What is the initial generalist workup for recurrent pregnancy loss?

Initial Generalist Workup for Recurrent Pregnancy Loss

The initial generalist workup for recurrent pregnancy loss (RPL) should begin after two consecutive pregnancy losses, as evidence shows no significant difference in the prevalence of abnormalities between patients with two versus three losses for key conditions like uterine abnormalities and antiphospholipid syndrome. 1

Definition and Prevalence

RPL affects approximately 5% of couples trying to conceive 2 and is defined as:

• Two or more consecutive pregnancy losses before 20-24 weeks of gestation 3, 2
• Includes both embryonic and fetal losses

Initial Diagnostic Workup Algorithm

1. Comprehensive Medical History

• Reproductive history: Previous pregnancy outcomes, gestational age at losses 4
• Family history: Birth defects, genetic disorders, recurrent miscarriages 4
• Medical conditions: Autoimmune disorders, thyroid disease, diabetes
• Lifestyle factors: Smoking, alcohol consumption, BMI, environmental exposures 4

2. Essential Laboratory Testing

• Parental karyotyping: To identify chromosomal abnormalities 4
• Antiphospholipid antibody panel: 2
  • Lupus anticoagulant
  • Anticardiolipin antibodies (IgG and IgM)
  • Anti-β2 glycoprotein-I antibodies (IgG and IgM)
• Thyroid function tests: TSH, free T4 4
• Complete blood count: To evaluate for anemia or other hematologic abnormalities
• Blood type and antibody screen

3. Anatomical Assessment

• Transvaginal ultrasound: To evaluate uterine morphology and ovarian structure 4
• Hysterosalpingography or sonohysterography: To assess uterine cavity and tubal patency 4
• Consider MRI: For better characterization of complex uterine anomalies if suspected on ultrasound

4. Additional Testing Based on Clinical Presentation

• Thrombophilia testing: Consider in cases with family history of thrombosis or late pregnancy losses
• Glucose tolerance testing: If PCOS or metabolic syndrome is suspected
• Sperm DNA fragmentation testing: In couples with failed ART cycles 4

Common Causes of RPL

1. Genetic factors (chromosomal abnormalities):

   • Parental chromosomal rearrangements account for 2-5% of RPL cases 5

2. Uterine anatomical abnormalities:

   • Congenital anomalies (septate uterus, bicornuate uterus)
   • Acquired abnormalities (fibroids, polyps, adhesions) 4

3. Antiphospholipid syndrome:

   • Present in 5-20% of women with RPL 5

4. Endocrine disorders:

   • Thyroid dysfunction
   • Uncontrolled diabetes
   • PCOS 4

Important Considerations

• Timing matters: Begin evaluation after two losses in women over 35, or after three losses in younger women 4
• Most cases remain unexplained: Up to 50-75% of RPL cases have no identifiable cause despite thorough evaluation 6, 5
• Prognosis is generally good: Even without treatment, subsequent pregnancies have up to a 70% chance of success 5

Pitfalls to Avoid

1. Delaying evaluation: Don't wait for three losses before initiating workup, especially in women over 35 1
2. Overdiagnosis: Be cautious about attributing RPL to factors with weak associations
3. Unnecessary testing: Avoid extensive thrombophilia panels without specific indications
4. Neglecting psychological impact: RPL causes significant emotional distress that requires acknowledgment and support 3
5. Recommending unproven treatments: Many proposed treatments for unexplained RPL lack evidence of efficacy 5

By following this systematic approach to the evaluation of recurrent pregnancy loss, clinicians can identify treatable causes while providing appropriate counseling and support to affected couples.