Ectopic pregnancy

Ectopic pregnancy occurs when an embryo attaches outside the uterine cavity, most commonly in the fallopian tubes. Risk factors include conditions that alter the anatomy of the fallopian tubes (e.g., history of pelvic inflammatory disease, previous ectopic pregnancy, tubal surgery) and nonanatomical factors (e.g., smoking, age > 35 years, assisted reproductive technology). Ectopic pregnancy most commonly manifests 6–8 weeks after the last menstrual period and should be considered in individuals who can become pregnant and who have abdominal pain and vaginal bleeding. The first diagnostic step is a serum quantitative β-hCG test and transvaginal ultrasound (TVUS) to determine pregnancy location. Serial β-hCG tests and TVUS are frequently necessary to establish the diagnosis. Management in stable patients consists of methotrexate, surgery (e.g., salpingostomy, salpingectomy), or, in selected patients, expectant management. Tubal rupture due to ectopic pregnancy manifests with severe abdominal pain and/or acute abdomen, signs of peritoneal irritation (e.g., shoulder pain, diarrhea), and sometimes signs of hemodynamic instability or shock (e.g., hypotension, tachycardia, syncope). Patients with signs of tubal rupture require immediate stabilization and emergency surgery.

• Ectopic pregnancy: a pregnancy in which the fertilized egg attaches in a location outside the uterine cavity
  • Tubal pregnancy: a pregnancy that occurs within the fallopian tube ^[1]
  • Interstitial pregnancy: a pregnancy that occurs within the interstitial portion of the fallopian tube (i.e., the segment that connects the tube to the endometrial cavity)
  • Cornual pregnancy: a pregnancy that occurs in the uterine cornua ^[2][3]
  • Cesarean scar pregnancy: a pregnancy that occurs in the uterine myometrium at the site of a cesarean delivery scar ^[4]
• Complicated ectopic pregnancy ^[5]
  • An ectopic pregnancy with severe bleeding (e.g., hemoperitoneum, vaginal bleeding), rupture (e.g., tubal rupture), and/or hemodynamic compromise
  • Gynecological emergency that requires surgical treatment
• Uncomplicated ectopic pregnancy ^[5]
  • An ectopic pregnancy without any features of complicated ectopic pregnancy
  • May resolve spontaneously
• Heterotopic pregnancy: a rare condition involving multiple gestations, in which one is intrauterine and another is ectopic; occurs more frequently in patients undergoing infertility treatments (e.g., in vitro fertilization) ^[6]

Localization ^[7]

• Fallopian tube (∼ 95% of cases)
  • Ampulla (∼ 70%)
  • Isthmus (∼ 12%)
  • Fimbriae (∼ 11%)
  • Interstitial (∼ 2%)
• Other
  • Ovary
  • Cesarean scar^[1]
  • Abdomen
  • Cervix
  • Uterine cornua

Risk factors for ectopic pregnancy ^[8]

Half of individuals with ectopic pregnancy have no risk factors. ^[1]

Anatomic alteration of the fallopian tubes

• History of PID (e.g., salpingitis)
• Previous ectopic pregnancy
• Surgeries involving the fallopian tubes (e.g. tubectomy, tubal ligation)
• Endometriosis
• Ruptured appendix ^[9]
• Kartagener syndrome
• Exposure to diethylstilbestrol (DES) in utero ^[10][11]
• Bicornuate uterus

Nonanatomical risk factors

• Smoking
• Age > 35 years
• Pregnancy with intrauterine device in place ^[8]
• Infertility
• In vitro fertilization

General symptoms ^[12][13][14]

Patients usually present with signs and symptoms 6–8 weeks after their last menstrual period.

• Lower abdominal pain and guarding (ectopic pregnancy is often mistaken for appendicitis due to the similarity of symptoms)
• Vaginal bleeding
• Signs of pregnancy
  • Amenorrhea
  • Nausea
  • Breast tenderness
  • Frequent urination
• Tenderness or painful mass in the area of the ectopic pregnancy
• Cervical motion tenderness, closed cervix
• Interstitial pregnancies tend to present late, at 7–12 weeks' gestation, because of myometrial distensibility.

