Recurrent Pregnancy Loss — When and What to Investigate

Two or more consecutive pregnancy losses fits the contemporary definition of recurrent pregnancy loss (RPL). This page explains the systematic investigation, what is treatable, and how to plan future pregnancies after loss.

1. Definitions

Recurrent pregnancy loss (RPL): two or more clinical pregnancy losses (gestational sac confirmed on ultrasound or histology) before 24 weeks. Earlier definitions required 3 losses; contemporary practice investigates after 2. Biochemical losses (positive test but no sac) are not typically included.

2. Causes, the systematic workup

Chromosomal: parental karyotype, products of conception cytogenetics in losses. Anatomic: hysteroscopy for cavity, transvaginal ultrasound, 3D ultrasound, MRI for selected cases. Endocrine: TSH, thyroid antibodies, HbA1c, prolactin, PCOS evaluation. Immunological: antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, beta-2 glycoprotein I). Thrombophilia: selectively in personal/family history of thrombosis. Endometrial: chronic endometritis (CD138 immunohistochemistry).

3. Antiphospholipid syndrome, the most treatable cause

Identified by persistent positive antiphospholipid antibodies on two occasions 12 weeks apart, plus clinical criteria including pregnancy loss. Treatment: low-dose aspirin plus low-molecular-weight heparin (enoxaparin) from positive pregnancy test through pregnancy. Improves live birth rate from approximately 30% to 70%.

4. Anatomic causes, uterine factors

Septate uterus (most treatable): hysteroscopic septum resection significantly improves outcomes. Submucous fibroids: hysteroscopic resection. Polyps: hysteroscopic removal. Intrauterine adhesions: lysis with prevention of recurrence. Congenital bicornuate or unicornuate uterus: usually not surgically corrected.

5. Genetic factors

Parental balanced translocations in 3–5% of RPL — karyotype both partners. Products of conception cytogenetics in losses identifies if cause was chromosomal (most cases) vs not (warrants more workup). PGT-A in subsequent IVF cycles for translocation carriers or recurrent aneuploidy.

6. Endocrine and metabolic

Hypothyroidism, even subclinical (TSH 2.5–4) — should be treated. Thyroid antibodies. Diabetes optimisation. PCOS evaluation. Vitamin D adequacy. Folate sufficiency. Hyperprolactinaemia treatment. Insulin resistance addressed.

7. Unexplained RPL

Approximately 50% of RPL has no identified cause after thorough workup. Empirical treatments (aspirin, progesterone supplementation, heparin in selected cases) have variable evidence. Most unexplained RPL couples eventually achieve successful pregnancy with supportive care alone.

8. Pregnancy after RPL — emotional and clinical

Anxiety is profound in pregnancies following RPL. Early and frequent ultrasounds. Beta-hCG monitoring in some cases. Mental health support proactively. The likelihood of healthy pregnancy is good, most couples eventually have children. Early specialist booking and close monitoring matter.