Genetic Links to Male Infertility

Infertility can be traced to the male in 30 to 50 percent of all cases. That's not a statistic that many are aware of, but so says Dr. Mark Leondires, medical director for Reproductive Medicine Associates of Connecticut. Historically, other than being told to stay away from hot tubs and switch to boxer shorts, male infertility issues weren't given a lot of attention. Fortunately, this is changing as science begins to investigate the genetic link in male infertility.

Beyond Sperm Counts
When a couple seems to be experiencing infertility issues, there are some basic physiological conditions that should be evaluated before any more intensive testing is done. "One of the things I tell my patients is that there are three basic components to fertility," says Dr. Leondires. "These are regular ovulation, open fallopian tubes and a good sperm count. Since sperm is easily accessible, that should be done first."

Unfortunately, it doesn't always work that way. "Even in the medical community, there's what I call medical sexism," says Dr. Leondires. "I just saw a patient the other day who discovered the problem was with her husband only after she'd been through four cycles of Clomid."

In the male, in addition to a simple semen examination, diagnosing male factor infertility should include a thorough exam to rule out obvious physical defects of the reproductive system, as well as hormonal deficiencies. Once these factors are eliminated, the semen analysis can help the physician diagnose a host of possible problems that may be a factor in infertility.

"In examining a semen analysis, sperm count becomes just one component," says Dr. Mark Perloe, medical director of Georgia Reproductive Specialists. "A semen analysis is like a UPS tracking number; it can tell us if the sperm is likely to get to the egg. Unfortunately, if the outside of the box is damaged, there may be some damage inside. Sometimes, physicians will overlook the underlying information, such as the presence of immature cells and clues that there may be some infection or abnormality that's damaging the sperm."

The Genetic Component
While any test for male factor infertility begins with a sperm count, a high sperm count isn't necessarily an indicator of fertility. For example, many men have adequate sperm and semen production, yet still receive a diagnosis of infertility because their sperm is not effective at penetrating the egg to achieve fertilization. Sometimes, seemingly healthy sperm may have a genetic abnormality.

"Whenever you see a case of severe male factor infertility, part of workup should be a chromosomal analysis," says Dr. Leondires. "There have been a lot of recent findings on microdeletions of the Y chromosomes that are crucial genes for sperm production."

Aside from these microdeletions, which occur at a cellular level and are tricky to diagnose, other genetic factors include existing genetic conditions such as cystic fibrosis and polycystic kidney disease. Another important genetic component is age, which is an especially important consideration as people tend to have families at later and later ages.

"There is new data coming out of IVF literature suggesting that men over the age of 60 have more breakdown in their sperm genetics and that there may be a higher incidence of various disorders with older men," says Dr. Leondires. "Men probably have a biological clock just as women do, but the magnitude of its affect is smaller. We're just learning about this because it's only been recently that there have been enough men over the age of 60 trying to reproduce for us to even gather these statistics."

Many of these factors can be overcome by advances in reproductive medicine, such as IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection), but it's also important to consider the risk of passing on genetic abnormalities to the next generation without more careful sperm and semen analyses.

No More Jokes
Overall, genetic research into male infertility is in its infancy, but the subject has taken on a new urgency as something that was once a joke in the reproductive field appears to be reality: the possible extinction of the male of our species. "We don't think it's our imagination anymore," says Dr. Leondires. "There definitely appears to be lower global sperm counts. We don't know why this is. It may be environmental, or it may be because since there's only one Y chromosome, the DNA and amino acids are starting to break down."

One reason for the speculation that our environment may be the cause is because, to the great surprise of researchers, some of the lowest sperm counts were identified in America's heartland. The perception of this part of the country may be of a healthy, corn-and-beef-fed population, but, in fact, the chemicals used in agriculture over the years have made it particularly toxic.

Regardless of the reason, the breakthroughs in genetic causes for male infertility can help promote treatment at the genetic level, even though those treatments may be many years down the road. "I think we're very far away from being able to manipulate the human genome to offer much hope at this point for treating infertility at the genetic level," says Dr. Leondires. "Human reproduction seems simple enough, but in reality it's extremely complicated, and there is still a lot we don't understand about how it all works."

By Kelly Burgess