Does Sperm Get Worse With Age?

Everyone knows that a woman’s eggs don’t improve with age. If you are a woman, especially one over 35, this is hammered into you with frequency. Obstetricians have a special category for pregnant women over 35: “advanced maternal age.” If you get pregnant, the pregnancy is “geriatric.” Some of this is overstated — fertility doesn’t fall off a cliff at 35 — but it is true that female fertility declines with age.

What about male fertility? The question is less obvious. We know men can, in principle, continue to father children into their 80s and possibly beyond. However, increasingly, there is discussion of the problem of aging sperm. Let’s look at what the data says. 

Does older sperm negatively impact fertility?

Let’s consider fertility first. You might think that it would be easy to figure out how sperm quality declines by comparing pregnancy rates for the partners of older and younger men. And in fact, some scientific papers do this. But they have a central problem: Older heterosexual men tend to be matched with older women. And since we know female fertility declines with age, it’s hard to figure out whether male age has any additional effect. This study in the American Journal of Obstetrics and Gynecology is a good example of a case where older men appear to have lower fertility, but the effect is impossible to detect when you also adjust for partner age.

It turns out this problem is surmountable with a simple trick: observe cases where couples are using donor eggs. There’s no reason that the age of the egg donor would be related to the age of the person with sperm (indeed, in the data, it typically is not), which means you can examine the impact of the person with sperm’s age independent of the egg donor’s.

Studies that do this — here is one nice review in the journal Fertility and Sterility — tend to find that while semen volume (and, hence, sperm count) does decline with age, there is little overall impact on reproductive success (the ability of the sperm to penetrate the egg, fertilize it, etc.). A related paper shows no impact of paternal age on various metrics of IVF success (all with young donor age). 

This is all encouraging, although we also know that sperm count and motility decline with age, so it is possible that outside of an IVF context we would see fertility impacts. This is simply hard to estimate.  

Does older sperm increase the potential for autism and ADHD?

The evidence on autism and other behavioral disorders appears less reassuring. The authors of a 2011 review article in Molecular Psychiatry combined a number of studies comparing children of older and younger fathers. They concluded that relative to children born to 20- to 29-year-old fathers, those with fathers ages 30 to 39 were 1.2 times as likely to have autism; those with fathers ages 40 to 49 were 1.8 times as likely; and those with fathers over 50 were 2.5 times as likely. The studies used in the meta-analysis were all pretty consistent. They did not all find the same size of effect, but virtually all pointed to increased potential for autism with increased paternal age.

A more recent review covers a much broader range of neurological metrics and argues that paternal age is associated with an increased risk for a variety of issues, including ADHD and mood and anxiety disorders.  

For the most part, these studies try to adjust for maternal age — though they can’t do as much as the donor-egg studies — but this analysis also runs into two additional problems. First, the type of men who have children later in life may be different in other ways. Second (possibly semantic), it may be hard to separate the older sperm from the older dad. If older fathers approach parenting differently, that could drive effects. 

We would clearly prefer to have a study that compared children born to the same man at different times in his life. This fixes a few problems. First, since the father’s genetics stay the same among children, there is no longer a concern that, say, men who are autistic themselves have children later. Second, we avoid any concern that some kinds of dads are more likely to have their kids evaluated for autism or other disorders. Third, to the extent that we think that parenting is often similar across children, this may help us with our older sperm vs. older dad issue.

An analysis like this is referred to as a “sibling fixed effects” regression, a comparison between or among siblings. It’s been used to good effect in an analysis of breastfeeding, for example.

The journal JAMA Psychiatry published a study about paternal age that included this design, and, to put it mildly, the results were alarming. The study used a full census of births in Sweden from 1973 to 2001 and merged together information on parent age, siblings, other family members, psychiatric diagnoses, grades in school, and on and on. It’s a Big Data dream — as if you were inside the house of every person in Sweden for 30 years, taking notes on their every move.

The researchers ran regressions where they effectively compared children born to the same father at different times in his life, and they reported enormous changes in psychiatric problems. They found big effects on autism: children born to men over 45 were 3.5 times as likely to be diagnosed with autism as those born to men ages 20 to 24.

But even more striking, and notable, were the effects on ADHD diagnosis: relative to children born to men 20 to 24 years old, those who were born to men over 45 were 13 times as likely to be diagnosed with ADHD. Even children born to men 30 to 34 were more than three times as likely to be diagnosed with ADHD as those born to the youngest father group. 

Taking a closer look at the data

But let’s look a little more closely at the data and statistics here. The authors actually ran three analyses. First, they looked at the raw data and asked, on average, are children born to older fathers more likely to have ADHD? Second, they controlled for some demographics, such as education and income, and maternal age. And finally, they ran their “sibling fixed effects” regression. They reported their results in helpful graphs, and below we’ve replicated the one for ADHD.

In the first analysis, using raw data, older men do not appear to be more likely to have children with ADHD. In the second analysis, when the researchers adjusted for some characteristics of the father, mother, and so on, we see that the children of older fathers are less likely to be diagnosed with ADHD. It’s only when we move to the siblings analysis that we see a huge positive effect of paternal age on a child’s likelihood of an ADHD diagnosis.

One theory for this gap in results is, of course, that the final analysis is the most accurate because it examines children under near ideal conditions: they were born to the same father at different times in his life. But when there is such a big difference in findings across analyses, it’s worth asking if something odd is going on.

To answer this, we need to be clear on what this “sibling fixed effects” analysis really does. Consider a dad with two children, born four years apart. A basic fixed-effects model would ask whether the older child is less likely to have ADHD than the younger, and then attribute any observed difference to paternal age.

Running this basic analysis would have the same problem with maternal age that we discussed earlier. Because mothers often age along with fathers within a family, if we analyzed sibling pairs with the same mother and the same father, it would be impossible to separate the effects of maternal and paternal age.

This paper does claim to separate these effects. How? The data includes half-siblings — children who share a father but not a mother. The authors can infer the effects of the father’s age separately from the mother’s age by looking within groups of siblings who share a father but not a mother.

That means the huge positive effect seen in the chart above essentially tells us that a later-born child of a father who has multiple kids with multiple partners is more likely to be diagnosed with ADHD. In the paper, this difference is attributed to paternal age.

Why push so deeply into the statistics here? Seeing what the data is really saying lets us think a little more about what else might be happening. Now that we know the effects are driven by differences across half-siblings, we can start asking what else — beyond paternal age — might be driving the difference. Most obviously, we may wonder whether being a child in a fluid family situation could itself have an impact on potential for ADHD diagnosis (as other studies have found).

Another, if more mundane, explanation for the big effect that paternal age appears to have on a child’s ADHD potential is that by striving so hard to isolate the effect of paternal age, the paper’s authors ended up studying a small number of individuals. And this makes it more likely that the results they saw were just due to chance.

I do not put much stock in this particular paper, but what is very helpful here is the desire to push the methods beyond the simple comparison-across-men that most of the data has. I would hope we would see more creative approaches to the data, especially given the strong correlations. Until then, I think the jury is still out. 

The bottom line

• Semen volume and sperm count decline with age, but there is little overall impact on the reproductive success of that sperm. However, even though the number of sperm doesn’t matter much when using donor eggs or doing in vitro fertilization, it will matter if you’re procreating via intercourse. So more sex may be necessary.
• Some studies suggest that older sperm increases the potential for autism and ADHD, but it is difficult to say definitively.

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