Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study.

Abstract

BACKGROUND:

Elevated plasma gonadotropins were associated with desensitization of Sertoli and Leydig cells in the male testis. Testis spermatogenesis ability would be improved via inhibiting high endogenous gonadotropin in patients with severe oligozoospermia. Whether it would be beneficial for non-obstructive azoospermia (NOA) patients was still unclear.

METHODS:

Goserelin, a gonadotropin releasing hormone agonist (GnRHα) was used to suppress endogenous gonadotropin levels (gonadotropin reset) in the NOA patients, improving the sensitization of the Sertoli and Leydig cells. Then human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) were injected to stimulate them to ameliorate the ability of testicular spermatogenesis. The main outcome measure was the existence of spermatozoa in the semen or by testicular sperm extraction (TESE). Elevation of inhibin B and/or ameliorative expression pattern of ZO-1 was the secondary objective.

RESULTS:

A total of 35 NOA men who failed to retrieve sperm via TESE were enrolled. Among these, 10 patients without treatment were selected as control group and secondary TESE was performed 6 months later. Of the 25 treated men, inhibin B was elevated in 11 patients in the first 4 weeks (Response group), while only 5 patients had constant increase in the following 20 weeks (Response group 2). Of the 5 men, 2 men acquired sperm (Response group 2B), while 3 failed (Response group 2A). Immunofluorescence of mouse vasa homologue (MVH) and ZO-1 showed that both positive MVH signals and ZO-1 expression were significantly increased in the Response group 2, but only Response group 2B showed ameliorative ZO-1 distribution.

CONCLUSIONS:

Gonadotropin reset, a new therapeutic protocol with GnRHα, was able to improve the ability of testicular spermatogenesis in the NOA patients through restoring the sensitivity of Sertoli and Leydig cells, which were reflected by elevated inhibin B and ameliorative ZO-1 expression and distribution.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT02544191 .

• Authors: Xuechun Hu, Zheng Ding, Zhiwei Hong, Zhichuan Zou, Yuming Feng, Ruilou Zhu, Jinzhao Ma, Xie Ge, Chaojun Li, Bing Yao
• Journal: Reproductive biology and endocrinology : RB&E (Reprod Biol Endocrinol) Vol. 16 Issue 1 Pg. 91 (Sep 22 2018) ISSN: 1477-7827 [Electronic] England
• PMID: 30243299 (Publication Type: Journal Article)

Chemical References

• Chorionic Gonadotropin
• TJP1 protein, human
• Zonula Occludens-1 Protein
• inhibin B
• Goserelin
• Gonadotropin-Releasing Hormone
• Inhibins
• Menotropins

Topics

• Adult
• Azoospermia (drug therapy)
• Case-Control Studies
• Chorionic Gonadotropin (therapeutic use)
• Gonadotropin-Releasing Hormone (agonists)
• Goserelin (therapeutic use)
• Humans
• Inhibins (metabolism)
• Male
• Menotropins (therapeutic use)
• Middle Aged
• Pilot Projects
• Spermatogenesis (drug effects)
• Zonula Occludens-1 Protein (metabolism)