Efficacy of Gonadotropin Therapy to Induce Spermatogenesis and Fertility in Men with Pathologic Gonadotropin Deficiency

Gonadotropin treatment to induce spermatogenesis for gonadotropin-deficient men is the only medically treatable cause of male infertility. However, time-dependent analyses of fertility outcomes in large cohorts are lacking. We evaluated the time to, and determinants of, fertility outcomes in men with pathologic gonadotropin-deficiency undergoing gonadotropin treatment.

Consecutive infertile men (n = 99) with congenital or acquired pathologic gonadotropin deficiency were treated with urinary or recombinant human chorionic gonadotropin and FSH according to a standardized protocol between 1983 and 2024. Kaplan-Meier and multivariate Cox regression analyses examined time to prespecified sperm density thresholds and pregnancy.

Men aged 35 ± 1 years with female partners 30 ± 1 years underwent 160 treatment cycles. The proportion (%) and median time (months) to achieve sperm thresholds of >0, >2, >5, >10, and >20 million (M) sperm/mL was 78% (5 months), 56% (12 months), 49% (14 months), 37% (21 months), and 24% (not determined), respectively. The major determinant of successful pregnancy was the presence of adverse fertility factors in the female partner (hazard ratio 0.20, 95% confidence interval 0.10-0.40; P < .001), with time to pregnancy also significantly increased by the presence of adverse female factors (15 vs 43 months; P < .0001). The median sperm concentration associated with partner pregnancy was 2.8 (0.2, 52.6) M/mL without and 35.4 (15.1, 52.6) M/mL with adverse female factors.

Most men with pathologic gonadotropin deficiency treated with hCG/FSH achieve sperm output and fertility within a year, with the greatest impact on fertility outcomes being detrimental female fertility factors.