A Y-chromosome microdeletion can help explain azoospermia or a very low sperm count in selected men. The affected AZF region matters for the chance of finding sperm and for genetic counseling. This diagnosis is not evidence that someone caused infertility through their lifestyle.
When Genetic Testing Can Explain a Very Low Sperm Count
Human history is, in essence, the history of genes. Countless pieces of information passed from father to son, and then to grandson, are recorded within tiny chromosomes to be transmitted to the next generation. What happens if part of this record disappears?
The Y-chromosome microdeletion, often encountered while covering male infertility, is a story that begins with exactly that question.
Many people are quite surprised when they first hear the diagnosis because of the term “chromosome deletion.” However, in reality, it is a very small genetic deletion that is invisible and completely imperceptible in daily life.
Yet, because that small deletion can affect a man’s sperm production capacity and, in some cases, be passed down to the next generation, it is far from a minor issue.
Most people have 46 chromosomes, with typical sex-chromosome patterns of XX or XY, although variations exist. The Y chromosome contains genes important for sperm production; chromosomal sex should not be equated with gender identity.
An interesting fact is that the Y chromosome has a more unstable structure than one might think. Most chromosomes exist in pairs, allowing them to exchange genetic information with each other and having the opportunity to correct errors. However, the Y chromosome effectively exists alone. Furthermore, similar gene sequences are repeatedly copied inside it—much like a book where the same sentence is repeated dozens of times.
The problem is that this structure is vulnerable to copying errors.
During cell division, if repeated sentences align incorrectly with one another, an event can occur where several pages in the middle of the book disappear entirely. Geneticists call this “non-allelic homologous recombination.” A significant portion of Y-chromosome microdeletions occurs during this exact process.
In particular, there is a region within the Y chromosome called AZF (Azoospermia Factor). As the name implies, it is a zone where the genes necessary for making sperm are gathered. This region is divided into three parts: AZFa, AZFb, and AZFc.
Complete AZFa or AZFb deletions generally carry a very poor prognosis for surgical sperm retrieval. Partial deletions require separate interpretation, so the exact laboratory result matters.
AZFc deletion is relatively diverse. While it can manifest as azoospermia (total absence of sperm), in some cases, a small number of sperm are still produced. Consequently, there are reports of successful pregnancies using micro-TESE (micro-surgical sperm extraction) to locate sperm, followed by IVF and ICSI (intracytoplasmic sperm injection).
What causes Y-chromosome microdeletion? Many men, upon receiving the diagnosis, try to find the cause within themselves. “Did I drink too much alcohol?” “Was it because of too much stress?” “Is it because I didn’t exercise?”
Y-chromosome microdeletion is generally known not to be caused by individual lifestyle habits, but rather as a structural change that happens by chance during the DNA replication process. It is no one’s fault.
Y-chromosome microdeletions are an established genetic cause of impaired sperm production. Their frequency depends on the population and severity of the semen findings, so testing is targeted rather than required for every low count.
So, what happens if a man with a Y-chromosome microdeletion has a son through IVF?
The conclusion is that it is passed down (inherited). The Y chromosome is transmitted from father to son. Therefore, the deletion is also highly likely to be transmitted. Indeed, reports have long existed of sons born to men with Y-chromosome microdeletions inheriting the exact same deletion.
For this reason, in genetics, the Y-chromosome microdeletion test is viewed not merely as an infertility test, but as the starting point for genetic counseling. This is because one must explain not only the current possibility of pregnancy but also the potential impact on future generations.
Who may be offered testing
The 2024 AUA/ASRM guideline recommends Y-microdeletion analysis for primary infertility with azoospermia or sperm concentration at or below 1 million/mL when accompanied by elevated FSH, testicular atrophy or impaired production. A deletion transmitted on the Y chromosome can be inherited by sons, making genetic counseling important. AUA/ASRM guideline.
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