In a 33-year-old woman with three consecutive early miscarriages, what is the most common cause of recurrent early pregnancy loss?

Most Common Cause of Recurrent Early Pregnancy Loss

Chromosomal abnormalities (Option C) are the most common cause of recurrent early pregnancy loss, accounting for 50-60% of early miscarriages. 1, 2

Understanding the Causes by Frequency

Chromosomal Abnormalities (Most Common)

• Over 50% of early pregnancy losses are attributed to chromosomal abnormalities, making this the predominant cause 2, 3
• These include both de novo nondisjunctional events (most common) and balanced parental translocations (small but important percentage) 2
• Fetal chromosomal defects are non-modifiable factors that would not be affected by any intervention 4
• Parental karyotyping should be performed on both partners to identify chromosomal rearrangements 1
• Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) 3
• In your patient's case with three consecutive losses and now a sixth-week pregnancy without fetal heartbeat, chromosomal abnormalities remain the most likely underlying cause 2, 5

Antiphospholipid Syndrome (Important but Less Common)

• The American College of Chest Physicians recommends screening for antiphospholipid antibodies in all patients with recurrent early pregnancy loss (three or more miscarriages before 10 weeks) 1
• Women with confirmed antiphospholipid syndrome should receive treatment with unfractionated heparin or LMWH plus low-dose aspirin 1
• Testing for lupus anticoagulant and anticardiolipin antibodies should be offered prior to pregnancy 3
• While clinically significant, this accounts for a smaller proportion of cases compared to chromosomal abnormalities 3

Cervical Incompetence (Not Relevant for Early Losses)

• Cervical incompetence does NOT cause early first-trimester pregnancy losses 1, 6
• This condition causes second-trimester losses through premature cervical dilation 6
• Your patient's losses are all early (before 10 weeks based on the current 6-week presentation), making cervical incompetence an incorrect answer 1
• Uterine cavity abnormalities affecting up to 38% of women with recurrent miscarriage are structural issues, but cervical incompetence specifically manifests later in pregnancy 4

Recommended Evaluation for Your Patient

Essential Initial Testing

• Screen for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, anti-β2-glycoprotein I) 1, 3
• Parental karyotyping on both partners to identify chromosomal rearrangements 1, 3
• Thyroid function tests (TSH, free T4) and thyroid peroxidase antibodies 1, 3
• Transvaginal ultrasound to assess for uterine cavity abnormalities 1, 7

Male Partner Evaluation

• Evaluate the male partner with consideration for karyotype testing 1, 6
• Consider sperm DNA fragmentation testing, as increasing evidence links elevated fragmentation with recurrent pregnancy loss 1, 6

What NOT to Test

• Do NOT routinely screen for inherited thrombophilias (factor V Leiden, prothrombin G20210A mutation, protein C/S deficiency) in women with recurrent early pregnancy loss 1, 3
• Routine immunological screening (HLA, cytokine, natural killer cell tests) is not recommended outside research contexts 3

Common Pitfalls to Avoid

• Do not assume cervical incompetence causes early losses—this is a second-trimester issue only 6
• Do not over-test for thrombophilias—only antiphospholipid antibodies are recommended for early recurrent loss 1, 3
• Do not discourage physical activity—regular exercise within guidelines is safe and may benefit modifiable risk factors like insulin resistance and obesity 4, 1, 6
• Do not prescribe aspirin and/or heparin for unexplained recurrent miscarriage—these are only indicated for confirmed antiphospholipid syndrome 3