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.

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Available from: Roumen Roussev
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    • "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. "
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    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.
    Full-text · Article · Jul 2014 · Gene
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    • "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. "
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    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.
    Full-text · Article · Jun 2012
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    • "An association between thrombophilia due to FVL or PGM and recurrent implantation failure was observed in a small series of Italian patients (Grandone et al., 2001). Other case–control studies (from Middle East, USA and Europe) investigating patients with recurrent IVF failure have provided heterogeneous results (Azem et al., 2004; Coulam et al., 2006; Qublan et al., 2006; Vaquero et al., 2006 ; Bellver et al., 2008; Simur et al., 2009). In our study, the number of the patients with repeated IVF failure in the mutation carrier group was too low to allow a reliable analysis. "
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    ABSTRACT: The influence of thrombophilia on fertility and on IVF outcome is very controversial. The objectives of this study were: (i) to compare the prevalence of Factor V Leiden (FVL) and prothrombin gene G20210A mutation (PGM) in women undergoing IVF to women with spontaneous pregnancy; (ii) to compare the IVF outcomes and the risk of complications in FVL and PGM carrier to non-carrier women. From March 2005 to December 2009, a total of 510 women requiring IVF were recruited in a prospective cohort study. A separate population of 490 nulliparous women who conceived naturally was also evaluated as fertile controls. All women were tested for the presence of FVL and PGM. The prevalence of thrombophilic mutations was the same among women requiring IVF (6.9%) and women with spontaneous pregnancy (6.9%). A total of 480 patients underwent 1105 IVF cycles. There were 30 women carriers (86 IVF cycles) and 450 non-carriers for thrombophilic mutations (1019 IVF cycles). No significant differences in the mean number of oocytes retrieved and the number of good quality embryos transferred were found between the mutation carrier and non-mutation carrier women; likewise the reproductive outcome and the IVF complications were not statistically different between the two groups. The cumulative live birth rate after six IVF cycles was similar in the mutation carrier and non-mutation carrier women. For the mutation carrier women, the optimistic estimate of cumulative live birth rate after six IVF cycles was 60.8% and the conservative estimate was 50.0%. Corresponding rates for the non-mutation carrier women were 56.8 and 36.2%, respectively. The results of this study suggest that FVL and PGM presence in asymptomatic women and in the absence of other risk factors do not influence IVF outcome, or represent risk factors for ovarian hyperstimulation syndrome (OHSS), or favour thrombosis after IVF. Screening for FVL and PGM does not appear to be justified to identify the patients at the risk for IVF failure, and/or for OHSS, and/or for thrombotic complications.
    Preview · Article · Aug 2011 · Human Reproduction
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