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Ectopic Pregnancy

American College of Obstetrics and Gynecology Practice Bulletin – Tubal Ectopic Pregnancy, 2018

  • >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
  • Incidence is estimated 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.
  • 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.
  • 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
  • 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.
ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy. Obstet Gynecol. 2018;131(3):e91-e103. PubMed , Free Access

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