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

Recurrent Miscarriage Workup

The essential workup for recurrent miscarriage should include antiphospholipid antibody testing, parental karyotyping, thyroid function tests, and transvaginal ultrasound assessment of uterine anatomy. 1, 2

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

Recommended Initial Investigations

Laboratory Testing

1. Antiphospholipid antibody screening:

   • Lupus anticoagulant
   • Anticardiolipin antibodies
   • These tests are essential as antiphospholipid syndrome is a treatable cause of recurrent miscarriage 1, 2

2. Thyroid function tests:

   • TSH, free T4
   • Thyroid peroxidase (TPO) antibodies
   • Important as subclinical hypothyroidism is associated with miscarriage 1, 2

3. Complete blood count:

   • To rule out underlying hematological disorders 1

Genetic Evaluation

1. Parental karyotyping:

   • Particularly indicated when pregnancy tissue shows an unbalanced structural chromosomal abnormality
   • Should be offered when pregnancy tissue testing is unsuccessful or unavailable 2

2. Cytogenetic analysis of pregnancy tissue:

   • Should be performed on the third and subsequent miscarriage(s)
   • Also recommended for any second trimester miscarriage 2

Structural Assessment

1. Transvaginal ultrasound:
   • 3D ultrasound is preferred for assessment of congenital uterine anomalies
   • Can identify structural causes such as uterine septum, fibroids, or polyps 1, 2

Specialized Testing (Based on Clinical Indication)

Thrombophilia Testing

• Not routinely recommended for all patients
• Consider testing for Factor V Leiden, prothrombin gene mutation, and protein S deficiency in women with second trimester losses 2
• Routine testing for protein C, antithrombin deficiency, and MTHFR mutation is not recommended 2

Tests to Avoid (Not Recommended)

• Routine immunological screening (HLA, cytokine, natural killer cell tests)
• Routine infection screening
• Sperm DNA testing
• These tests should only be performed in research contexts 2

Management Based on Findings

Antiphospholipid Syndrome

• If diagnosed, treatment with low-dose aspirin (81 mg daily) preconception and unfractionated heparin (5000 U every 12 hours) immediately post-conception, continuing to term 1
• Success rate with this approach is approximately 98% 1, 3

Thyroid Dysfunction

• Levothyroxine supplementation for clinical hypothyroidism
• Note: Thyroxine supplementation is 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
• Hysteroscopic resection for submucosal fibroids or polyps if identified 1

Unexplained Recurrent Miscarriage

• Supportive care in a dedicated recurrent miscarriage clinic 2
• Consider progesterone supplementation (400 mg micronized vaginal progesterone twice daily) for women who present with bleeding in early pregnancy, continuing until 16 weeks gestation 2
• Avoid empirical use of aspirin and/or heparin in unexplained cases 2

Additional Recommendations

• Advise maintaining BMI between 19-25 kg/m²
• Recommend smoking cessation
• Limit alcohol consumption
• Limit caffeine to less than 200 mg/day 2

Monitoring in Subsequent Pregnancies

• Regular monitoring with serial ultrasonography in the first trimester
• Psychological support and reassurance throughout pregnancy 1
• High-risk obstetric care with screening for preterm birth, fetal growth restriction, and stillbirth risks 1

By following this systematic approach to recurrent miscarriage evaluation, approximately 50-60% of cases will have an identifiable and potentially treatable cause, with excellent outcomes when appropriate management is implemented.