Recurrent pregnancy loss and thrombophilia in women with PCOS.

In this issue Kazerooni and colleagues have authored an interesting article entitled “Correlation between thrombophilia and recurrent pregnancy loss in patients with polycystic ovary syndrome (PCOS): A comparative study”. Based on the absence or presence of recurrent pregnancy loss (RPL) and polycystic ovary syndrome (PCOS), the authors have tried to determine the association of thrombophilia and RPL in patients with and without PCOS, using a case-controlled comparative study, and separating the subjects into four groups. This study attempted to shed light on two medically challenging areas in obstetrics and gynecologydRPL and PCOSdthe etiology of both of which is still uncertain. RPL is defined by two or more failed pregnancies, and up to 50% of cases of RPL will not have a clearly defined etiology. The potential etiologic factors in the association and causation of RPL can be separated into three categories: definite, probable, and doubtful. Factors that have a definite association with RPL include parental genetics, uterine abnormalities, PCOS, antiphospholipid syndrome (APS), and factor V Leiden (FVL) mutation. Probable associations with RPL include uncontrolled thyroid disease, uncontrolled diabetes, T-helper type 1 (Th1) cell cytokine bias, increased natural killer (NK) cell cytotoxicity, and maternal human leukocyte antigen (HLA) levels. The only definite causation of RPL has been found to be parental genetics. Other causes of RPL include uterine abnormalities, uncontrolled thyroid disease, uncontrolled diabetes, PCOS, APS, FVL mutation, Th1 cytokine bias, increased NK cell cytotoxicity, and maternal HLA alleles. One of the challenges for most researchers is how to identify those limited RPL cases with genetic defects who are destined to miscarry, from other treatable ones. In addition, screening for inherited or acquired thrombophilias (especially FVL and prothrombin gene mutations, such as prothrombin G20210A gene mutations, and protein C, protein S, and antithrombin deficiencies, as noted by Kazerooni et al, might be reasonably acceptable when patients have personal history of venous thromboembolism in a nonrecurrent risk factor setting, or if there is a first-degree relative with a known or suspected high-risk thrombophilia. However, any association between hereditary thrombophilias and RPL has not been supported by two prospective cohort studies. In addition, it is acknowledged that APS is the only thrombophilia known to have a direct influence on pregnancy loss, although much