It’s only been about a generation or so since we have come to realize that a significant chunk of male infertility is caused by subtle genetic changes in male DNA. Sure, syndromes based on larger, chromosomal alterations such as Klinefelter syndrome have been known for 60 years, but the finding of smaller DNA mutations causing male infertility is far more recent. Add to this the fact that assisted technology (IVF-ICSI) now offers the opportunity for biological fatherhood in many men with genetic infertility, and you can understand why I am now asked regularly: “Will my son also be infertile?”
A Mixed Bag
There are lots of reasons why men are infertile; a set of dilated veins in the scrotum, termed varicocele, is the most common (40%) and correctable among them. Lifestyle and recreational factors, including diet, tobacco, alcohol and marijuana use, hot baths or saunas, and medications are a close second. Medical conditions such as obesity, diabetes, infections, thyroid disease and cancers and the drugs needed to treat them take third on the list. And underlying genetic causes round things out at about 5% of cases of infertile men with low sperm counts.
We believe that there are about 2,000 genes that control sperm production. Among them, fewer than 50 are well defined and measurable, most of which are found on the Y or male chromosome. That means that there is likely a whole slew of men out there with currently undefinable genetic infertility. For these men, the question of whether sons will inherit their fathers’ infertility is the most interesting and complex to answer.
Mendelian Math
If the father’s Y chromosome has a mutation causing infertility, then the expectation is that only male heirs will inherit the problem, as the Y chromosome is only passed to sons. If one of two of the mother’s X chromosomes harbors a male infertility gene mutation (which, by the way, can happen!) then there is a 50:50 chance that her son will inherit the problem. If any other chromosome harbors a gene mutation, whether it be the mother or the father, then there is a 25% at most (autosomal dominant) chance that their son will be affected. The occurrence of new, sporadic mutations causing male infertility is an entirely separate issue that complicates these inheritance predictions.
Regardless of the source of parental gene mutation, and whether the gene was known or not, a study of adult male offspring of dads with low sperm counts who needed assisted reproduction (IVF-ICSI) to conceive showed that the sons’ sperm counts were low, just as their dads’ were.
A Delicate Matter
So, what’s a parent to do? The decision to share baby making information of any kind with offspring is a very personal matter. If assisted reproduction was used, sharing that information needs consideration. If the genetic infertility is known, that is another issue that merits pondering. If the inheritance involves sons having low sperm counts, then natural fertility among sons is possible, although less likely. If the inheritance in sons is azoospermia or no sperm counts in the ejaculate, then infertility is assured. Testing of semen quality and genetic issues to confirm inheritance is possible once sperm is being made (typically after age 16), but the need and timing of this is entirely a parental decision. When it comes to the sharing of sensitive knowledge in such matters, consider the words of Don Miguel Ruiz: “Use the power of your word in the direction of truth and love.” And, if further guidance is needed, a certified genetic counselor or reproductive urologist is available for the asking.
