What are the differential diagnoses for ectopic pregnancy?

Differential Diagnosis for Ectopic Pregnancy

When evaluating a patient with suspected ectopic pregnancy, your differential must include intrauterine pregnancy (viable or failing), spontaneous abortion (threatened, incomplete, or complete), pregnancy of unknown location, corpus luteum cyst, ovarian torsion, pelvic inflammatory disease, appendicitis, and ovarian cyst rupture or hemorrhage. 1

Primary Gynecologic Differentials

Pregnancy-Related Conditions

• Normal intrauterine pregnancy (IUP): The most critical distinction, as this represents a viable pregnancy that should not be disrupted. Transvaginal ultrasound showing a gestational sac with yolk sac or fetal pole definitively establishes IUP. 1, 2

• Spontaneous abortion (miscarriage): Includes threatened abortion (viable IUP with bleeding), incomplete abortion (retained products of conception), or complete abortion (passed tissue with declining β-hCG). These conditions present with similar symptoms of pain and bleeding but have different ultrasound findings and β-hCG patterns. 1

• Pregnancy of unknown location (PUL): This is a transient diagnostic category where β-hCG is positive but ultrasound shows neither intrauterine nor ectopic pregnancy. Approximately 5% of early pregnancy presentations fall into this category initially. Of these, 69% resolve spontaneously, 22% become normal IUPs, and 7% are ultimately diagnosed as ectopic pregnancies. 1, 3

Non-Pregnancy Gynecologic Conditions

• Corpus luteum cyst: Can present with unilateral pain and may have associated hemorrhage or rupture. Ultrasound typically shows a complex adnexal mass, which can be confused with ectopic pregnancy. The key distinguishing feature is a negative β-hCG. 1

• Ovarian torsion: Presents with acute unilateral pelvic pain, often severe and sudden. Ultrasound shows an asymmetrically enlarged ovary with or without an underlying mass and a twisted pedicle (best seen on multiplanar reformations). Absent or decreased Doppler flow is suggestive but not diagnostic. 1

• Pelvic inflammatory disease (PID): Presents with bilateral lower abdominal pain, cervical motion tenderness, and often fever. May have associated vaginal discharge. Can coexist with early pregnancy. 3, 4

• Hemorrhagic ovarian cyst: Presents with acute pelvic pain, often unilateral. Ultrasound shows a complex cystic adnexal mass with internal echoes representing blood products. 1

Non-Gynecologic Differentials

• Appendicitis: Right lower quadrant pain with peritoneal signs, fever, and elevated white blood cell count. CT with IV contrast is diagnostic if ultrasound is inconclusive, though ultrasound may incidentally detect gynecologic pathology. 1

• Urinary tract conditions: Includes nephrolithiasis (flank pain radiating to groin, hematuria) and urinary tract infection (dysuria, frequency, urgency). 1

• Acute diverticulitis: Typically left lower quadrant pain in older patients, though can occur on the right. CT with IV contrast is diagnostic. 1

Critical Diagnostic Pitfalls

Do not rely solely on β-hCG discriminatory zones to exclude ectopic pregnancy. The traditional threshold of 1,500-2,000 mIU/mL has poor diagnostic performance, with only 25% sensitivity for detecting ectopic pregnancy below this level. Critically, 41-50% of ectopic pregnancies present with β-hCG <1,500 mIU/mL at initial presentation. 5

Transvaginal ultrasound should be performed regardless of β-hCG level because it can detect ectopic pregnancy in 92% of cases even when β-hCG is <1,000 mIU/mL. 5

Absence of intrauterine pregnancy on transvaginal ultrasound when β-hCG is >3,000 mIU/mL is highly suggestive (though not diagnostic) of ectopic pregnancy, with 98% specificity for IUP detection above 1,500 mIU/mL. 1, 5

Specific Ultrasound Findings That Narrow the Differential

• "Tubal ring" sign: Classic finding for ectopic pregnancy with high specificity. This represents an extrauterine gestational sac with a thick echogenic ring. 1

• Adnexal mass without IUP: Has a positive likelihood ratio of 111 for ectopic pregnancy, making transvaginal ultrasound the single best diagnostic modality. 1

• Lack of adnexal abnormalities: Decreases the likelihood of ectopic pregnancy with a negative likelihood ratio of 0.12. 1

• Endometrial thickness <8 mm: Virtually excludes normal IUP. 1

• Endometrial thickness ≥25 mm: Virtually excludes ectopic pregnancy (present in only 4 cases in one study of 591 patients). 1

Risk Stratification Approach

For hemodynamically unstable patients: The differential narrows to ruptured ectopic pregnancy, ruptured hemorrhagic corpus luteum, ovarian torsion with necrosis, or ruptured tubal abscess. Immediate surgical consultation is required rather than prolonged diagnostic workup. 5, 6, 3

For stable patients with indeterminate ultrasound: Serial β-hCG measurements 48 hours apart combined with repeat ultrasound in 7-10 days is the standard approach. Normal IUP should show β-hCG doubling every 48-72 hours, while ectopic or failing pregnancies typically show suboptimal rise or plateau. 2, 5