Recurrent Pregnancy Loss (RPL) can be devastating to a couple, both physically and emotionally. When a couple has more than one pregnancy loss, a thorough review of the couple’s history should be undertaken. RPL is a complex problem and can be due to Aneuploidy, anatomic factors, endocrinologic and/or immunologic abnormalities, and thrombophilias.

The relationship between pregnancy loss and thrombophilia is a much-debated topic. A metaanalysis published in Lancet in 2003 (Rey E, et al., Lancet 2003) combined data from 31 studies judged to be of good quality. The authors concluded that there was an increased prevalence of thrombophilias in women with unexplained RPL compared with women without a history of adverse pregnancy outcome.

Evaluation for Thrombophilias can include:

  • Antiphospholipid antibodies (lupus anticoagulant, LAC and anti-cardiolipin, ACA)
  • Factor V Leiden mutation
  • Prothrombin G20210A mutation • Antithrombin III activity
  • Protein C and Protein S activity
  • Either a fasting homocysteine level or methylenetetrahydrofolate reductase
  • (MTHFR) polymorphism analysis

Antiphospholipid antibodies are directed against negatively charged phospholipid molecules on the cell surface and in organelles. LAC is an immunoglobulin that interferes with phospholipiddependent in-vitro coagulation. There is consensus that antiphospholipid antibodies should be looked for in RPL patients because not only are they are found with increased prevalence, but also, obstetric outcomes are worse. The chance of a live birth can be improved with heparin and low-dose aspirin therapy. Diagnosis of the antiphospholipid antibody syndrome requires one laboratory and one clinical criteria. In order to satisfy the laboratory criteria, the same antibody must be positive twice when drawn at least 12 weeks apart.

Laboratory Criteria

  • Anticardiolipin IgG and/or IgM present in medium or high titers (> 40 GPL/MPL)
  • Detection of Lupus anticoagulant antibody

Clinical Criteria

  • One of more clinical episodes of arterial, venous or small vessel thrombosis
  • One of more unexplained pregnancy loss of a morphologically normal Fetus of at least 10 wks Gestation
  • One or more premature births of a morphologically normal newborn at or before the 34th week of gestation because of severe pregnancy induced hypertension or severe placental insufficiency
  • Three or more unexplained consecutive miscarriages before 10 weeks gestation with anatomic, hormonal and parental structural genetic factors excluded.

Other studies have demonstrated an association between RPL and FVL, prothrombin G20210A gene mutation, reduction in protein C and protein S activity, MTHFR and antithrombin III deficiency.

As of yet, there are no randomized controlled trials evaluating the efficacy of thromboprophylaxis with heparin and aspirin in women with FVL, G20210A prothrombin, protein C and protein S, antithrombin III deficiency to optimize pregnancy outcomes. Until these trials are completed, treatment with heparin and low-dose aspirin is empiric, and a careful discussion of the risks and benefits of thromboprophylaxis must be discussed in detail with each patient. For patients with MTHFR polymorphisms and hyperhomocysteinemia, 4 mg/d of folic acid is sufficient.