Ectopic Pregnancy

Location

  • >90% of ectopics are fallopian, 1% abdominal, 1% cervix, 1-3% ovarian, 1% c-section scar
  • Heterotopic pregnancy risk 1/4000 – 1/30,000 in general population
  • Heterotopic pregnancy risk in patients receiving in vitro fertilization, up to 1/100

Epidemiology

  • Incidence isestimated to be 1-2% (25 per 1000 pregnancies per CDC).
  • CDC Data tracking stopped in 1992.
  • 2011–2013, ruptured ectopic pregnancy was 2.7% of all pregnancy-related deaths and the leading cause of hemorrhage-related mortality. 
  • Up to 18% prevalence of ectopic pregnancy in women presenting to an emergency department with first-trimester vaginal bleeding, or abdominal pain

Risk Factors (50% cases have none)

  • Single prior ectopic (10% risk), multiple prior ectopics (25% risk)
  • Prior fallopian tube damage (surgical or infectious)
  • Hx PID
  • Hx fallopian or pelvic surgery
  • In vitro fertilization (multiple embryo implantation)
  • Hx of infertility
  • Less significant = cigarettes smoking, age >35
  • Use of IUD reduces chances of pregnancy, therefore reduces chances of ectopic compared with women using NO birth control. However, up to 53% of pregnancies with IUD in place are ectopic.

Ultrasound

  • Definitive if gestational sac AND yolk sac or embryo is seen.
  • Intrauterine gestational sac and yolk sac should be seen 5-6 weeks by dates.

Beta-hCG

  • Discriminatory level is only accurate in 50-70% of cases
  • 3500 mIU/ml is recommended by ACOG and is set higher than previous cut offs in order to prevent termination of early pregnancy.
  • Levels plateau at 10 weeks near 100,000mIU/ml
  • If no pregnancy is seen, level should be rechecked in 2 days
  • Expected rate of increase:
    • 49% for an initial hCG level of less than 1,500 mIU/mL
    • 40% for an initial hCG level of 1,500–3,000 mIU/mL
    • 33% for an initial hCG level greater than 3,000 mIU/mL 
  • 99% of normal intrauterine pregnancies will have a rate of increase faster than this minimum
  • hCG pattern consistent with IUP or miscarriage does not eliminate the possibility of an ectopic pregnancy
  • 95% of women with a spontaneous miscarriage will have 21–35% hCG decrease in 2 days
  • Decreasing hCG level in a possible ectopic pregnancy should be monitored until non-pregnant levels are reached because rupture of an ectopic pregnancy can occur while levels are decreasing or are very low.
  • Reported risk of rupture of an ectopic pregnancy during surveillance was as low as 0.03 % among all women at risk and as low as 1.7% among all ectopic pregnancies diagnosed

Treatment

  • Clinically stable women with non-ruptured ectopic may have surgery or methotrexate therapy.
  • Surgical management is necessary if there is hemodynamic instability, ongoing ruptured ectopic mass (pelvic pain), or signs of intraperitoneal bleeding.
  •  Methotrexate therapy:
    • Intramuscular methotrexate is the only medical treatment for ectopic pregnancy
    • A high initial hCG level is considered a relative contraindication.
    • Failure rate >14.3% if hCG level > 5,000 mIU/mL compared with a 3.7% failure rate for hCG levels less than 5,000 mIU/mL (48)
    • Failure rate 3.7% if hCG level < 5,000 mIU/mL
    • Success rate 70% to 95%
    • Absolute contraindications:
      • IUP
      • Immunodeficiency
      • Moderate to severe anemia, leukopenia, thrombocytopenia
      • Active pulmonary disease (except asthma)
      • Active PUD
      • Clinically significant hepatic or renal dysfunction
      • Breastfeeding
      • Ruptured ectopic
      • Hemodynamic instability
      • Inability to obtain follow-up
    • Relative contraindications include:
      • Embryonic cardiac activity
      • High initial HCG
      • Ectopic > 4cm size by transvaginal US
      • Refusal to accept blood transfusion
    • Single, double, and multi dose regimens have been studied for methotrexate.
    • Single dose regimen:
      • 50 mg/m2 IM
      • hCG level day 4 + 7
      • If the decrease is greater than 15%, measure hCG levels weekly until nonpregnant level
      • If decrease is less than 15%, give methotrexate at a dose of 50 mg/m2 intramuscularly and repeat hCG level
      • If hCG does not decrease after two doses, consider surgical management
    • Two dose regimen:
      • 50 mg/m2 IM day 1
      • 50 mg/m2 IM day 4
      • If the decrease is greater than 15%, measure hCG levels weekly until non-pregnant level
      • If decrease is less than 15%,give methotrexate at a dose of 50 mg/m2 intramuscularly day 7 and repeat hCG level day 11
      • If hCG levels decrease 15% between day 7 and 11, continue to monitor weekly until non-pregnant level
      • If the decrease is less than 15% between day 7 and 11, give methotrexate on day 11 and check hCG levels on day 14
      • If hCG does not decrease after four doses, consider surgical management
    • Fixed multi-dose regimen:
      • 50 mg/m2 IM day 1,3,5,7
      • Alternate with folinic acid 0.1 mg/kg IM days 2,4,6,8
      • Obtain hCG levels on methotrexate days (1,3,5,7) and continue until 15% decrease from prior measurement.
      • If decrease is more than 15%, discontinue methotrexate and measure hCG levels weekly until non-pregnant level.
      • If hCG does not decrease after 4 doses, consider surgical management.

Further Reading

First Trimester Pregnancy Emergencies: Recognition and Management Date Release: Jan 2019 Common first-trimester ED presentations include miscarriage, ectopic pregnancy, nausea and vomiting, urinary tract infections, and potential appendicitis. This issue reviews the evidence on these common conditions to ensure swift and safe management.

References

ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy. Obstet Gynecol. 2018;131(3):e91-e103. PubMed

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