Effects of Hormones on Spermatogenesis in Men with Histological Diagnosis of Spermatogenic Arrest at the Primary Spermatocyte (PS) Stage or Sertoli Cell-Only Syndrome (SCOS)

Abstract

Objectives: Men with absence of spermatozoa in the therapeutic testicular biopsy (TTB) material represent the most difficult cases of non-obstructive azoospermia (NOA). Even when alive round spermatids (RSs) are present in the TTB samples of the latter men, the outcome of ooplasmic injections of RSs rarely alleviates the couple’s infertility. We evaluated the effects of a combined administration of Profasi (Serono Co.) and Gonal-F (Serono Co.) on testicular spermatogenic and steroidogenic function. Design: Diagnostic testicular biopsy (DTB; hematoxylin-eosin stain) outcome and TTB (mincing testicular tissue and processing it for assisted reproduction trial) outcome were compared before and after hormonal treatment in three groups of NOA-men. Materials and Methods: All men had peripheral serum LH and FSH values less than twice the upper normal level of each respective hormone. TTB was performed at least four months after the performance of DTB. At the time of DTB, intratesticular testosterone (ITT) was measured, whereas, at the time of TTB, fractions of dispersed cells were processed for fluorescent in situ hybridization (FISH) techniques or observation via transmission electron microscope (TEM). Gonal-F (50 IU three times a week) and Profasi (2,500 IU twice a week) were administered for 12–24 months in a) 21 men whose DTB showed arrest at the PS stage and the TTB revealed absence of RSs and spermatozoa (group A), b) 7 men whose DTB demonstrated arrest at the PS stage and the TTB was positive for RSs but negative for spermatoa/elongating/elongated spermatids (group B), and c) 5 men whose DTB showed SCOS and the TTB demonstrated few PSs but not RSs (group C). New DTB, TTB, FISH, and TEM techniques were performed at the end of the treatment. Results: At the end of the homonal treatement, DTB images showed the same level of spermatogenic arrest as prior to treatment in all men of groups A, B, and C. Peripheral serum testosterone increased in all the participants. Observations of TTB samples post-treatment demonstrated few RSs in 8 men of group A. One of the latter 8 men showed spermatozoa, as well. No RSs were observed in TTB-samples of group C post-treatment. TEM showed elongating or elongated spermatids having tail length 0.004–0.047 mm in the TTB materials of 5 men of group B post-treatment. However, testicular spermatozoa were found in only two of the latter men. When the groups A and B were analyzed together it was found that the 13 men who responded to the treatment (development of RSs in the second TTB for group A; spermatid elongation in the second TTB for group B) had (prior to the hormonal treatment) significantly lower (P<0.05; Wilcoxon’s test) ITT profiles than the 15 remaining men who did not respond to the treatment. There was a large variation in ITT profiles prior to the treatment in groups A and B (taken together the groups A and B: 76–2675 ng/g testis). Four out the five men of group B who responded to the treatment had relatively low ITT profiles (less than 300 ng/g testis) pre-treatment. Conclusions: Hormonal treatment in men with early maturation arrest stimulates spermatogenesis in a clinically significant percentage (46%). Prior to the hormonal administration, the presence of RSs in the TTB of men with histological diagnosis of early maturation arrest or small ITT levels indicates good prognosis for response to the treatment. Hormonal treatment in SCOS-men without foci of RSs/spermatozoa is not recommended. This research was supported by a grant from the JG Fertility Institute.