What are the top differential diagnoses for a suspected miscarriage?

Differential Diagnosis of Miscarriage

When evaluating a patient with suspected miscarriage, the critical differential diagnoses to exclude are: (1) ectopic pregnancy, (2) heterotopic pregnancy, (3) gestational trophoblastic disease, (4) incomplete versus complete miscarriage, and (5) cervical ectopic pregnancy or cesarean scar ectopic pregnancy. 1, 2, 3

1. Ectopic Pregnancy

This is the most critical diagnosis to exclude due to life-threatening hemorrhage risk. 1

• Must be explicitly excluded in any patient with positive β-hCG and pelvic pain, even with confirmed intrauterine pregnancy on prior ultrasound 4
• A negative serum β-hCG essentially excludes both intrauterine and ectopic pregnancy 1
• Elevated β-hCG in a non-pregnant patient may indicate miscarriage, ectopic pregnancy, pituitary production, paraneoplastic production, or gestational trophoblastic disease 1
• After clinical assessment suggesting complete miscarriage, 6% of women with empty uterus on ultrasound will have ectopic pregnancy 5
• Critical pitfall: A known pre-existing intrauterine pregnancy can be falsely reassuring and delay diagnosis of concurrent ectopic pregnancy 4

2. Heterotopic Pregnancy

This diagnosis must be considered in patients with pelvic pain following miscarriage or in the context of known viable intrauterine pregnancy. 4

• Represents concurrent intrauterine and ectopic pregnancy 4
• Increasing in prevalence and represents a time-critical diagnosis with potential for adverse outcome 4
• Can present as worsening pelvic pain after initial diagnosis of miscarriage 4
• Requires combination of clinical assessment, serial β-hCG levels, point-of-care ultrasound, and formal transvaginal ultrasound to explicitly exclude 4

3. Gestational Trophoblastic Disease

This includes hydatidiform moles (complete or partial) where abnormal trophoblastic tissue grows in the uterus. 3

• Must be excluded through histopathologic examination of tissue to confirm intrauterine pregnancy 3
• Can present with elevated β-hCG in non-pregnant patient 1
• Requires serial hCG monitoring until levels return to non-pregnant state 3

4. Classification of Miscarriage Type

Distinguishing between incomplete and complete miscarriage is essential as management differs significantly. 2, 3, 5

Incomplete Miscarriage

• Presence of intracavitary tissue with internal vascularity or persistent gestational sac following pregnancy loss 3
• After clinical assessment suggesting complete miscarriage, 45% of women will have retained tissue on ultrasound 5
• Ultrasound findings include retained products of conception with blood flow 2

Complete Miscarriage

• No persistent gestational sac or intracavitary tissue following pregnancy loss 3
• Cannot be diagnosed with transvaginal ultrasound alone without serial biochemical confirmation unless intrauterine gestational sac was previously visualized 5

Missed Miscarriage (Embryonic/Fetal Demise)

• Embryonic or fetal death without spontaneous expulsion 2, 3
• Diagnostic criteria: crown-rump length ≥7 mm without cardiac activity, mean sac diameter ≥25 mm without embryo, or absence of embryo ≥14 days after visualization of gestational sac 2, 3
• Active evacuation recommended due to increased risk of intrauterine infection, coagulopathy, and maternal sepsis with prolonged retention 2

Anembryonic Pregnancy

• Gestational sac measuring 25 mm or larger without embryo, or absence of embryo on serial examinations at discriminatory time intervals 3

5. Cervical Ectopic Pregnancy or Cesarean Scar Ectopic Pregnancy

Low-lying gestational sac can mimic miscarriage but represents high-risk ectopic pregnancy requiring different management. 6

• Overlapping imaging features between miscarriage of low-lying gestational sac and cervical ectopic pregnancy 6
• Misdiagnosis can lead to significant maternal morbidity, including massive hemorrhage (up to 2000 mL) requiring transfusion 6
• High-risk features include trophoblastic extension into cervical canal with minimally vascular tissue distending upper cervical canal 6
• Cervical stroma should be clearly visualized circumferential to any distending tissue 6
• Critical pitfall: Dilatation and curettage of cervical ectopic can result in brisk cervical bleeding and life-threatening hemorrhage 6
• Maintain high index of suspicion even when majority of women have no risk factors for ectopic pregnancy 6
• These cases should be recommended for surgical management with appropriate precautions 6

Additional Differential Considerations in Acute Pelvic Pain Context

When miscarriage presents with acute pelvic pain, broader gynecological and non-gynecological etiologies must be considered: 1

• Gynecological causes: hemorrhagic ovarian cysts, pelvic inflammatory disease, ovarian torsion, placental abruption (if later gestation) 1
• Non-gynecological causes: appendicitis, inflammatory bowel disease, infectious enteritis, diverticulitis, urinary tract calculi, pyelonephritis, pelvic thrombophlebitis 1

Diagnostic Approach

Thorough clinical evaluation correlating history, physical examination, and laboratory testing is required before choosing radiologic examination. 1

• Serum β-hCG test is essential when premenopausal patient presents with acute pelvic pain 1
• Transvaginal ultrasound is the diagnostic method of choice 2
• Evidence-based criteria must be employed for diagnosis of delayed and incomplete miscarriage 5
• Serial β-hCG monitoring until return to non-pregnant state 3
• Histopathologic examination of tissue to confirm intrauterine pregnancy and rule out gestational trophoblastic disease 3