What are the diagnostic and treatment options for recurrent miscarriages?

Diagnostic and Treatment Options for Recurrent Miscarriages

Women with recurrent miscarriages should undergo a comprehensive evaluation for underlying prothrombotic states, genetic abnormalities, uterine anomalies, and hormonal disorders, with treatment tailored to the identified cause. Recurrent pregnancy loss, defined as two or more spontaneous pregnancy losses, affects 2-5% of couples and requires systematic investigation to identify treatable causes.

Diagnostic Evaluation

1. Thrombophilia Screening

• Blood coagulation tests: Screening for antiphospholipid syndrome (APS), which accounts for approximately 67% of procoagulant defects in recurrent miscarriage 1
  • Include testing for anticardiolipin antibodies, lupus anticoagulant, and antiphospholipid subgroup antibodies (antiphosphatidyl-serine, -inositol, -ethanolamine, -choline, -glycerol)
• Additional thrombophilia testing:
  • Sticky platelet syndrome (21% of cases)
  • Tissue plasminogen activator (TPA) deficiency (9%)
  • Factor V Leiden mutation (7%)
  • Plasminogen activator inhibitor-1 (PAI-1) levels
  • Protein S deficiency (5%)
  • Lipoprotein(a) levels
  • Antithrombin deficiency (2%)
  • Protein C deficiency (1%)

2. Genetic Evaluation

• Parental karyotyping: To identify chromosomal translocations or other abnormalities 2
• Thromboelastography (TEG): Can identify hypercoagulable states in women with recurrent miscarriages 3
  • Maximum amplitude (MA) ≥64 mm has 68% sensitivity and 82% specificity for predicting subsequent miscarriage

3. Anatomical Assessment

• Transvaginal ultrasound: First-line imaging to evaluate uterine structure 3
• Sonohysterography (SIS): For better visualization of intrauterine abnormalities
• Hysterosalpingography or 3D ultrasound: To evaluate uterine cavity shape and detect anomalies

4. Hormonal Evaluation

• Thyroid function tests
• Prolactin levels
• Evaluation for polycystic ovary syndrome
• Assessment for luteal phase deficiency (though controversial)

Treatment Options

1. Antiphospholipid Syndrome and Thrombophilias

• Low-dose aspirin (81 mg/day): Started preconception 1
• Unfractionated heparin: 5,000 units every 12 hours, added immediately post-conception and continued to term 1
  • This combination therapy has shown a 98% success rate in achieving normal term delivery in women with procoagulant defects

2. Genetic Abnormalities

• Genetic counseling: For couples with chromosomal abnormalities
• Preimplantation genetic testing: May be considered in selected cases of unexplained recurrent losses, though evidence is limited 4

3. Uterine Anomalies

• Surgical correction: For significant structural abnormalities (septate uterus, submucosal fibroids, intrauterine adhesions) 4

4. Unexplained Recurrent Miscarriage

• Supportive care and monitoring: Regular early pregnancy monitoring with serial ultrasound examinations 5
• Empiric treatments: Often used despite limited evidence
  • Progesterone supplementation
  • Low-dose aspirin
  • Immunomodulatory treatments

5. Special Considerations for Dysfibrinogenemia

For women with dysfibrinogenemia and recurrent pregnancy loss 3:

• Fibrinogen replacement: Target fibrinogen level ≥1 g/L in cases of recurrent miscarriages
• During pregnancy: Maintain fibrinogen level ≥1.5 g/L in case of vaginal bleeding
• For pregnancy loss management: Surgical management with fibrinogen replacement (target ≥1.5 g/L for 3 days) and tranexamic acid

Prognosis and Follow-up

• Overall prognosis: Generally good, with most couples eventually achieving a successful pregnancy 4
• Psychological support: Essential component of management due to significant emotional toll of recurrent losses
• Monitoring in subsequent pregnancies: Early and regular ultrasound monitoring with hCG level assessment

Common Pitfalls to Avoid

1. Incomplete evaluation: Failing to screen for all potential causes, particularly thrombophilias beyond standard antiphospholipid antibodies
2. Premature empiric treatment: Implementing unproven therapies without thorough investigation
3. Overlooking psychological impact: Neglecting the emotional aspects of recurrent pregnancy loss
4. Relying solely on standard tests: Missing subgroup antiphospholipid antibodies that may be present in 24% of cases without standard anticardiolipin antibodies 1
5. Delayed diagnosis: Waiting for three or more losses before initiating evaluation, when investigation after two losses may be appropriate 6

By systematically evaluating and addressing the underlying causes of recurrent miscarriage, clinicians can significantly improve outcomes for affected couples.