Ectopic Pregnancy

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

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 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.

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.