Does Advanced Paternal Age Increase the Rate of Paternally Derived Aneuploidy as Detected by SNP Array?

Abstract

Objective: Recent studies have investigated the impact of paternal age on the incidence of embryo aneuploidy using young oocyte donors to control for maternal age, with conflicting results observed. This study takes a different approach, looking at the parental source of embryo aneuploidy as detected by SNP array. The aim was to determine whether the incidence and type of paternal-origin aneuploidy would increase with advancing paternal age. Design: A retrospective study of PGT outcomes from 1541 embryos with trio SNP array linkage-based testing from 2012-2020 across three paternal age groups: <35yrs (n=410), 35-40yrs (n=789) and >40yrs (n=315). The primary outcome was frequency of paternally derived aneuploidy in each age bracket. The secondary endpoint was comparison of the complex abnormality rate and the rates of specific trisomies and monosomies of paternal origin. Results: There was no association between advancing paternal age and prevalence of paternal-origin aneuploidy (<35yrs: 17.8%, 35–40yrs: 16.2%; >40yrs: 17.1%). Moreover, no differences were found between age cohorts in the occurrence of paternal-origin trisomy and paternal-origin monosomy. However, the rate of paternally derived complex abnormal embryos appeared increased with advancing paternal age (<35yrs: 2.9%; 35-40yrs: 3.8%; >40yrs: 4.4%) but did not reach statistical significance. Analysis of specific chromosomes showed the >40yrs cohort had a marked increase in rates of trisomy 4 (2.22% vs. 1.22% <35yrs; 0.63% 35–40yrs), trisomy 10 (0.95% vs. 0.49% <35yrs; 0.38% 35-40yrs), trisomy 12 (1.27% vs. 0.49% <35yrs; 0.51% 35-40yrs) and trisomy 19 (1.59% vs. 0.73% <35yrs; 0.76% 35-40yrs). Unlike previously reports, no clear difference was observed in the rate of trisomy 21 with advancing paternal age. Conclusion: We conclude that there is no association between paternal age and the overall rate of paternal-origin aneuploidy. However, our findings suggest a possible effect of advanced paternal age (>40yrs) on the rate of paternally derived complex abnormalities, as well as increased rate of specific paternal-origin trisomies (4, 10, 12, 19).