What is the recommended workup for a patient with recurrent miscarriage?

Recommended Workup for Recurrent Miscarriage

The recommended workup for recurrent miscarriage should include antiphospholipid antibody testing, parental karyotype analysis, thyroid function tests, and transvaginal ultrasound assessment of uterine anatomy as essential components. 1

Definition and Prevalence

• Recurrent miscarriage is defined as the loss of three or more consecutive pregnancies before 24 weeks gestation
• Affects approximately 1% of women of reproductive age
• Clinical discretion may be used to initiate evaluation after two first-trimester miscarriages if pathological causes are suspected 2

Essential Investigations

1. Medical History Assessment

• Detailed obstetric history including previous pregnancy outcomes
• Family history of miscarriages
• Environmental toxin exposure
• BMI assessment (recommend maintaining BMI between 19-25 kg/m²) 1, 2
• Lifestyle factors (smoking, alcohol, caffeine intake)

2. Laboratory Testing

• Antiphospholipid antibody testing 1, 2

  • Lupus anticoagulant
  • Anticardiolipin antibodies
  • Consider testing for antiphosphatidyl-serine, -inositol, -ethanolamine, -choline, -glycerol antibodies in select cases 3

• Thyroid function tests 1, 2

  • TSH
  • Free T4
  • Thyroid peroxidase (TPO) antibodies

• Complete blood count

3. Genetic Evaluation

• Cytogenetic analysis of pregnancy tissue from the third and subsequent miscarriage(s) 2
• Parental peripheral blood karyotyping when pregnancy tissue shows unbalanced structural chromosomal abnormality or when no tissue is available for testing 2

4. Structural Assessment

• Transvaginal ultrasound (preferably 3D) to assess for uterine anomalies 1, 2
• Consider hysterosalpingogram if 3D ultrasound is not available

5. Selective Testing Based on Clinical Presentation

• Thrombophilia testing in select cases:
  • For women with second-trimester miscarriages: Factor V Leiden, prothrombin gene mutation, protein S deficiency 2
  • Not routinely recommended: protein C, antithrombin deficiency, and MTHFR mutation testing 2

What NOT to Include in Routine Workup

• Immunological screening (HLA, cytokine, natural killer cell tests) outside research context 2
• Infection screening outside research context 2
• Sperm DNA testing outside research context 2
• Routine testing for inherited thrombophilias in all cases 2

Management Based on Findings

Antiphospholipid Syndrome

• Low-dose aspirin (81 mg daily) preconception and unfractionated heparin (5000 U every 12 hours) immediately post-conception, continuing to term 1, 3

Thyroid Dysfunction

• Levothyroxine for clinical hypothyroidism to normalize TSH levels 1
• Not routinely recommended for euthyroid women with TPO antibodies 2

Structural Abnormalities

• Consider resection of uterine septum for women with recurrent first or second-trimester miscarriage 2

Unexplained Recurrent Miscarriage

• Consider progesterone supplementation (400 mg micronized vaginal progesterone twice daily) for women who present with bleeding in early pregnancy until 16 weeks gestation 2
• Do not routinely offer aspirin and/or heparin 2

Supportive Care

• Referral to a dedicated recurrent miscarriage clinic 2
• Psychological support and counseling 1
• Regular monitoring with serial ultrasonography in the first trimester of subsequent pregnancies 4
• High-risk obstetric care in future pregnancies with screening for preterm birth, fetal growth restriction, and stillbirth risks 1

Common Pitfalls to Avoid

• Initiating empiric treatments without confirmed diagnoses
• Overlooking psychological impact of recurrent losses
• Failing to screen for antiphospholipid antibodies, which account for a significant percentage of treatable causes
• Missing subclinical thyroid dysfunction
• Not providing appropriate counseling about prognosis (generally good with most couples eventually achieving successful pregnancy) 1