Current and emerging medical therapeutic agents for idiopathic male infertility

ABSTRACT

Introduction: Infertility is one of the great challenges of modern healthcare. It afflicts about 8–12% of reproductive-aged couples worldwide, but the prevalence is even higher in industrialized countries. In 50% of cases, a male factor of infertility underlies the problem, but in about 30% of these cases the etiology of male infertility remains unknown. This eventuality, called idiopathic infertility, requires empirical medical therapy and/or assisted reproductive techniques.

Areas covered: This article reviews the literature about the medical treatments available for idiopathic male infertility. These treatments can be divided into two main categories: hormonal therapies and non-hormonal therapies. The compounds with the strongest evidence of efficacy and the most used in clinical practice for the treatment of idiopathic male infertility are follicle-stimulating hormone (FSH) and estrogen receptor selective modulators (SERMs). Non-hormonal treatments include a series of compounds with antioxidant and prokinetic properties, supported by variable degrees of evidence of clinical efficacy.

Expert opinion: Patients with idiopathic infertility have peculiar clinical features that differentiate them from each other. Therapy must, therefore, be personalized to each patient. Furthermore, scientific research must investigate the pathophysiological mechanisms that underlie infertility; only in this way, new targeted therapies can be developed.

KEYWORDS:

• Idiopathic male infertility
• empiric treatment
• medical therapy
• azoospermia
• oligozoospermia
• oligoasthenoterato-zoospermia
• FSH
• hCG
• aromatase inhibitors
• SERMs

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Article highlights

• A male factor is responsible in about 50% of cases of couple infertility. In 30% of cases, the cause of male infertility remains unknown, despite an accurate diagnostic work up

• The treatment of idiopathic male infertility consists in the application of ART or empirical medical therapy, which may be hormonal or non-hormonal

• Among the hormonal therapies the most effective are SERMs and FSH; among non-hormonal therapy the strongest evidences of effectiveness are about carnitines, coenzyme Q10, myoinositol, some vitamins and trace elements

• It would seem that the association between hormonal and non-hormonal therapy is more effective than using one or the other; but, in all cases, the therapy must be personalized for each patient

• Scientific research must engage in further clarifying the pathophysiology of infertility to reduce the number of cases still considered idiopathic. An emerging research field could be the interaction between intestinal microbiota and reproductive function

• Clinicians must always carry out a careful diagnostic work-up to identify any factors that may hinder conception (including seminal rheological alterations and unrecognized infections), before starting an empiric therapy for infertility

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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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This manuscript was not funded.