SAT-181 Audit of spermatogenesis induction in men with hypogonadotropic hypogonadism in clinical andrology practice

Abstract Disclosure: Y. Park: None. S. Sarlos: None. R.I. McLachlan: None. I. Sim: None. R. Upreti: None. C.A. Allan: None. Introduction: Infertility affects one-third of couples, with male factors contributing up to 50%. Spermatogenesis induction (SI) can be an effective treatment for men with hypogonadotropic hypogonadism (HH). However, the impact of pre-SI testosterone replacement therapy, especially its modality, on fertility outcomes remains unclear. Methodology: In a retrospective cohort study, men treated for SI by clinical andrologists from an Australian tertiary centre, either in the public outpatient service (2012-2020) or private clinics (2003-2024), were screened. Human chorionic gonadotropin (hCG) was titrated to achieve normal serum total testosterone. Recombinant follicular stimulating hormone (FSH) was typically added after 6 months for persisting azoospermia. SI was defined as any detectable sperm. Pre-SI testosterone replacement therapy (TRT), if any, was documented. Results: 47 azoospermic men with HH were treated for infertility with a median age of 34 years. Causes were classified as congenital, defined by pre-pubertal onset or absence of spontaneous puberty (n=25) and acquired, defined by post-pubertal onset (n=22). The causes of HH included iatrogenic pituitary pathology (n=16), idiopathic (n=15), congenital HH (CHH) including Kallmann syndrome (n=8), iron overload (n=4), prolactinoma (n=3) and opioids (n=1). 42 men (89.4%) achieved SI. The median (Q1-Q3) time to SI was 19.0 (12.0-33.1) months. Those on pre-SI testosterone replacement therapy (TRT) (n=22) had a comparable time to SI than those without pre-SI TRT (n=17) (19.0 [12.0-28.2] vs. 20.0 [12.4-36.3] months; p=0.79). Pre-SI TRT modality (long-acting [n=14] and short-acting intramuscular [n=2], transdermal [n=5] or oral [n=1]) was not associated with the time to SI (18.8 [16.0-24.0 vs. 18.9 [5.2-32.6] vs. 19.0 [12.0-22.0] vs. 29.0 [29.0-29.0] months; p=0.77). Congenital causes of HH (n=20) required a longer time to SI than acquired causes (n=19) (23.5 [18.0-37.5] vs. 16.0 [7.0-20.3] months; p=0.02). Time to SI was different across HH aetiologies (Table 1, p=0.04), with the longest time in CHH (n=7, 29.0 [22.9-47.0] months) and the shortest from opioids (n=1, 3.5 months). A greater pre-SI testicular volume was associated with a shorter time to SI (n=28, rho=-0.446, p=0.02). Of those who are known to have achieved pregnancy (n=26), assisted reproductive technology was commonly used (65%) compared to natural conception (27%). Conclusions: Neither pre-SI TRT status nor its modality was associated with SI outcomes. Congenital causes of HH and lower pre-SI testicular volume were associated with a longer time to SI compared to acquired causes of HH. There were significant differences in time to SI across HH aetiologies, with the longest in CHH followed by idiopathic HH. Larger studies are warranted to further elucidate the potential clinical importance of TRT modality before SI. Presentation: Saturday, July 12, 2025