Investigational follicle-stimulating hormone receptor agonists for male infertility therapy

ABSTRACT

Introduction

According to estimates by the World Health Organization, about 17.5% of the adult population – roughly 1 in 6 globally – experience infertility. The causes of male infertility remain poorly understood and have yet to be fully evaluated. Follicle-stimulating hormone (FSH) represents an available and useful therapeutic strategy for the treatment of idiopathic infertility.

Areas covered

We provide here an overview of the molecular mechanisms by which FSH stimulates Sertoli cells and the schemes, dosages, and formulations of FSH most prescribed so far and reported in the literature. We also evaluated the possible predictor factors of the response to FSH administration and the indications of the latest guidelines on the use of FSH for the treatment of male infertility.

Expert opinion

FSH therapy should be considered for infertile male patients with oligoasthenoteratozoospermia and normal serum FSH levels to quantitatively and qualitatively improve sperm parameters and pregnancy and birth rates. The grade of evidence is very low to low, due to the limited number of randomized controlled studies and patients available, the heterogeneity of the studies, and the limited effect size. To overcome these limitations, preclinical and clinical research is needed to evaluate the most effective dose and duration of FSH administration.

KEYWORDS:

• Follicle-stimulating hormone
• FSH
• infertility
• oligozoospermia
• spermatozoa
• therapy

Article highlights

• FSH therapy should be considered for infertile male patients with oligozoospermia and normal serum FSH levels to quantitatively and qualitatively improve sperm parameters and pregnancy and birth rates.

• The grade of evidence is very low to low, due to the limited number of randomized controlled studies and patients available, the heterogeneity of the studies, and the limited effect size.

• Efforts have been made and are ongoing to find predictors of response to FSH administration. Apart from testicular histology, no other reliable predictors have been acknowledged by international societies’ guidelines so far.

• Studies are urgently needed to standardize the weekly dosage, as well as the duration of the treatment, for male infertility.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed they have received Fellow Health (equity), Roman (scientific advisory board) compensation and stock options not executed, American Board of Bioanalysts (Secretary Treasurer), Honorarium American Association of Bioanalysts (Board member) Honorarium, American Society for Reproductive Medicine (Speaker Travel costs). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.