Current drawbacks and future perspectives in the diagnosis and treatment of male factor infertility, with a focus on FSH treatment: an expert opinion

Santi D; Corona G; Salonia A; Ferlin A

doi:10.1007/s40618-024-02524-x

Male Fertility Male Factor Treatment

Current drawbacks and future perspectives in the diagnosis and treatment of male factor infertility, with a focus on FSH treatment: an expert opinion

Santi D, Corona G, Salonia A, Ferlin A

Published May 2025 Journal of endocrinological investigation

DOI 10.1007/s40618-024-02524-x PMID 39804439 PMC PMC12049307

RRM Academy Synopsis

Semen analysis alone cannot diagnose male factor infertility

A semen analysis is the first step in a male workup and cannot give the diagnosis alone. The four authors reviewed the recent research for this expert opinion. They propose six diagnostic groups to guide treatment. They describe follicle-stimulating hormone (FSH) as the best evidence-based treatment option for selected men whose low sperm count or motility has no found cause.

Key Findings

Male factors account for 50% of couple infertility cases. Almost 30% of men with impaired sperm parameters have no identifiable cause, which the paper calls idiopathic male infertility.
One full diagnostic workup covered 1,147 white-European men from couples with primary infertility. The workup identified a causal category for 81% of them.
Despite normal sperm parameters, medical history and physical examination, 15 to 40% of the men are still infertile. The paper calls this unexplained male infertility.
Over 20 clinical trials, summarized in four meta-analyses, have tested FSH in idiopathic male infertility. For one pregnancy, the number needed to treat is 10 to 18 men.
An Italian survey found that 55% of 718 men eligible for FSH under national rules were effectively treated.

Interpretation

This paper is an expert opinion built on a narrative review of the current evidence on male infertility. The authors present six diagnostic categories to guide a stepwise male fertility workup and identify FSH as the leading evidence-based treatment for men with idiopathic low sperm count or motility. The authors note that the FSH threshold they recommend rests on normative aspects more than on clinical studies. The findings support larger studies that identify which men respond best to FSH treatment.

RRM Context

The authors want doctors to work up both partners at the same time and to find the cause before treating. They say a guideline that puts intrauterine insemination first for idiopathic infertility leaves no real room to investigate the man. Restorative reproductive medicine also puts finding the cause first.

Our editorial summary of this paper, not the article's abstract.

Abstract

Purpose

Infertility is defined as the inability to conceive after 1 year of unprotected intercourse, affecting approximately 15-20% of couples in Western countries. It is a shared problem within the couple; when the main issue lies with one of the partners, it is preferable to refer to "male factor" or "female factor" infertility rather than simply male or female infertility. Despite male factor infertility accounting for half of all couple infertility cases, the clinical approach to the male partner is not uniformly standardized across international guidelines.

Methods

To provide an expert overview, we have comprehensively reviewed and critically analyzed the most up-to-date literature on this sensitive topic, leading to the development of a proposal for tailored assessment of the diagnostic-therapeutic pathway and preventive strategies. The diagnostic approach also considers that infertile men are objectively less healthy than their fertile counterparts of the same age and ethnicity.

Results

This article discusses the diagnostic flow, the classification of male factor infertility, the definition of idiopathic infertility, the involvement of general health, and treatment recommendations, emphasizing follicle-stimulating hormone treatment in selected groups of patients.

Conclusion

We provide expert opinion on current drawbacks and future perspectives in this field, with practical advice for the clinical practice of general practitioners and expert in reproductive medicine.

Topics

Male Fertility › Male Factor Treatment › Medical Management · Diagnostics › Hormone Testing › Serum Panels · Therapeutics › Hormonal Agents › Gonadotropins

PMID 39804439 39804439 DOI 10.1007/s40618-024-02524-x 10.1007/s40618-024-02524-x Santi et al. 2025, Santi 2025

Current drawbacks and future perspectives in the diagnosis and treatment of male factor infertility, with a focus on FSH treatment: an expert opinion

Semen analysis alone cannot diagnose male factor infertility

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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