Multiple Thrombophilic Gene Mutations Are Risk Factors for Implantation Failure

Pregnancy Success Centre of the Rinehart Centre for Reproductive Medicine, Chicago, IL, USA.
Reproductive biomedicine online (Impact Factor: 3.02). 04/2006; 12(3):322-7. DOI: 10.1016/S1472-6483(10)61004-8
Source: PubMed


While the role of inherited thrombophilia has been accepted as a cause of recurrent late pregnancy complications, the contribution of mutated thrombophilic genes to implantation failure has not been studied. Proteins involved in fibrinolysis are necessary for trophoblast invasion into the endometrium. This study compared the prevalence of 10 thrombophilic gene mutations among 42 women with a history of recurrent implantation failure after IVF-embryo transfer with 20 fertile control women. Buccal swabs were taken from all of the women for DNA analyses. Women with a history of implantation failure after IVF-embryo transfer displayed a higher prevalence of PAI-1 4G/5G mutations than controls (P = 0.007). No differences in the frequency of the other specific gene mutations were detected. However, the prevalence of total gene mutations among patients with implantation failure was significantly higher than among controls. More than three gene mutations among the 10 genes studied were observed in 74% of women with implantation failure and 20% of controls (P = 0.0004). It is concluded that inherited thrombophilias are associated with implantation failure. This association is manifest by total number of mutations as well as with PAI-1 mutations.

Download full-text


Available from: Roumen Roussev,
  • Source
    • "Although many studies in recent years have focused on the genetic polymorphisms in coagulation cascade, fibrinolysis, thrombophilic (Coulam et al., 2006; Goodman et al., 2006; Yenicesu et al., 2010), cytokines (Daher et al., 2003), histocompatibility antigens (Abbas et al., 2004) and metabolic enzymes (Nair et al., 2012) to find out candidate genes for RPL, the genes involved in RPL are still an unanswered enigma. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of apolipoprotein E gene polymorphisms in the pathogenesis of recurrent pregnancy loss remains controversial. Therefore, our objective was to investigate the association between recurrent pregnancy loss and apolipoprotein E gene polymorphisms among northwest Iranian women, and also to predict the impact of these nonsynonymous single nucleotide polymorphisms on structure and function of apolipoprotein E protein. The subjects of our current study consisted of 100 women that have had two or more consecutive idiopathic first trimester miscarriages, and one hundred healthy women from the same geographical areas were used as a control group. After DNA extraction, we used a polymerase chain reaction-restriction fragment length polymorphism to genotype of the apolipoprotein E gene. In addition, we predicted the possible effects of amino acid substitutions at codons 112 and/or 158 on the structure and function of apolipoprotein E protein using Polymorphism Phenotyping online software v2. Our results showed that the rate of apolipoprotein E ε4 carriers and the frequency of the ε4 allele in the case group were statistically and significantly higher than those in the control group (P<0.05). Therefore, our data support the association of the Apo ε4 allele with RPL; however, in silico analysis predicted that the amino acid substitution at residue 112 (Apo ε4 allele) is a benign mutation. Accordingly, further studies are required to elucidate the mechanism(s) underlying the link between RPL pathogenesis and the Apo ε4 allele.
    Gene 07/2014; 549(2). DOI:10.1016/j.gene.2014.07.055 · 2.14 Impact Factor
  • Source
    • "The association between thrombophilia and female infertility due to pregnancy loss is well known both for inherited thrombophilia and acquired thrombophilia [1], while the association between thrombophilia and unexplained female sterility is still matter of discussion in particular for women who underwent repeated in vitro fertilisation (IVF) and embryo transfer (ET) failures [2]. Some authors found an association between thrombophilia and/or hypofibrinolysis and repeated failures to assisted reproduction techniques (ART) [3] while other authors did not [4]. A thrombotic risk is associated with hormonal therapies. "
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    06/2012; 6(2):116–118. DOI:10.1016/j.itjm.2011.09.007
  • Source
    • "These findings for Factor V Leiden were not replicated by other studies (Martinelli et al., 2003; Azem et al., 2004); however, Azem et al. again showed a significantly higher prevalance of heritable thrombophilias in women with four or more failed IVF cycles when compared with spontaneous conceptions (OR 3.6, 95% 1.25 – 10.6), or women who conceived after their first cycle (OR 2.9, 95% CI 1.02–8.4) (Azem et al., 2004), findings replicated by Coulam (Coulam et al., 2006). In conclusion, heritable thrombophilia does appear to contribute to repeated ART failure and although the contribution of any single thrombophilia to implantation failure is likely to be small, it is likely that for any given individual, this association will reflect the total number of mutations rather than the involvement of specific genes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Heparan sulphates play key roles in conception and early pregnancy events. The role of heparin, a structural analogue, and its application to assisted conception, is largely unknown. Relevant studies were identified by searching PubMed 1966-November 2007 and Google Scholar without limitations. Sensitive search strategies were combined with relevant medical subject headings and text words. The similarities of heparin and heparan, the haemostatic changes induced by ovarian stimulation and the risk of thrombosis, the contribution of thrombophilia to pregnancy and infertility outcomes, early embryo-maternal dialogue and how these various aspects of assisted conception may be modified by heparin are reviewed. Heparin can alter the haemostatic response to controlled ovarian stimulation and modify the risk of thrombosis. It can also modulate many of the fundamental physiological processes required for blastocyst apposition, adherence and implantation and as well as trophoblast differentiation and invasion due to its similarities with heparan sulphates and has the potential to improve pregnancy rates and outcomes.
    Human Reproduction Update 09/2008; 14(6):623-45. DOI:10.1093/humupd/dmn031 · 10.17 Impact Factor
Show more