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Ectopic pregnancy

Last updated: March 3, 2021

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Ectopic pregnancy occurs when an embryo attaches outside 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.

Localization [3]

Risk factors [4][5][6][7]

Anatomic alteration of the fallopian tubes

Nonanatomical risk factors

General symptoms [12][13][14]

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

Tubal rupture [12][13][14]

Approach [1][16]

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

Laboratory studies [1][16][17]

Serum β-hCG level

Additional studies

Imaging [16][18]

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]

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

Endometrial biopsy [20]

See also “Acute abdominal pain: Differential diagnoses.”

Painful vaginal bleeding

Overview of differential diagnoses of painful vaginal bleeding [21]
Differential diagnosis Description of pain Characteristics
Ectopic pregnancy
  • Lower unilateral abdominal pain and guarding
Benign neoplasms Adenomyosis
  • Chronic pelvic pain
Uterine leiomyoma
  • Back or pelvic pain/discomfort
Ovarian cyst rupture
  • Sudden onset of unilateral abdominal pain
  • Onset usually during physical activity (exercise, sexual intercourse)
Infection/Inflammation PID
  • Lower bilateral abdominal pain


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

Painless vaginal bleeding

Overview of differential diagnoses of painless vaginal bleeding [21]
Differential diagnosis Characteristics


Endometrial hyperplasia

Endometrial polyp

Malignant neoplasms Cervical cancer
Endometrial cancer
(e.g., anticoagulants, oral contraceptives, intrauterine devices)

Anembryonic pregnancy [22]

  • Can be asymptomatic
  • Vaginal bleeding, loss of pregnancy symptoms, and falling β-hCG levels
  • Endovaginal ultrasound findings
    • No visible embryo in a gestational sac measuring ≥ 25 mm
    • No visible embryo during a follow-up endovaginal ultrasound ≥ 11 days after confirming the presence of a gestational sac with a yolk sac
    • No visible embryo during a follow-up endovaginal ultrasound ≥ 2 weeks after confirming the presence of a gestational sac without an embryo or a yolk sac

The differential diagnoses listed here are not exhaustive.

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][16]


Methotrexate regimens for medical treatment of ectopic pregnancy [1]
Single-dose regimen Two-dose regimen Multiple-dose regimen
  • 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
  • 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][16]

  • Indications
    • Hemodynamic instability
    • Symptoms of impending rupture (e.g., pelvic pain)
    • Signs of intraperitoneal bleeding
    • Risk factors for rupture [23]
    • 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


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

Nonruptured ectopic pregnancy [1]

Ruptured or impending rupture of ectopic pregnancy [1]

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