What is the management approach for recurrent pregnancy loss?

Management of Recurrent Pregnancy Loss

The management of recurrent pregnancy loss should focus on identifying and treating specific underlying causes, with comprehensive evaluation of genetic, anatomical, endocrine, and immunological factors to improve outcomes.

Evaluation of Potential Causes

Anatomical Factors

• Uterine cavity abnormalities, including Müllerian anomalies, intrauterine synechiae, and cervical incompetence, should be evaluated as they can interfere with implantation and cause recurrent pregnancy loss 1
• Recommended imaging studies include:
  • Transvaginal ultrasound (TVUS) as an initial screening tool 2, 1
  • Sonohysterography (SIS) for better assessment of the uterine cavity, particularly for detecting intrauterine adhesions, endometrial polyps, and leiomyomas 2, 1
  • Three-dimensional SIS has shown 100% accuracy in classification of uterine anomalies when compared with hysteroscopy 2

Genetic Factors

• Parental karyotyping should be considered, especially in couples with multiple losses 3, 4
• Genetic testing of miscarriage tissue with 24-chromosome microarray can provide valuable information about the cause of pregnancy loss 5
• Some patients with recurrent complete hydatidiform moles may have mutations in NLRP7 and KHDC3L genes 1, 6

Endocrine Factors

• Evaluation should include:
  • Thyroid function tests (TSH) 1
  • Assessment for polycystic ovary syndrome (PCOS), which is associated with higher rates of pregnancy loss 1
  • Evaluation of ovarian reserve, as diminished reserve may be associated with increased miscarriage risk 1, 6
  • Screening for gestational diabetes in current pregnancies 1

Thrombophilias

• Testing for antiphospholipid syndrome is recommended as it is an established cause of recurrent pregnancy loss 3, 4
• Evaluation for inherited thrombophilias may be considered, particularly in women with later pregnancy losses 1, 6

Male Factor Evaluation

• Male partners should be evaluated in couples with two or more pregnancy losses 1
• Consider karyotype and sperm DNA fragmentation testing 1

Management Strategies

Evidence-Based Treatments

For Anatomical Factors

• Surgical correction of uterine anomalies when appropriate 3
• Cervical cerclage for cervical incompetence 7

For Antiphospholipid Syndrome

• Combination of low-dose aspirin and heparin therapy 3, 4

For Endocrine Disorders

• Calcium and vitamin D supplementation for women with 22q11.2 deletion syndrome 2
• Optimization of thyroid function 1
• Regular monitoring for gestational diabetes 2

For Thrombophilias

• Women with homozygous factor V Leiden or prothrombin 20210A mutation with positive family history for venous thromboembolism should receive antepartum prophylaxis with prophylactic or intermediate-dose low molecular weight heparin 1, 6

Management of Unexplained RPL

• Despite thorough evaluation, approximately 50% of RPL cases remain unexplained 3, 4
• Supportive care is essential, as the prognosis is generally good with 60-80% chance of successful pregnancy even without intervention 8
• Early and regular ultrasound monitoring in subsequent pregnancies 1
• Psychological support for affected couples 3

Lifestyle Modifications

• Regular physical activity within guidelines is unlikely to increase the risk of pregnancy loss and may benefit factors that increase miscarriage risk, such as insulin resistance and obesity 9
• Avoid smoking, alcohol, and recreational drugs 2
• Standard preconception folate/vitamin supplementation 2
• Maintain good nutrition and physical activity 2

Management Algorithm for Current Pregnancy with History of RPL

1. Confirm viable intrauterine pregnancy with early ultrasound 1
2. Regular prenatal visits with serial ultrasound monitoring 1
3. Monitor for and promptly treat any endocrine conditions (thyroid dysfunction, gestational diabetes) 2, 1
4. Implement appropriate treatment based on identified cause:
   • Antiphospholipid syndrome: aspirin and heparin 3
   • Thrombophilias: consider prophylactic anticoagulation based on specific risk factors 1, 6
   • Endocrine disorders: hormone supplementation as needed 1
5. Consider delivery at a tertiary care center for high-risk cases 2

Important Caveats and Pitfalls

• Avoid unproven empirical treatments that lack evidence-based support 5
• There is no evidence supporting the use of low-molecular-weight heparin for the sole indication of prevention of recurrent fetal growth restriction 1
• Sildenafil and activity restriction are not recommended for in utero treatment of fetal growth restriction 1
• Be cautious about overdiagnosis of thrombophilias and unnecessary anticoagulation 5
• Recognize that multiple pregnancy losses can have significant psychological impact on couples 3