II. Indications: Ectopic Pregnancy Criteria

  1. Hemodynamically stable
  2. Quantitative bhCG < 5,000 mIU/ml
    1. Some recommend limiting Methotrexate protocol to bHCG <2000 mIU/ml (see efficacy below)
  3. Ectopic Pregnancy fully visualized on Ultrasound
    1. Embryo size under 3 cm
    2. Tubal serosa intact (no rupture)
    3. No fetal heart activity
  4. Normal lab testing (see screening below)
  5. No active bleeding

III. Advantages

  1. Allows for possible future fertility on affected side

IV. Contraindications

  1. Active lung disease
  2. Lactation
  3. Immunodeficiency
  4. Poor compliance
  5. History Peptic Ulcer Disease
  6. Fetal cardiac activity noted on Ultrasound
  7. Ectopic mass >3.5 to 4 cm
  8. Gestational Sac >3.5 cm
  9. Blood dyscrasias
    1. White Blood Cell Count <3000 (Leukopenia)
    2. Platelet Count <100,000 (Thrombocytopenia)
    3. Severe Anemia
  10. Liver disease or elevated Aspartate Aminotransferase (AST)
    1. Methotrexate has hepatotoxicity potential
  11. Renal Disease or decreased Creatinine Clearance <50 ml/min/1.73 m3
    1. Methotrexate is renally excreted
  12. bHCG >5000 mIU/ml
    1. Some recommend a relative contraindication at bHCG >2000 mIU/ml (see efficacy below)

V. Efficacy

  1. bHCG <1000 mIU/ml
    1. Success Rate: 88%
  2. bHCG <1000 to 2000 mIU/ml
    1. Success Rate: 71%
  3. bHCG <2000 to 3000 mIU/ml
    1. Success Rate: 59%
  4. bHCG <3000 to 4000 mIU/ml
    1. Success Rate: 50%
  5. bHCG >4000 mIU/ml
    1. Success Rate: 42%
  6. References
    1. Sagiv (2012) Int J Gynaecol Obstet 116(2): 101-4 [PubMed]

VI. Labs: Baseline

VII. Protocol: Single Dose (preferred protocol)

  1. Contraception until bHCG returns to 5 mIU/ml or less
  2. Methotrexate 50 mg/m2 BSA IM for 1 dose (some protocols have used IV or PO)
  3. bHCG monitoring as below (days 4, 7 and then weekly until bHCG 0 mIU/ml)
    1. Repeat Methotrexate dose if bHCG does not drop 15% between days 4 to 7
    2. Consider surgery
  4. Adjuncts (some protocols)
    1. Consider Leucovorin rescue
  5. Outcomes
    1. Success rate: 88.1% if starting bHCG <1000 mIU/ml (>1 dose needed in 14% of cases)
    2. Adverse effects: 31.3%
      1. See Methotrexate

VIII. Protocol: Multiple Dose (older protocol)

  1. Contraception until bHCG returns to 5 mIU/ml or less
  2. bHCG monitoring as below
  3. Alternate agents up to 4 doses of each drug
    1. Methotrexate 1 mg/kg PO or IV on days 1, 3, 5, and 7
    2. Leucovorin 0.1 mg/kg on days 2, 4, 6, and 8
  4. Outcomes
    1. Success rate: 92.7%
    2. Adverse effects: 41.2%

IX. Adverse Effects

  1. Mild Abdominal Pain
    1. Typically onset days 2-3 following Methotrexate start
    2. Resolves within 24-48 hours
    3. Pain appears to be associated with separation of implanted pregnancy
    4. Distinguish from Abdominal Pain of tubal rupture
      1. May be more severe
      2. May be associated with hemodynamic instability
      3. Obtain immediate HCG and Transvaginal Ultrasound if any signs not consistent with typical Methotrexate protocol pain
  2. Vaginal Bleeding
  3. Gastrointestinal distress
    1. Nausea or Vomiting
    2. Diarrhea
    3. Flatulence or bloating (common)
  4. Lab and diagnostic changes
    1. bHCG transiently increased on starting Methotrexate
    2. LFTs may transiently increase (typically <2 fold increase) on starting Methotrexate
    3. Size of ectopic may asymptomatically increase in up to 56% of women (associated with hematoma formation)

X. Labs: Initial (See Contraindications)

XI. Monitoring

  1. Inadequate bHCG response requires intervention
    1. Methotrexate may be repeat dosed in Protocol 1
      1. Indicated for inadequate bHCG decrease between days 4-7
    2. Surgical intervention if failed protocol
      1. Indicated if bHCG increasing despite 2 or more doses of Methotrexate or
      2. Signs of hemodynamic instability
  2. Follow Quantitative bhCG
    1. First Week: Draw bHCG days 4 and 7
      1. Anticipate 25% bHCG decrease between days 1 and 7
      2. Anticipate 15% bHCG decrease between days 4 and 7
      3. If inadequate decrease, repeat Methotrexate protocol above
    2. Subsequent Weeks: Draw bHCG weekly
      1. Anticipate drop to 5 mIU/ml by 3-4 weeks
  3. Serum Progesterone may also be followed
    1. Anticipate drop to 1.5 mg/ml by 2-3 weeks

XII. Prognosis

  1. Recurrent Ectopic Pregnancy risk: 10-20%
  2. Chance of subsequent intrauterine pregnancy: 40-60%

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