Older dads are becoming more common

In 1993, fathers aged <35 years accounted for 74% of live births within marriage, while only 25% of such births were to fathers aged 35–54 years. Ten years later, these percentages were 60% and 40%.  When the reproductive potential of older men is discussed, several celebrities who became fathers at advanced age such as Rod Stewart, Pablo Picasso, Charlie Chaplin, Warren Beatty, Tony Randall and Anthony Quinn are often cited as examples.

While the public regards these cases with a mixture of admiration and skepticism, birth statistics show that there are quite a number of children born to fathers aged >50 years in the general population and this is true of Eastern and Western cultures alike. However, it is well known that practically no children are born to mothers aged >50 years and it is common to all older fathers that they have younger partners.    

The effect of aging on the sperm

Semen is studied under the microscope. A typical semen analysis will evaluate a specimen for the total volume of the ejaculate, the number of sperm (concentration), the percentage of moving sperm (motility) and the percentage of sperm with a normal appearance (morphology). Studies have tried to determine if any of these semen parameters decrease over time. These are difficult studies to perform since many variables are present. The majority of studies seem to indicate that the volume of the ejaculate decreases with age as well as the percentage of moving sperm. There is no definite conclusion about whether the concentration of sperm or the microscopic appearance of the sperm (morphology) changes or not.

Age-dependent alterations of semen parameters may have several causes. In addition to age per se, factors such as infections, vascular diseases or an accumulation of toxic substances may be responsible for a deterioration in semen parameters. In a study of almost 4000 infertile men, researchers showed an infection rate in some of the reproductive  glands in 6.1% in patients aged <25 years but in 13.6% of patients >40 years. More importantly, total sperm counts were significantly lower in men with infections compared to those without.

Fertility of older men

Fertility has been documented scientifically in men up to an age of 94 years. If fertility in men decreases with age, it may in part be due to erectile dysfunction. In a large survey of Italian men, the frequency of erectile dysfunction rose from 4.6% in men <25 years to 37.6% in men >74 years. A history of cigarette smoking essentially doubled the risk of erectile dysfunction as men aged.

Several studies have been performed that tried to control for these and other variables in male fertility. For example, a study of birth rates in married couples in Ireland before the widespread use of contraception found that the probability of birth decreased for men starting from 42–43 years of age. Another study found that men >45 years old are 4.6-fold more likely to take over 1 year to get their partners pregnant relative to men aged < 25 years old.

With the use of fertility treatments , age related sperm problems may be bypassed. In fact, the more invasive the treatment, the less important male age appears to be. For example, several studies looking a the success rates of intrauterine insemination where sperm is injected directly into the uterus of a woman on the day of ovulation,  found an adverse impact of increased male age. On the other hand, several studies looking at the use of ICSI in which sperm is injected directly into an egg, did not find an effect of male age.  However, recently a group of researchers analyzed data from a German IVF registry from 1998 to 2002. They found a significantly reduced pregnancy rate in couples with male age >50 years and female age between 31 and 40 years, compared to couples with a male age <50 years. They suggest that this effect may have escaped the notice in previous studies because of a lower number of couples in this male age category.

There may also be an increase in the risk of miscarriage in older men. A recent study of over 5000 pregnant women in California concluded that the risk of miscarriage increased with increasing paternal age, and found that the association was stronger for miscarriages that happened in the first trimester. A study completed in 2002 found that the risk of miscarriage increased in older men but only when the women were also older.

Miscarriage risk according to father's age

                                  This study suggests that for women under age 30, the age of the father does not increase the risk of miscarriage. Women who are aged 30 to 34 are at increased risk for miscarriage if the male is over age 40. Women who are over age 35 are at particularly high risk if their partners are over age 40. In this group, the risk for miscarriage was 6 times higher.

The causes for the increase in miscarriages with male aging is unknown. It is well known that the risk for chromosomal abnormalities in fetuses increases as women age and that these chromosomal abnormalities are responsible for the increase in miscarriage risk. No studies have ever found an increase in the rate of chromosomal abnormalities in fetuses with increasing male age however.

Risks to babies with older fathers

Women have all of the eggs they are ever going to have in their lives before they are born. The cells in the ovary which are destined to become eggs will go through several cell divisions and then stop. The eggs will then remain in this “off position” for the entire duration of a woman’s life until the egg is ovulated. It is this process that is thought to be responsible for the increased risk of chromosome abnormalities in eggs and embryos as women age. Men, on the other hand, produce sperm continuously all through their lives. The cells that produce sperm are constantly dividing during a man’s life. Every time a cell divides, the DNA must be exactly copied so that each “daughter cell” is identical to the “parent cell”. However, the more times a cell divides, the greater the chances for an error to be made when the DNA is being copied. These errors in DNA are called mutations.

