High-Tech Answers to the Age-Old Mystery of Male Infertility

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Male infertility plays a part in half of all infertility cases. Now more than ever researchers are finding genetic links to male infertility. While specific advances on the genetic treatment side are years away, doctors and patients must be aware of the possible genetic source of their problem in order to determine the quickest and most effective treatment.

For decades, a diagnosis of male infertility came with not much more than some advice about avoiding tight-fitting clothing and hot tubs in the hopes of increasing sperm counts and motility. But recent high-tech advances are increasing the effectiveness of diagnostics and treatments for a host of male infertility problems, which play a part in half of all infertility cases.

“The past problem with male infertility treatment was two-fold,” explains Dr. Mark Leondires, MD, a board-certified Reproductive Endocrinologist and medical director at Reproductive Medicine Associates of Connecticut (RMA of CT). “First, most protocols focused mainly on correcting low sperm counts, and for many men, that was not the issue. Secondly, male infertility treatment was considered less important than female treatment, since many believed that women’s infertility problems were more prevalent and complex,” Dr. Leondires notes. In fact, according to the National Institutes of Health, male infertility is wholly responsible for about 30% of all infertility cases, and is identified as a contributing factor in another 15-20%.

It’s in the genes…as well as the jeans

Dr. Leondires confirms that the usual suggested lifestyle changes, drinking less alcohol, quitting smoking, and even avoiding sports like mountain biking, which can damage the male reproductive tract and impair sperm production, still have value. Also switching to boxer shorts can’t hurt. But today, researchers are learning that the answers to male infertility lie as much more in the genes than they do in the jeans.

For example, many men have adequate sperm and semen production, yet still receive a diagnosis of infertility. “Their sperm is simply not effective at penetrating the egg to achieve fertilization,” Dr. Leondires explains. In a study published in the November 2001 issue of Science, researchers from the Mayo Clinic found a link between the absence of a certain protein in the sperm’s “warhead” (which is responsible for burrowing through the egg wall to fertilize it) and infertility. When the scientists deleted the gene that makes this Hrb protein in mice, it rendered the male animals completely infertile.

This research was followed by a study that identified yet another protein, called SED1, as a culprit in male infertility. The study, published in the August, 2003 issue of Cell, found that SED1 was responsible for allowing sperm to bind to the egg, and also for identifying and avoiding an egg that had already been fertilized. Researchers believe this study is the first to determine cell-to-cell binding capability as a key factor in male infertility.

What’s more, a 2002 Duke University study determined that the absence of yet another gene, called miwi, leads to complete sterility in mice, and would likely do the same in humans when the equivalent gene, called hiwi, is deleted. The hiwi gene, scientists explain, resides in the human reproductive stem cells, and is responsible for promoting their development into fully functioning sperm cells. And numerous prior studies since 2000 have identified other key genetic problems affecting the sperm, from autoimmune malfunctions that cause the body to attack its own sperm, to the degeneration of sperm caused by some cancer treatments or glandular disorders.

“Baby steps” today…giant leaps for the future

“While these findings will have a significant impact on future male infertility treatments,” Dr. Leondires predicts, ”we are still some years away from any specific advances on the genetic treatment side.” However, he notes that infertility specialists must appreciate these revelations in order to treat patients more quickly and effectively than ever. “When we can confirm that semen production, sperm counts and motility are normal but there is no evidence of fertilization we can make a faster leap to treating possible genetic problems in male factor infertility cases using manual fertilization,” Dr. Leondires adds.

For example, Dr. Leondires notes that prior to these genetic discoveries, a standard approach to IVF treatment might begin with a traditional in vitro egg-sperm fertilization protocol – wherein the sperm and eggs were joined in the petri dish to fertilize naturally. “Particularly if sperm counts and motility were judged to be normal, this would be a widely accepted approach.” Now, more doctors might be likely to use Intracytoplasmic Sperm Injection (ICSI) if they suspect subtle sperm defects might be at play. During ICSI, the sperm is injected directly into the egg, rather than allowing it to attempt natural penetration. ICSI has generated a virtual revolution in the treatment of male factor infertility.


Dr. Mark P. Leondires, M.D., FACOG, is a leading authority on reproductive medicine. Dr. Leondires is board certified in Reproductive Endocrinology and Infertility. He is a member of the Society of Reproductive Endocrinologists, the American College of Obstetrics and Gynecology, and the American Society for Reproductive Medicine. Dr. Leondires earned his medical degree from the University of Vermont College of Medicine and completed his residency in Obstetrics and Gynecology at Maine Medical Center in Portland, Maine. Dr. Leondires completed a fellowship in Reproductive Endocrinology and Infertility at the National Institutes of Health in Bethesda, Maryland. After completion of his training, he fulfilled his military obligation by serving as the ART Director for the largest and most successful program in the military health care system at Walter Reed Army Medical Center. During this time he was an Assistant Professor at the Uniformed Services University of Health Sciences and clinical faculty for the Combined Fellowship in Reproductive Endocrinology. Dr. Leondires is currently Medical Director and lead physician with Reproductive Medicine Associates of Connecticut (RMA-CT) in Norwalk. Along with numerous teaching and research activities, Dr. Leondires has published articles in professional medical journals, national consumer magazines and newspapers, as well as abstracts and book chapters. More information about Reproductive Medicine Associates of Connecticut is available at http://www.rmact.com.


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Melissa Chefec
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