O-233 The current landscape for carrier screening in donor conception; a game of chance for donors and recipients?

Abstract

Abstract Study question How do international regulatory and commercial factors influence donor carrier screening and pose dilemmas for donors, clinics, and recipients. Summary answer Inconsistencies in international carrier screening guidelines and practice for donor conception create a two-tier system for donors and recipients. What is known already Carrier screening is used to identify those who are at risk to have a child with an autosomal recessive or X-linked genetic disorder. Donor banks adopt a commercially viable approach for carrier screening for their market and export, which creates inequalities in donor recruitment and reproductive risk for recipients. For example, UK guidelines require donors to be screened only for cystic fibrosis, with non-European donors screened for conditions known to be more common by ancestry. Real-world pan-ethnic approaches, however, are taken in varying degrees in other countries via extended carrier screening, posing dilemmas for donors, recipients, and clinics. Study design, size, duration Using current available public information, 14 UK, European, and US donor banks were surveyed to understand the screening level for recessive conditions and how this was conveyed to the patient or clinic client. Separately, expanded carrier screening (ECS) results (283 - 502 genes) from 1742 prospective donors from a > 6 year period at a US sperm bank were analysed to calculate acceptance rates if minimal screening and exclusion criteria were applied. Participants/materials, setting, methods UK, European, and US donor gamete banks were identified and surveyed using public information (2023). Separately, internal data from a US sperm bank related to ECS results from 2017 – 2023 was extracted, collated, and evaluated against the UK donor sperm genetic screening guidelines. Main results and the role of chance All donor banks surveyed state donors are genetically screened. For recessive conditions, UK and European banks screened for a small panel of between 3-20 genes, published on a general screening page on the donor bank website, and exclude donors that are carriers. Some offer an additional paid ECS genetic matching service without revealing what the donor or recipient may be carriers for. US banks who perform ECS include these results with a donor profile; some banks exclude carriers of more common recessive disease, while others accept all donors regardless of carrier status. Results from the US sperm bank indicated that of 1742 prospective donors who had ECS, only 117 (6.7%) of carriers would have been reported if screening under minimal guidelines. 665 of the 782 US positive carrier donors would not have been identified as carriers if tested according to UK guidelines. This, together with the observed varying regulation and commercial ECS panels used by donor banks internationally, demonstrate a tiered system of information availability and sharing for reproductive risk knowledge for donors and recipients; recipients are not consistently informed of the limitations of screening of a selected donor, and acceptance of donors to programs is inconsistent. Limitations, reasons for caution The panel composition and number of genes are variable by commercial ECS provider and donor banks may vary their carrier screening policy or commercial ECS options over time. Additionally, other European countries may have differing recommendations in regards to carrier screening practices. Wider implications of the findings As donor sperm imports from within and outside Europe increase, registered donors within countries will present differing genetic risk. Review and implementation of current carrier screening guidelines are required to ensure consistency of methodology and availability of transparent information for donors, recipients, and clinics to consider the wider implications. Trial registration number not applicable