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Causes of recurrent pregnancy loss may be maternal, paternal, fetal, or placental.

Common maternal causes include

• Uterine or cervical abnormalities (eg, polyps, myomas, adhesions, cervical insufficiency)

• Maternal (or paternal) chromosomal abnormalities (eg, balanced translocations)

• Poorly controlled chronic disorders (eg, hypothyroidism, hyperthyroidism, diabetes mellitus, hypertension, chronic kidney disease)

Acquired thrombotic disorders (eg, related to antiphospholipid antibody syndrome with lupus anticoagulant, anticardiolipin [IgG or IgM], or anti-beta2 glycoprotein I [IgG or IgM]) are associated with ≥ 3 recurrent losses after 10 weeks, after other maternal and genetic causes have been excluded. Loss of one or more apparently normal pregnancies after 10 weeks can raise suspicion of antiphospholipid antibody syndrome (1). The association with hereditary thrombotic disorders is less clear but does not appear to be strong, except for possibly factor V Leiden mutation.

Paternal causes are less clear, but risk of miscarriage is higher if the father has certain semen analysis abnormalities. Paternal age > 35 has been studied, but data about increased risk of spontaneous abortion were conflicting.

Placental causes include preexisting chronic disorders that are poorly controlled (eg, systemic lupus erythematosus [SLE], chronic hypertension).

Fetal causes are usually

• Chromosomal or genetic abnormalities

• Anatomic malformations

Chromosomal abnormalities in the fetus may cause 50% of recurrent pregnancy losses; losses due to chromosomal abnormalities are more common during early pregnancy. Aneuploidy is involved in up to 80% of all spontaneous abortions occurring at < 10 weeks gestation but in < 15% of those occurring at ≥ 20 weeks.

Whether a history of recurrent pregnancy loss increases risk of fetal growth restriction and premature delivery in subsequent pregnancies depends on the cause of the losses.

• Clinical evaluation

• Tests to identify the cause

The diagnosis of recurrent pregnancy loss is clinical, based on history of 2 or 3 prior spontaneous abortions.

Evaluation for recurrent pregnancy loss should include the following to help determine the cause:

• Genetic evaluation (karyotyping) of both parents and any products of conception as clinically indicated to exclude possible genetic causes

• Screening for acquired thrombotic disorders: Anticardiolipin antibodies (IgG and IgM), anti-beta2 glycoprotein I (IgG and IgM), and lupus anticoagulant

• Thyroid-stimulating hormone

• Diabetes testing

• Hysterosalpingography or sonohysterography to check for structural uterine abnormalities

Cause cannot be determined in up to 50% of women. Screening for hereditary thrombotic disorders is not routinely recommended unless supervised by a maternal-fetal medicine specialist.

• Treatment of the cause if possible

Some causes of recurrent pregnancy loss can be treated. If the cause cannot be identified, the chance of a live birth in the next pregnancy is 27 to 75% (1, 2).

• Recurrent pregnancy loss is ≥ 2 to 3 spontaneous abortions.

• Causes of recurrent pregnancy loss may be maternal, paternal, fetal, or placental.

• Chromosomal abnormalities (particularly aneuploidy) may cause 50% of recurrent pregnancy losses.