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

Tubal rupture ^[12][13][14]

• Acute course with sudden and severe lower abdominal pain (acute abdomen)
• Signs of hemorrhagic shock (e.g., tachycardia, hypotension, syncope)
• Features of peritoneal irritation (e.g., shoulder pain, vomiting, diarrhea, urinary symptoms) due to bleeding ^[8]
• More common in interstitial pregnancy

Approach ^[1][15]

Consider ectopic pregnancy in all individuals who can become pregnant who present with general symptoms of ectopic pregnancy, and in pregnant individuals with known risk factors for ectopic pregnancy in whom pregnancy location is unknown.

• Hemodynamically unstable patients
  • Start acute stabilization measures (see “Management of ruptured ectopic pregnancy”).
  • If trained, perform a point-of-care ultrasound (see “POCUS in early pregnancy” and “FAST”) to identify intraperitoneal free fluid or confirm intrauterine pregnancy (IUP).
    • If IUP is confirmed, evaluate for alternate causes of hemodynamic instability (see “Shock”).
    • If any of the following are present, refer for immediate surgical exploration without awaiting further diagnostic studies:
      • Free intraperitoneal fluid
      • Findings suggestive of ectopic pregnancy, e.g., adnexal mass
      • No visible IUP (if there is high clinical suspicion for ectopic pregnancy)
  • Urgently consult OB/GYN for surgical exploration based on clinical suspicion supplemented by POCUS findings (if performed).
  • Obtain a formal ultrasound (transvaginal ultrasound) as soon as the patient is stable enough.
• Stable patients: Send serum β-hCG and arrange or perform a pelvic ultrasound (e.g., POCUS for early pregnancy or formal ultrasound) regardless of β-hCG level. ^[15]
  • Ectopic pregnancy visible on imaging (diagnosis confirmed): Begin treatment.
  • IUP visible on imaging (ectopic pregnancy unlikely): Consider alternative diagnoses.
  • Indeterminant ultrasound (pregnancy of unknown location) ^[16]
    • Arrange follow-up, serial β-hCG, and repeat imaging.
    • Undesired pregnancy: Consider diagnostic uterine aspiration or medical abortion followed by serial β-hCG measurements. ^[1][8]

Sexually active individuals who can become pregnant and who present with abdominal pain and/or vaginal bleeding should undergo a pregnancy test, regardless of contraception use. ^[1]

Up to 20% of patients with ectopic pregnancy can be hemodynamically unstable and require immediate therapy. Do not delay stabilization and definitive treatment to confirm the diagnosis! ^[17]

Laboratory studies ^[1][8][18]

Serum β-hCG level

• Single β-hCG measurement
  • Increased β-hCG is verifiable from the eighth day after ovulation, when fertilization has occurred. ^[8]
  • A single measurement cannot be used to determine viability or pregnancy location. ^[1][19]
  • β-hCG discriminatory level: the β-hCG level at which an IUP is typically visible on ultrasound ^[15]
    • Cutoffs for transvaginal ultrasound range from 1500 to 3500 mIU/mL β-hCG. ^[1][8]
    • Inability to visualize pregnancy on ultrasound above the β-hCG discriminatory level may suggest ectopic pregnancy or pregnancy loss.
  • Multiple pregnancies may have higher β-hCG levels.
• Serial β-hCG measurements (every 48 hours): better diagnostic accuracy than a single β-hCG level in differentiating IUP from ectopic pregnancy ^[1][8]
  • The expected percentage increase in β-hCG after 48 hours for normal IUPs is based on the initial level.
    • Initial level < 1500 mIU/mL: > 49% expected increase
    • Initial level 1500–3000 mIU/mL: > 40% expected increase
    • Initial level > 3000 mIU/mL: > 33% expected increase
  • A lower than expected increase or any decline in β-hCG may indicate a failed IUP (e.g., spontaneous abortion) or an ectopic pregnancy.
    • A drop of ≥ 21% suggests failed IUP.
    • A drop of < 21% is more likely to indicate an ectopic pregnancy.
  • An insufficient decline in serial β-hCG measurements following induced abortion should raise suspicion for ectopic pregnancy (for more information, see “Induced abortion”).^[1]

The β-hCG discriminatory level has limited accuracy and should not be used as the sole parameter to diagnose the location or viability of a pregnancy. Assessing trends on serial β-hCG monitoring is recommended instead. ^[1][15]

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 ^[8][20][21]

Transvaginal ultrasound (TVUS)

Can be performed as a formal ultrasound or POCUS for early pregnancy. ^[22]

