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 (for confirmed APS with three or more losses): low-dose aspirin, ideally started before conception, plus a preventive dose of heparin (usually low-molecular-weight heparin such as enoxaparin) from the positive pregnancy test, continued through pregnancy as planned by your specialist. Adding heparin to aspirin may increase the chance of a live birth compared with aspirin alone, but the evidence comes mostly from small or older trials and is rated low certainty.

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

A small proportion of couples with RPL carry a balanced chromosomal rearrangement. Karyotyping both partners is advised after individual assessment, for example, when testing of pregnancy tissue shows an unbalanced rearrangement. 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. Aspirin and heparin do not improve the chance of a live birth in unexplained RPL, so they are not recommended. Vaginal progesterone may help some women, particularly after three or more losses with bleeding in early pregnancy, and is decided together with your specialist. 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.