P-548 IMPORTANCE OF EXPANDED CARRIER SCREENING AMONG OOCYTE DONORS - questions and concerns

Abstract Study question To examine the utility of a range of expanded screening panels for oocyte donors. Summary answer Expanded carrier screening with NGS data identified that 86% of gamete donors were carriers of at least one condition while 302 genes were tested. What is known already The level of genetic testing for oocyte donors is not regulated in most countries. The use of expanded carrier screening is recommended more widely. If the egg donor is a carrier, there is a 50% chance that the offspring will also be carriers. Expanded carrier screening is performed to determine the potential effects of positive carrier status, which guarantees safety for future pregnancy. From practical experience, more genes are tested for a donor, more potential mutations are detected. Study design, size, duration A cohort of 92 potential oocyte donor applicants aged 18-30 years old, who were qualified for oocyte donation after full screening, tested negative on an initial cystic fibrosis carrier test for 11 most common CFTR mutations (PCR panel), was further screened with expanded commercial carrier testing panel (302 genes) using next-generation sequencing (NGS) data. Participants/materials, setting, methods A cohort of 92 potential oocyte donor applicants aged 18-30 years old, who tested negative on an initial cystic fibrosis carrier test for 11 most common CFTR mutations (PCR panel), was further screened with expanded commercial carrier testing panel (302 genes) using next-generation sequencing (NGS) data. Main results and the role of chance Genotyping results for all donors were analyzed; 38% (35/92) of donors were identified as carriers for one condition, 34% (31/92)- for two conditions, 7% (6/92)- for three conditions and 7% (6/92)- for four conditions, including cystic fibrosis. Among the most prevalent conditions in our study were: Hemochromatosis: Type 1: HFE Related- 22%, Cystic Fibrosis: CFTR-related conditions 11%, Biotinidase deficiency– 7,6%, 21-Hydroxilase-Deficient Congenital Nonclassical Adrenal Hyperplasia- 6,5%, Krabbe disease – 6,5%, Usher syndrome: USH2A-related conditions – 6,5%, Nonsyndromic deafness: GJB2- related conditions- 5,4% and Smith-Lemli-Opitz syndrome (5,4%). Limitations, reasons for caution Each donor was consented for genetic testing Wider implications of the findings This study shows a need to provide the explicit requirement for oocyte donor genetic testing and guidelines to satisfy quality and safety and not reduce the number of