Protecting the health of donor-conceived offspring.

Abstract

Genetic screening of gamete donors bears critical importance for protecting donor-conceived offspring. This case report describes a woman in her forties who discovered through genealogical testing that she carries a Lynch syndrome-related pathogenic MSH2 variant inherited from an anonymous sperm donor. Her genetic father died of colorectal cancer at a young age, and among her identified genetic half-siblings, one had already developed advanced colorectal cancer. Had the donor been screened for actionable pathogenic variants-such as the Lynch syndrome-associated mutation identified in this case, for which surveillance and preventive measures are available-this information could have enabled early surveillance, prevention, and informed reproductive decision-making for both the donor and offspring. We review current screening approaches, which rely on family history assessment that while requiring a three-generation pedigree per regulatory guidelines, may be incomplete due to the donor's young age, limited family knowledge, or low disease penetrance, and on targeted genetic panels that may miss actionable pathogenic variants. Recent advances in population genomic screening, including expanded carrier screening and testing for adult-onset conditions, now make screening for actionable pathogenic variants in gamete donors increasingly feasible. We address ethical considerations including donor autonomy, the right to know genetic information, and information disclosure policies. We examine international legal frameworks governing gamete donation and genetic screening. Our recommendations include comprehensive genetic screening of all donors for actionable pathogenic variants, centralized registries linking donors to offspring, standardized protocols for updating families with new genetic information, and clear policies addressing donor anonymity in the genomic era. Implementation of these recommendations would significantly reduce preventable morbidity and mortality in donor-conceived individuals while respecting the rights of all parties involved.