BLASTOCYST QUALITY BUT NOT ANEUPLOIDY IS AFFECTED BY ADVANCED PATERNAL AGE IN DONOR OOCYTE IVF CYCLES

It is well known that advanced paternal age (APA) exerts a negative impact on semen quality and offspring health. However, there is conflicting evidence if increasing paternal age has an association with embryo development and chromosome constitution. The purpose of this study was to investigate the impact of paternal age on embryonic outcomes in a large consecutive series of donor oocyte IVF cycles. This single center, retrospective, clinical study investigated consecutive, donor oocyte IVF cycles that underwent preimplantation genetic testing for aneuploidy (PGT-A; VeriSeq, Vitrolife) from January 2017 to December 2022. Embryos were grouped by paternal age: APA (n=1761 biopsies; ≥45 years, mean 49.8±4.6 years) and young fathers (n=3049 biopsies; <45 years, mean 38.6±3.8 years). The primary outcomes were blastocyst development and chromosome constitution. Chi-square Test for independence was used for statistical analysis, with p<0.05 considered significant. A reduced percentage of transferrable quality (≥grade 3BB) blastocysts was observed on day 5 of embryonic development for the APA group relative to young (49.9% APA vs. 52.7% young; p=0.0549) which corresponded with a trend towards a decrease in top quality day 5 grade AA blastocysts (14.6% APA vs. 15.5% young; p=0.0605). Concurrently, a higher proportion of day 7 blastocysts were observed for APA fathers (5.7% APA vs. 3.5% young; p=0.0003), representing a reduced reproductive potential.Interestingly, the prevalence of aneuploidy was significantly lower in the APA cohort compared to young (30.4% APA vs 33.7% young; p=0.0238) with full segmental aneuploidy errors also significantly lower (4.0% APA vs. 6.3% young; p=0.0011), though mosaic errors were equivalent between groups (3.1% APA vs. 3.4% young; ns). Likewise, the proportion of APA blastocysts derived from male factor infertility cases (MF; count <15% million/mL, motility <40%, or morphology <4%) was significantly lower in the older fathers compared to young (6.4% APA vs. 8.7% young; p=0.005) with a similarly trending proportion of men diagnosed with MF infertility producing segmental aneuploidy errors (2.7% APA vs. 7.2% young; p=0.098). In this large study of consecutive, donor oocyte IVF cycles, no effect of APA was observed on the prevalence of embryonic aneuploidy, however a significant impact was detected on the timing and quality of blastocyst development. While APA has been correlated with declining semen parameters, our dataset presented with a lower prevalence of MF infertility compared to the younger group. The increased aneuploidy rate observed in the cohort of blastocysts derived from younger fathers are in fact represented by full segmental aneuploidy errors, reported by our group and others to be predominantly paternally inherited, and oftentimes observed in conjunction with male factor infertility.