New developments in Preimplantation Genetic Testing: towards noninvasive, comprehensive chromosome screening
Preimplantation genetic testing (PGT) is performed during an in vitro fertilisation (IVF) treatment and aims to prevent the birth of a child with a genetic disorder or to increase the implantation potential for carriers of balanced chromosomal rearrangements. Recent technological advances have revolutionized the field, but have also raised several new questions. The introduction of genome-wide technologies enables comprehensive chromosome screening (CCS), empowering the detection of aneuploidies and structural rearrangements unrelated to the genetic defect under investigation. While this might seem valuable to further improve the success rate of PGT, questions remain about the validity and relevance of these (mosaic) aberrations in the trophectoderm and their relation to embryo development. In this thesis we will explore the relation between (mosaic) aberrations in the trophectoderm biopsy and the development of the inner cell mass at the peri-implantation stage. Next, we will investigate the added value of genotyping-by-sequencing (GBS) for the simultaneous detection of monogenic disorders and CCS, and evaluate its added value for mosaicism detection. Lastly, we will investigate newer, noninvasive methods for PGT, safeguarding the embryo. Tackling these issues will provide us more knowledge about (mosaic) chromosomal rearrangements and their relation to (normal) embryonic development. Furthermore, this knowledge will further improve the success rate of PGT.