Administer a Second Dose of Methotrexate
The most appropriate next step is to administer a second dose of methotrexate (50 mg/m² IM), as the β-hCG levels have failed to decline appropriately between days 4 and 7, rising from 1200 to 2100 mIU/mL. 1
Rationale for Second Dose
The standard protocol for single-dose methotrexate requires monitoring β-hCG levels on days 1,4, and 7, with a second dose indicated if levels fail to decrease by at least 15% between days 4 and 7. 1, 2 In this case:
- Day 4 to Day 7 change: The β-hCG increased from 1200 to 2100 mIU/mL (a 75% rise), clearly indicating treatment failure of the initial dose 1
- Initial β-hCG level: At 1000 mIU/mL on day 1, this patient falls well below the 5,000 mIU/mL threshold where methotrexate failure rates substantially increase, making her an appropriate candidate for continued medical management 3
Why Not Immediate Surgery?
Immediate surgical intervention (Option B) is not indicated at this point because:
- The patient remains hemodynamically stable with no mention of rupture signs 4, 1
- Rising β-hCG levels after methotrexate are common and expected in some patients who ultimately achieve resolution 5
- Treatment failure with single-dose methotrexate occurs in 3-36% of cases, and a second dose successfully resolves most of these 1
- Research demonstrates that 94% of ectopic pregnancies can be successfully managed with systemic methotrexate, including cases requiring multiple doses 2
Expected Pattern After Second Dose
After administering the second dose, you should anticipate:
- Initial rise possible: β-hCG levels may continue to rise for the first 3 days after treatment before declining—this is a recognized pattern and does not indicate failure 6, 5
- Monitoring protocol: Continue weekly β-hCG measurements until levels fall below 5 mIU/mL 2
- Day 7 assessment: Only day 7 β-hCG levels (not day 4) reliably predict successful single-dose therapy, so the second dose assessment should similarly focus on the day 4-7 interval 7
Critical Safety Monitoring
While proceeding with the second dose, ensure close surveillance for:
- Rupture symptoms: Severe abdominal pain, hemodynamic instability, heavy vaginal bleeding, or shoulder pain indicating diaphragmatic irritation 1
- Common pitfall: Gastrointestinal side effects from methotrexate (nausea, abdominal pain) can mimic acute ectopic rupture—rule out rupture before attributing symptoms to drug toxicity 1
- Rare complication: Delayed hemorrhage may occur and require blood transfusion, though this is uncommon 6
When Surgery Becomes Necessary
Surgical intervention would be indicated if:
- The patient develops hemodynamic instability or signs of rupture 1, 8
- After the second dose, β-hCG levels continue to rise or plateau without appropriate decline 8
- The patient develops contraindications to continued methotrexate therapy 4
Why Not Just Wait and Recheck?
Simply repeating β-hCG in one week (Option A) without intervention is inappropriate because the rising trend from day 4 to day 7 already demonstrates treatment failure requiring action. 1 The multi-dose regimen (Option D) with admission is unnecessarily aggressive at this stage when a second single dose is the standard next step. 1