Biological therapy for non-obstructive azoospermia

ABSTRACT

Introduction: Most male patients with non-obstructive azoospermia (NOA) have no therapeutic options outside of assisted reproductive techniques to conceive a biological child. If mature sperm cannot be obtained from the testes, these patients must rely on options of donor sperm or adoption. Several techniques are in the experimental stage to provide this patient population alternatives for conceiving.

Areas covered: This review discusses three of the experimental techniques for restoring fertility in men with NOA: spermatogonial stem cell transplantation, the use of adult and embryonic stem cells to develop mature gametes and gene therapy. After this discussion, the authors give their expert opinion and provide the reader with their perspectives for the future.

Expert opinion: Several limitations, both technical and ethical, exist for spermatogonial stem cell transplantation, the use of stem cells and gene therapy. Well-defined reproducible protocols are necessary. Furthermore, several technical barriers exist for all protocols. And while success has been achieved in animal models, future research is still required in human models.

KEYWORDS:

• Gene therapy
• non-obstructive azoospermia
• spermatogonial stem cell transplantation
• pluripotent stem cell

Article highlights

• Existing therapeutics for non-obstructive azoospermia (NOA) are limited and depend on the ability to harvest mature sperm from the testis for ICSI

• Spermatogonial stem cell transplantation is a promising option to repopulate the germinal epithelium in men with NOA

• The use of embryonic and adult stem cells to develop mature male gametes may provide patients with an alternative therapeutic option.

• At present, a complete understanding of the stem cell niche is still lacking

• For cases of NOA caused by a to a mutation at a single gene locus, gene therapy may be a definitive treatment for infertility.

This box summarizes key points contained in the article.

Declaration of interest

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.

Additional information

Funding

This manuscript has not been funded.