Abstract
Disclosure: J.V. Gialouris: None. A.J. Conway: None. A. Idan: None. S. Savkovic: None. R. Hermosilla: None. C.A. Muir: None. F. Bacha: None. T. Zhang: None. V. Jayadev: None. D.J. Handelsman: None.
Introduction: Gonadotropin treatment to induce spermatogenesis and fertility for gonadotropin-deficient men is the only treatable cause of male infertility, excluding IVF bypass. Methods: Using a standardized protocol, 99 consecutive infertile men with congenital or acquired gonadotropin deficiency due to pathologic disorders of the hypothalamus or pituitary were treated using urinary or recombinant hCG and FSH to induce spermatogenesis and fertility. Results: Men aged 35 ± 1 years with female partners 30 ± 1 years had mostly prepubertal onset (73%) of gonadotropin deficiency, with few having cryptorchidism (3% unilateral, 10% bilateral) or other testis pathology (7%). Gonadotropin deficiency was due to congenital hypogonadotropic hypogonadism in 64 men, acquired (pituitary or cerebral tumors or hypothalamic disorders) in 30 men and other/mixed etiology (5). Univariate and multivariate Cox regression and Kaplan-Meier plots of outcomes in 161 treatment cycles (58 with one, 22 two, 17 three, 2 four) with a median duration of 15 (IQR 10, 30) months assessed (a) time to pre-specified sperm density thresholds, (b) time to partner pregnancy and (c) efficacy of urinary vs recombinant gonadotropins. Potential covariables for time to outcome comprised age, female partner’s age, cause of gonadotropin deficiency, onset age, anthropometry, pre-treatment testis volume, cryptorchidism, treatment cycle number and adverse female factors. 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. The major determinant of time to pregnancy was absence of adverse female fertility factors (75 vs 33%, 15 vs 43 months, HR 0.24 95% CI 0.12-0.48; p<0.001). Other significant predictors of time to attainment of sperm thresholds or time to pregnancy (eg pre-treatment testis volume, bilateral cryptorchidism, 2nd or later cycle) varied between thresholds but were generally consistent with better prognosis for acquired (post-pubertal onset) gonadotropin deficiency. The 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. Time to >0 and >2 million sperm per mL thresholds was significantly faster for recombinant vs urinary hCG, but not significantly different for higher sperm thresholds or pregnancy, nor was there significant differences in time to sperm threshold for urinary vs recombinant FSH. Conclusion: This analysis of time-dependent spermatogenesis and pregnancy outcomes in 99 men undergoing hCG/FSH treatment for pathologic gonadotropin deficiency confirms that most men will achieve sperm output and fertility within a year, with greatest impact on fertility being detrimental female fertility factors.
Presentation: Saturday, July 12, 2025