It is possible, therefore, that older men may be at greater risk for having sperm with small errors (mutations) in the DNA and that these errors could cause certain diseases in the children of older men.

Risk of chromosome abnormalities

Two studies have found that older men have a greater risk for producing children with Down’s Syndrome (Trisomy 21).  In one study, men over age 40 were compared to men under age 25. The other study compared men 50 and older to men aged 25 to 29. Both studies found the risk for producing Down’s syndrome was higher.

Risk of genetic mutations

In August 2012, a study found that dads pass on an average of 25 new mutations at age 20, increasing to 65 mutations at age 40.   In the last several years, studies have focused on diseases caused be genetic mutations in the DNA and whether their is a relationship to the age of the father. Genetic diseases which are strongly thought to be related to the age of the father include:

Achondroplasia, the most common form of dwarfism. Occurs in 1 in 15000 to 1 40,000 live births
Craniosynostotic diseases, characterized by premature fusion of the bones of the skull. Includes:
— Crouzon’s syndrome
— Pfeiffer’s syndrome
— Apert’s syndrome – 1 70 000 live births
Other skeletal diseases – thanatophoric dysplasia

Other genetic diseases show a much weaker impact of male age:

Osteogenesis imperfecta — a disease of weak bones
Neurofibromatosis
Retinablastoma — a cancer of the back of the eye. One study suggested a threefold increase in risk for father who are older than 45 at the time of conception. Another study found a lesser risk and still a third study did not find any increase in risk at all.

A Danish population based study of 1920 affected births of 1.5 million live births concluded that paternal age is associated with cleft lip and cleft palate, independently of maternal age. Single gene mutations are the suggested mechanism.

Other diseases may have both a genetic and an environmental component and are referred to as complex or multi-factorial diseases. Some of these diseases have been identified as possibly occurring more commonly in older father.

Acute lymphoblastic leukaemia — one study found a 50% increased risk for fathers aged 35 years or more
Congenital heart disease — overall one study estimated that 5% of cases may be due to advanced paternal age
— Ventricular septal defect — the risk if the father is over 40 is 69% higher than if the father is less then 40
— Atrial septal defect — 95% increase in risk if the father is over aged 35

It should be pointed out that several studies did not find a relationship between congenital heart defects and paternal age.

Alzheimer’s disease — 4 studies concluded there was an increase risk with paternal age but 4 other studies concluded that there was no increase in risk.
Schizophrenia — Virtually all studies have concluded that there is an increase risk with increased age of the father. One study estimated that about 25% of cases of schizophrenia could be attributed to paternal age. Another study concluded that if there was no family history of schizophrenia then the relationship was even stronger, with as many as 60% of cases of schizophrenia being due to paternal age.
A population based study of childhood brain cancers reported to the Swedish Cancer Registry between 1960 and 1994 concluded that there is a paternal age affect, estimated to confer about 25% excess risk in fathers >35 years of age.
Advanced paternal age has also been associated with increased risk of breast cancer and prostate cancer in their children.

Risk of autism from older fathers

The cause of autism and related disorders (ASDs) is unknown; however, results from twin and family studies provide evidence for a strong genetic contribution. Environmental influences may also be important. The reported prevalence of ASDs has increased significantly during the past few decades. In this same period, the average age of men and women at the time of conception has also increased.  

The results of several large, well performed studies on the effects of parental age have yielded conflicting results. In an Australian population, one study found that increased female age, but not male age, was associated with autism. In a Danish population, a study found that the risk of autism was associated with increasing male age but not female age. A second Danish study reported no association between risk of autism and either male or female age. In April, 2007, the results of a large American study were published. This study concluded that both male and female age were associated with an increased risk of autism and related disorders even after adjusting for other factors. The older the parent, the greater the increase in risk.   In August, 2012, a study of families with an autistic child concluded that a father’s age could account for 15% to 30% of cases of autism due to the occurrence of new mutations the occur as men age.

Conclusion

Increasing male age may cause a decrease in fertility if the female is also older. The chance for miscarriage also seems to increase but the mechanism is not due to the most common reason for miscarriage which is numerical chromosome abnormalities. The overall impact of male age is far less than the impact of female age. Several diseases caused by gene mutations as well as several with multiple genetic and environmental causes are related to increasing paternal age. Despite these increased risks, the absolute risk of the diseases remains small.