Impact of male age on paternal aneuploidy: single-nucleotide polymorphism microarray outcomes following blastocyst biopsy.

ABSTRACT

RESEARCH QUESTION Does advanced paternal age (APA; ≥40 years) contribute to a higher incidence of paternal origin aneuploidy in preimplantation embryos? DESIGN: This was a multicentre retrospective study of single-nucleotide polymorphism (SNP) microarray (Natera and Karyomapping) preimplantation genetic testing (PGT) outcomes of blastocyst-stage embryos. Whole-chromosome aneuploidy analysis was performed on 2409 embryos from 389 male patients undertaking 681 assisted reproductive technology (ART) cycles between 2012-2021. Segmental aneuploidy analysis was performed on 867 embryos from 140 men undertaking 242 ART cycles between 2016-2021. Embryos were grouped based on paternal age at sperm collection <35, 35-39 and ≥40 years. Paternal and maternal origin aneuploidy rates were compared between groups using chi-squared and/or Fisher's exact tests. RESULTS: There was no significant difference across groups in paternal origin whole-chromosome aneuploidy rate, overall (P=0.7561) or when segregated by type (trisomy and monosomy P=0.2235 and 0.8156) or complexity (single versus 2, 3 or ≥4 aneuploidies P=0.9733, 0.7517, 0.669 and 0.1481). Conversely, maternal origin whole-chromosome aneuploidy rate differed across groups (P<0.0001) in alignment with differing mean maternal age (P<0.001). Paternal origin deletions were 2.9-fold higher than maternal origin deletions (P=0.0084), independent of age stratification. No significant difference in paternal origin deletions was observed with APA ≥40 compared with the younger age groups (4.8% versus 2.5% and 2.8%, P=0.5292). Individual chromosome aneuploidy rates were too low to perform statistical comparisons. CONCLUSIONS: No significant association was found between APA and the incidence of paternal origin aneuploidy in preimplantation embryos, irrespective of type or complexity. Thus, APA may not be an indication for PGT.