Male fertility and age: How does the choice of a sperm cell affect for an assisted reproduction treatment?

When it comes to fertility, most of the attention is focused on women. However, a growing body of research shows that a man’s age also influences fertility and the health of the future baby.

A study presented at the 42nd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), led by Dr. Patricia Díaz-Gimeno and Dr. Nicolás Garrido, the study’s principal investigator and the director of the IVI Foundation, respectively, highlights how the passage of time affects sperm genetics and its potential implications.  

Male fertility and age: How does sperm change?

One of the study’s main findings is that sperm undergoes mutations over the course of a man’s life. This phenomenon is directly linked to the continuous production of sperm, which involves multiple cell divisions and, therefore, a higher likelihood of genetic errors.

Furthermore, the research reveals a key finding: mutations found in sperm don’t always match those detected in blood.

“We have found that there are mutations that are only present in sperm and do not appear in blood, which means they can go unnoticed in current genetic studies,” explains Dr. Patricia Díaz-Gimeno.

This represents a significant shift from what was previously assumed, as traditional genetic analyses have been based on blood samples.

What types of mutations are found in sperm?

The analysis goes beyond simply quantifying mutations; it also identifies their potential impact on health.

The alterations detected include:

• Mutations of uncertain significance
• Changes in genes related to the nervous system
• Alterations associated with the autism spectrum and intellectual disability
• Variants linked to serious cardiovascular diseases
• Mutations linked to liver diseases
• Alterations in severe immunodeficiencies
• Possible links to tumor processes

These results indicate that the genetic quality of sperm can have an impact beyond fertility, also affecting embryonic development and the baby’s future health.

Advanced paternal age: when does the risk increase?

Although mutations can occur at any age, their frequency increases with time. The study’s data shows that men over 45 have 31% more mutations in their sperm than those under 30.

This increase is linked to the biological process of male aging itself. Unlike women, whose ovarian reserve is finite, men produce sperm throughout their lives, which leads to the gradual accumulation of genetic alterations.

Impact on the baby’s health

The study reinforces an important idea: sperm not only plays a role in conception, but also in the transmission of key genetic information.

Some mutations can:

• Manifest from birth
• Appear throughout life
• Have no known clinical effects

This means that the father’s age can have both short- and long-term implications, although experts emphasize that this does not mean that there is a problem in every case.

The goal, therefore, is not to cause alarm, but to provide information so that people can better understand the potential risks and make informed decisions.

Implications of male fertility and age for assisted reproduction

One of the study’s most significant aspects is its potential impact on clinical practice.

Currently, genetic testing for carriers is performed using blood samples, assuming that DNA is uniform throughout the body. The results, however, suggest that this approach may be incomplete.

This opens the door to new strategies in assisted reproduction:

• Incorporating genetic analysis directly into sperm
• Adjusting the criteria of sperm donation programs
• Improving genetic risk assessment before pregnancy

According to the researchers, this type of testing could be especially useful for men of advanced paternal age, when the mutation load is higher.

The evolving concept of male fertility

Traditionally, male fertility has been assessed based on parameters such as sperm concentration, motility, and morphology.

However, this approach is evolving toward a more comprehensive model that includes the genetic quality of sperm.

• Sperm is not genetically static
• A man’s age does influence reproduction
• Male genetics play a significant role in a baby’s health

Conclusions

This study yields several important conclusions:

• Male fertility also changes with age
• Sperm can undergo mutations over time
• Some of these mutations are not detected by standard tests
• The genetic quality of sperm can influence offspring

In short, scientific evidence suggests that a father’s age is a factor to consider when planning for a family.

Furthermore, the study represents a step forward in understanding human fertility. The notion that the “biological clock” only affects women is giving way to a more balanced view, where the role of men is also key.

The ability to directly analyze the genetic material in sperm opens up new opportunities to:

• Improve prevention
• Personalize treatments
• Reduce genetic risks

Dr. Patricia Diaz Gimeno

Leader of the Genomic and Systems Reproductive Medicine group at FIVI Valencia. Specialized in endometrial receptivity, reproductive pathologies, female fertility, and psychology applied to reproduction.

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