• Indication: best initial imaging test for determining the location of the pregnancy
• Ultrasound findings suggestive of ectopic pregnancy
  • Empty uterine cavity in combination with a thickened endometrial lining
  • Possible free fluid within the pouch of Douglas (nonspecific)
  • Additional findings in tubal pregnancy
    • Possible extraovarian adnexal mass
    • Tubal ring sign (blob sign): an echogenic ring that surrounds an unruptured ectopic pregnancy ^[23]
  • Additional findings in interstitial pregnancy
    • Interstitial line sign: an echogenic line that extends from the gestational sac into the upper uterus (thought to be the echogenic appearance of the interstitial portion of the tube)
    • A thin myometrial layer (< 5 mm) surrounding the gestational sac
• Additional considerations
  • Ultrasound findings in normal pregnancy: An IUP (i.e., a gestational sac and yolk sac, or embryo or fetus with cardiac activity in the uterus) typically becomes visible at 5–6 weeks' gestation. ^[1][15]
  • If the gestational sac cannot be seen at all on ultrasound, the patient is diagnosed with pregnancy of unknown location. ^[1]

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
• POCUS can be performed using the transabdominal approach to rapidly rule in IUP if present.

Uterine aspiration ^[1][8]

• Indication: Consider in cases of pregnancy of unknown location when pregnancy is undesired or nonviability is certain.
• Findings on uterine aspirate examination ^[24]
  • Ectopic pregnancy: decidualization of the endometrium without chorionic villi
  • IUP: Chorionic villi and gestational sac are present.

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

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

• See “Differential diagnosis of lower abdominal pain in women of reproductive age.”
• See “Acute abdominal pain: Differential diagnoses.”
• See “Common causes of adnexal mass” and “Mimics of adnexal mass.”

The differential diagnoses listed here are not exhaustive.

The following recommendations are consistent with the 2018 (reaffirmed 2025) ACOG practice bulletin on tubal ectopic pregnancy. ^[1]

Approach

• Unstable patients: See “Management of ruptured ectopic pregnancy.”
  • Begin acute stabilization.
  • Obtain an immediate OB/GYN consult for emergency surgery.
• Stable patients: Determine whether medical, surgical, or expectant management is appropriate.
  • Consider clinical, laboratory, and radiological findings.
  • Share decision-making with patients in consultation with OB/GYN.
• Patients suited to medical or expectant management at home
  • Provide education on red flag symptoms indicating rupture, e.g., severe worsening pain, shoulder tip pain, dizziness, or heavy bleeding.
  • Arrange appropriate follow-up prior to discharge.
• All patients: Provide supportive care.
  • Pain management
  • Prenatal and contraceptive counseling once treatment is complete ^[25]
  • Anti-D immunoglobulin for Rh-negative patients (for more information see “Dosages of RhIG”) ^[26]

Do not forget anti-D immunoglobulin in all Rh-negative patients with bleeding!

Medical therapy (methotrexate) ^[1][8]

MTX is the treatment of choice.

• Mechanism of action: inhibits folate-dependent steps in DNA synthesis to terminate the rapidly dividing ectopic pregnancy.
• Indications
  • Uncomplicated ectopic pregnancies
  • Hemodynamically stable patients
  • Unruptured mass < 4 cm on TVUS ^[1]
  • No fetal heartbeat
• Absolute contraindications
  • Chronic conditions
    • Pulmonary (except asthma)
    • Renal (e.g., creatinine clearance < 50 mL/min/1.73 m²)
    • Hepatic (e.g., alcohol use disorder, chronic liver disease) ^[8]
    • Hematologic (e.g., leukopenia, thrombocytopenia, severe anemia)
  • IUP
  • Breastfeeding
  • MTX sensitivity
  • Immunodeficiency
  • Peptic ulcer disease
  • Ruptured ectopic pregnancy
  • Unable to engage in follow-up
• Administration: Regimen is determined by ultrasound and clinical findings, patient preferences, and β-hCG level. ^[1][8]
  • β-hCG < 3600 mIU/mL: single-dose regimen
  • β-hCG 3600–5000 mIU/mL: Consider two-dose regimen.

• Adverse effects: See “Adverse effects of 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

MTX therapy is contraindicated in ruptured ectopic pregnancy!

Nonurgent surgical management ^[1][8]

See “Management of ruptured ectopic pregnancy” for emergency surgical indications and preferred approach.

