IMR Press / JOMH / Volume 17 / Issue 3 / DOI: 10.31083/jomh.2021.016
Open Access Review
Chromosomal aneuploidies and associated rare genetic syndromes involved in male infertility
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1 Laboratory of Regenerative Medicine & Biomedical Innovations, Pasteur Institute of Iran, Tehran, Iran
2 Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Biochemistry, Sari Branch, Islamic Azad University, Sari, Iran
*Correspondence: (Issa Layali)
J. Mens. Health 2021, 17(3), 7–17;
Submitted: 28 December 2020 | Accepted: 12 January 2021 | Published: 8 July 2021
(This article belongs to the Special Issue Male Infertility Risk Factors)
Copyright: © 2021 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

Background and objectives: Recent investigations have reported more than 70 genetic syndromes involved in male infertility; however, the majority of these syndromes are extremely rare. We aimed to report the most common chromosomal abnormalities and associated rare genetic syndromes in the context of human male infertility.

Materials and Methods: We performed a review of published articles considering the most common chromosomal aneuploidies and rare genetic syndromes associated with male infertility on PubMed, Web of Science, and Scopus.

Results: Chromosomal abnormalities are frequently found in infertile men, with an incidence rate of 2-15%. The chromosomal aberrations include the sex and autosomal chromosome abnormalities, as well as numerical and structural defects in chromosomes. There are various rare genetic syndromes involved in male infertility that are caused by structural and numerical abnormalities in chromosomes. Klinefelter syndrome is the most common type of sex chromosome aneuploidy in infertile males. Besides, Y chromosome microdeletions, particularly in azoospermia factor regions, serve as the second most common genetic cause of impaired spermatogenetic in infertile men. These molecular genetic abnormalities not only can be inherited, but also they may transmit to the next generation through assisted reproductive techniques and result in the birth of boys with higher risk of congenital abnormalities and infertility. Despite the normal secondary male sexual characteristics, some patients are azoospermic or severe oligozoospermic men. Therefore, identification of these molecular genetic factors and rare genetic disorders is essential in men with unexplained infertility.

Discussion and conclusion: Since most of molecular genetic abnormalities can be transmitted to the next generation, identification of these rare genetic disorders is crucial for men with unexplained infertility. It is also essential for clinicians and physicians of reproductive medicine and andrologists to initiate genetic evaluation, aneuploidy screening and counseling prior to any therapeutic procedures.

Assisted reproductive techniques
Chromosomal aneuploidies
Male infertility
Rare genetic syndromes
Y chromosome
Fig. 1.
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