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NewYork-Presbyterian/Weill Cornell Research Brings New Insights, Hope for the Treatment of Male Infertility

Microsurgery Restores Fertility to Men with Klinefelter Syndrome, and an Expert Reviews Available Sperm DNA Tests

NEW YORK (Nov 11, 2005)

New research is expanding what we know about the causes, diagnosis, and treatment of infertility in men.

In one recent paper, a team from NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City demonstrated the effectiveness of microsurgical sperm extraction and intracytoplasmic sperm injection (ICSI) techniques developed by Weill Cornell scientists in restoring fertility to men previously considered sterile due to Klinefelter syndrome.

And in a commentary published in the October issue of Fertility and Sterility, NewYork-Presbyterian/Weill Cornell Urologist-in-Chief and Weill Cornell Urology Chair Dr. Peter N. Schlegel compared the ease and efficacy of available sperm DNA tests.

Dr. Schlegel was also senior researcher on the study on Klinefelter syndrome, just published in the November issue of the Journal of Clinical Endocrinology & Metabolism. Both the Department of Urology and Center for Reproductive Medicine and Infertility, led by Dr. Zev Rosenwaks, collaborated on the study.

"Klinefelter syndrome affects about one in 500 or 600 men," Dr. Schlegel explained. "It occurs when the men are born with an extra X chromosome for reasons that are still unclear, this can dramatically lower the number of sperm in the testes. In fact, counts are so low that sperm don't leave the body, and these men were long considered sterile and untreatable."

Using a technique first described by his team in 1998 in the New England Journal of Medicine, Dr. Schlegel used microsurgery to detect viable sperm within the testes of men affected by the syndrome. Once detected, this sperm was extracted and then introduced into a mature egg using a high-tech form of in vitro fertilization called intracytoplasmic sperm injection (ICSI), previously developed by Weill Cornell scientist Dr. Gianpiero Palermo of Rosenwaks' team.

This latest study confirms the efficacy of that breakthrough technology, Dr. Schlegel said. Working with 42 men with Klinefelter syndrome, his team first used drugs called aromatase inhibitors to help boost the men's sperm production. Twenty-nine of the patients had sufficient sperm found in their testes for extraction, which were then injected into mature eggs, resulting in 18 pregnancies and 21 live births.

"The treatment allows you to use very small numbers of sperm, and it works because of surgical techniques developed here at NewYork-Presbyterian/Weill Cornell," Dr. Schlegel said. "It's given new hope to men who otherwise would never have been able to become biological fathers."

Sperm DNA Testing
In the second paper, co-authored by Dr. Schlegel and Dr. Darius Paduch of NewYork-Presbyterian/Weill Cornell and The Population Council in New York City, the two experts review laboratory tests currently in use to examine chromatin (genetic) damage in sperm.

"Experts are realizing that a breakdown in chromatin integrity in sperm can cause fertility problems that we would never have assumed in the past were linked to sperm," Dr. Schlegel said. "For example, defects in sperm can cause problems in late embryonic development or even miscarriage. The message is that sperm don't stop their work at the moment of fertilization their DNA continues to play a key role in the embryo's development throughout pregnancy."

Numerous tests have been developed to screen sperm for key DNA damage, and Dr. Schlegel said that, in large part, "the tests' efficacy and results parallel each other."

In their review in Fertility and Sterility, the two experts comment on a new sperm chromatin screen, called Halosperm, recently developed by the Spanish company Laboratorios Indas.

"The test doesn't add a lot to what's already out there," Dr. Schlegel said. "It's a new way of looking at how sperm starts to de-condense or unravel, but that's something we can already directly measure with other tests."

The Klinefelter syndrome study was funded by The Brady Urology Foundation and The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.

Co-authors on the Journal of Clinical Endocrinology & Metabolism paper include Dr. Jonathan D. Schiff, Dr. Gianpiero Palermo, Dr. Lucinda Veeck, Dr. Marc Goldstein, and Dr. Zev Rosenwaks all of NewYork-Presbyterian Hospital/Weill Cornell Medical Center. Dr. Goldstein also has an appointment at The Population Council.

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