• Single-dose methotrexate fails in 3-36% of cases, and a second dose successfully resolves most treatment failures 1
• The patient's baseline β-hCG of 1000 mIU/mL is well below the 5000 mIU/mL threshold associated with high failure rates, making her an appropriate candidate for continued medical management 1
• Surgery is indicated only if the patient develops hemodynamic instability, signs of rupture (severe abdominal pain, peritoneal signs, shoulder pain), or significant hemoperitoneum on ultrasound 1, 4
• The question stem does not indicate any clinical signs of rupture or hemodynamic compromise, making continued medical management appropriate 1

Protocol for Second Dose Administration

• Administer methotrexate 50 mg/m² (or 1 mg/kg) intramuscularly as the second dose 1
• Continue monitoring β-hCG levels on days 4 and 7 after the second dose, looking for the same 15% decline criterion 1
• Overall success rates reach 94% when including patients who require multiple methotrexate doses 1

Critical Safety Monitoring Requirements

• The patient must be counseled to return immediately for severe abdominal pain, hemodynamic instability (dizziness, syncope, tachycardia), heavy vaginal bleeding, or shoulder pain 1, 4
• Close surveillance is non-negotiable, as rupture rates of 0.5-9% occur even during appropriate medical management 1
• Gastrointestinal side effects from methotrexate (nausea, abdominal pain) can mimic acute rupture—rule out rupture before attributing symptoms to drug toxicity 1

Common Pitfall to Avoid

• Do not proceed directly to surgery based solely on rising β-hCG in a hemodynamically stable patient without signs of rupture, as this represents expected treatment failure that responds to additional dosing in most cases 1
• The 38% rupture rate cited in guidelines refers to patients who develop rupture symptoms during treatment, not asymptomatic patients with rising β-hCG 4
• Research demonstrates that even patients with higher β-hCG levels can be successfully managed with repeat dosing when they remain clinically stable 5, 6

When to Convert to Surgery

• Immediate surgical intervention becomes necessary if the patient develops hemodynamic instability, peritoneal signs, or significant hemoperitoneum on ultrasound—not simply rising β-hCG levels alone 1, 4
• If β-hCG continues rising after the second dose or the patient cannot comply with close follow-up, surgical management should be pursued 1