The role of d-dimer as first marker of thrombophilia in women affected by sterility: implications in pathophysiology and diagnosis of thrombophilia induced sterility
Authors: Di Micco Pierpaolo , D'Uva Maristella , Strina Ida , Mollo Antonio , Amato Valeria , Niglio Alferio , De Placido Giuseppe 
Published: November 2004

Abstract
Background
D-dimer is considered a marker of hypercoagulable state and of endogenous fibrinolysis, so increased d-dimer is detectable in patients affected by thrombosis. Yet, several studies showed that also infertility, in particular secondary infertility due to recurrent fetal losses, has been often related to thrombotic events, in particular in women carrying thrombotic risk factors such as inherited thrombophilia (MTHFRC677T, PTHRA20210G, Factor V Leiden polimorphisms and/or inhAfter this screening we selected 39erited protein C, protein S, AT III deficiency) or acquired thrombophilia (primary antiphospholipid syndrome, acquired protein C, protein S, AT III deficiency, drugs induced thrombophilia). However, because its high predictive negative value in case of suspected thrombosis, increased d-dimer has been often associated to subclinical thrombophilia. The aim of this study is to investigate the role of d-dimer as first marker of thrombophilia in women affected by unexplained infertility and subsequently to search the cause of increased d-dimer, such as inherited and/or acquired thrombophilia.

Patients and Methods
We selected 79 patients with unexplained primary or secondary infertility. We excluded 40 patients affected by hydrosalpinx, uterine fibroids, uterine malformations, endocrinological and immunological diseases, luteal insufficiency, cytogenetical alterations. All remaining 39 patients were tested for d-dimer and divided in two groups: the patients of group A (25 patients) showed increased plasma d-dimer, in group B were included 14 patients with normal plasma level of d-dimer. After this step all 39 patients were screened for MTHFRC677T, PTHRA20210G, Factor V Leiden polimorphisms, protein C, protein S, AT III, anticardiolipin IgM and IgG, lupus anticoagulant. In the control group were included 15 age matched women without sterility problems referred to our outpatient's section of vascular medicine for suspected deep venous thrombosis.
Statistical analysis was based on χ2 test, differences were considered to be significant if p < 0.05.

Results
D-dimer was increased in 25/39 and 20/25 showed inherited/acquired thrombophilia while patients with normal d-dimer showed inherited/acquired thrombophilia in 7/14 (p: < 0.05, s).

Discussion
D-dimer is a well known marker of hypercoagulable state, in particular its high predictive negative value in case of suspected thrombosis has been recognised by several reports. Yet, increased d-dimer has been identified also for subclinical thrombophilia besides for vascular thrombosis. Our data, in fact, for the first time suggest an interesting role of d-dimer to identify women affected by unexplained primary or secondary infertility and thrombophilia. So, probably there is a role for d-dimer in these subjects for its predictive positive value. Of course, further data on large based population are needed to confirm our results, because these findings may speed up a diagnostic screening in these patients also for a good cost/effectiveness of this test.