Verlinsky O. Family-specific prеimplantation genetic testing for the prevention of monogenic and chromosomal pathology in humans

The dissertation identifies molecular genetic / cytogenetic characteristics of individuals from families that most often need assisted reproductive technologies (ART) and optimization of preimplantation genetic testing of aneuploidies / structural changes (PGT-A / SR) and monogenic pathologies (PGT-M) taking into account these characteristics. The results showed that preimplantation genetic testing of embryos should be performed on the fifth day of their development in vitro. The largest share of embryos was obtained from parents with translocations of chromosomes A and C groups ‒ 37.0% and 22.5% of all tested, and the largest share of euploid embryos with balanced chromosome sets ‒ from parents with translocations of chromosomes B and D groups ‒ 21 ‒ 4- 18.2%, respectively. The difference between mothers and fathers carrying translocations in the ratio of embryos with balanced and unbalanced translocations was established. Among the individuals from whom five-day-old embryos were obtained and analyzed, the male-to-female ratio was 3 : 1, and the incidence of successful pregnancies was almost one and a half times higher in the male translocation groups. It was found that comparable results after using NGS and FISH methods to assess chromosome set were obtained for 78.6% of embryos on the fifth day of development. Aneuploidy of chromosome 6 was found in 6.0% of embryos in families with monogenic pathologies requiring PGT-M with HLA-typing, which will affect the final result of HLA-typing in the absence of PGT-A. It has been shown that HLA-typing during preimplantation genetic testing of gene mutations and aneuploidies allows the birth of a healthy HLA-identical donor for the treatment of individuals with pathologies requiring allogeneic bone marrow transplantation. A negative relation between parental age and the number of embryos with a euploid set of chromosomes has been proven, so the using of PGT-A during PGT-M