Thursday, May 10, 2007

The Genetics of male Infertility and Age Related Male Infertility

Today at Cornell

Center established to focus on genetics of infertility, combining strengths of Cornell's Ithaca campus with Weill medical college
Cornell University has established the Center for Reproductive Genomics, which will combine basic and clinical research in reproductive sciences on Cornell's Ithaca campus and at Weill Cornell Medical College (WCMC) in New York City, which has one of the country's leading fertility clinics. Infertility affects 10 to 15 percent of couples of childbearing age.
The collaborative center will focus on the genetics of infertility, with specific emphasis on meiosis, the specialized cell division that results in recombination of genetic material and the production of sperm in the male throughout life and eggs in the female fetus, which then develop over 20-plus years.


Genetics of male infertility

It is clear that a significant proportion of infertile male with azoospermia and severe oligospermia have a genetic etiology for reproductive failure. While recent advances in assisted reproductive technologies make possible and practical for many infertile men with severe male factor infertility to father children, they also raised concerns about passing on genetic abnormalities to the offspring of these men. Intracytoplasmic sperm injection (ICSI) is the most invasive technique for assisted reproduction. ICSI bypasses all the physiological mechanisms related to fertilization as well as all protective barriers against sperm with genetic defects and allow even altered spermatozoon to fertilize an oocyte. Since infertile patients with non-obstructive azoospermia are able to achieve pregnancy with surgically retrieved testicular sperm, ICSI carries risk of transmitting both genetically determined diseases and genetically determined infertility. It is imperative for the clinicians involved in the treatment of these couples to initiate genetic evaluation and counseling prior to any therapeutic procedures.


Age Raises Infertility Risk in Men, Too
Risks associated with men's biological clocks may be similar to women's.

By Elizabeth Heubeck, MA
WebMD Feature

Reviewed By Brunilda Nazario, MD

On playgrounds across the country, it's getting tougher to tell who's watching the kids -- dad or granddad. Experts predict the trend of older fathers will continue creeping upward. Why the rise and, more importantly, at what cost?

"The women set the baby-making agenda," says Harry Fisch, MD, director of the Male Reproductive Center at Columbia-Presbyterian Medical Center in New York and author of The Male Biological Clock: the Startling News about Aging and Fertility in Men. As more and more women wait to have children, their spouses are forced to postpone parenthood, too. Back in 1970, less than 15% of all men fathering children were over 35. Today, that percentage has risen to almost one-quarter. Even among men in the 50 to 54 age group, there's been a notable increase in fatherhood.

While it has become more socially acceptable to put off fatherhood, experts caution that the decision is not without risks.

"The role of the male in infertility has been grossly overlooked by lay and professionals alike," says Peter Schlegel, MD, urologist-in-chief at New York-Presbyterian Hospital/ Weill Cornell Medical Center, and president of the Society for Male Reproduction and Urology.

Effects of Age on Male Fertility

Whereas most women realize that their biological clock ticks as they age, the same cannot be said for men. "Not only are men not aware of the impact their age has on infertility, they deny it. They walk around like they're 18 years old," Fisch tells WebMD. It's no wonder.

Until recently, popular belief held that men could father children as easily at 78 as they could at 18. But a mounting body of evidence is showing otherwise.

In one study of couples undergoing high-tech infertility treatments, researchers concluded that a man's chances of fathering a child decrease with each passing year. In the study, the odds of a successful pregnancy fell by 11% every year; their chances for obtaining a successful live birth declined even farther. The study was reported in a 2004 issue of the American Journal of Gynecology.

As sure as men age, so too do their sperm. German researchers compiling the most recent data on aging sperm reported that the volume, motility (ability to move toward its destination, an awaiting egg), and structure of sperm all decline with age. They published this update in a 2004 issue of Human Reproduction Update.

Rise of Other Reproductive Risks

For aging men, the risks extend beyond reduced fertility. "The original view that men's contribution to normal reproduction stopped at fertilization needs to be completely revamped," Schlegel tells WebMD. A broader and more accurate view would acknowledge the significant impact of aging sperm on birth outcomes.

We know that once women reach their mid-30s, their risk of having a child with a genetic abnormalities increases sharply. Now we know that the age of fathers can also contribute to that risk. In the most revealing study on this topic to date, Fisch and his colleagues evaluated more than 3,400 cases of Down syndrome. They found the father's age played a significant role when both parents were over 35 at the time of conception. The effect was most pronounced when the woman was over 40. In those cases, says Fisch, "We found the incidence of Down syndrome is related to sperm approximately 50% of the time." These findings appeared in the June 2003 issue of The Journal of Urology.

Children born to older men also run a higher risk of developing schizophrenia, a devastating mental disorder. In one study on the subject, researchers discovered that men between the ages of 45 to 49 were twice as likely to have children with schizophrenia as were men 25 and younger. That risk tripled for men over the age of 50. Investigators, reporting in a 2001 issue of the Archives of General Psychiatry, drew their results from a sample of more than 85,000 people.

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