Male Infertility—Diagnosis and Treatment

Dear Colleagues,

The inability to conceive after 12 consecutive months of unprotected and timely sexual intercourse—commonly known as infertility—is an emotionally and financially stressful condition for young couples wishing to start families. Nearly one-half of infertility globally is ascribable to male infertility, which has far-reaching health consequences, often offering a valuable insight into general health.

Male infertility is a multifactorial reproductive disorder caused by endocrinopathies, infections, anatomical causes, and genetic and epigenetic factors. While the cause is easily identifiable in some cases, a clear-cut diagnosis is out of reach for many patients. This is referred to as idiopathic male infertility. Though it is typically visible in abnormal semen analyses, no currently available diagnostic tests can identify the cause of those abnormalities. Another sub-category of infertility is unexplained male infertility, in which no apparent abnormalities can be identified in the semen profile.

The current diagnostic tests based mainly on semen analysis fail to provide a proper diagnosis of male infertility. Indeed, the 6th edition of the World Health Organization Manual for the Laboratory Examination and Processing of Human Semen, released in 2021, has addressed these shortcomings by proposing expanded and advanced tests to improve male factor infertility detection.

Despite these efforts, the molecular or intracellular causes of infertility in infertile men remain undetermined due to the lack of more advanced, affordable, and reliable diagnostic tests. While ART, including ICSI, has revolutionized the treatment of male infertility, the technology is prohibitively expensive and inaccessible for many couples worldwide. While microfluidics and hyaluronic acid binding have been used to select sperm with lower DNA fragmentation for ART, these measures have not translated into better patient outcomes.

In recent years, several new approaches to diagnosis of male infertility have been proposed, with some modest success. These include a DNA fragmentation index test and measurement of oxidative stress induced by reactive oxygen species; tests that assess sperm function, such as acrosome integrity, mitochondrial activity, and the ability to undergo capacitation; multiomics comprising genomics, epigenetics, transcriptomics, proteomics, and metabolomics; reliable and efficient integration of emerging technologies, such as artificial intelligence (AI), in male infertility testing and diagnosis.

For this special issue, we are seeking many reviews and research articles exploring the challenges and recent developments in male infertility testing and diagnosis. Potential topics include (but are not limited to):

1. The role of specific genes, sperm epigenetic alterations, mitochondrial DNA alterations, and specific proteins in sperm and seminal plasma, in male infertility. 
2. The role of intracellular structures such as sperm centriole in male infertility.
3. Full-scale untargeted genomics, epigenomics, transcriptomics, proteomics, and metabolomics studies of male infertility.
4. The role of Leukocytospermia in clinical management of male infertility.

Dr. Puneet Sindhwani
Dr. Tariq Shah
Guest Editors

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• male infertility
• unexplained male infertility
• iatrogenic male infertility
• male infertility diagnosis
• male infertility and multiomics
• advanced male infertility testing
• sperm DNA fragmentation