Detection of Microdeletions in the Azoospermia Factor (AZF) Regions on the Human Y Chromosome in Infertile Male Patients

Infertility has plagued more than 10% of the world's couples of childbearing age, of which male factors account for half. There are many causes of male infertility, including infection, genital malformations, immune dysfunction, varicocele, erectile dysfunction, drug side effect and chromosomal abnormality. Microdeletion of Azoospermia factor (AZF) in the long arm of the Y chromosome is one of the main genetic factors leading to dyszoospermia. The incidence of AZF microdeletions is 2%~19.4% among male infertile patients in Asia, which is related to the inclusion criteria, STS site selection, population and genetic background.

At present, there are large numbers of studies on AZF microdeletions in male infertility, and provide rich information on male infertility. However, as the main means of detection is multiplex PCR-capillary electrophoresis method, which usually detects sequence-tagged sites(STS) such as AZFa-sY84，sY86，AZFb-sY127，sY134，AZFc- sY1191, sY1291, sY1189,sY254 and sY255, information on other loci is still lacking.

In addition, the shortcomings of this method include false positive and false negative results caused by fuzzy electrophoresis strip or pollution and the presence of high repetition and a large number of palindrome in complex AZF region. Because some microdeletions can't be detected it is difficult to make an accurate judgement on the fertility of the patients.

This study will use Multiplex ligation-dependent probe amplification and NGS method to improve the detection rate of AZF microdeletion, and analyze the microdeletion data and the patient's fertility results, so as to improve genetic counseling. A total of 5000 male infertility patients will be enrolled. At least 1000 parents and 1000 normal fertile men will be asked to donate their peripheral blood for DNA.

In addition, in patients with azoospermia or severe oligozoospermia, the overall deletion rate of AZF is about 8.77% (1.75%-24.70%), so there are other unknown genetic factors leading to azoospermia or severe oligozoospermia. This study will also try to make a preliminary study of these factors.