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Research sheds light on genetic basis of infertility

From the genetic basis of male reproductive dysfunction to the psychology of those who suffer from it, men who experience infertility issues continue to benefit from research into all facets of the condition.

A number of today's most exciting new studies were presented at the 2006 AUA annual meeting, according to Craig S. Niederberger, MD, chief of andrology at the University of Illinois at Chicago. Dr. Niederberger identified the following take-home messages as presentation highlights from the meeting.

High-grade and bilateral varicoceles may be indicative of chromatin damage.

"It may seem arcane," said Dr. Niederberger, "but it's an important facet of DNA integrity, along with DNA fragmentation as measured by the Comet and TUNEL assays. SCSA is both a clinical and a research tool, though we're still getting a handle on its utility in a clinical setting."

While the correlation between SCSA and sperm density is striking, Dr. Niederberger added that researchers are trying to get a handle on what these thresholds represent clinically.

"Still, this study is an indication that SCSA is useful as an investigative tool," he said.

Dr. Niederberger also referenced a recent multicenter study showing that DNA integrity as measured by SCSA decreases as men age (Proc Natl Acad Sci USA 2006; 103:9601-6).

Intracytoplasmic sperm injection (ICSI)-conceived children of men with triplet repeat DNA expansions were found to often inherit unstable alleles leading to certain neurodegenerative diseases.

"Urologists need to know that ICSI can lead to an increase in the frequency of genomic abnormalities," said Dr. Niederberger. "If a varicocele can cause sperm dysfunction, that's one thing. But if a condition or treatment causes problems with the sperm's primary function-making a healthy baby-that's quite a problem and quite important."

Sperm retrieval rates for salvage microdissection testicular sperm extraction (TESE) are equivalent to those for primary TESE.

Microsurgical TESE is a relatively new and powerful technique that may lead to retrieval of sperm in men with very severe hypospermatogenesis and very focal areas of spermatogenesis in the testicles.

"The question, though, is whether the technique will work in patients in whom conventional TESE has failed," Dr. Niederberger said.

Japanese researchers tackled the question by evaluating 46 patients with nonobstructive azoospermia in whom salvage microdissection TESE was performed after failed conventional TESE. They compared those men with 134 others who underwent microdissection TESE without first having the conventional procedure.

They found that the sperm retrieval rate by microdissection TESE was 45.7% in men with initial conventional TESE and 44% in men without it, a negligible difference.

As the authors themselves stated, "The possibility of successful spermatozoa retrieval by salvage microdissection TESE remains regardless of the previous failure of any other TESE procedure and of testicular histology."

In a related study, an Egyptian researcher reported that measuring seminiferous tubule diameter during microdissection TESE can improve sperm retrieval rates. Specifically, tubule diameter of 300 microns or more was associated with the most successful sperm retrieval.

Depression or anxiety occurs in 29% to 47% of men undergoing infertility evaluation or treatment.

For hundreds of years, the study of fertility has focused almost exclusively on women. Only recently have men been added to the equation, both biologically and psychologically.

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