Y- chromosome microdeletions:
Cystic Fibrosis diseases:
A couple’s inability to get pregnant after one year is called non-contraceptive sex by definition of infertility. Infertility occurs in 15 to 20% of couples. The causes of infertility can be male or female, or both. About 40% of male infertility problems are about 40% for women and about 10% for both. About 10% of couples have infertility as well.
Genetic Causes of Infertility in Men:
Men with very low sperm count; may have a chance of fathering through ICSI (sperm injection into the egg cell cytoplasm). Also, in some cases of azoospermia, one can even have a child by removing sperm from the testicles. In general, infertile men have a much higher chance of structural abnormalities and a number of chromosomes than the fertile community, since these disorders in addition to infertility can in some cases cause genetic syndromes in the next generation. Therefore, in people with a history of infertility and low fertility genetic testing on peripheral blood and in some cases on sperm samples is necessary. The most important genetic disorders in male infertility are briefly described below.
Chromosomal structural abnormalities:
Chromosomal abnormalities can occur in a number of (trisomy) or structural (reversal or chromosomal displacements). A large study of about 10000 infertile men shows that chromosomal abnormalities are present in 6% of them, which in the meantime the role of the sex chromosome is about 4.5% and the rest of the chromosomes (autosomes) is about 1.5%. This percentage was only 0.38% in the randomly selected population. Thus, the chances of chromosomal abnormalities in infertile men are 16 times higher than in the general population. Also, in patients whose sperm count is less than 5 million ml, the chances of chromosome abnormalities are 10 times higher. Other chromosomal abnormalities in infertility are chromosomal translocations. In general, chromosomal translocations can cause genetically unbalanced gametes. In these cases, the majority of gametes produced by these individuals are not fertile and If fertilized, fetuses created by gametes may have genetic disorders. In some cases, due to chromosomal abnormalities in the fetus, these embryos become aborted before the mother becomes aware. Therefore, in cases of recurrent miscarriage or infertility, Karyotype testing for couples is highly recommended. IVF / ICSI cases for patients with chromosomal abnormalities, PGD (preimplantation genetic diagnosis) and PND (pre-pregnancy genetic diagnosis) are required. According to the above, a coyote test for men with less than 1 million sperm per milliliter of semen is indicated. Of course, if you have a family history of recurrent miscarriage; infants with apparent malformations and mental retardation; Karyotyping is essential regardless of the sperm count before fertilization.
Disorders of a number of sex chromosomes:
Klinefelter Syndrome (47.XXY) and its forms:
It is the most common chromosomal abnormality in men. Men with Klinefelter Syndrome have a small, rigid testis and their phenotype can range from a man with normal masculine traits to loss of masculine traits with androgen depletion. One out of every 500 to 1000 men, one with non-obstructive azoospermia has this syndrome.
(……………..) Sperm content in men with Klinefelter Syndrome mosaic (47.XXY / 46’XY) varies. In cases where mosaicism is Kleinfilter, up to 50% of sperm harvest cases will be successful and people can have children. However, in some studies PGD testing is recommended to prevent births of babies with a number of chromosomal abnormalities.
Y- long arm chromosome microdeletions:
Various studies have shown that a series of Y-chromosome microdeletions can cause male infertility. This area is called azoospermia factor (AZF). There are three regions on the Y chromosome that play an important role in sperm production and maturation. These regions are termed AZFa, AZFb, and AZFc. Frequency of AZF deletion in men with low sperm count (oligoospermia) is 3-7%. This rate in those without sperm (azoospermia) is 8-12%. Determining these microdeletions is particularly important. These include:
1) Diagnosing the cause of infertility.
2) Determining the Prognosis of an Infertile Person.
3) Determine the method of treatment.
4) Determination of sperm recovery.
Since the Y chromosome is likely to be passed on to the next-generation son, so parents should be informed that if their child is a son, he or she will have a gene deletion on the Y chromosome if their child is a son. Y-chromosome microdeletions after Kleinfilter syndrome is the most common genetic cause of infertility in men and They are about 1 in 2000 to 3000 males. About 10% of these cases have severe oligospermia and about 5% have azoospermia. Evaluation of Y- chromosome microdeletions allows to identify the cause of azoospermia / oligo spermatozoa and provide a prognosis to the patient as well as determine the method of obtaining sperm from their testes (appropriate treatment protocol).
The role of deletion of AZF regions in infertility:
● AZFa: About 6% of men with Y- chromosome microdeletions have deletions in the AZFa. Deletion in the AZFa region causes only Sertoli cells to be produced and sperm maturation is not performed. In people whose AZFa area has been completely eliminated, it is not possible to recover sperm from testicular tissue in these patients and any procedure for sperm retrieval is prohibited.
● AZFb: About 14% of men with Y- chromosome microdeletions have deletions in the AZFb region. There are germ cells in these patients. Complete deletion of AZFb disrupts spermatogenesis and only Sertoli cells are observed. It is also not possible to recover sperm from testicular tissue in these patients and any procedure to recover sperm is also prohibited.
● AZFc: About 66% of Y- chromosome microdeletions are devoted to complete deletion of the AZFc region. Deletion in the AZFc region is associated with reduced spermatozoa in the late stages. Most men with AZFc deletion, in some cases, because of their low sperm count, they are often referred to as azoosperms. While there is sperm in the testicles of these individuals. The success rate of sperm removal from their testes using MESA (Microsurgical Epididymal Sperm Aspiration) is about 85%. In general, the success rate of sperm removal from the testes of men with complete deletion; AZFa AZFb; deletion of AZFb+ c and complete deletion of Y- long arm chromosome is close to zero. Therefore, screening for Y- chromosome microdeletions is essential for men with non-obstructive azoospermia before performing.
Cystic Fibrosis diseases:
Cystic Fibrosis (CFTR gene) is an autosomal recessive disease caused by mutations in the transcriptional regulator gene. Cystic Fibrosis is a progressive lung disease that also affects the gastrointestinal tract and the pancreas. One of the symptoms of this disease is present in 98-99% of patients. Vas Defensis is a bilateral deficiency that causes bilateral obstructive azoospermia. Some mutations in this gene can manifest as non-typical cystic fibrosis and only show CBAVD. More than half of the CBAVDs have mutations in the CFTR gene. The importance of detecting mutations in these individuals is that if treated with ICSI MESE and if the mother is a carrier, their offspring can develop cystic fibrosis. Therefore, in cases of CBAVD in man, CFTR gene screening in the mother is necessary to prevent the child from developing CF. Shiraz Infertility Treatment Center is one of the first centers of infertility services in the country. In 2007, a Genetics Laboratory equipped with world-class facilities for providing services to infertile patients was opened at the center, during which many clients from across the country and countries of the region visited the center for services. The center is known as the only provider of pre-implantation diagnostics (PGD) services in the south of the country and is one of the most successful centers for molecular PGD in the Middle East. Many patients from the Persian Gulf and Middle East countries visit PGD every year. Up to now, about 1500 cases of PGD have been done at the center, making it one of the best PGD centers in the world. The survey shows that the success rate at this center is about 15% higher than the global average