What lab investigations should be done for a 22-year-old female (yof) with repeated miscarriages?

Laboratory Investigations for Recurrent Miscarriages in a 22-Year-Old Female

The essential laboratory investigations for a 22-year-old female with recurrent miscarriages should include testing for antiphospholipid antibodies, thrombophilia, thyroid function, and a transvaginal ultrasound examination. These investigations target the most common and treatable causes of recurrent pregnancy loss.

First-Line Investigations

Immunological/Thrombophilia Testing:

• Antiphospholipid antibodies panel:
  • Lupus anticoagulant
  • Anticardiolipin antibodies
  • Anti-β2 glycoprotein-I antibodies 1
• Coagulation profile:
  • Sticky platelet syndrome testing
  • Factor V Leiden mutation
  • Protein S levels
  • Protein C levels
  • Antithrombin levels
  • Tissue plasminogen activator (TPA) levels
  • Plasminogen activator inhibitor-1 (PAI-1) levels 2

Endocrine Evaluation:

• Thyroid function tests (TSH, free T4) 1
• Fasting glucose and HbA1c

Imaging:

• Transvaginal ultrasound to assess uterine anatomy 1
  • Evaluate for congenital uterine anomalies (septate uterus, bicornuate uterus)
  • Rule out uterine fibroids or polyps

Genetic Testing:

• Karyotyping of both partners 3
• Consider preimplantation genetic testing in future pregnancies if indicated

Rationale for Testing Selection

Antiphospholipid syndrome is found in approximately 14% of women with recurrent miscarriages 3, and up to 67% when including subgroup antibodies 2. This condition is highly treatable with aspirin and heparin therapy, with success rates approaching 98% when properly identified and treated 2.

Thrombophilia testing is crucial as blood coagulation protein/platelet defects account for approximately 55% of recurrent miscarriages 2. These include Factor V Leiden mutation (7%), protein S deficiency (5%), and other coagulation abnormalities that can lead to placental vascular occlusion.

Thyroid dysfunction, particularly subclinical hypothyroidism, is an important treatable cause of recurrent pregnancy loss. Treatment with levothyroxine in women with subclinical hypothyroidism can significantly improve pregnancy outcomes 1.

Uterine anatomical abnormalities are detected in a significant proportion of women with recurrent miscarriages. Hysterosalpingography or transvaginal ultrasound can identify structural issues such as uterus bicornis or uterus septus that may require surgical correction 4.

Clinical Significance

Research indicates that when patients are properly screened and treated for identified causes, success rates for subsequent pregnancies are high. For example, in women with thrombotic defects who received preconception aspirin and postconception heparin, studies have shown a 100% success rate in achieving normal-term deliveries 5.

It's worth noting that polycystic ovarian morphology is found in up to 56% of women with recurrent miscarriages, with 58% of these women demonstrating LH hypersecretion 3. This suggests that hormonal evaluation may be beneficial in selected cases.

Pitfalls to Avoid

1. Incomplete antibody testing: Testing only for anticardiolipin antibodies and lupus anticoagulant may miss 24% of antiphospholipid syndrome cases that only have subgroup antibodies 2.

2. Premature cessation of investigation: Even after identifying one cause, continue with the complete panel as multiple factors may coexist. Studies show that 38% of patients had more than one defect 2.

3. Delayed testing: Begin investigations after two consecutive miscarriages rather than waiting for three, as earlier intervention may improve outcomes 5.

By systematically addressing these key areas of investigation, the underlying cause of recurrent miscarriages can be identified in more than 50% of cases, allowing for targeted treatment and improved pregnancy outcomes 3.