Causes of Recurrent Pregnancy Loss
Recurrent pregnancy loss (RPL) is multifactorial and causes can be grouped into several categories. Below are the common categories with typical findings and suggested tests.
1. Genetic Causes
- Parental chromosomal abnormalities (for example, balanced translocations)
- Embryonic aneuploidy — often age-related
Tests: Karyotyping (both partners), PGT (preimplantation genetic testing) in IVF
2. Anatomical Causes
- Uterine anomalies: septate uterus, fibroids, intrauterine adhesions
- Cervical insufficiency
Tests: Sonohysterography (saline infusion sonography), HSG, pelvic MRI, 3D ultrasound
3. Thrombophilic Disorders
- Inherited thrombophilias (e.g., Factor V Leiden)
- Acquired thrombophilias (e.g., antiphospholipid syndrome)
Tests: Thrombophilia panel, lupus anticoagulant, anticardiolipin antibodies
4. Endocrine Causes
- Thyroid disorders (especially hypothyroidism, presence of TPO antibodies)
- Uncontrolled diabetes
- Polycystic ovary syndrome (PCOS) with insulin resistance and hyperandrogenism
- Luteal phase defect (controversial as a formal diagnosis)
Tests: TSH, TPO antibodies, HbA1c, serum progesterone, AMH
5. Immunologic Factors
- Antiphospholipid syndrome (APS) — the only well-established immune-related cause
- Other immune markers (e.g., NK cell testing, HLA matching) remain controversial and are not routinely recommended
6. Infections
- Chronic endometritis (persistent inflammation of the uterine lining)
- Sexually transmitted infections or TORCH infections (rare causes)
Tests: Endometrial biopsy with culture/PCR, targeted STI testing
7. Lifestyle & Environmental Factors
- Smoking, excessive alcohol use, obesity
- High caffeine intake
- Environmental exposures (for example, pesticides or other toxins)