Preimplantation genetic diagnosis : evaluation of results and experiences

Preimplantation genetic diagnosis (PGD) is an established alternative for couples at high risk of having an affected child, with the advantage that the genetic testing is performed at the embryo stage and the couple can thereby avoid a pregnancy termination of an affected foetus. The disadvantage is that an IVF treatment is required, which can be a stressful experience. The main indications for PGD are monogenic disorders and chromosome abnormalities and there is an increasing demand for PGD each year. The PGD process can be divided into three steps 1) The IVF treatment, 2) The biopsy and 3) The genetic analysis. The aim with this thesis was to identify factors of importance for an optimal PGD and to learn more about patient’s experience of PGD in order to improve the advisory procedure and care of these patients. Another aim was to gain more knowledge regarding the segregation of different reciprocal translocations and their influence on fertility. Carriers of reciprocal translocations are usually healthy but have an increased risk of producing sperm or oocytes with an unbalanced chromosome content which gives them a high risk of repeated miscarriages, infertility and an increased risk to have an affected child. The unbalance arises during meiosis when the sperm and oocytes are formed and are present in every cell in the body in the offspring. However, some abnormalities arise after conception during the early embryo development resulting in mosaicism where some cells have the abnormality and some do not. This was the case in Paper I where germline mosaicism was demonstrated to be the cause of repeated pregnancies with the same unbalanced chromosome abnormality, although karyotypes from both parents initially were interpreted to be normal. Extended investigations with microsatellite markers and FISH analysis revealed the same abnormality in 4-6% of the mother’s fibroblasts. The couple went through four PGD cycles and the abnormality was found in 35% of the embryos. The low level mosaicism in the fibroblasts ...