Efficacy of rFSH Pretreatment Followed by combined rFSH+rHCG versus combined rFSH+rHCG for Inducing Fertility in Congenital Hypogonadotropic Hypogonadism Males: Open Label Pilot RCT
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Acheivement of spermatogenesis
研究概览
简要总结
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 ³ 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 45.00 Year(s)（—）
- 性别
- Male
入选标准
- •Age more than 18 years with confirmed diagnosis of severe CHH (defined as absence of puberty with testicular volume less than 4 ml, low serum total testosterone (less than 1ng/ml) with low or inappropriately normal FSH/LH, normal levels of other anterior pituitary hormones and normal MRI scans of the hypothalamic-pituitary region).
排除标准
- •Partial hypogonadotropic hypogonadism (testicular volume more than 4 ml) 2) Secondary hypogonadism due to non-congenital causes like pituitary tumors or craniopharyngioma 3) Pre-existing medical conditions affecting sexual development or fertility like thalassemia, cranial irradiation for malignancies etc 4) History of prior gonadotropin/GnRH use 5) Hypergonadotropic hypogonadism 6) Incapability to store and self-administer study drug.
结局指标
主要结局
Acheivement of spermatogenesis
时间窗: Semen analysis will be done on 6, 9, 12 and 15 months
次要结局
- Testicular volume(Baseline, 2, 4, 6, 9, 12 and 15 months)
- Sertoli cell function as assessed by AMH and inhibin B(Baseline, 6 and 15 months)
- Serum Testosterone(Baseline, 2, 4, 6, 9, 12 and 15 months)
研究者
Tushar Bandgar
KEM Hospital