# Impact of advanced paternal age on reproductive outcomes in preimplantation genetic testing cycles of young female: a retrospective cohort study

## TL;DR

Older fathers have higher sperm DNA damage, which may reduce embryo quality and pregnancy chances, even when mothers are young.

## Contribution

This study shows that advanced paternal age increases sperm DNA fragmentation, which negatively affects embryo development and pregnancy outcomes.

## Key findings

- Men aged ≥40 had significantly higher sperm DNA fragmentation compared to younger men.
- APA was linked to reduced blastocyst and high-quality blastocyst formation rates.
- Higher DNA fragmentation was independently associated with lower clinical pregnancy rates.

## Abstract

Although advanced paternal age (APA) is increasingly scrutinized in reproductive medicine, its independent impact on embryo development and clinical outcomes remains contentious, particularly when controlling for maternal age and embryo ploidy.

This retrospective cohort study analyzed 357 preimplantation genetic testing for aneuploidy (PGT-A) cycles from couples with non-advanced maternal age (≤35 years). Cycles were stratified by paternal age into three groups: <35, 35–39, and ≥40 years. We compared sperm DNA fragmentation index (DFI), embryo development metrics, and clinical outcomes across these groups.

Men aged ≥40 years exhibited significantly higher levels of sperm DFI compared to both younger groups (both P < 0.05). While no significant differences were observed in normal fertilization, high-quality embryo rates, or euploid blastocyst rates across paternal age groups, blastocyst development was notably impaired in the APA group. Specifically, the ≥40-year group demonstrated significantly reduced blastocyst formation rates (57.3% vs. 68.6% and 67.2%) and high-quality blastocyst formation rates (33.2% vs. 41.3% and 40.2%) compared to the <35 and 35–39 groups, respectively. Crucially, multivariate regression analysis identified DFI as an independent factor, with higher DFI significantly associated with a reduced likelihood of forming high-quality blastocysts (OR = 0.987, P = 0.046) and achieving a clinical pregnancy (OR = 0.961, P = 0.036). The sensitivity analysis demonstrates that even when examining a population of very young women (≤32 years) where the influence of maternal age on oocyte quality is expected to be minimal and uniform, the negative association between sperm DFI and embryo development potential persists (aOR = 0.980, P = 0.009).

Our findings indicate that APA itself does not directly affect blastocyst ploidy status but is associated with significantly elevated sperm DNA fragmentation. Despite the lack of direct evidence, the detrimental effects of APA on high-quality blastocyst formation and clinical pregnancy rates are probably associated with this increase in DFI. This study underscores the critical role of sperm DNA integrity in reproductive success and suggests that DFI assessment should be considered in the clinical evaluation of older men undergoing infertility treatments.