Recurrent Pregnancy Loss and Thrombophilia

Emerging data seem to be available also on the role of active thromboprophylaxis with heparin and pregnancy outcome. In the last decades we found many data concerning the association between a hypercoagulable state and its causes and adverse pregnancy outcome, in particular recurrent pregnancy loss (RPL). First studies which focused on the association between thrombophilia and RPL underlined the role of reduced clotting inhibitors and RPL, and subsequent studies underlined a pathogenetic role of gene variant associated to hypercoagulable state in the occurrence of RPL. On the other hand, acquired thrombophilic abnormalities as antiphipsholipid syndrome are a well known cause of RPL and should be considered for a screening. These data are relevant because recent studies suggested a role of an extensive thromprophilaxis in women with RPL that should be addressed only in case of known thrombophilia and high risk of venous thromboembolism

Lower limb ischemia in a thrombophilic woman during ovarian stimulation for assisted reproduction techniques

Introduction Women receiving hormone therapy as part of assisted reproduction protocols are at increased risk for thrombosis. Controlled ovarian stimulation may be a risk factor for thrombotic events, and thrombophilic subjects are more prone to develop thrombosis during hormone therapies. Materials and methods We report a case of arterial thrombosis of the iliacofemuropopliteal axis, which occurred in a young woman with Factor V Leiden-related thrombophilia, who was receiving recombinant follicle-stimulating hormone and leuprorelin in preparation for in vitro fertilization and embryo transfer, and pharmacological thromboprophylaxis with enoxaparin. Results The thrombosis resulted in critical limb ischemia whose clinical evolution is described. Discussion Further research is needed to identify the best strategy for reducing the thrombotic risk associated with assisted reproduction protocols and to determine whether these women should receive pharmacological thromboprophylaxis

The role of d-dimer as first marker of thrombophilia in women affected by sterility: implications in pathophysiology and diagnosis of thrombophilia induced sterility

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 (MTHFR(C677T), PTHR(A20210G), 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 MTHFR(C677T), PTHR(A20210G), 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 χ(2 )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

Hyperhomocysteinemia in women with unexplained sterility or recurrent early pregnancy loss from Southern Italy: a preliminary report

<p>Abstract</p> <p>Background</p> <p>Hyperhomocysteinemia has been described as a risk factor for unexplained recurrent pregnancy loss. Increased levels of homocysteine may be due to inadequate dietary intake of folate and vitamin B12 and inherited defects within the methionine-homocysteine pathway such as MTHFR C677T gene polymorphism. However, the association between hyperhomocysteinemia and sterility problems have been underlined only for recurrent pregnancy loss while a relationship between hyperhomocysteinemia and female sterility is still matter of discussion.</p> <p>Aim</p> <p>This study sought to find out a possible relationship between sterility (primary sterility or secondary sterility due to recurrent pregnancy loss) and homocysteine metabolism.</p> <p>Patients and Methods</p> <p>We selected 20 patients with recurrent pregnancy loss, 20 patients with unexplained female sterility and 20 healthy women as control group. Several whole blood samples were collected by venipuncture. Firstly homocysteinemia and other related variables were tested (i.e. folate and vitamin B12 levels); thereafter DNA was extracted by a further whole blood sample collected in EDTA in order to screen MTHFR C677T gene polymorphism. Statistical analysis was performed by chi square test; differences were considered to be significant if p < 0.05.</p> <p>Results</p> <p>The median fasting total plasma homocysteine concentration was 19.2 ± 6.14 μM for patients with recurrent pregnancy loss, while was 21.05 ± 8.78 μM for patients with unexplained sterility, vs 7.85 ± 3.31 μM of control group (p < 0.05). Fifteen patients with unexplained female sterility showed MTHFR C677T homozigosity vs 17 with recurrent pregnancy loss and 3 in the control group (p < 0.05). On the other hand no significant differences were found in the levels of vitamin B 12 in the three groups, while reduced folate concentrations were found in women with unexplained female sterility and recurrent pregnancy loss (p < 0.05 vs control group.</p> <p>Discussion</p> <p>MTHFR C677T gene polymorphism is frequent in the studied populations. These data raise questions on the role of the homocysteine metabolism in sterility problems. Even though increased homocysteine (i.e. > 15 μM) and MTHFR C677T homozigosity have already been described as risk factors for recurrent pregnancy loss, few studies evaluated their role in women with unexplained sterility. Further studies on larger series are needed to better understand the role of homocysteine metabolism, including folate metabolism, in this clinical setting.</p

Lower limb ischemia in a thrombophilic woman during ovarian stimulation for assisted reproduction techniques

Introduction Women receiving hormone therapy as part of assisted reproduction protocols are at increased risk for thrombosis. Controlled ovarian stimulation may be a risk factor for thrombotic events, and thrombophilic subjects are more prone to develop thrombosis during hormone therapies. Materials and methods We report a case of arterial thrombosis of the iliacofemuropopliteal axis, which occurred in a young woman with Factor V Leiden-related thrombophilia, who was receiving recombinant follicle-stimulating hormone and leuprorelin in preparation for in vitro fertilization and embryo transfer, and pharmacological thromboprophylaxis with enoxaparin. Results The thrombosis resulted in critical limb ischemia whose clinical evolution is described. Discussion Further research is needed to identify the best strategy for reducing the thrombotic risk associated with assisted reproduction protocols and to determine whether these women should receive pharmacological thromboprophylaxis

Dragon Gene Start Finder identifies approximate locations of the 5′ ends of genes

Recognition of gene starts is a difficult and yet unsolved problem. We present a program, Dragon Gene Start Finder (DGSF), which assesses the gene start in mammalian genomes and predicts a region which should overlap with the first exon of the gene or be in its proximity. The program has been rigorously tested on human chromosomes 4, 21 and 22, and in a strand specific search achieves an overall sensitivity of ∼65% and a positive predictive value of ∼78%. The sensitivity for the CpG-island related promoters is >88%. DGSF is free for academic and non-profit users at http://sdmc.lit.org.sg/promoter/dragonGSF1_0/genestart.htm; the download version of the program integrated within the TRANSPLORER(TM) package can be obtained from Biobase GmbH, at http://www.biobase.de/