Currently, half of the countries in the world have a fertility rate below the replacement level (Fauser et al., 2024). It is predicted that numerous countries will witness a population decline of over 50% from 2017 to 2,100 (Fauser et al., 2024). This will result in demographic shifts with far-reaching societal consequences. One of the key factors contributing to this scenario is the growing trend of delayed marriage and childbearing. As individuals age, the likelihood of natural conception declines. There are concerns about the fertility risks associated with older men, such as infertility and lower success rates in achieving pregnancy (Ramasamy et al., 2015). Consequently, Assisted Reproductive Technologies (ART), which can effectively facilitate conception, have attracted substantial attention (du Fossé et al., 2020).

The analysis of sperm quality parameters stands as the principal approach for evaluating male fertility (World Health, 2021). Over the past several decades, a discernible and gradual decline in male sperm quality has been witnessed. This decline is characterized by decreases in semen volume, total sperm count, sperm motility, and sperm concentration (Bahri et al., 2021; Liu et al., 2020). Multiple factors can exert an impact on sperm quality, including environmental exposures, lifestyle decisions, genetic elements, and endocrine and metabolic dysfunctions (Chung et al., 2019; Ohlander et al., 2016; Siegel et al., 2022; Zhang et al., 2024).

As paternal age advances, a substantial decline in reproductive cells, encompassing testicular interstitial cells, Sertoli cells, and germ cells, has been observed (Dakouane et al., 2005; Kaler and Neaves, 1978). A decrease in hormone levels, such as total serum testosterone, free testosterone, and androgen concentrations, is apparent (Harman et al., 2001; Kaufman and Vermeulen, 2005). Moreover, it has been discovered that chromosomal aberrations in sperm (Brahem et al., 2011; Ozkosem et al., 2015), DNA fragmentation (Albani et al., 2019; Moskovtsev et al., 2006; Singh et al., 2003), abnormal DNA methylation patterns, the accumulation of deleterious de novo mutations, and alterations in sperm telomere length are associated with male aging (Jónsson et al., 2017; Kong et al., 2012; Yang et al., 2015). The primary manifestation of these age-related alterations is the deterioration of semen parameters, such as semen volume and sperm progressive motility (Almeida et al., 2017; Hammiche et al., 2011; Johnson et al., 2015; Verón et al., 2018).

The sperm DNA fragmentation index (DFI) is considered a highly reliable indicator of fertilization capacity and the potential for embryonic development (Aflatoonian et al., 2024; Evenson DP. and Wixon R. 2006). Previous research has demonstrated that when the DFI exceeds 30%, it poses significant challenges to natural conception. This elevated DFI can give rise to pre-implantation embryonic abnormalities and early miscarriage (Esteves et al., 2020; Rex et al., 2017; Zhao et al., 2014). The degree of sperm DNA damage has a substantial impact on the success rates of intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) (Evenson D. and Wixon R. 2006; Zini et al., 2008). Additionally, sperm DNA damage substantially increases the risk of genetic disorders, birth defects, and unfavorable offspring outcomes (Aitken et al., 2014).

Considering the progressive decline in sperm quality with increasing paternal age, the transmission of genetic abnormalities may enhance the likelihood of early pregnancy loss or the occurrence of genetic disorders in offspring (Kaarouch et al., 2015; Lindman et al., 2024). The procedure of ART tends to have females actively involved, such as ovarian stimulation, embryo culture, and embryo transfer, but frequently ignores males, as sperm providers, and simplifies male-related factors and evaluation standards for instance sperm quality controls. As a consequence, limited clinical data are available to assess the male impact on the ART. Therefore, although maternal age is a well-recognized factor influencing the outcomes of the ART, whereas research exploring the relationship between paternal age and pregnancy outcomes remains relatively limited (Ezoe et al., 2023).

In this research, we explored the relationship between male age and sperm quality, along with its potential implications for the success rate in the ART. We identified a marked decline in sperm quality and an elevation in sperm DFI as male age advanced. Notably, neither male age nor sperm quality exerted a conspicuous influence on ART outcomes. Our study has underscored the inverse correlation between male age and sperm quality and has also elucidated the pattern of the ART success rate in relation to increasing male ages.

The challenges faced by older couples in achieving natural conception have escalated owing to age-related deteriorations in physical functions. The ART has emerged as a highly effective solution. Despite the growing prevalence of ART, research regarding the relationship between paternal age and pregnancy outcomes remains relatively underdeveloped. In this study, we analyzed the sperm quality of 6,805 Chinese males ranging in age from 20 to 63 years old. Additionally, we systematically collected data from 1,205 cases undergoing ART treatment. In clinic practice in China, men who visit the infertility clinic are required to take sperm quality tests. However, only men who are of advanced age or have experienced repeated implantation failures are required to take the sperm DFI test. Moreover, some infertile patients choose to receive clinical treatments such as ovulation monitoring, antioxidant therapy, and traditional Chinese medicine treatment. Therefore, a limited number of patients receive the ART in the end.

