Congenital isolated hypogonadotropic hypogonadism (CHH) occurs due to impaired development, migration, and function of gonadotropin-releasing hormone (GnRH) neurons or defective synthesis or secretion of gonadotropins. In normal infants during first few months of life, crucial testicular development occurs as Sertoli cells (SCs) proliferate in response to the increased FSH levels. This is called minipuberty. CHH has two reproductive phenotypes: severe and partial. Males with CHH-severe reproductive phenotype   lack the minipubertal and pubertal periods of SCs proliferation and present with prepubertal testes (<4 mL) and low serum testosterone (<1 ng/ml). Males with CHH-partial reproductive phenotype have testicular volume of Â³ 4 ml and low serum testosterone (<1 ng/ml). Due to poor SCs mass, fertility treatment in CHH-severe reproductive phenotype may not yield desired response. In addition, there is evidence that testosterone action in SCs will lead to final maturation-differentiation. The recombinant follicle stimulating hormone (rFSH) pretreatment will lead to proliferation of SCs in CHH patients before these cells are exposed to recombinant human chorionic gonadotropin (rHCG) directed intratesticular testosterone. This has potential to yield better fertility prospects.

Previously a study by Dwyer et al (rFSH pre-treatment followed by pulsatile GnRH vs pulsatile GnRH) was conducted on small number of patients (total 13, 7 and 6 in each group). This study reported trend toward higher maximal sperm counts in rFSH pre-treatment group.

Gonadotropin based therapy (rFSH pre-treatment followed by combined rFSH+rHCG or combined rFSH+rHCG) are used at different centres for pubertal and fertility induction as a standard of care. There is no data comparing these two treatment options. Hence, we aim to compare efficacy of these two treatment options to induce fertility (spermatogenesis) in male CHH patients.