Sperm maturation arrest: Better late than early

San Francisco-The likelihood of successful sperm extraction may be higher at later-stage sperm maturation arrest (MA), according to a study conducted by researchers at Baylor College of Medicine, Houston, and presented at the American Society for Reproductive Medicine annual meeting.

Sperm MA is widely recognized as a contributing factor to male infertility, but there is little information in the literature to help characterize its stages. Researchers in Japan have reported that men with earlier stages of MA have higher levels of follicle stimulating hormone (FSH). Recent data from Cornell University showed that men with MA who had normal FSH levels had a lower sperm retrieval rate, lower fertilization rate, and lower pregnancy rate compared to other men with nonobstructive azoospermia.

The ways in which MA itself might affect the success of mature sperm extraction remain largely unknown. The Baylor researchers hypothesized that patients with earlier stages of MA might be associated with higher levels of FSH resulting from increased sertoli cell or other testicular damage. They also suggested that the likelihood of successful sperm extraction is higher at later-stage MA.

Dr. Weedin and his co-researchers retrospectively reviewed all patients who underwent site-specific sextant biopsies (testis mapping) by a single urologist at Baylor between 2002 and 2008. They identified 149 patients with nonobstructive azoospermia and 32 patients with severe oligospermia (sperm density less than 10,000 per mL).

Patients were grouped by their major and any minor histopathology patterns. Categories included sertoli-cell only (SCO), early maturation arrest (EMA), late maturation arrest (LMA), and hypospermatogenesis (HS). EMA was defined as maturation arrest up to the level of the primary spermatocyte and LMA from the secondary spermatocyte to the formation of the immature spermatid.

Each of the patient groups was analyzed for serum FSH concentration, testicular volume, chromosomal abnormalities (including karyotype abnormalities and Y-chromosome microdeletions), and the presence of sperm during testicular mapping.

Genetic component detected

The analysis found 61 patients with MA and 20 with concomitant SCO histology. The mean serum FSH level in men with EMA was 18.7 compared to 7.6 mIU/mL in men with LMA, a statistically significant difference (p=.0043). FSH levels correlated positively with testis pathology, but not with the probability of obtaining sperm at biopsy. The frequency of successful sperm extraction during testis mapping increased with the later stages of MA, from 14.3% in EMA to 26.7% in SCO/mixed MA, 37.5% in mixed MA, and 46.1% in LMA.

"Men with earlier maturation arrest have higher FSH levels, which matched the findings of one other report," Dr. Weedin said. "There is also a higher chance of finding sperm in men with later stages of maturation arrest than in the earlier stages. Some men with late MA potentially have full maturation somewhere in their testicle that we might be finding, or not. There is a difference between the early MA group and later MA that could have some clinical correlation in the future."

Researchers identified a potential genetic component in more than three-quarters of the men in the review. Karyotypic abnormalities were seen in 15.5% of men, but there was no correlation with stage of maturation arrest. Microdeletions in the Y chromosome were far more common and varied by MA classification: 36.8% in EMA, 15.6% in LMA, 23.5% in mixed MA, and 2.1% in all other patients (p=.0001).

"Some men seem to have a gene that is deleted or nonfunctioning that prevents their sperm from maturing," Dr. Weedin said. "At some point, we may be able to manipulate the genetic pathway to alleviate the problem."