Cribado ampliado de portadores en un programa de donación de ovocitos: Implementación de un nuevo test y resultados tras dos años de experiencia

The present study describes the implementation of a carrier screening test for autosomal recessive and X-linked diseases in an Oocyte Donation Programme (donors and male partners of the recipients). The Next-Generation Sequencing (NGS) based test covered 200 genes (68 genes by complete sequencing of the coding region and 132 sequenced by a targeted mutation analysis) associated with 314 diseases (277 recessive autosomal diseases and 22 X-linked). The results obtained after 2.5 years showed a high degree of acceptance (implementation rate > 80%). Among participants, 56.4% (761/1350) were identified as carriers of at least one gene mutation. It was also identified that 1.9% of donor candidates were carriers of X-linked diseases, and for this reason were excluded from the Oocyte Donation programme. The mean carrier burden was 0.84 mutations per sample. There were 3.4% of preassigned donor-recipient matches with a high reproductive risk for transmitting a severe autosomal-recessive genetic condition to their offspring (cystic fibrosis, classical congenital adrenal hyperplasia, autosomal-recessive non-syndromic sensorineural deafness, alpha thalassemia, familial Mediterranean fever, Niemann-Pick disease, thyroid dyshormogenesis type 6 and cartilage-hair hypoplasia). The definitive matching was made taking into account the genetic results. A carrier state for an autosomal recessive condition was not an exclusion criterion for the Oocyte Donation programme, although it implied the assignation of the donor to a recipient whose male partner was not a carrier for the same recessive condition. Genetic counselling at different stages of the clinical process was essential in order to achieve the purposes of decreasing anxiety in the gamete donors and recipient couples, to achieve a high understanding of the results, and to give appropriate recommendations about their own reproductive risk or that of their relatives, when necessary.