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  • Writer's pictureNatasha Quinton-Hibberd

The Unappreciated Reality of the Male Biological Clock: Men have a fertility cliff too!

By: Natasha Quinton-Hibberd, fourth-year MSc in Biology at St Catherine's College, University of Oxford. All opinions are her own.



The Ageing Female Partner


It is a well-documented phenomenon that a women’s fecundity (fertility) naturally declines with increasing age. Many studies have shown that female fertility declines from the age of 30, with it rapidly deteriorating after the age of 35. The term “biological clock” has traditionally been used to describe this age-associated decline in fertility documented in women. However, it is becoming increasingly recognised that women are not solely responsible for age-related fertility issues. Advanced paternal age and its’ relationship with fertility, a historically neglected area of research, is also beginning to be investigated and recognised as a key player in fertility issues, begging the question: Do men, too, have a biological clock?


The Ageing Male Partner


Although stories of men in their 60s becoming fathers has encouraged the notion that male fertility is timeless, recent research is beginning to disprove this common misconception. The World Health Organisation (WHO) has defined a set of factors, known as semen parameters, that influence healthy sperm, including sperm count, seminal volume, morphology (shape) and motility (movement). As men age, there are changes in these semen parameters that correlate with decreased fertility. Below outlines what research so far has ascertained on the effects of ageing on semen parameters.


Figure 1. Some of the WHO defined semen parameters that change with age


Sperm Count & Concentration


The data on whether sperm concentration changes with advancing male age is inconsistent. Whilst some studies have reported a decrease in sperm concentration of up to 3.3% per annum, other publications have reported no change in sperm concentration up to the age of 50. However, numerous studies have illustrated that after the age of 50, anomalous sperm concentrations become much more common. Whilst there is a clear decline in sperm concentration after the age of 50, more research will be required to determine whether there is a correlation between age and sperm concentration before the age of 50.


Sperm Motility


In contrast to sperm concentration, evidence strongly and consistently suggests that sperm motility decreases as age advances. Studies have found a significant decrease in motility of between 0.17% to 0.6% per year of age. More recently, one study on men aged between 22 to 80 years of age, by Sloter and colleagues, found that motility decreased by 0.8% per year of age, and linear motion decreased by 0.2% per year. Sperm motility is paramount to fertilisation and so will strongly influence male fertility.


Sperm Morphology


Analogous to motility, morphology also appears to decline with advancing male age. Studies have suggested declines in normal sperm morphology of between 0.2 to 0.9% per year of age. Which, over a 20-year period, is a decrease of between 4% to 18% in normal morphology.


Seminal volume


Evidence so far on seminal volume indicates a mild decrease with age, of only between 0.15% to 0.2% per year of age. So, over a 20-year period, data suggests only a 3-4% decrease in seminal volume. However, in men aged over 45 years, studies suggest that seminal volume begins to drop significantly. Ejaculate volume is mainly comprised of seminal vesicle fluid, and so it is believed that this decrease in volume is related to seminal vesicle insufficiency. More research is required to determine the conclusive scientific reasons behind this decrease in seminal volume.


Sperm DNA fragmentation


The amount of sperm DNA fragmentation indicates the amount of damaged DNA inside a sperm, and thus the quality of the sperm. As men age, the risk of presenting anomalous levels of sperm DNA fragmentation also increases.


Hormonal changes in Ageing Men and the “Andropause”

Alongside changes in sperm and semen production, hormonal changes that affect libido and can cause erectile dysfunction (ED) may also influence male fertility. As with women, male hormone levels change with age. It has been shown that male testosterone levels, after the age of 30, decline by roughly 1% per year, and this phenomenon has been termed andropause. These declining testosterone levels can lead to reduced libido, ED, and difficulty achieving ejaculation. A second hormone, sex-hormone binding globulin (SHBG), increases in males at a rate of 1.6% per annum, which scientists have also speculated may further reduce testosterone levels.

Figure 2. Graph to show how testosterone levels change with age in men. (Image: Charleston Physicians)


Adverse Impacts of Paternal Age on Infants?


As well as the influence of ageing on male physiology and reproductive health, there is also new research to suggest that advancing male age may have harmful effects on the health of new-born infants. One study, analysing more than 40.5 million births in the United States, revealed that advanced paternal age had many adverse effects. It was found that babies born to fathers aged 45 years or older had 14% higher odds of premature birth, and 18% higher odds of seizures, when compared with infants of fathers aged 25 to 34 years.


This study clearly indicates that advanced paternal age may have negative consequences for infants. The odds of gestational diabetes were also found to be 34% higher in mothers with the oldest partners, suggesting that advanced paternal age may also be associated with adverse effects on mothers. However, despite strong correlational evidence, causal relationships are yet to be investigated, and are required to prove a direct link between advanced paternal age and adverse consequences for mothers and babies.


The Ageing Couple


Whilst it has long been accepted that a woman’s age affects their fertility, there is beginning to be a new-found appreciation for how paternal age can too influence fertility. As men age, both changes in sperm quality, and hormonal changes, can reduce male fertility, deeming the male biological clock a real and under-appreciated cause of infertility. As well as changes to male reproductive physiology, advancing age also seems to have an adverse influence on infant and mother health.


Thanks to current research, it is becoming more established and widely known that women are not solely responsible for age-related fertility issues. Infertility is no longer just a “woman’s problem”. This newfound awareness of the influence of the male biological clock on fertility will allow for couples to more comprehensively address their fertility issues, facilitating the proper testing, diagnosis, and potential treatment of male infertility issues.


References

1. Lambert, S.M., Masson, P. and Fisch, H. (2006) ‘The male biological clock’, World Journal of Urology, 24(6), pp. 611–617.

2. Harris, Isiah D et al. “Fertility and the aging male.” Reviews in urology vol. 13,4 (2011): e184-90.

3. Pasqualotto, Fabio Firmbach et al. “The male biological clock is ticking: a review of the literature.” Sao Paulo medical journal = Revista paulista de medicina vol. 126,3 (2008): 197-201.

4. Khandwala Y S, Baker V L, Shaw G M, Stevenson D K, Lu Y, Eisenberg M L et al. Association of paternal age with perinatal outcomes between 2007 and 2016 in the United States: a population-based cohort study BMJ 2018













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