Recurrent pregnancy loss: causes and next steps

Understanding Recurrent Miscarriage

Experiencing repeated pregnancy loss is emotionally devastating and physically exhausting. Couples are often told "everything looked normal on ultrasound" without receiving an explanation of why the pregnancy stopped developing.

Clinical guidelines from ESHRE and ASRM urge thorough diagnostic evaluation after two clinical pregnancy losses. When investigated systematically, an identifiable underlying etiology is uncovered in up to 70% of couples.

The Five Diagnostic Pillars of RPL Workup

• Embryonic & Parental Cytogenetics:
• - In 3% to 5% of couples, one partner carries a balanced reciprocal or Robertsonian chromosomal translocation. While the parent is completely healthy, their gametes produce unbalanced genetic arrangements in embryos.
• Anatomical Uterine Cavity Assessment:
• - High-resolution 3D transvaginal ultrasound or diagnostic office hysteroscopy detects congenital uterine septa, intracavitary fibroids, endometrial polyps, or intrauterine adhesions that restrict vascular placental growth.
• Autoimmune & Thrombophilic Disorders:
• - Antiphospholipid Syndrome (APS): Lupus anticoagulant, anticardiolipin antibodies, and anti-beta-2-glycoprotein antibodies cause micro-thromboses in developing placental vessels.
• - Inherited Thrombophilias: Factor V Leiden, Prothrombin gene mutation, and Protein C/S deficiencies.
• Endocrine Factors:
• - Subclinical hypothyroidism (TSH should be optimized <2.5 mIU/L), poorly controlled diabetes (HbA1c), elevated prolactin, and severe luteal phase progesterone deficiency.
• Paternal Factors:
• - Elevated Sperm DNA Fragmentation Index (>30%) causes late paternal genomic breakdown during first-trimester organogenesis.

Evidence-Based Treatments

• Aspirin & Low Molecular Weight Heparin (LMWH): The gold-standard therapy for Antiphospholipid Syndrome, reducing miscarriage risk by over 50%.
• Surgical Hysteroscopic Metroplasty: Resecting a congenital uterine septum restores normal cavity vascularity.
• PGT-A Screening with IVF: For couples with balanced translocations or age-related aneuploidies, pre-transfer chromosomal screening prevents non-viable conceptions.