P–559 Proof of principle for Extended Carrier Screening (ECS) in medically assisted reproduction: First 33 cases of genetic matching for donors and recipients

Abstract

Abstract Study question Does implementation of ECS to reduce reproductive risk when using a donor with a known carrier status serves as a wider model for ART patients. Summary answer ECS should be routinely offered to ART patients using their own or donor gametes to reduce risk of having a child with a recessive condition. What is known already Responsible implementation of ECS in assisted reproduction is required as commercial offerings increase and become more accessible; ESHRE ethical guidelines are shortly to be published after consideration of stakeholder reviews. Increasingly ECS is included in donor screening, rejecting potential donors for a known carrier status will reduce donor gamete availability. Clinics should consider potential match yield in carrier panels to develop tools and specialist support to deliver and guide patients to help make informed decisions for ECS. Study design, size, duration Retrospective evaluation of ECS results for the first 33 patients who undertook counter screening in the clinic setting from April 2020 to December 2020 before using a donor with known carrier status. The findings would serve as proof of concept for wider application. Participants/materials, setting, methods Patients had opted to undertake ECS after discussion of risk estimates, family history review and personal options.Testing was commissioned between two ECS providers for international donor banks using panels of 283+ genes. Incidence of carrier match, the number of variants reported, and their clinical significance were reviewed. Main results and the role of chance: Of the 33 co-carrier tests, one carrier match for a patient and potential donor was identified. 41%, 26%, 9% and 3% of patients were carriers of 1, 2, 3 and 4 pathogenic variants respectively in 30 different genes. In 21% of patients, no pathogenic variants were reported. Of the variants identified as incidental findings, six were actionable and eligible for cascade screening to the wider family. This included Cystic Fibrosis, Sickle cell and Thalassemia. A variant for Familial hypercholesterolemia had preventative value. An incidental finding of a fragile X pre-mutation allowed for PGT-M as part of planned treatment Limitations, reasons for caution Findings from this first cohort of 33 tests may not represent the general population, follow up evaluation as participant numbers increase is required. Wider implications of the findings: Implementation of guidelines is required to ensure consistency of methodology and availability of transparent information for ECS to ART patients. Incidental findings may be of value to the patient and wider family. Trial registration number Not applicable