Procedure may be unnecessary for men with non-obstructive azoospermia, study says.


WASHINGTON, D.C.—Diagnostic testis biopsies in men with non-obstructive azoospermia (NOA) will not provide definitive proof as to whether sperm will be found with a more intensive evaluation of the testes, according to researchers at New York-Presbyterian Hospital-Weill Cornell Medical Center in New York.

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The investigators say a diagnostic biopsy should be performed if the etiology of azoospermia is not clear, the risk of carcinoma in situ is high, or the biopsy results will affect a couple’s choice to undergo testicular sperm extraction (TESE) and/or intracytoplasmic sperm injection (ICSI). In the case of NOA, however, new data indicate that it is unnecessary to require a diagnostic testis biopsy prior to TESE-ICSI.


“We used to assume that doing a biopsy would tell us whether sperm were present in the testis, but it turns out that a single biopsy alone really provides no information because the areas of sperm production can be so limited that you miss them with a single biopsy,” said Peter Schlegel, MD, professor and chairman of urology. Testis biopsies can reveal whether these men have a predominant pattern of Sertoli cell-only pattern, maturation arrest, or hypospermatogenesis, but does not determine if sperm are somewhere else in the testicle, not sampled by a single random biopsy. He presented study findings here at the annual meeting of the American Society for Reproductive Medicine.


NOA affects approximately 1% of the male population and 10% of males who seek fertility evaluation, he said, noting that evaluation and counseling for these men have changed significantly over the past 10 years.


Until recently, it was assumed that men with NOA were untreatable and these men were often referred to as being “sterile” or having testicular failure. Recent observations have changed the approach, according to Dr. Schlegel. Direct evaluation of testis biopsy specimens often demonstrates sperm in men with NOA, despite severe defects in spermatogenesis. This observation has been interpreted to mean that a low level of sperm production may occur in the testes of men with azoospermia, but the sperm do not survive epididymal transit and ejaculation (Silber et al, Human Reproduction. 1997;12 (11):2422-2428).


It was previously thought that sperm had to transverse the entire male reproductive tract before acquiring the ability to fertilize an egg.


Dr. Schlegel said the successful treatment of men with obstructive azoospermia using sperm extracted from the epididymis or testis has changed this view. Although testicular sperm have dramatically lower motility than those that have transited the male reproductive tract, these sperm can be used for ICSI during in vitro fertilization (IVF). He noted that these observations have led researchers to perform TESE with ICSI for men with NOA. To date, he said, low sperm retrieval rates have been reported using the biopsy or multi-biopsy approach, with a success rate of 20% to 45% per attempt.

Recently, in a review of nearly 800 NOA cases, Dr. Schlegel and his colleagues examined the likelihood of sperm retrieval with microdissection TESE after prior random biopsies had failed to find sperm in azoospermic males. For males with no prior biopsies, the chance of retrieval was more than 50%. The chance of retrieval with microdissection TESE was no different regardless of whether one or two random biopsies per testis failed to find sperm. If three or more biopsies were done per testis and no sperm were found, the likelihood of successful microdissection TESE decreased to only 22%.


Dr. Schlegel said sperm retrieval for use with ICSI is now possible for most men with NOA. Men with NOA, however, may have unique genetic defects that should be evaluated prior to an attempt at conception. He and his colleagues have attempted TESE in nearly 800 men during programmed IVF cycles, retrieving sperm in 59% of couples despite NOA. Among these couples, 48% achieved a clinical pregnancy using the retrieved sperm and ICSI.


“Treatment is quite possible for men with non-obstructive azoospermia,” Dr. Schlegel told Renal & Urology News. “A biopsy will make the diagnosis but it will not tell us whether sperm are present and the couple is treatable.”