Infertility and Genetic Defects

The biological clock has always been defined in strictly female terms. In the classic cartoon, it's the career woman who is rushing to work when she suddenly realizes: "Oh, no! I forgot to have children!"

But a provocative new book by a Columbia University urologist, called The Male Biological Clock, challenges the notion that men can always have kids later, warning dads-to-be that postponing fatherhood can decrease male fertility and possibly contribute to birth defects.

Dr. Harry Fisch's ideas fly in the face of social convention and scientific consensus. His book has sparked controversy with top fertility experts proclaiming aspects of it "foolishness," "absolutely untrue," "a misrepresentation," even "dangerous." One expert suggested it was a publicity stunt to increase business for urologists.

"It's dangerous . . . because you raise red flags that aren't warranted," said Dr. Larry Lipshultz, a prominent male reproductive-health specialist at Baylor College of Medicine in Houston, who read an early draft of the book. "You're going to have a lot of very anxious guys running to the doctor, and it's based on information that is totally untrue."

Mainstream medicine acknowledges males contribute to infertility, estimating that a male part plays a role in 30 percent to 50 percent of infertile couples. But although women stop producing hormones and run out of eggs when the clock strikes midnight, generally around age 50, sperm counts and testosterone levels generally drop very gradually over the life span, experts say, and usually with little impact. Tony Randall became a father at 78, and Saul Bellow at 84.

Advanced maternal age is still believed to be the primary cause of birth defects such as Down syndrome, even though the link between older fathers and some rare and usually fatal anomalies is acknowledged. But recent studies are providing insights into the possible effect of older fathers on their offspring's well-being.

"There seems to be a contribution in later years of a man's age, too," said Dr. Robert Schenken, president of the American Society for Reproductive Medicine and a reproductive endocrinologist. "It's still under investigation."

Fisch, who is director of the Male Reproductive Center at Columbia University Medical Center in New York, agrees the "male menopause" has a different arc than the female's but says the clock "ticks faster" for some men. The vehement reaction of his peers caught him by surprise, he said.

"Our culture never wants to blame men for anything, which is why most societies will never accept this," he said. "We equate male fertility with sexuality; this is a direct hit to the male ego."

Few infertility experts quibble with Fisch's take-home message, which he hopes women will hear: that the male partner in an infertile couple should undergo a comprehensive evaluation, including a physical exam, instead of the standard cursory semen analysis.

Millions of Americans each year suffer from impaired fertility, as both men and women are waiting longer to have children; according to national health statistics, the percentage of fathers older than 35 increased from 14 percent in 1970 to 21 percent in 1999.

Fisch says fertility problems in men often can be treated and may indicate underlying health problems. Low testosterone, for example, is associated with diabetes, depression and difficulty losing weight, and can affect sexual drive and sexual performance, he said. Alcoholism, obesity, testosterone supplementation, smoking and infections can take a toll on male fertility.

But many specialists say the treatments Fisch recommends to enhance sperm quality, including antibiotic treatment for infections that can impair fertility and a controversial surgery to repair varicoceles, have mixed results. Varicoceles are enlarged veins in the scrotum that may impair male fertility.

Many fertility experts also dismiss the new studies that have linked older fathers to medical problems and birth defects in children. Fisch says they are ignoring a growing body of scientific evidence, including two large studies that have found an association between older paternal age and an increased incidence of schizophrenia in children. One, done by the New York State Psychiatric Institute, found a doubling of schizophrenia in children of fathers who were aged 45 to 49 and a tripling of the rate in children whose fathers were over 50; the mother's age had no effect.

Fisch and others analyzed thousands of births in a New York state study that found older fathers added to the risk of Down syndrome in children if the mothers were over 35, and concluded the father's age was a factor in 50 percent of the Down syndrome babies born to women over 40. In younger women, the study found, the father's age had no effect.

A European study found that older men may contribute to an increased miscarriage rate, and a 2001 review paper found that advanced male age was associated with declines in semen volume, sperm motility and shape. Yet another study found that partners of men over 35 were twice as likely to have problems conceiving as those of men 25 and younger.

"Twenty percent of women who go through IVF have infertility in the male partner, and another 20 percent have a combination of male and female problems," he said. "A lot of women are going for invasive treatment when the man has a problem, and they do nothing for the man."

To prepare for in-vitro treatments, women must take medications that stimulate them to develop multiple eggs, which are retrieved with a needle passed through the top of the vagina. The success rate per egg retrieval is 29.4 percent, and there are risks involved. But fertility experts, many of whom are gynecologists, say time is of the essence -- for the woman.

"You don't want to waste time," said Dr. Frederick Licciardi, of the New York University Program for IVF Reproductive Surgery and Infertility. "If you have a woman who's 38, and you work up her husband [for treatment] for six months, and wait six months, and now a year's gone by, she's 39 -- she may have just fallen off a cliff."