59. PREIMPLANTATION GENETIC TESTING FOR HERITABLE CONNECTIVE TISSUE DISEASES

Introduction Heritable connective tissue disorders (HCTD) are a group of mostly autosomal dominant genetic diseases, characterized by cardiovascular involvement, tissue fragility, joint hypermobility and skin involvement. Some of them are associated with life threatening events such as aortic dissection and rupture, and a high mortality rate. We recently introduced Preimplantation Genetic Testing for monogenic disease (PGT-M) with a focus on HCTD and set up an explorative qualitative study to investigate the lived experiences and feelings of women, as well as their attitudes and psychological responses to PGT-M. Materials & Methods All couples are seen by a clinical geneticist and a psychologist, and blood samples of the couple are drawn for karyotyping, exclusion of carriership of cystic fibrosis, spinal muscular atrophy and fragile-X syndrome. Informative linked microsatellite markers flanking the causal (familial) mutation are identified for each couple. Once these parameters are defined, DNA, obtained from trophectoderm cells biopsied from a day 5-6 embryo, is genome-wide amplified. Subsequently, the informative linked microsatellite markers as well as the underlying disease causing mutation are analysed in each of these day 5-6 embryo's. In total, twelve HCTD couples have undergone the PGT-M procedure (FBN1: 4, SMAD3: 2, one each for TGFBR1, TGFB2, COL3A1, COL1A2, COL2A1 and WNT10A). In total, 52 embryos have been tested, 19 of them carried the healthy haplotype (microsatellite analysis) and did not carry the familial mutation (Sanger sequencing) and thus were suitable for transfer to the mother. Data of seven women, aged 26-39years, were collected by semi-structured interviews and interpreted by thematic analysis. At the time of the interviews, one participant had one child through PGT-M, two participants were pregnant after embryo transfer and four women did not have a successful embryo transfer leading to pregnancy yet. Results Our study shows that PGT-M is both physically and emotionally a demanding procedure. The main reason for choosing PGT-M is the severity of the disease. None of the couples wants to transmit the disease to their offspring. Since termination of pregnancy is not acceptable to them, PGT-M is preferred over prenatal diagnosis. The “drop-out race”, as all interviewed women call it, going from an encouraging number of available oocytes (after pick-up), to a limited number of useful embryos, is perceived as extremely stressful. Due to the frequent hospital visits and the prescribed strict timing of hormone injections, all women stated it is impossible to keep the PGT-M procedure hidden from their friends and colleagues. Women emphasize that receiving adequate information, during every step of the PGT-M process, is essential to learn more about the entire PGT-M trajectory. They also express the need of psychological support to help them in coping with this physical and psychological demanding technique. Conclusions PGT-M is a valuable option of reproductive technology for HCTD couples. Due to the significant emotional impact the PGT-M procedure causes, we advise that it should always go hand-in-hand with effective communication and psychological care in order to prevent distress in couples.