ASSOCIATION OF INTERLEUKIN-1α GENE POLYMORPHISM (ENCODED REGION rs1800587 5`UTR) WITH EFFICIENCY OF IN VITRO FERTILIZATION

Due to quite low efficiency and high costs of in vitro fertilization protocols, there is a necessity for development of new diagnostic criteria for selection of patients. The purpose of this study was complex analysis of association of polymorphic variants of IL-1α gene (rs1800587 5`UTR region) and main diagnostic criteria of women with tubo-peritoneal infertility and success rate of in vitro fertilization procedure. We have examined 120 women with tubo-peritoneal infertility who were subjected to the microflare protocol of controlled ovarian hyperstimulation which was followed by embryo transfer. Concentration of IL-1α in blood serum was defined by ELISA method by means of test systems of the "Cytokine LLC" (St. Petersburg, Russian Federation). Polymorphic marker rs1800587 at 5`UTR region was analysed with PCR method followed by the sequencing. We have detected no particular features in distribution of polymorphic IL-1α gene variants in pregnant women. The T/T genotype seems to be a conditionally favorable predictor for pregnancy resulting from in vitro fertilization. It has been shown that the IL-1α content in blood serum of pregnant women was increased as compared to women who did not become pregnant. It was also shown that pregnant women with T/T genotype had higher serum IL-1α levels than women with other genotypes. During transvaginal puncture, we have detected that pregnant women with T/T genotype had more oocytes than women with C/C genotype. We have not found significant differences in 17-oxyprogesterone, estradiol, follicle-stimulating hormone, testosterone contents for groups of women with different IL-1α genotypes. As based on this study, the IL-1a involvement in the implantation become more evident. Further studies are required concerning influence of IL-1a on folliculogenesis, ovulation, implantation, decidualization and placenta formation.

1. Gromova A.Yu., Simbirtsev A.S. Gene polymorphisms of interleukin-1 family cytokines. Tsitokiny i vospalenie = Cytokines and Inflammation, 2005, Vol. 4, no. 2, pp. 5-7. (In Russ.)

2. Komissarova Yu.V., Kuzmichev L.N. Tuboperitoneal infertility: clinical value of determination of vascular endothelial growth factor in the prediction of ovarian hyperstimulation syndrome. Akusherstvo i ginekologiya = Obstetrics and Gynecology, 2010, no. 4, pp. 50-54. (In Russ.)

3. Korsak V.S., Smirnova A.A., Shurygina O.V. Russian VRT register, 2014. Problemy reproduktsii = Russian Journal of Human Reproduction, 2016, Vol. 22, no. 5, pp. 10-21. (In Russ.)

4. Kulakov V.I., Leonov B.V., Kuzmichev L.N. Treatment of female and male infertility. Auxiliary reproductive technologies. Moscow: MIA, 2005. 592 р.

5. Motovilova N.O., Kogan I.Yu., Syssoev K.A., Buinova A.N., Griaznov A.Yu., Totolian A.A. Impact of some cytokines to efficiency of infertility treatment by means of in vitro fertilization. Meditsinskaya immunologiya = Medical Immunology (Russia), 2012, Vol. 14, no. 4-5, pp. 373-382. (In Russ.) doi: 10.15789/1563-0625-2012-4-5-373-3826.

6. Nazarenko T.A. Stimulation of ovarian function. Moscow: MEDpress-inform, 2015. 288 р.

7. Seidova L.A., Yavorovskaya K.A. Molecular-biological foundations of implantation control. Voprosy ginekologii, akusherstva i perinatologii = Questions of Gynecology, Obstetrics and Perinatology, 2010, Vol. 9, no. 3, pp. 79-83. (In Russ.)

8. Sokolov D.I., Selkov S.A. Immunologic control of placenta development. Zhurnal akusherstva i zhenskikh bolezney = Journal of Obstetrics and Women Diseases, 2010, Vol. LIX, no. 1, pp. 6-10. (In Russ.)

9. Simbirtsev A.S. Cytokines – classification and biologic functions. Tsitokiny i vospalenie = Cytokines and Inflammation, 2004, Vol. 3, no. 2, pp. 16-22. (In Russ.)

10. Gérard N., Caillaud M., Martoriati A., Goudet G., Lalmanach A.-C. The interleukin-1 system and female reproduction. Journal of Endocrinology, 2004, Vol. 180, no. 2, pp. 203-212.

11. Ma N.-Z., Chen L., Dai W., Bu Z.-Q., Hu L.-L., Sun Y.-P. Influence of endometrial thickness on treatment outcomes following in vitro fertilization/intracytoplasmic sperm injection. Reproductive Biology and Endocrinology, 2017, Vol. 15, p. 5.

12. Uri-Belapolsky S., Shaish A., Eliyahu E., Grossman H., Levi M., Chuderland D., Kamari Y. Interleukin-1 deficiency prolongs ovarian lifespan in mice. Proceedings of the National Academy of Sciences of the United States of America, 2014, Vol. 111, no. 34, pp. 12492-12497.

13. Simon C., Frances A. Embryonic implantation in mice is blocked by interleukin-1 receptor antagonist. Endocrinology, 1994, Vol. 134, no. 2, pp. 521-528.