VEGF, TP1 may mark presence of sperm in men with NOA

Chicago-A widely studied protein can help urologists find sperm to be used for in vitro fertilization and may even indicate another future pharmaceutical application of the substance, according to research presented here at the American Society of Andrology annual meeting here.

The protein, vascular endothelial growth factor (VEGF), was one of several substances studied by Joel L. Marmar, MD, Susan Benoff, PhD, and colleagues, in a procedure used successfully to fertilize a number of couples suffering from azoospermia due to Sertoli cell-only (SCO). Dr. Marmar is professor of surgery and urology, Robert Wood Johnson Medical School, and head of the urology training program at Cooper University Hospital/Medical Center, Camden, NJ, and Dr. Benoff is director of fertility research at the North Shore-Long Island Jewish Hospitals, Manhasset, NY.

"As a urologist who does a lot of infertility work, I am called upon on a regular basis to get sperm from patients that have no sperm in their ejaculate," said Dr. Marmar, who discussed clinical cases using his technique. "We do a semen analysis, and there is no sperm. But that doesn't mean they can't have sperm in the testicles.

If a biopsy finds nonobstructive azoospermia, sperm are significantly underproduced, and there are three categories, Dr. Marmar explained. In the case of hypospermatogenesis, limited numbers of sperm may be found in the semeniferous tubules, which are not enough for the sperm to enter the ejaculate.

"If you have maturation arrest, the sperm fail to go through full development, and if you're looking at a case of Sertoli cell-only, the biopsy may show no sperm," he said.

Current clinical experience supports the proposition that sperm retrieval is possible in up to 15% to 45% of SCO cases with multiple biopsies and open microsurgical techniques. However, the current research found that a related substance, transition protein 1 (TP1), is present in the seminiferous tissue of more than 80% of men with SCO, which suggests that there may be more sperm in these cases because TP1 is a marker of sperm.

Dr. Marmar and Dr. Benoff determined that the presence of TP1 was 10-fold greater in the tissue near the artery, indicating that sperm may be more likely harvested in arterial regions because these are the regions in which VEGF and CD34 are also found as indicators of increased vascularity. Even in this third-most-severe category of azoospermia, urologists can retrieve sperm for fertilization purposes, Dr. Marmar said.

Reliable markers

A number of markers are useful as research tools for indicating the existence and location of sperm cells in men suffering from azoospermia, according to Dr. Marmar.

"If you see VEGF and CD34, you're going to see a lot of vessels. If you find TP1, there's got to be some sperm in the neighborhood," he said.

Dr. Marmar and his colleagues performed a clinical study to explore whether there is a way to identify preferential areas for biopsy to obtain a higher yield of sperm.

"Using a color Doppler ultrasound and a needle, we can identify the most vascular areas in the testes. When we biopsied the region closest to the big vessels, we found the most sperm," Dr. Marmar said, noting that his group found sperm in two-thirds of the men in a study of 35 patients with TP1 over a period of 2 years.

The method has led to successful fertilization in 21% of cases in which sperm re-trieval was achieved. The study suggests that VEGF or other substances theoretically could be used in a pharmaceutical treatment for infertility to stimulate vascularity.

"But that's far off in the horizon," Dr. Marmar conceded.