The frequency of genetic factors of thrombophilia in women with recurrent pregnancy losses

  • L. B. Chorna
  • H. V. Makukh
  • D. V. Zastavna
  • N. V. Prokopchuk
  • N. V. Helner


Aim. There is growing evidence that recurrent pregnancy losses (RPL) are associated with the presence of inherited thrombophilias but data are inconsistent. The present study aimed to assess the distribution of inherited risk factors of thrombophilia among women with RPL. Methods. We studied 68 women with RPL and 120 healthy women of control group, inhabitants of Western Ukraine. In all subjects the detection of genetic factors of thrombophilia were determined by polymerase chain reaction and restriction fragment length polymorphism method. Results. The prevalence of heterozygotes for FV 1691G/A among women with RPL and controls were: 12 % versus 4 %, respectively. Women heterozygosity for factor V Leiden was significantly more prevalent in the RPL group than in controls (OR 3.11, 95 % CI 1.02–9.46). Results showed that carriers of PAI-1 4G allele have increased odds on more than 2 times in comparison to the carriers of homozygous 5G5G genotypes. A significant relationship between allele variation 677T of MTHFR gene (OR 1.70, 95 % CI 1.09–2.67) and RPL was observed. Conclusions. Significance of 1691G/A mutation of V blood coagulation factor gene, alleles variations of 677T of MTHFR gene and 4G of PA1-1 gene in the structure of predisposition to RPL in group of west Ukrainian women was established.

Keywords: genetic factors, hereditary thrombophilia, molecular genetic testing, RPL.


Sidel'nikova V.M. Nevynashivaniye beremennosti – sovremennyy vzglyad na problemu [Miscarriage of pregnancy – a modern view of the problem]. Akusherstvo i ginekologiya. 2007. No. 5. S. 24–27.

Branch D.W., Gibson M., Silver R.M. Clinical practice. Recurrent miscarriage N. Engl. J. Med. 2010. Vol. 36311. P. 1740–17472. doi: 10.1056/NEJMcp1005330.

Lund M., Nielsen H.S., Hviid T.V., Steffensen R., Nyboe Andersen A., Christiansen O.B. Hereditary thrombophilia and recurrent pregnancy loss: a retrospective cohort study of pregnancy outcome and obstetric complications. Hum. Reprod. 2010. Vol. 25, No. 12. P. 2978–2984. doi: 10.1093/humrep/deq280

Kujovich J.L. Factor V. Leiden thrombophilia. Genet. Med. 2011. Vol. 13, No. 1. P. 1–16. doi: 10.1097/GIM.0b013e3181faa0f2

Poort S.R., Rosendaal F.R., Reitsma P.H. Bertina R.M. A Common Genetic Variation in the 3' Untranslated Region of the Prothrombin Gene Is Associated with Elevated Plasma Prothrombin Levels and Increase in Venous Thrombosis. Blood. 1996. Vol. 88, No. 10. P. 3698–3703.

Rosendaal F.R., Reitsma P.H. Genetics of venous thrombosis. J. Thromb. Haemost. 2009. Vol. 7. P. 301–304. doi: 10.1111/j.1538-7836.2009.03394.x.

Beckerath von N., Koch W., Mehilli J. Böttiger C., Schömig A., Kastrati A. Glycoprotein Ia gene C807T polymorphism and risk for major adverse cardiac events within the first 30 days after coronary artery stenting. Blood. 2000. Vol. 95, No. 11. P. 3297–3301.

Bojesen S.E., Tybjaerg-Hansen A., Nordestgaard B.G. Integrin ß3 Leu33Pro Homozygosity and Risk of Cancer. JNCI. 2003. Vol. 95. P. 1150–1157. doi: 10.1136/jmg.2006.047498

Burzotta F., Iacoviello L., Di Castelnuovo A., Zamparelli R., D'Orazio A., Amore C., Schiavello R., Donati M.B., Maseri A., Possati G., Andreotti F. 4G/5G PAI-1 promoter polymorphism and acute – phase levels of PAI-1 following coronary by pass surgery: a prospective study. J. Thromb. Thrombolysis. 2003. Vol. 16. P. 149–154. doi: 10.1023/B:THRO.0000024052.79415.62

Buchholz T., Lohse P., Rogenhofer N., Kosian E., Pihusch R., Thaler C.J. Polymorphisms in the ACE and PAI-1 genes are associated with recurrent spontaneous miscarriages. Hum Reprod. 2003. Vol. 18. P. 2473–2477. doi: 10.1093/humrep/deg474

Inge Ebisch M.W., Thomas Chris M.G, Wetzels Alex M.M., Willemsen Wim N.P., Sweep Fred C.G.J., Steegers-Theunissen Regine P.M. Review of the role of the plasminogen activator system and vascular endothelial growth factor in subfertility. Fertil Steril. 2008. Vol. 90. P. 2340–2350. doi: 10.1016/j.fertnstert.2007.10.026

Isotalo P.A.,. Wells G.A, Donnelly J.G. Neonatal and fetal methylenetetrahydrofolate reductase genetic polymorphisms: an examination of C677T and A1298C mutations. Am. J. Hum. Genet. 2000. Vol. 67. P. 986–990. doi: 10.1086/303082

Bailey L.B., Gregory J.F. Polymorphisms of methylenetetrahydrofolatereductase and other enzymes: metabolic significance, risks and impact on folate requirement. J. Nutr. 1999. No. 129. P. 919–922.

Fatini C., Conti L., Turillazzi V., Sticchi E., Romagnuolo I., Milanini M.N., Cozzi C., Abbate R., Noci I. Unexplained infertility: association with inherited thrombophilia. Thromb Res. 2012. Vol. 129, No. 5. e185-8. doi: 10.1016/j.thromres.2012.02.012

Coulam C.B., Jeyendran R.S. Thrombophilic gene polymorphisms are risk factors for unexplained infertility. Fertil Steril. 2009. Vol. 91. P. 1516–1517. doi: 10.1016/j.fertnstert.2008.07.1782.

Safdarian L., Najmi Z., Aleyasin A., Aghahosseini M., Rashidi M., Asadollah S. Recurrent IVF failure and hereditary thrombophilia Iran J Reprod Med. 2014. Vol. 12, No. 7. P. 467–470.

Chorna L.B., Makukh H.V., Akopyan H.R., Zastavna D.V., Prokopchuk N.M Analiz polimorfnykh variantiv heniv MTHFR, MTR, MTRR ta mutatsiy heniv FV ta FII zhortannya krovi sered zhinok z navykovym nevynoshuvannyam vahitnosti [Analysis of polymorphic variants of MTHFR, MTR, MTRR genes and mutations of FV and FII genes of blood coagulation in women with a history of miscarriage]. Zhurnal Kharkivskoho natsionalnoho universytetu im. V.N. Karazina. Ser. Biolohiya. 2011. Vol. 13, No. 947. P. 118–124.