• Indications for nonurgent surgery
  • 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.
• Approach Laparoscopy (preferred)
• Procedure: salpingostomy, i.e., removal of ectopic pregnancy without removing the affected fallopian tube (tube‑conserving operation)
  • Preferred in patients with unruptured tubal pregnancy who do not meet the criteria for conservative treatment
  • Complications
    • Risk of persistent ectopic pregnancy
    • Risk of repeat ectopic pregnancy
  • Additional considerations
    • Patients require serial hCG measurement.
    • Consider a prophylactic dose of MTX if there is concern for incomplete resection.
  • Salpingectomy may be required in select cases (e.g., large ectopic mass).

Expectant management ^[1]

Asymptomatic patients with very low β-hCG levels may experience spontaneous resolution of ectopic pregnancy without medical or surgical treatment. Consider this approach in select patients after consultation with OB/GYN. ^[1]

• Indications
  • Minimal symptoms
  • No evidence of ectopic mass on TVUS
  • Confirmed plateauing or decreasing serial β-hCG levels
• Considerations during expectant management
  • Provide extensive counseling on the risks of complications in addition to general counseling (see “Approach”).
  • Arrange close surveillance and serial β-hCG measurement (e.g., every 2–7 days).
• Conversion to medical or surgical therapy
  • Increasing symptoms, e.g., pain, signs of ruptured ectopic pregnancy
  • Insufficient decrease, persistent plateau, or increase in β-hCG levels

Follow the ABCDE approach for patients with obvious signs of rupture and those at high risk of impending rupture.

Rapid assessment

Suspect ruptured ectopic pregnancy in patients in their first trimester with any of the following:

• Clinical features of shock: e.g., tachycardia, hypotension, pallor
• Severe abdominal or pelvic pain
• Peritoneal signs on examination
• Significant vaginal bleeding
• POCUS positive for intraperitoneal free fluid
• Clinical deterioration after receiving MTX therapy ^[15]

Obtain emergency OB/GYN consult without delay if ruptured ectopic pregnancy is likely!

Acute stabilization

• Obtain IV access; send an urgent type and screen and crossmatch.
• Start immediate IV fluid resuscitation.
• Rapidly deliver blood transfusion as soon as blood products are available.
• Activate massive transfusion protocol if necessary.
• Consider tranexamic acid for persistently unstable patients in consultation with OBGYN. ^[27][28][29]
• If hypotension persists, start vasopressors (see “Shock”).
• Consider interventional radiology referral for angioembolization in consultation with OB/GYN.

Surgical management

• Indications for immediate surgical referral
  • Hemodynamic instability
  • Symptoms of impending rupture (e.g., severe pelvic pain)
  • Signs of intraperitoneal bleeding (e.g., peritonitis, POCUS positive for free fluid)
  • Extrauterine embryo with cardiac activity seen on ultrasound ^[8]
  • Risk factors for rupture ^[30]
• Approach: Laparotomy is preferred for large intraperitoneal bleeding or critically unstable patients; otherwise a laparoscopic approach is typically performed.
• Procedure: salpingectomy, i.e., partial or complete removal of the affected fallopian tube (does not preserve tube function)
  • Preferred approach for:
    • Ruptured tube
    • Heavy bleeding
    • Large ectopic mass
    • Severe damage to the fallopian tube
  • Additional considerations
    • If the patient desires future pregnancies: Evaluate the status of the contralateral fallopian tube before salpingectomy.
    • If the patient does not desire future pregnancies: Bilateral salpingectomy may be performed.

Nonruptured ectopic pregnancy ^[31]

• OB/GYN consult for consideration of medical treatment, surgical treatment, or expectant management
• Close monitoring
• Laboratory studies (CBC, type and screen)
• Analgesics (see pain management)

Ruptured or impending rupture of ectopic pregnancy ^[31]

• IV access with two large-bore peripheral IV line
• Start IV fluid resuscitation.
• Check CBC, type and screen, and prepare for blood transfusion.
• Urgent OB/GYN consult for emergency salpingectomy
• NPO
• Provide immediate hemodynamic support as needed.
• For patients with hemorrhagic shock, start transfusion as soon as blood products are available and consider massive transfusion protocol.
• Parenteral analgesics: Opioids are preferred.
• Continuous telemetry and frequent blood pressure checks
• Transfer to OR.

• The condition is fatal for the fetus.
• Maternal mortality rate: ∼ 0.6/100,000 in the US ^[32]
• Future fertility: depends primarily on fertility status prior to ectopic pregnancy
• Recurrence: approx. 10% ^[1]