Thrombophilias and recurrent pregnancy loss: a critical appraisal of the literature.

Thrombophilias are suggested to play a role in recurrent miscarriage. The aim of this study was to evaluate the literature of the past 10 years regarding the association between thrombophilias and recurrent miscarriage. We concluded that there is a large variety in applied study methodology. Therefore, we defined criteria for an adequate study on the relationship of thrombophilias on recurrent pregnancy loss: (i) no exclusion criteria for patients or at least the same criteria for patients and controls; (ii) a clear definition of the gestational age at previous losses; (iii) a well-described control group; (iv) clear description of the test methods and moment of testing; and (v) a clear description of the (non) significant differences or odds ratio between cases and controls. Eleven out of 69 studies fulfilled these criteria. Their results show significant higher serum homocysteine levels among women with a history of recurrent miscarriage. No relation was found between recurrent miscarriage and the methylenetetrahydrofolate reductase C667T mutation. No relation was observed for the levels of antithrombin, protein C and protein S. Seven studies on the association of factor V Leiden (FVL) and/or pathologic activated protein C ratio (pAPCR) showed that FVL may play a role in second trimester losses, as do antiphospholipid antibodies. Studies on the prothrombin gene mutation yielded conflicting results. Consequently, large prospective studies according to the aforementioned criteria are needed to establish if there is a relationship between thrombophilias and recurrent miscarriage at all. At present, there is only justification for testing for homocysteine levels, antiphospholipid antibodies and FVL in women with a history of recurrent miscarriage.