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: 2.98). 04/2006; 12(3):322-7. DOI: 10.1016/S1472-6483(10)61004-8
Source: PubMed

ABSTRACT 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, Jul 27, 2015
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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.
    06/2012; 6(2):116–118. DOI:10.1016/j.itjm.2011.09.007
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    • "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. "
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    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 · 8.66 Impact Factor
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    • "Increased rates of hereditary thrombophilia in women with RIF were found in recent two case-control studies (Grandone et al., 2001; Azem et al., 2004) but not in another large one (Martinelli et al., 2003). The prevalence of PAI-1 mutation and multiple thrombophilic gene mutations among patients with RIF was significantly higher than among fertile controls (Coulam et al., 2006). Hence, screening of thrombophilia in RIF is still controversial. "
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    ABSTRACT: Pregnancy rate following one cycle of IVF and ET can be as high as 60%. But even in the very successful units, some couples fail repeatedly. The causes for repeated implantation failure (RIF) may be because of reduced endometrial receptivity, embryonic defects or multifactorial causes. Various uterine pathologies, such as thin endometrium, altered expression of adhesive molecules and immunological factors, may decrease endometrial receptivity, whereas genetic abnormalities of the male or female, sperm defects, embryonic aneuploidy or zona hardening are among the embryonic reasons for failure of implantation. Endometriosis and hydrosalpinges may adversely influence both. In this mini review, we discuss the suggested methods for evaluation and treatment of RIF: repeated hysteroscopy, myomectomy, endometrial stimulation, immunotherapy, preimplantation genetic screening (PGS), assisted hatching, zygote intra-Fallopian transfer (ZIFT), co-culture, blastocyst transfer, cytoplasmic transfer, tailoring stimulation protocols and salpingectomy for hydrosalpinges.
    Human Reproduction 01/2007; 21(12):3036-43. DOI:10.1093/humrep/del305 · 4.59 Impact Factor
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