• investigation of factor leiden G1691A mutation and polymorphism4G/5G in PAI-1 gene from thrombophilia panel in infertile or women with previous abortion
  • faezeh alinia,1,*
    1. azad university of babol


  • Introduction: Fertility is a meaningful term that has attracted many views from the past. Fertility or the ability to have children, Success in reproduction and the beginning of rebirth for couples and the opposite of infertility, with impaired reproduction, always Sometimes treatable and sometimes untreatable will have many unintended consequences for couples. in the years Recent factors, such as the changing role of women in social activities and the desire to continue their education and employment, have delayed marriage. These factors have led to the increasing age of women when deciding on childbirth and the problems that follow (Dericvand- Moghadam et al., 2013). Infertility is one of the most widespread medical problems in the world today, with a 50% increase in prevalence since 1955. And now 10-15% of couples are suffering from this problem which is 13.2% in Iran. (Dericvand-moghadam et al., 2013). According to the World Health Organization, it is estimated that 9% of couples live in Around the world have experienced some types of infertility, and 56% of couples seek medical care for infertility. (Sharifi et al., 2016). Thrombophilia is actually an increased tendency to coagulate in the coagulation system, which has various causes. In the division The causes of thrombophilia can be divided into two main causes. The first group is the cause of the coagulation system, the occult Coagulation factors resulting from mutations are either genetic mutations or secondary immunological factors. The second group of disorders It is related to arteries that do not contribute to coagulation and increase clot formation. Some of these disorders are due to mutations and disorders It is a genetic disorder that occurs in humans, especially in adolescents. Thrombophilia as venous thromboembolism, Deep vein thrombosis, pulmonary embolism, myocardial infarction, and cerebral vein thrombosis (Soligo et al.,2016)During pregnancy there is no problem as long as there is a balance between the mother's coagulation system and fibrinolysis, because Prevents fibrin deposition in the vasculature and spaces between the villi, and the base plate remains stable, but in females Thrombophilia not only has the risk of thromboembolism in pregnancy but also other vascular complications such as bladder Eclampsia and miscarriage are also common in them (Abbate et al., 2002). Recently, studies have shown that the genetic background of thrombophilia is associated with recurrent miscarriage. The relationship between abortion Repeated and thrombophilia is a very promising position that has been studied extensively and the results are inconsistent. Confirmation and rejection have been obtained (Glueck et al., 2008). Hemostasis disorders can be hereditary or acquired due to hereditary variants, mutations of coagulant genes such as antithrombin III. , C and S proteins or coagulation factors such as prothrombin, FVL, and methylene tetrahydrofolate enzyme. Is reductase (MTHFR). In addition to genetic problems recently, mutations in other genes, such as plasminogen activator inhibitor (PAI-1), factor 13 (FXIII) and angiotensin converting enzyme (ACE) have also been noted (Glueck et al., 2004). It seems to be a gene mutation of this gene They need to be effective in preventing miscarriage themselves (Kotze et al., 2005). High values ​​of PAI-1 Endothelial cells reduce fibrinolysis and thrombosis (Tsanadis et al., 2002). The PAI-1 gene is normally expressed by the 5G / 5G allele. A polymorphism identified in this 4G / 4G gene It is present in the promoter region. This polyphase morphism is at 675bp before the original translation domain. (Balta et al., 2002). The translation-regulating factors bind to the 4G allele and produce more PAI-1 protein than the 5G allele. the amount of Above PAI-1 produced by the 4G allele can increase bare birth because in the fibrinolysis and coagulation system, Diagnosis occurs (1) and can cause recurrent thrombosis and premature placental abruption (Charles et al., 2001). Angiotensin converters (ACE) regulate clot formation by converting angiotensinogen 2 to 1. In fact, endothelial PAI-1 synthesis It is controlled by angiotensin-2 (Buchholz et al., 2003). It has been reported that the polymorphism of this gene also plays a role in the regulation of the enzyme, which is a deletion / enhancement of a polymorphism. The resolution is 278bp on the intron. Coagulation factor 5 plays a key role in regulating the homeostasis of coagulation pathways. G1691A point mutation in the gene The coagulation factor 5 is called the thrombophilic factor Leiden (FVL) and eliminates a fracture site in factor 5. Coagulation and consequently due to the effect of thrombinase complex function due to 5-coagulation factor resistance to activated protein C APCR (Castoldi et al., 2000) is associated with recurrent miscarriage (Zammiti et al., 2006; Torabi et al., 2006). al., 2008). FV Leiden polymorphism leads to increased risk of miscarriage in carriers of this polymorphism up to three-fold (from 6% to 16%) It becomes healthy (Glueck et al., 2008). Endometrial acceptance highlights the importance of examining the relationship between thrombophilia and infertility, as it involves vessels Is during the implantation process (Simon and Laufer., 2012). In a 2014 study of 45 infertile women, Petukhova and her colleagues found that 32 women had thrombophilia: 71% had hereditary thrombophilia and 16% had genetic and acquired. The results indicated the importance of thrombophilic agents in the incidence of infertility has it. The role of thrombophilia and infertility in this study is controversial. The purpose of the present study was to investigate the association Between thrombophilia and infertility and abortion.
  • Methods: This clinical trial is performed on 100 infertile women or women with a history of abortion in 1398 with a consent form. Their characteristics include family history, thrombotic events, age, body mass index (BMI), smoking, medications Consumption, history of surgery, history of hematologic, malignant, and liver diseases are recorded. Women enrolled in the study The ages will be fertile. Exclusion criteria for the study of women with Cushing's syndrome, hyperprolactinemia, liver disease (hepatitis, Cirrhosis and ...) and recent myocardial infarction, cancers, women with a history of miscarriage or surgical practice over the past 5 months, history Use of anticoagulant drugs such as aspirin and heparin for 15 days and people treated with sex steroids and metformin Are. Hormonal assays including LH, FSH, Prolactin, Total Testosterone, FBS, and GTT 75 grams Hours are performed between 7 and 10 am on the third day of the menstrual cycle and after 12 hours of fasting. To perform the test, each individual received 5 ml of blood in the presence of EDTA anticoagulant and extracted DNA by Salting method. out was performed using proteinase K. To investigate the G1691A mutation in Leiden factor and 4G / 5G polymorphism PAI-1 gene from thrombophilic panel in infertile women or with a history of abortion polymerase chain reaction using specific primers and The specificity is performed and PCR products are examined using RFLP technique
  • Results: 71% had hereditary thrombophilia and 16% had genetic and acquired. The results indicated the importance of thrombophilic agents in the incidence of infertility has it. The role of thrombophilia and infertility in this study is controversial. The purpose of the present study was to investigate the association Between thrombophilia and infertility and abortion.
  • Conclusion: 71% had hereditary thrombophilia and 16% had genetic and acquired. The results indicated the importance of thrombophilic agents in the incidence of infertility has it. The role of thrombophilia and infertility in this study is controversial. The purpose of the present study was to investigate the association Between thrombophilia and infertility and abortion.
  • Keywords: Trombophillia infertile abortion