What is the likely cause of recurrent early miscarriages in a patient with a history of three previous early pregnancy losses, now presenting with a non-viable pregnancy at 6 weeks?

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Antiphospholipid Syndrome as the Likely Cause

Yes, antiphospholipid syndrome (APS) is a highly probable cause of this patient's recurrent early pregnancy losses and should be tested immediately. The American College of Chest Physicians explicitly recommends screening for antiphospholipid antibodies (APLAs) in women with three or more miscarriages before 10 weeks of gestation 1, 2.

Why APS is the Priority Diagnosis

  • This patient meets the exact clinical criteria for mandatory APLA screening: three early pregnancy losses (all before 10 weeks) with now a fourth non-viable pregnancy at 6 weeks 1.

  • APS is one of only four universally accepted causes of recurrent pregnancy loss, alongside parental chromosomal abnormalities, uterine malformations, and cervical incompetence 3.

  • APS has proven effective treatment with heparin and low-dose aspirin—the only intervention for recurrent pregnancy loss established through properly controlled trials 3.

  • The prevalence is significant: approximately 14% of women with recurrent miscarriage test positive for circulating antiphospholipid antibodies 4.

Complete Diagnostic Workup Required

While APS is highly likely, a comprehensive evaluation should identify all potential causes:

Mandatory Testing (Grade 1B Evidence)

  • Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, anti-β2-glycoprotein I antibodies) 1, 2
  • Parental karyotyping to detect chromosomal rearrangements (present in 3.6% of couples with recurrent loss) 4

Additional Considerations

  • Uterine anatomical evaluation via transvaginal ultrasound, sonohysterography, or hysterosalpingography to identify Müllerian anomalies or intrauterine synechiae 5
  • Endocrine assessment including evaluation for polycystic ovary syndrome (found in 56% of women with recurrent loss) and LH hypersecretion 4
  • Inherited thrombophilias are NOT routinely recommended for screening in women with pregnancy complications alone (Grade 2C) 1

Critical Management Points

If APS is confirmed, combined therapy with aspirin and heparin is the evidence-based treatment that significantly improves live birth rates 2, 3.

Important caveat: Even with complete evaluation, over 50% of recurrent pregnancy loss cases remain unexplained 3, 6. However, these patients should be counseled that subsequent pregnancies have up to a 70% chance of success without treatment 3.

Do not use antithrombotic prophylaxis in women with two or more miscarriages but without APLA or thrombophilia (Grade 1B recommendation against) 1.

Why Not Other Thrombophilias First?

The guidelines specifically recommend against screening for inherited thrombophilias (Factor V Leiden, prothrombin mutations, protein C/S deficiency) in women with pregnancy complications alone 1. These should only be tested if there is a personal or family history of venous thromboembolism 2, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Detection of Thrombophilia in Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Recurrent pregnancy loss: summary and clinical recommendations.

Seminars in reproductive medicine, 2000

Guideline

Genetic and Anatomical Factors in Recurrent Pregnancy Loss

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Recurrent pregnancy loss.

Nature reviews. Disease primers, 2020

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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