Analysis of KIR genotyping results in women with recurrent implantation failure

  • K. O. Sosnina State Institution «Institute of Hereditary Pathology of the National, Academy of Medical Sciences of Ukraine», Ukraine, 79008, Lviv, M. Lysenko str., 31a https://orcid.org/0000-0003-4527-2010
  • D. V. Zastavna State Institution «Institute of Hereditary Pathology of the National, Academy of Medical Sciences of Ukraine», Ukraine, 79008, Lviv, M. Lysenko str., 31a https://orcid.org/0000-0002-3858-7180
  • O. I. Terpyliak State Institution «Institute of Hereditary Pathology of the National, Academy of Medical Sciences of Ukraine», Ukraine, 79008, Lviv, M. Lysenko str., 31a https://orcid.org/0000-0001-6274-8362
Keywords: KIR genotyping, Recurrent Implantation Failure (RIF), in vitro fertilization (IVF)

Abstract

Aim. To analyze the frequency and distribution of KIR genotypes in women with recurrent implantation failure after cycles of in vitro fertilization. Methods. DNA extraction and purification, PCR-SSP, agarose gel electrophoresis. Results. The spectrum of KIR genes and the frequency of KIR genotypes in women with recurrent implantation failure were determined. The study group was divided according to history, in particular, a group of 84 women whose diagnosis was outlined by the concept of "repeated failed implantations" was singled out. Statistical analysis of the obtained results using the Pearson test (χ2) indicates a significantly lower frequency of the KIR-AB genotype (χ2 = 9.7; p < 0.005) and a significantly higher frequency of the KIR-AA genotype (χ2 = 7.35; p < 0.01) in women with repeated failed implantations compared to the general group of women with reproductive failures. Conclusions. Taking into account the results of statistical data processing (OR = 2.05; CI 95 %: 1.21-3.45), we consider the KIR-AA genotype to be a significant risk factor for recurrent implantation failure after IVF. We define KIR genotyping as a genetic test to assess the risk of the embryo being rejected by the maternal immune system, and thus to direct medical interventions in order to achieve a successful pregnancy.

References

Alecsandru D., García-Velasco J. A. Why Natural Killer Cells Are Not Enough: A Further Understanding of Killer Immuno-globulin-Like Receptor and Human Leukocyte Antigen. Fertil. Steril. 2017. Vol. 107. P. 1273–1278. doi: 10.1016/j.fertnstert.2017.04.018.

Somigliana E., Vigano P., Busnelli A., Paffoni A., Vegetti W., Vercellini P. Repeated Implantation Failure at the Crossroad Between Statistics, Clinics and Over-Diagnosis. Reprod. BioMed Online. 2018. Vol. 36. P. 32–38. doi: 10.1016/j.rbmo.2017.09.012.

Busnelli A., Reschini M., Cardellicchio L., Vegetti W., Somigliana E., Vercellini P. How Common is Real Repeated Implantation Failure? An Indirect Estimate of the Prevalence. Reprod. BioMed Online. 2020. Vol. 40. P. 91–97. doi: 10.1016/j.rbmo.2019.10.014.

Zhang X., Wei H. Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications. Front. Immunol. 2021. Vol. 12. P. 1–14. doi: 10.3389/fimmu.2021.728291.

Yeung H.-Y., Dendrou C. A. Pregnancy Immunogenetics and Genomics: Implications for Pregnancy-Related Complications and Autoimmune Disease. Annual Rev. of Genom. and Hum. Genet. 2019. Vol. 20. P. 73–97. doi: 10.1146/annurev-genom-083118-014943.

Piekarska K., Radwan P., Tarnowska A., Wiśniewski A., Radwan M., Wilczyński J. R., Malinowski A., Nowak I. ERAP, KIR, and HLA-C Profile in Recurrent Implantation Failure. Front Immunol. 2021. Vol. 22 (12): 755624. P. 1–13. doi: 10.3389/fimmu.2021.755624.

Hammond J. A., Carrington M., Khakoo S. I. A Vision of KIR Variation at Super Resolution. Immunology. 2016. Vol. 148. P. 249–252. doi: 10.1111/imm.12606.

Blunt M. D., Khakoo S. I. Activating Killer Cell Immunoglobulin-Like Receptors: Detection, Function and Therapeutic Use. Int. J. Immunogenet. 2020. Vol. 47. P. 1–12. doi: 10.1111/iji.12461.

Maftei R., Doroftei B., Popa R., Harabor V., Adam A-M., Popa C., Harabor A., Adam G., Nechita A., Vasilache I-A., Mihalce-anu E., Bivoleanu A., Lunguleac G., Cretu A-M., Armeanu T., Diaconu R., Cianga P. The Influence of Maternal KIR Haplotype on the Reproductive Outcomes after Single Embryo Transfer in IVF Cycles in Patients with Recurrent Pregnancy Loss and Implantation Failure – A Single Center Experience. Journal of Clinical Medicine. 2023. Vol. 12 (5): 1905. doi: 10.3390/jcm12051905.

Nowak I., Wilczyńska K., Wilczyński J. R., Malinowski A., Radwan P., Radwan M., et al. KIR, LILRB and Their Ligands' Genes as Potential Biomarkers in Recurrent Implantation Failure. Arch. Immunol. Ther. Exp. (Warsz). 2017. Vol. 65. P. 391–399. doi: 10.1007/s00005-017-0474-6.

Makukh H. V., Zastavna D. V., Tyrkus M. J., Tretiak B. I., Chorna L. B. Sposib vydilennia DNK z leikocytiv peryferijnoi krovi: pat.32044 Ukraina: MPK G01N33/49 (2006.01); No u200801896; appl. 14.02.2008; publ. 25.04.2008, bul. No. 8. [in Ukrainian]

Tajik N., Shahsavar F., Nasiri M., Radjabzadeh M. F. Compound KIR-HLA genotype analyses in the Iranian population by a novel PCR-SSP assay. Int J. Immunogenet. 2010. Vol. 37 (3). P. 159–168. doi: 10.1111/j.1744-313X.2010.00906.x.