Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Prolonged Time to Fertility with Spermatogenesis Induction Therapy in a Man with Congenital Hypogonadotropic Hypogonadism without Spontaneous Pubertal Development (#620)

Yeung-Ae Park 1 2 , Carolyn Allan 1 2 3 , Stella Sarlos 1 2 3
  1. Endocrinology Unit, Monash Health, Clayton, Victoria, Australia
  2. Hudson Centre for Endocrinology and Metabolism, Melbourne, Victoria, Australia
  3. School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia

Background: Congenital hypogonadotropic hypogonadism (HH) results in gonadal failure due to insufficient hypothalamic gonadotrophin-releasing hormone or pituitary gonadotropins.1 In HH, spermatogenesis induction (SI) therapy with human chorionic gonadotropin (hCG) and follicular stimulating hormone (FSH) enables the restoration of endogenous testosterone production and spermatogenesis.2 We present the fertility outcome of SI therapy in congenital HH.

Case: A 31-year-old man with idiopathic isolated HH on testosterone therapy sought fertility planning. He had received pubertal induction with testosterone and continued this into adulthood. He had not previously received gonadotrophin therapy. Long-acting intramuscular testosterone was switched to transdermal formulation prior to commencing hCG. Baseline total testicular volume was 8 mL. Time taken to reach testosterone level >10 nmol/L with hCG was 17 months, with hCG titrated from 1500 IU twice weekly to 3000 IU twice weekly. With persisting azoospermia, FSH was introduced at 6 months. Time to first detectable sperm was 20 months, and the maximum sperm concentration (0.28 x 106/mL) was achieved after 28 months on Pregnyl 3000 IU twice weekly and Gonal-F 100 IU thrice weekly. There were no identified female factors for subfertility. After 52 months , the couple underwent in vitro fertilisation with 1 cycle, resulting in a live birth and cryopreservation of additional embryos and sperm. After the delivery, the patient reverted to a transdermal testosterone preparation.

Conclusion: A prolonged time may be required for spermatogenesis induction in congenital HH not preceded by spontaneous pubertal development. Limited studies suggest that prior gonadotrophin therapy may shorten the time to successful SI in men with HH.3-5 Even if normal semen parameters are not achieved, increased sperm count enables a trial of assisted reproductive technology for improved fertility outcomes.6 Advanced family planning is therefore crucial, and discussions regarding fertility treatment are recommended at least two years before the ideal desired fertility time.

  1. Boehm U, Bouloux P-M, Dattani MT, de Roux N, Dodé C, Dunkel L, et al. European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment. Nature Reviews Endocrinology. 2015;11(9):547-64.
  2. Swee DS, Quinton R. Managing congenital hypogonadotrophic hypogonadism: a contemporary approach directed at optimizing fertility and long-term outcomes in males. Ther Adv Endocrinol Metab. 2019;10:2042018819826889.
  3. Liu PY, Baker HW, Jayadev V, Zacharin M, Conway AJ, Handelsman DJ. Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab. 2009;94(3):801-8.
  4. Rohayem J, Hauffa BP, Zacharin M, Kliesch S, Zitzmann M, Group” tGAHHS. Testicular growth and spermatogenesis: new goals for pubertal hormone replacement in boys with hypogonadotropic hypogonadism? -a multicentre prospective study of hCG/rFSH treatment outcomes during adolescence. Clinical Endocrinology. 2017;86(1):75-87.
  5. Grob F, Keshwani R, Angley E, Zacharin M. Fertility outcomes in male adults with congenital hypogonadotropic hypogonadism treated during puberty with human chorionic gonadotropin and recombinant follicle stimulating hormone. Journal of Paediatrics and Child Health. 2024;60(2-3):53-7.
  6. Jiesisibieke D, Tian T, Zhu X, Fang S, Zhang N, Ma J, et al. Reproductive Outcomes of Conventional In Vitro Fertilization and Intracytoplasmic Sperm Injection in Patients with Non-Severe Male Infertility Across Poor and Different Sub-Optimal Ovarian Response Categories: A Cohort Study Based on 30,352 Fresh Cycles from 2009-2019. Reprod Sci. 2024;31(5):1353-62.