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Molecular testing of AZF region of Y chromosome

One of the causes of male infertility is associated with changes in the Y chromosome: microdeletions in the AZF region.

Under normal conditions, a large part of the genes localised in the Y chromosome ensure a successful spermatogenesis process throughout life, starting from puberty.

Microdeletion syndrome in the AZF region results in markedly impaired spermatogenesis or its complete arrest. The clinical picture in such patients is typically characterised by azoospermia or severe oligospermia, which may be the cause of male infertility.

Molecular diagnosis of the genetic status of the Y chromosome microdeletion syndrome plays the key role in determining the factor of the male infertility within the area of reproductive medicine. The result of the diagnosis determines the future steps for the patients who wish to become parents.

Molecular Testing of the AZF Region of the Y chromosome

The iVF Clinic in Rīga offers new diagnosis of male infertility – molecular testing of the AZF region of the Y chromosome.

Microdeletion syndrome of the Y chromosome as a genetically determined factor in male infertility

The Y chromosome as a factor in determining gender

As we all know, a normal set of human chromosomes (also known as the karyotype) consists of 23 pairs of chromosomes (46 in all). 22 of the pairs are the same for women and men, but the remaining pair consists of gender chromosomes that determine the gender of the individual – XX for women and XY for men.  The normal karyotype for women, thus, is 46,XX, while the normal one for men is 46,XY.

During pregnancy, if the embryo has a masculine set of chromosomes, the Y chromosome determines the masculine development of the embryo. Testes are the first to develop, and the testosterone that they produce stimulates the ongoing global process of masculinisation. Most genes in the Y chromosome ensure the genesis of sperm throughout the man’s life if the health of the individual is normal.

The role of the Y chromosome in male infertility

It is important to note that if the Y chromosome is subject to mutation, one problem can be microdeletion syndrome, also known as the azoospermia factor (AZF). This hinders the genesis of sperm or completely blocks it. This is azoospermia or oligospermia, which can cause male infertility.

Klinefelter Syndrome (karyotype 47,XXY) involves AZF microdeletion, and that is the most frequent diagnosis for male infertility. AZF microdeletion is found, on average, in one man per 4,000, though according to various studies the percentage of infertile males in a population can be between 2 and 17%.

The AZF region of the Y chromosome consists of three sub-regions (AZFa, AZFb and AZFc), so there can be various types of microdeletion (see table). This determines the manifestations of the syndrome’s phenotype or the extent to which the patient is infertile.

Type of deletionFrequency of occurrenceClinical manifestation
AZFa0.5-4%

Azoospermia 

(Sertoli Syndrome)

AZFb1-5%Azoospermia
AZFbc1-3%Azoospermia
AZFc~80%Oligospermia or azoospermia
AZFabcVery rareAzoospermia

The molecular diagnosis of the genetic status of the microdeletion of the Y chromosome is of primary importance in determining male infertility factors as part of reproductive medicine. The results of the diagnosis will determine what couples who wish to become parents can do.  The genetic laboratory of the iVF Rīga clinic is offering a new diagnostic approach for male infertility. This involves the molecular testing of the AZF region of patients with the following indications:

  • Azoospermia
  • Oligospermia <5 x 106/mL
  • ICSI manipulation

Molecular testing of the AZF region is not indicated for men with other chromosomal aberrations (apart from 46,XY/45,X), obstructive azoospermia or hypogonadotropic hypogonadism. Clinical findings such as the level of hormones, the size of testes, varicocelles, undeveloped testes, etc., have no predictive value when it comes to the genetic status of the AZF region.