Probability of high-risk genetic matching with oocyte and semen donors: complete gene analysis or genotyping test?

Abstract

To estimate the probability of high-risk genetic matching when assisted reproductive techniques (ART) are applied with double gamete donation, following an NGS carrier test based on a complete study of the genes concerned. We then determine the results that would have been obtained if the genotyping tests most widely used in Spanish gamete banks had been applied. In this descriptive observational study, 1818 gamete donors were characterised by NGS. The pathogenic variants detected were analysed to estimate the probability of high-risk genetic matching and to determine the results that would have been obtained if the three most commonly used genotyping tests in ART had been applied. The probability of high-risk genetic matching with gamete donation, screened by NGS and complete gene analysis, was 5.5%, versus the 0.6-2.7% that would have been obtained with the genotyping test. A total of 1741 variants were detected, including 607 different variants, of which only 22.6% would have been detected by all three genotyping tests considered and 44.7% of which would not have been detected by any of these tests. Our study highlights the considerable heterogeneity of the genotyping tests, which present significant differences in their ability to detect pathogenic variants. The complete study of the genes by NGS considerably reduces reproductive risks when genetic matching is performed with gamete donors. Accordingly, we recommend that carrier screening in gamete donors be carried out using NGS and a complete study with nontargeted analysis of the variants of the screened genes.