Common male infertility disorders: Aging

Abstract

As life expectancy increases and our lives become busiest every day, many couples are –waiting longer to establish their families. The recent trend toward delayed parenthood raises concerns because of the adverse effects of aging on fertility. The effects of paternal age on a couple's fertility are real and may be greater than has previously been thought. After adjustments for other factors, it has been demonstrated that the probability of a fertile couple will take >12 months to conceive nearly doubles from 8% when the man is <25 years to 15% when he is >35 years; thus, paternal age is a further factor to be taken into account when deciding the prognosis for infertile couples. Also, the increased male age is associated with a significant decline in fertility (fivefold longer time to pregnancy at age of 45 years), which is independent of the woman's age, coital frequency, and lifestyle effect, as well as the effect of other subfertility risk factors. Furthermore, fathering at older ages may have significant effects on the viability and genetic health of human pregnancies and offspring, primarily as a result of structural chromosomal aberrations in sperm. The evidence for sex chromosomal aneuploidy suggests that there may be about a twofold increase in risk at the age of 50. In fact, the risk for a father over 40 years old to have a child with an autosomal dominant mutation equals the risk of Down syndrome for a child whose mother is 35–40 years old. Although individual Leydig cell volume does change with age, the total Leydig cell volume and the absolute number of Leydig cells decrease significantly with age. Also, anatomical studies of Sertoli cell populations in humans show that the young adult male testis is endowed with 500 million Sertoli cells and appears to decline to approximately 300 million cells in the older adult, suggesting that there is also an age-related decline in Sertoli cell numbers in the human testis. Furthermore, estimations of individual germ cell populations in younger and older men suggest that the age-related decrease in sperm production results from an absolute decrease in primary spermatocytes or a decrease in spermatogonial proliferation rather than a cellular degeneration in the spermatid to mature sperm stages of spermatogenesis. Mechanisms of cell senescence have been well studied in the last decade, and the free radical theory has brought considerable attention. Despite the established effects of free radicals on biomarkers of aging, their correlation with male infertility is not completely elucidated.