Mitigating adverse pregnancy and neonatal outcomes through expanded carrier screening in an oocyte donation programme

How frequent are adverse outcomes in an oocyte donation programme, and how many recessive conditions can be prevented by implementing expanded carrier screening (ECS)?

This retrospective observational study used data from oocyte donation cycles between January 2014 and December 2021 at the Reproductive Medicine Unit of a University Hospital in Spain. Adverse outcomes were studied in 4565 oocyte donation cycles assigned as low-risk at the time of genetic matching. The number of high-risk assignations was identified when ECS was applied to the oocyte donor and recipient's male partner (or sperm donor for double donation).

Of 4565 oocyte donation cycles, 67 recipients (1.47%) reported an adverse obstetric or neonatal outcome. A genetic aetiology was confirmed in 25 (37.3%). The remaining 42 (62.7%) cases included congenital malformations, neurodevelopmental disorders and other conditions with unknown genetic origins. Moreover, 211 (4.6%, 211/4565) high-risk assignations were identified where both the oocyte donor and recipient's male partner were carriers of the same autosomal recessive condition. This could have led to an additional 1.15% of children born with an autosomal recessive condition (25% × 4.6%). Additionally, 52 (2.8%, 52/1875) oocyte donor candidates were carriers of X-linked conditions, which would have led to an additional 0.7% (25% × 2.8%) being born with an X-Linked disorder. ECS implementation resulted in a 55.7% reduction in adverse outcome risk, from a potential rate of 3.32% (1.47% + 1.15% + 0.7%) to an actual incidence of 1.47%.

ECS reduces the probability that children born from oocyte donation will inherit the recessive conditions screened for. However, certain adverse outcomes remain unavoidable.