Unexplained IVF Failure: Can it be Caused by a Hereditary Clotting Defect (Thrombophilia)?

Hereditary thrombophilia is defined as the genetic predisposition to develop intravascular thrombosis. It affects as many as one in five people in the United States and at least 60% of women who experience recurrent pregnancy loss (RPL) and/or recurrent IVF failures (RIF). It is due to hypercoagulability of the blood leading to impairment of initial vascularization that takes place during implantation. Aside from increasing the risk of RPL and RIF, hereditary thrombophilia is also associated with late pregnancy-induced complications such as preeclampsia, premature separation of the placenta (abruptio placenta), placental insufficiency with intrauterine growth retardation and in still birth. This having been said, it is a fact that most women with a thrombophilia experience healthy pregnancies.

Thrombophilia occurs in association with one or more of the following risk factors:

• Mutational defect involving methylenetetrahydrofolate reductase (MTHFR), which occurs in at least 20% of affected cases. Homozygosity for a common C677T mutation in the MTHFR gene that is associated with hyperhomocysteinemia is the most common form of hereditary thrombophilia leading to a 3-fold increase in risk of complications.
• Mutation of factor V Leiden (FVL), which increases the risk of recurrent early pregnancy loss, 3-4 fold
• A mutation of prothrombin G20210A, which reportedly increases the risk of early pregnancy loss 2-4 fold
• Deficiency of antithrombin III
• Deficiency of protein C
• Deficiency of protein S
• Increase in antiphospholipid antibodies (APA), i.e. “APA Syndrome”

All pregnant women with a history of having had a blood clot should be offered testing for hereditary thrombophilias. Also women with a family history of blood clots, pulmonary embolism (blood clot in the lung), strokes, or a history of the pregnancy complications referred to above should be tested.

Low-dose aspirin with the B vitamins folic acid, B6 and B12 can be given to women who have milder thrombophilias and no history of pregnancy complications. Women found to have severe varieties (e.g. homozygous MTHFR mutations. Protein C deficiency or prothrombin G20210A mutation) and those who have experienced one or more of the thrombophilia-related complications mentioned above , are best treated , with low-molecular weight heparin (LMWH), begining with the chemical diagnosis of pregnancy and continuing for at least 6 weeks following delivery.