What are the other Names for this Condition? (Also known as/Synonyms)

• Deleted in AZoospermia (DAZ)
• Male Sterility due to Y-Chromosome Deletions
• Y Chromosome Microdeletions

What is Y Chromosome Infertility? (Definition/Background Information)

• Y Chromosome Infertility is a condition that affects the production of sperm, making it difficult or impossible for affected men to father children. In this condition, the affected men may produce:
  • No sperm cells (azoospermia)
  • A smaller than usual number of sperm cells (oligospermia), or
  • Sperm cells that are abnormally shaped or that do not move properly
• As its name indicates, Y Chromosome Infertility is a form of infertility that is caused by changes in the Y chromosome, one of the sex chromosomes. It is usually caused by deletions of genetic material in regions of the Y chromosome called azoospermia factor (AZF) A, B, or C. Genes in these regions are believed to provide instructions for making proteins involved in sperm cell development, although the specific functions of these proteins are not well understood
• Some men with Y Chromosome Infertility who have mild to moderate oligospermia may eventually father a child naturally. Assisted reproductive technologies may help other affected men. Since men with this condition are unable to father children, it is caused by new deletions on the Y chromosome (occurring in men with no history of the disorder in their family)
• However, when men with Y Chromosome Infertility do father children, either naturally or artificially, they can pass on the genetic changes on the Y chromosome to all (and only) their sons. As a result, the sons will also have Y Chromosome Infertility

(Source: Y Chromosome Infertility; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Y Chromosome Infertility? (Age and Sex Distribution)

• Y Chromosome Infertility is a rare congenital disorder. The condition exclusively affects males
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Y Chromosome Infertility? (Predisposing Factors)

• Boys born to Y Chromosome Infertility affected fathers have a very high risk for the disorder to be manifested in them
• Currently, no environmental and lifestyle (including dietary) factors have been implicated
• The syndrome is not caused by what the expectant mother does or does not do, either prior to or during pregnancy

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Y Chromosome Infertility? (Etiology)

• Y Chromosome Infertility is an uncommon disorder that is typically caused by deletions of genetic material in regions of the Y chromosome called azoospermia factor (AZF) A, B, or C
• Genes in these regions are believed to provide instructions for making proteins involved in sperm cell development, although the specific functions of these proteins are not well-understood
• In rare cases, changes to a single gene called USP9Y, which is located in the AZFA region of the Y chromosome, can cause Y Chromosome Infertility
• Some men with Y Chromosome Infertility who have mild to moderate oligospermia may eventually father a child naturally
• When men with Y Chromosome Infertility do father children, either naturally or with the aid of assisted reproductive technologies, they pass on the genetic changes on the Y chromosome to all their sons. As a result, the sons will also have Y Chromosome Infertility

(Source: Y Chromosome Infertility; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Additional (general) information on chromosomes, which is helpful in understanding the disorder:

Chromosomes are microscopic thread-like protein structures present in each cell nucleus that carry genetic information in the form of DNA (deoxyribonucleic acid). DNAs are nucleic acids that encodes the genetic information of any organisms; a basic unit of the DNA is termed a gene with a specific set of instructions and a defined function. Each chromosome is “X” shaped with a center, called the centromere, and two short arms (termed p arms) and two long arms (termed q arms).

Humans have 46 chromosomes in the cell nucleus, in 23 pairs, of which one pair is named the sex chromosome. In males, it is designated XY, for chromosome X and chromosome Y; while, in females, it is designated XX, for a pair of chromosome X. The other 22 pairs of chromosomes are numbered chromosome 1 through 22, approximately according to size (with chromosome 1 being the largest; chromosome 21 being the smallest) and are referred to as autosomes or somatic chromosomes. During conception, the embryo inherits one copy of each chromosome from each parent (i.e., mother and father). Any alteration in the chromosome numbers or structure, such as via addition or deletion of chromosomal material, can result in mild to severe genetic abnormalities that may manifest as birth defects, growth delays, and intellectual disabilities.

What are the Signs and Symptoms of Y Chromosome Infertility?

The signs and symptoms of Y Chromosome Infertility that are observed in males include:

• Abnormality of metabolism
• Homeostasis-related abnormalities; homeostasis refers to the state of steady internal, physical, and chemical conditions
• Sperm cell abnormalities that include:
  • Sperm cells that are abnormally shaped or that do not move properly
  • A smaller than usual number of sperm cells (oligospermia), or
  • No sperm cells (azoospermia)
• No other physical, mental, and growth deficits are observed

How is Y Chromosome Infertility Diagnosed?

Y Chromosome Infertility is diagnosed on the basis of the following information:

• Complete physical examination and thorough medical history evaluation, including family medical history
• Assessment of the presenting signs and symptoms
• Laboratory tests, as necessary
• Semen analysis
• Radiological studies of the affected regions, as needed
• Prenatal studies including abdominal ultrasonography
• Specialized genetic testing techniques are often required to confirm the diagnosis. This may include:
  • Fluorescence in situ hybridization (FISH) testing
  • Array comparative genomic hybridization (array-CGH)
  • DNA sequencing

Often, karyotyping of the chromosome is not adequate to diagnose the condition, since individuals with this condition can have normal karyotype chromosomal studies.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Y Chromosome Infertility?

The complications of Y Chromosome Infertility may include:

• Severe emotional stress due to infertility
• Low self-esteem
• Depression
• Social isolation and ostracism

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Y Chromosome Infertility Treated?

• Presently, there is no cure for Y Chromosome Infertility since it is a genetic condition
• Men who want to father children may be suggested assisted reproductive technologies

How can Y Chromosome Infertility be Prevented?

Y Chromosome Infertility may not be preventable since many of these genetic disorders are diagnosed at or following the birth of the child. A majority of cases are sporadic occurrences, which means there is no family history of the condition.

• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Y Chromosome Infertility? (Outcomes/Resolutions)

The prognosis of Y Chromosome Infertility is dependent upon the severity of the condition.

• Men with mild to moderate conditions may father children
• Men with severe cases can take recourse to artificial techniques to father children

Additional and Relevant Useful Information for Y Chromosome Infertility:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/