Our findings indicated a significant decline in sperm quality and an increase in sperm DFI with advancing male age. However, male age and sperm quality did not have a discernible impact on ART outcomes. This study uncovered the correlations among male ages, sperm quality, and ART outcomes. The insights gleaned from this research are expected to offer valuable and instructive information for future ART applications involving older males, potentially guiding medical practitioners in optimizing treatment strategies.

Our comprehensive examinations of semen volume, total motility, and progressive motility revealed that male age exerts a negative influence on sperm quality. Specifically, we found that sperm total motility and progressive motility reach their peak levels prior to the age of 30. Subsequently, a decline commenced after the age of 35, with the most pronounced decrease being observed in men over 40. This phenomenon is likely linked to alterations within the hypothalamic-pituitary-gonadal axis. A reduction in male hormone secretion from the adrenal cortex can potentially impact testicular spermatogenesis, as proposed in reference (AbdulHussain et al., 2020). In addition, we found that the sperm concentration increases with age. This may be due to the reduction in seminal plasma secretion caused by increasing age and reproductive tract infections, resulting in a decrease in semen volume and an increase in sperm concentration (Zitzmann, 2013).

Furthermore, the process of aging induces substantial changes in reproductive organs, including the testicles, vas deferens, and prostate. These anatomical and physiological alterations may further compromise sperm quality (Ashapkin et al., 2023). Additionally, our analysis of DFI demonstrated a significant positive correlation with advancing age, clearly indicating a decline in sperm DNA integrity. Older males are more prone to exposure to environmental hazards and reproductive diseases. Such exposures can modify enzymes like glutathione peroxidase and phospholipase. As a consequence, these changes may ultimately result in increased sperm DNA damage associated with the aging process (Aitken, Smith, Jobling, Baker and De Iuliis, 2014). As age progresses, the antioxidant capacity of the epididymis and the sperm DNA repair mechanisms gradually deteriorate. This continuous decline may further contribute to the elevation of the sperm DFI(Zhou et al., 2024). In conclusion, our findings strongly support an inverse relationship between male age on one hand, and sperm quality and DNA integrity on the other.

In an effort to explore the relationship between male age and the ART outcomes, we deliberately selected female participants who were 37 years old or younger and had generally normal ovarian reserve function. This selection criterion was implemented to minimize the confounding influence of female factors on the study results. During our analysis, we did not observe any significant differences in fertilization methods or the available embryo rate among different male age groups. It is known that early embryo development is predominantly regulated by the maternal genome. Paternal genes typically become activated and expressed only when the embryo reaches the six to eight cell stage. This biological phenomenon implies that male age is unlikely to have a substantial impact on early embryo development within the context of ART. However, our data on the available blastocyst rate suggested a decreasing trend in groups with older male partners.

Previous studies have demonstrated that sperm of low quality can impede blastocyst formation and increase the incidence of sex chromosome aneuploidy. These effects, in turn, raise the probability of adverse pregnancy outcomes (Coates et al., 2015). In our analysis of data from ART procedures, we did not identify any statistically significant differences in the pregnancy rate, miscarriage rate, live-birth rate, and cumulative pregnancy rate across different male age groups for each transplantation cycle. This finding aligns with previous reports (Gallardo et al., 1996; Paulson et al., 2001). However, a statistically significant difference was noted in the cumulative live birth rate. In addition, the oldest males recruited in this studies were 63. A sperm damage threshold might exist in older males, which exceeding this threshold might have an impact on the ART. The future study should recruit more males including those older than 65.

Early embryonic development is likely to be predominantly influenced by maternal genetic material. This is supported by research indicating that the oocyte has the capacity to repair DNA damage inflicted by sperm (Lord and Aitken, 2015). The oocyte’s repair mechanisms may buffer the potential negative impacts of sperm-related factors, such as those associated with different male age groups, on early embryo viability and subsequent live-birth outcomes. As a result, the observed lack of significant differences in many pregnancy-related metrics across male age groups could be attributed to the dominant role of the maternal contribution during the early stages of embryo development.

In conclusion, our research has shown that as male age advances, both sperm quality and DNA integrity deteriorate. Despite the fact that we did not detect any significant disparities in the outcomes of the ART among different male age groups, it is evident that advanced paternal age is linked to a certain level of declined fertility. Our study has revealed the correlations among male ages, sperm quality and ART outcomes, which will provide instructive information for future implementation of ART procedures involving older males.