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  • Clinician

Ectopic pregnancy

Summary

Ectopic pregnancy occurs when an embryo attaches outside of the uterus, most commonly in the fallopian tubes. It is frequently associated with pelvic inflammatory disease (PID), which may lead to stenosis of the fallopian tubes. This prevents the fertilized egg from passing through to the uterus, instead causing it to attach to the tube itself. In addition to signs of pregnancy, symptoms include abdominal pain and vaginal bleeding. The first diagnostic step is to confirm the pregnancy with a β-hCG test, which should be followed by a transvaginal ultrasound to determine the location of the pregnancy and the fetal heartbeat. Uncomplicated ectopic pregnancies often resolve spontaneously and are usually difficult to diagnose. Patients are typically hemodynamically stable with low, declining hCG concentrations (< 5000 IU/L). Complicated cases may involve tubal abortion or rupture, which can lead to intraabdominal bleeding and shock. Whereas uncomplicated cases are treated conservatively (e.g., methotrexate or expectant management), complicated ectopic pregnancy requires surgical removal. In cases of abdominal pain in women of reproductive age, it is therefore important to rule out ruptured ectopic pregnancy.

Definition

Etiology

Localization

  1. Fallopian tube (96% of cases): ampulla >> isthmus > fimbriae > interstitial pregnancy : e.g., cornual pregnancy
  2. Ovary (3% of cases)
  3. Abdomen (1% of cases)
  4. Cervix (very rare)

Risk factors

References:[3][4][5][6][7][8][9][10][11]

Clinical features

General symptoms of ectopic pregnancy

Patients usually present with signs and symptoms 4–6 weeks after their last menstrual period.

Right lower quadrant pain may indicate appendicitis! Cervical motion tenderness may be a sign of PID!

Tubal rupture

References:[12][13][14]

Diagnostics

Consider ectopic pregnancy in all women of childbearing age presenting with general symptoms of ectopic pregnancy or with known risk factors (e.g., anatomic alteration of the fallopian tubes). If the patient is hemodynamically unstable, provide hemodynamic support and consider immediate surgical exploration. The diagnosis is confirmed with transvaginal ultrasound (TVUS). [1][15]

Every woman of reproductive age with abdominal pain should undergo a pregnancy test, regardless of contraception use. [1]

Laboratory studies [1][15]

Serum β-hCG level [1][15][16]

Additional studies

  • CBC: Anemia may be seen in patients with vaginal bleeding.
  • Blood type and screen: ABO and Rh testing to identify patients who might need Rho immunization
  • LFT, BMP: to determine baseline liver and renal function

Imaging [15]

Transvaginal ultrasound (TVUS)

Transabdominal ultrasound (TAUS)

  • Can be used to exclude differential diagnoses (e.g., acute appendicitis)
  • Provides a general picture of the pelvic anatomy and upper abdomen but is less sensitive than TVUS in detecting extrauterine pregnancy

Exploratory laparoscopy [1]

  • Indications
    • Unstable patients suspected of having an ectopic pregnancy
    • In pregnancy of unknown location if the location is still uncertain after 7–10 days
      • Consider earlier laparoscopic exploration for high-risk patients (e.g., previous ectopic pregnancy).

Do not delay laparoscopy in unstable patients with suspected ectopic pregnancy.

Endometrial biopsy [18]

Differential diagnoses

See also differential diagnoses of acute abdomen.

Differential diagnoses of abnormal vaginal bleeding in women of reproductive age

Painful vaginal bleeding

Differential diagnosis Description of pain Findings
Ectopic pregnancy
  • Lower unilateral abdominal pain and guarding
Benign neoplasms
(e.g., adenomyosis, uterine leiomyoma)
Ovarian cyst rupture
  • Sudden onset of unilateral abdominal pain
  • Onset usually during physical activity (exercise, sexual intercourse)
Infection/Inflammation
(e.g, PID, cervicitis)

Endometriosis

  • Chronic pelvic pain that worsens before the onset of menses
Trauma
(e.g., foreign body, sexual abuse)

Painless vaginal bleeding

Differential diagnosis Findings

PCOS

Endometrial hyperplasia

Endometrial polyp

Malignant neoplasms
(e.g., cervical cancer, endometrial cancer)
Iatrogenic
(e.g., anticoagulants, oral contraceptives, intrauterine devices)


References:[19][20][21][22][23][24][25][26][27]

The differential diagnoses listed here are not exhaustive.

