Induction of Spermatogenesis and Its Predictors in Men with Prepubertal-Onset Hypogonadotropic Hypogonadism Undergoing Gonadotropin Therapy.

Purpose: To evaluate the outcomes of gonadotropin therapy (GT) using human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (rFSH) for inducing spermatogenesis in men with prepubertal-onset hypogonadotropic hypogonadism (HH), compare these outcomes between men with congenital and acquired etiologies, and identify factors associated with successful spermatogenesis.

Materials and methods: This retrospective study included 65 men with prepubertal-onset HH who underwent GT to induce spermatogenesis. Baseline assessments included serum luteinizing hormone (LH), FSH, and testosterone levels, and testicular volume (TV) measurements. Treatment began with hCG injections administered thrice weekly for four weeks, followed by combined rFSH and hCG therapy. Serum testosterone levels were measured after hCG pretreatment. TV and semen analyses were evaluated every three months following the rFSH addition. Successful spermatogenesis was defined as the detection of at least one sperm in a semen sample.

Results: Median baseline testosterone, LH, and FSH levels were 0.10 ng/mL, 0.05 IU/L, and 0.50 IU/L, respectively, with a median baseline TV of 4.0 mL. After hCG pretreatment, median serum testosterone level increased to 3.16 ng/mL. Treatment outcomes were analyzed in 50 patients who continued GT until spermatogenesis induction or for at least 12-months. Following therapy, median TV increased to 9.0 mL. Spermatogenesis was successfully induced in 41 patients (82.0%), with a median induction time of 7.5-months. In these patients, median sperm concentration, total motility, and morphology were 5.2×10⁶/mL, 35%, and 4%, respectively. Success of spermatogenesis induction did not differ between patients with congenital and acquired HH etiologies. Larger baseline TV was the only predictor of successful outcomes. Earlier spermatogenesis was correlated with larger baseline TV. Among six patients seeking conception, four achieved conception.

Conclusions: GT can successfully induce spermatogenesis in 82% of patients with prepubertal-onset HH, regardless of etiology. Baseline TV was confirmed as a predictor of successful outcomes and earlier spermatogenesis induction.