Expanded Carrier Screening in gamete donation identifies clinically relevant donor-recipient genetic incompatibilities

Most individuals carry pathogenic variants associated with autosomal recessive disorders. In donor-assisted Assisted Reproductive Technology (ART), broader carrier screening may identify additional donor-recipient genetic risks beyond standard donor screening. This study evaluated the frequency of donor-recipient shared carrier findings identified through Expanded Carrier Screening (ECS) and explored their potential clinical relevance.

In this retrospective cohort study, 250 couples undergoing donor-assisted ART between January 2022 and September 2025 were analyzed. The cohort included 220 oocyte donation cycles (88%), 20 sperm donation cycles (8%), and 10 double-donation cycles (4%). 1 ECS was used to assess carrier status and donor-recipient genetic compatibility according to the study's recorded matching criteria. All participants received pre-test genetic counseling.

The use of ECS increased markedly over the study period. A donor-recipient shared carrier status was identified in 26-44% of couples undergoing ECS-based donor-recipient matching. Shared carrier status was observed in 35% of sperm-donation, 24% of oocyte donation, and 20% of double-donation cycles (p > 0.05). The probability of incompatibility increased with increasing individual pathogenic variant burden (p < 0.05), reaching 40-50% in individuals carrying two to four pathogenic variants before ECS-based donor matching.

ECS identified a substantial proportion of donor-recipient shared carrier findings. However, the clinical relevance and incremental contribution of ECS beyond standard donor screening depend on the specific condition and the genes and variants already assessed in the donor. These findings support the use of ECS as a broader approach to reproductive risk assessment, while highlighting the need for gene-level matching data to quantify its incremental clinical utility.