Gonadotrophin treatment to induce spermatogenesis for gonadotrophin-deficient men is the only medically treatable cause of male infertility. However, time-dependent analyses of fertility outcomes in large cohorts are lacking. We aimed to evaluate the time to, and determinants of, fertility outcomes in men with pathologic gonadotrophin-deficiency undergoing gonadotrophin treatment.
Consecutive infertile men (n=99) with congenital or acquired pathologic gonadotrophin deficiency were treated according to a standardised protocol between 1983 and 2024, including 161 cycles of treatment with urinary or recombinant hCG and FSH. Kaplan-Meier and multivariate Cox regression analyses examined time to pre-specified sperm density thresholds, pregnancy, and impact of urinary vs recombinant gonadotrophin.
Men aged 35±1 years with female partners 30±1 years had mostly prepubertal onset (73%) of gonadotrophin deficiency. The proportion (%) and median time (months) to achieve sperm thresholds of >0, >2, >5, >10, and >20 million sperm/mL was 82% (4 months), 59% (10 months), 51% (12 months), 39% (22 months), and 27% (37 months) respectively. Higher baseline testes volume was independently associated with earlier appearance of sperm (HR 1.04, 95% CI 1.01-1.07; p=0.01). The major determinant of successful pregnancy was the presence of adverse fertility factors in the female partner (HR 0.24, 95% CI 0.12-0.49; p<0.001), with time to pregnancy also significantly increased by the presence of adverse female fertility factors (15 vs 43 months; p<0.0001). Median sperm concentration and sperm output associated with partner pregnancy was 4.0 (0.4, 16.9) M/mL and 12.8 (0.7, 50.4) M/ejaculate, respectively, with and without adverse female factors. Time to >0 and >2 M/mL sperm thresholds was significantly faster for recombinant vs urinary hCG, with no difference in time to higher sperm concentrations.
Most men with pathological gonadotrophin deficiency treated with hCG/FSH will achieve sperm output and fertility within a year, with greatest impact on fertility outcomes being detrimental female fertility factors.