Focusing on parental origin of aneuploidy: does paternal age impact aneuploidy rates in embryos?

Abstract

While it is known that aneuploidy rates increase with advancing maternal age (MA) due to deterioration of the oocyte’s meiotic system,1 there has been no proven paternal age (PA) association. Some authors have postulated that advancing PA may be associated with increased risks for aneuploidy,2,3 while other studies have shown no association.4 In this study, we report the 24-chromosome preimplantation genetic testing for aneuploidy (PGT-A) results for trophectoderm (TE) samples from a series of men who underwent in vitro fertilization (IVF) cycles using oocyte donors, broken down by PA. Retrospective analysis. All PGT-A cases with TE biopsy and an oocyte donor between July 2010 and April 2019 were included in the analysis. TE and biological parental samples were run on Illumina Cyto12 SNP-based microarrays with informatics to determine parental origin of each chromosome and establish chromosome copy number. Statistical analysis was performed using a two-tailed t-test. Results were obtained on 13,018/13,394 (97.2%) of submitted TE samples. The average PA for this patient cohort was 43.5 ± 6.9 years (range 23‒73). Aneuploidy rates are broken down by PA using SART age groups (Table 1). Additional analysis performed for men >50 years showed an aneuploidy rate of 704/2031 (34.7%) which was not statistically different from the other PA groups. Moreover, there was no statistical difference in the paternal aneuploidy rates or aneuploidy of mixed origin between PA groups (p>.05).Table 1Aneuploidy rates by PAPaternal age (years)Cases (n)Embryos (n)Average number of embryos per case (n)Euploid Rate ± SD (%)Aneuploid Rate ± SD (%)Aneuploidy of Maternal Origin ± SD (%)Aneuploidy of Paternal Origin ± SD (%)Aneuploidy of Mixed Origin ± SD (%)<3517311566.766.3 ± 1.433.7 ± 1.450.6 ± 3.131.1 ± 2.918.3 ± 2.435-3723314526.267.7 ± 1.232.3 ± 1.254.3 ± 2.831.8 ± 2.613.9 ± 1.938-4028719726.966.5 ± 1.133.5 ± 1.157.4 ± 2.324.4 ± 2.018.2 ± 1.841-4220114937.467.6 ± 1.232.4 ± 1.259.2 ± 2.725.0 ± 2.415.8 ± 2.0>4296473217.666.4 ± 0.633.6 ± 0.654.1 ± 1.228.7 ± 1.117.2 ± 0.9Overall1858133947.266.7 ± 0.433.3 ± 0.454.9 ± 0.928.2 ± 1.216.9 ± 0.7 Open table in a new tab In this study, we did not observe an increase in aneuploidy rates with advanced PA, adding to existing literature showing a lack of PA effect. SNP microarrays with informatics uniquely allows determination of parental origin of aneuploidy in embryo samples. The difference in overall aneuploidy rates and paternally inherited aneuploidy rates among the PA groups was not statistically significant (p>0.05). This information can be used to aid in patient counseling by providing reassurance that estimates for aneuploidy rates should be based primarily on the age of the oocyte contributor.