Introduction

Infertility has become a worldwide problem, affecting up to 20% of couples trying to conceive [1, 2]. In this context, a few important facts should be emphasized: 1) male factors (coexisting with female factors) contribute to infertility in up to 20–70% of cases, and one-third of these cases are due to male factors alone [1–3]; 2) an actual decline in semen quality over the past decades has been observed globally [4]; and 3) paternal age is rising, as an increasing number of men are decide to became a father at an older age [5, 6].

It is known that the risk of poor reproductive outcomes can increase with a male age of >40 or even >35 y, commonly classified as advanced age. Age-dependent changes in male organism (e.g. vascular sufficiency, increase in incidence of systemic diseases and infections, disorders of histological structure of testes, decreased levels of sex hormones, oxidative stress, de novo mutations) are deleterious and the consequences of advanced paternal age include a prolonged waiting time to pregnancy, delayed embryo development in in vitro conditions, an increased incidence of embryo implantation failure and abortions, pregnancy problems and live birth outcome [7–9] (Figure 1). In addition, advanced paternal age also seems to affect children's health. There is a positive correlation between paternal age and the incidence of mental deprivation of offspring, such as those associated with the autism spectrum and diseases such as schizophrenia, especially when the paternal age is ≥40–50 y [10–13]. Furthermore, the frequency of genetic disorders, such as Klinefelter syndrome [14]; Down syndrome, when mother age is >35 y [15]; and autosomal dominant diseases such as Marfan syndrome (men >40 y), Pfeiffer and Crouzon syndrome (men >50 y), Apert syndrome (men >37 y), achondroplasia and neurofibromatosis type 1 rises in children of fathers >40 y. Unfortunately, the risk of central nervous system and breast cancers as well as leukaemia is growing [12]. More often, children with heart defects (e.g., ventricular septal defects, atrial septal defects, large vessel transposition), neural tube defects, anencephaly and tracheo-oesophageal fistula have been born to men >35, 40, and 45 y of age [13] (Figure 1) https://www.aging-us.com/article/102120/text