Recurrent pregnancy loss is usually defined as the loss of ≥ 2 pregnancies. Each pregnancy loss merits careful review to determine if evaluation of the woman or the couple may be appropriate. Recurrent pregnancy loss is not classified as infertility.
Etiology of Recurrent Pregnancy Loss
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 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 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 man 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 miscarriages; pregnancy 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.
Etiology reference
1. Committee on Practice Bulletins—Obstetrics, American College of Obstetricians and Gynecologists (ACOG): Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol 120 (6):1514–1521, 2012. doi:10.1097/01.AOG.0000423816.39542.0f
Diagnosis of Recurrent Pregnancy Loss
Clinical evaluation
Tests to identify the cause
The diagnosis of recurrent pregnancy loss is clinical, based on history of 2 or more 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 saline infusion 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 Recurrent Pregnancy Loss
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, 3).
Treatment references
1. Brigham SA, Conlon C, Farquharson RG: A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage. Hum Reprod 14 (11):2868–2871, 1999. doi: 10.1093/humrep/14.11.2868
2. Edlow AG, Srinivas SK, Elovitz MA: Second-trimester loss and subsequent pregnancy outcomes: What is the real risk? Am J Obstet Gynecol 197(6):581.e1–581.e6, 2007. doi: 10.1016/j.ajog.2007.09.016
3. Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012;98(5):1103-1111. doi:10.1016/j.fertnstert.2012.06.048
Key Points
Recurrent pregnancy loss is ≥ 2 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.