Treatment

In hemodynamically unstable patients with ruptured or impending rupture of ectopic pregnancy, emergency surgery is indicated. In all other patients, the decision for medical, expectant, or surgical treatment of ectopic pregnancy should be guided by the clinical, laboratory, and radiological findings as well as patient-informed choice based on a discussion of the benefits and risks of each approach.

Medical treatment [1][15]

The treatment of choice is methotrexate (MTX). [28]

Methotrexate

Methotrexate regimens for medical treatment of ectopic pregnancy [1]
Single-dose regimen Two-dose regimen Multiple-dose regimen
Characteristics
  • Lower risk of adverse effects than other regimens
  • More effective than single-dose regimen for patients with high initial β-hCG
  • More adverse effects than other regimens
  • Higher success rate than other available regimens
Methotrexate administration
β-hCG monitoring
Response to β-hCG monitoring results
  • Decrease > 15% from day 4 to day 7: Measure β-hCG weekly until negative.
  • Decrease < 15% from day 4 to day 7: Repeat MTX dose.
  • No decrease after 2 doses: Consider surgical management.
  • Decrease > 15% from day 4 to day 7: Measure β-hCG weekly until negative.
  • Decrease < 15% from day 4 to day 7: Repeat MTX dose on day 7 and measure β-hCG on day 11.
  • This may be repeated until the patient has received 4 doses.
  • No decrease after 4 doses: Consider surgical management.
  • Decrease > 15% in 2 consecutive measurements: Discontinue MTX and measure β-hCG weekly until negative.
  • No β-hCG decrease after 4 doses: Consider surgical management.
Follow up
  • If β-hCG levels increase or plateau during weekly follow up, consider persistent ectopic pregnancy.
  • Adverse effects: See “Side effects” in immunosuppressants.
  • Patients should avoid the following during MTX therapy:
    • Exercise and sexual activity
    • Folic acid supplements, foods with a high folic acid content, and NSAIDs
    • Prolonged exposure to sunlight
    • Alcohol and gas-producing foods

Methotrexate therapy is contraindicated in ruptured ectopic pregnancy!

Additional therapy

Surgical treatment [1][15]

  • Indications
    • Hemodynamic instability
    • Symptoms of impending rupture (e.g., pelvic pain)
    • Signs of intraperitoneal bleeding
    • Risk factors for rupture [29]
    • Contraindications for MTX
    • Unsuccessful medical treatment
    • A concurrent surgical procedure (e.g., bilateral tubal blockage) is necessary.
    • The patient has indicated a preference for surgical treatment.
  • Approaches
    • Laparoscopy (preferred)
    • Laparotomy should be considered for any of the following:
      • Difficult visualization on laparoscopy
      • Large intraperitoneal bleeding
      • Critically unstable patients

Procedures

  • Salpingostomy (tube‑conserving operation)
    • Indication: patients with unruptured tubal pregnancy who do not meet the criteria for conservative treatment
    • Procedure: removal of ectopic pregnancy without removing the affected fallopian tube
    • Complications
    • Additional considerations
      • Patients require serial hCG measurement.
      • Consider a prophylactic dose of MTX if there is concern for incomplete resection.
  • Salpingectomy (does not preserve tube function)

Expectant management [1]

Asymptomatic patients with very low β-hCG levels may experience spontaneous resolution of ectopic pregnancy without medical or surgical treatment. [1]

  • Indications
    • Minimal symptoms
    • No evidence of ectopic mass on TVUS
    • Low/decreasing levels of β-hCG
  • Considerations during expectant management
    • Patients should receive extensive counseling on the risks of complications.
    • Close surveillance is mandatory.
    • β-hCG should be obtained every 48 hours until a decrease is confirmed, then weekly until negative.
  • Conversion to medical or surgical therapy
    • Increasing symptoms
    • β-hCG levels increase or plateau

Acute management checklist

Nonruptured ectopic pregnancy [1]

Ruptured or impending rupture of ectopic pregnancy [1]

  • IV access with two large-bore peripheral IV lines
  • Urgent OB/GYN consult for emergency salpingostomy
  • NPO
  • Provide hemodynamic support as needed.
  • Check CBC, type and screen, and prepare for blood transfusion.
  • Parenteral analgesics: Opioids are preferred.
  • Continuous telemetry and frequent blood pressure checks
  • Transfer to OR.
last updated 11/23/2020
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