AbstractsMedical & Health Science

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 gave no phenotypic symptoms but since the abnormality seemed to be present at a higher frequency in her gonads, there was a high” hidden” recurrence risk for affected offspring or repeated miscarriages. In Paper II a linear regression analysis was performed of data from all 569 PGD cycles performed between 1996 and 2009. We found two factors of significant importance for the PGD outcome. Firstly, the age of the woman at stimulation start where women under 36 years were three times more likely to achieve a pregnancy P = 0.003 and odds ratio 3.1 [95% confidence interval (CI) 1.5-6.5]. Secondly, the number of biopsied cells from each embryo where PGD cycles with one cell removal were twice as likely to result in a pregnancy compared to those cycles were two cells had been removed P = 0.0013 and odds ratio 2.55 (95% CI 1.44 – 4.52). Accordingly, we have now introduced an age limit of 40 years at stimulation start for the woman and changed policy to one cell biopsy for almost all indications since 2009. Paper…