Restoration of spermatogenesis and subsequent fertility by direct intratesticular hormonal therapy.

Abstract

Testosterone-laden microspheres (TLM) were used in an attempt to restore spermatogenesis and sustain fertility in rats with previously suppressed gonadal function. Adult rats received 62.5 micrograms. gonadotropin-releasing hormone antagonist (GnRH-antagonist) per day for 15 days prior to being divided into three groups: 1) animals to be examined immediately, 2) animals to continue receiving 62.5 micrograms. GnRH-antagonist per day alone, and 3) animals to continue receiving GnRH-antagonist + a single intratesticular injection of 20 mg. TLM per testis. Unoperated control and sham-operated animals were also studied. Testicular interstitial fluid (TIF) testosterone concentrations, testicular sperm production and fertility were assessed 105 days after initiation of the experiment. Testicular interstitial fluid testosterone concentrations and sperm production were significantly reduced from control values after the initial 15-day GnRH-antagonist treatment (p < .05). After 105 days of GnRH-antagonist treatment, these values were further reduced (p < .05), but the TIF testosterone and sperm production values of GnRH-antagonist treated animals receiving TLM supplementation were not different from those of controls (p < .05). Fertility trials were also performed. Animals which had received GnRH-antagonist alone for 90 days were completely infertile, but animals receiving GnRH-antagonist + TLM for 90 days had fertility values not different from those of control animals (p < .05). Thus, spermatogenesis reduced because of testicular insufficiency was restored to normal, as was fertility, by intratesticular administration of TLM. This technique has possible clinical applications in selected groups of infertile men.