Paternal age and sperm DNA fragmentation independently affect embryonic ploidy but not euploid embryo implantation...

To systematically evaluate the associations between paternal factors (age, semen parameters, body mass index, sperm DNA fragmentation index (DFI), and leukocyte count), embryonic ploidy, and the clinical implantation potential of euploid embryos.

Single-center retrospective cohort study.

Couples who underwent intracytoplasmic sperm injection and simultaneous preimplantation genetic testing for aneuploidy between May 2019 and September 2024, with control for maternal confounding factors.

(1) The association between paternal factors and the risk of embryonic aneuploidy, derived using generalized estimating equations, with individual embryos as the unit of analysis (2). The association between paternal factors and clinical pregnancy outcomes, with individual euploid blastocyst transfer cycles as the unit of analysis.

We analyzed 1,410 biopsied embryos (euploid group: 744 embryos; aneuploid group: 666 embryos). Multivariate analysis revealed that advanced paternal age (≥ 35 years) and high DFI (≥ 20%) were independent risk factors for the formation of embryonic aneuploidy, with risks increasing with higher age and DFI (e.g., age ≥ 40 years: OR = 2.033; DFI ≥ 30%: OR = 2.206). The association between paternal age and aneuploidy appeared to be associated with chromosomes 6, 18, and 22, whereas high DFI manifested as a broad genomic instability effect. Both factors were associated with a reduced incidence of X-chromosome abnormalities, which may be explained by early embryonic selective elimination. Subsequent analysis of 307 euploid embryo transfer cycles revealed that no paternal indicators were significantly associated with clinical pregnancy rates.

Advanced paternal age and high DFI are key risk factors for embryonic aneuploidy; however, their negative effects were primarily related to chromosome composition. Once euploid embryos are obtained, these paternal factors do not have a significant independent effect on subsequent implantation potential. Our findings suggest that clinical efforts should differ across treatment stages: early treatment should prioritize active management of male factors to improve euploid embryo yield, whereas treatment during the transfer phase should prioritize optimizing maternal uterine receptivity.