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Men's Fertility Related to Advanced Paternal Age

We have all heard the term, "Advanced Maternal Age," which is the point when a woman's fertility begins to decline and the chance for birth defects rises. But what about men? Is there an "Advanced Paternal Age" where men's fertility declines and chances for passing birth defects rise? Recent studies say yes.

A decade ago, the only concern experts expressed with men's fertility was whether or not their sperm was healthy enough to lead to conception. The research that was anything near Advanced Paternal Age focused on "Time To Pregnant" (TTP), which is the amount of time it takes the sperm to result in pregnancy. A study held in the United Kingdom found age was associated with significantly increased TTP and decreased conception rates. Men younger than 25 years old were 4.6 times more likely to have had TTP of more than 1 or 2 years, where men older than 45 were 12.5 times more likely for the same TTP period. Today, the focus has shifted from TTP to the relationship between paternal age and birth defects. Research is showing the risk of birth defects related to Advanced Paternal Age is proving to be much greater than previously expected.

According to Dr. Natan Bar-Chama, associate professor of Obstetrics, Gynecology and Reproductive Science at the Icahn School of Medicine and director of Male Reproductive Medicine and Surgery at The Mount Sinai Hospital, his recent research has found: "The sperm-producing process called spermatogenesis is so extensive and ongoing that over time it begins to show cracks in the machinery, resulting in errors in the genetic code."

Women are born with all their eggs and eventually reach a point where they no longer can bear children; however, men can father children their entire lives because male sperm constantly reproduces. The older a man is, the more times his sperm replicates, which increases the chances for mutations in the DNA to occur. This is where the "cracks in the machinery" are prevalent. Due to these DNA mutations in sperm, researchers found some conditions, such as autism, schizophrenia, bipolar disorder, autism spectral disorder and neurocognitive impairment, are at increased relative risk associated with aging.

Another contributing factor to sperm DNA mutations is the various environmental toxins men are exposed to throughout their lives. According to researchers at The University of Newcastle: "The amount of DNA damage in sperm of men aged 36 to 57 is three times that of men younger than 35 years."

In a paper by Kári Stefánsson, chief executive of deCODE Genetics in Reykjavik, Iceland, studies showed fathers passed on almost "four times as many new mutations as mothers: on average, 55 versus 14. The father's age also accounted for nearly all the variation in the number of new mutations in a child's genome, with the number of new mutations being passed on rising exponentially with paternal age. A 36-year-old will pass on twice as many mutations to his child as a man of 20, and a 70-year-old eight times as many."

Because men of Advanced Paternal Age pass on significantly more random genetic mutations to their offspring, one might wonder if these mutations are to blame for the rise in diagnosed autism cases. But Mark Daly, a geneticist at Massachusetts General Hospital in Boston who studies autism, says that increasing paternal age is unlikely to account for the rise in autism prevalence. He notes that autism is highly heritable, but most cases are not caused by a single new mutation—predisposing factors must be inherited from parents but are distinct from the new mutations occurring in sperm.

Another recent discovery is the association between men's age and lower live birth rates. In a retrospective study of 18,806 stimulated intrauterine insemination (IUI) cycles, Dr. Bar-Chama and colleagues found that each 10-year increment in paternal age was associated with a 20 percent decrease in the live birth rate, after adjusting for standard predictors of live birth. This means, couples undergoing fertility treatments now have to add Advanced Paternal Age to their list of items to consider.

So, does all this mean older men shouldn't be fathers, or that they will definitely pass on the mutations that lead to still birth, autism, schizophrenia, or bipolar disorder? No, says Dr. Mark Pearce, an epidemiologist of Newcastle University: "It's important to note that the risks are small and not all older fathers are going to have these problems. A lot more research needs to be done before we start changing advice to fathers."

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