HEALTH OF WOMAN. 2019.8(144): 36–40; doi 10.15574/HW.2019.144.36
Yu.P. Vdovychenko¹, N.O. Firsova², K.H. Khazhylenko^2
1Shupyk National Medical Academy of Postgraduate Education, Kiev
²Isida-IVF Medical Center, Kyiv

The objective: to evaluate the prevalence of hemostasis and folate cycle gene polymorphisms in patients with a history of miscarriage.

Materials and methods. A survey was conducted of 125 women with habitual miscarriage who were in the first, main, group. The criteria for inclusion of patients in the study were the presence of two or more pregnancy losses in the anamnesis up to 22 weeks. The exclusion criteria were anatomical, endocrine, infectious, immunological, social causes of miscarriage, and the presence of benign uterine tumors and antiphospholipid syndrome. Group II (control) included 40 somatically healthy women, without reproductive losses, with a history of at least one physiological pregnancy.

All women underwent a molecular genetic study of 8 hemostatic system genes and 4 folate cycle genes by a multiplex allele-specific polymerase chain reaction in real time.

Results. As a result of the analysis in women with habitual miscarriage, statistically significantly more often revealed: homozygous polymorphism for the gene FGB 455G> A, ITGA2 (α₂-integrin) C807T, both homo- and heterozygous forms, homozygous polymorphism 5GG75GG7575G > 4G – homo- and heterozygous forms, as well as polymorphism of MTHFR 677C> T and MTHFR 1298A> C genes.

A statistically significant association of ITGA2 807C> T and PAI-1 675 5G> 4G polymorphisms was confirmed with more than six and sevenfold increased odds of habitual miscarriage (p=0.0002 and 0.0001, respectively). Carrying the mutant allele of the FGB 455G> A gene was associated with a 3.6-fold increase in the chances of reproductive loss. Multigenic forms of thrombophilia were detected in 109 (87.2%) women of the main group, which was 3.5 times higher than the corresponding indicators in the control group – 10 (25.0%); p <0.05.

Conclusion. In order to prevent recurrent reproductive losses in patients with a history of pregnancy miscarriage, with the exception of other causes, it is necessary to carry out an examination for the presence of clotting and folate cycle polymorphisms. Detection of the carrier of mutant alleles in patients with pregnancy miscarriage will help to properly study the activity of certain parts of the hemostasis system, to adequately select therapy and to realize the reproductive function of a woman.

Key words: habitual miscarriage, pregnancy polymorphism of hemostasis genes, folate cycle.

REFERENCES

1. Veropotvelyan PN, Veropotvelyan NP. 2011. Trombofilii i beremennost. Zdorove Ukrainy 9/10 (50):30–34.

2. Bushtyireva IO, Kuznetsova NB, Kovaleva AV s soavt. 2015. Rasprostranennost trombofilicheskih polimorfizmov zhenschin s privychnym nevyinashivaniem beremennosti v anameneze. Akusherstvo, ginekologiya i reproduktsiya 9 (2): 13–18.

3. Callejón G, Mayor-Olea A, Jiménez AJ et al. 2007. Genotypes of the C677T and A1298C polymorphisms of the MTHFR gene as a cause of human spontaneous embryo loss. Hum. Reprod. 22 (12): 3249–3254. https://doi.org/10.1093/humrep/dem337; PMid:17965025

4. Cao Y, Xu J, Zhang Z et al. 2013. Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: a meta-analysis. Gene. 514 (2):105–111. https://doi.org/10.1016/j.gene.2012.10.091; PMid:23201418

5. Chen H, Yang X, Lu M. 2016. Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis. Arch Gynecol. Obstet.  293 (2): 283–290. https://doi.org/10.1007/s00404-015-3894-8; PMid:26399758

6. Davenport WB, Kutteh WH. 2014. Inherited thrombophilias and adverse pregnancy outcomes: a review of screening patterns and recommendations. Obstet Gynecol. Clin North Am. 41 (1): 133–144. https://doi.org/10.1016/j.ogc.2013.10.005; PMid:24491988

7. Diejomaoh MF. 2015. Recurrent spontaneous miscarriage is still a challenging diagnostic and therapeutic quagmire. Med. Princ. Pract. 24 (1): 38–55. https://doi.org/10.1159/000365973; PMid:25428171 PMCid:PMC6489083

8. Hyde KJ, Schust DJ. 2015. Genetic considerations in recurrent pregnancy loss. Cold Spring Harb. Perspect Med. 5 (3): 23–39. https://doi.org/10.1101/cshperspect.a023119; PMid:25659378 PMCid:PMC4355257

9. Jeon YJ, Kim YR, Lee BE et al. 2013. Genetic association of five plasminogen activator inhibitor-1 (PAI-1) polymorphisms and idiopathic recurrent pregnancy loss in Korean women. Thromb. Haemost. 110 (4): 742–750. https://doi.org/10.1160/TH13-03-0242; PMid:23903286

10. Kaur R, Gupta K. 2016. Endocrine dysfunction and recurrent spontaneous abortion: an overview. Int. J Appl Basic Med. Res. 6 (2): 79–83. https://doi.org/10.4103/2229-516X.179024; PMid:27127734 PMCid:PMC4830160

11. Liu RX, Wang Y, Wen LH. 2015. Relationship between cytokine gene polymorphisms and recurrent spontaneous abortion. Int J Clin Exp Med 8(6): 9786– 9792.

12. Mtiraoui N, Borgi L, Hizem S et al. 2005. Prevalence of antiphospholipid antibodies, factor V G1691A (Leiden) and prothrombin G20210A mutations in early and late recurrent pregnancy loss. Eur J Obstet Gynecol Reprod Biol 119(2): 164–170. https://doi.org/10.1016/j.ejogrb.2004.07.003; PMid:15808373

13. Parand A, Zolghadri J, Nezam M, Afrasiabi A, Haghpanah S, Karimi M. 2013. Inherited thrombophilia and recurrent pregnancy loss. Iran Red Crescent Med J 15(12): e13708. https://doi.org/10.5812/ircmj.13708

14. Shahine L, Lathi R. 2015. Recurrent pregnancy loss: evaluation and treatment. Obstet. Gynecol. Clin North Am. 42 (1): 117–134. https://doi.org/10.1016/j.ogc.2014.10.002; PMid:25681844

15. Sugiura-Ogasawara M, Nakano Y, Ozaki Y, Furukawa TA. 2013. Possible improvement of depression after systematic examination and explanation of live birth rates among women with recurrent miscarriage. J Obstet. Gynaecol. 33 (2): 171–174. https://doi.org/10.3109/01443615.2012.745490; PMid:23445142

16. Wu X, Zhao L, Zhu H et al. 2012. Association between the MTHFR C677T polymorphism and recurrent pregnancy loss: a meta-analysis. Genet. Test Mol. Biomarkers. 16 (7): 806–811. https://doi.org/10.1089/gtmb.2011.0318; PMid:22313097