Single Nucleotide Polymorphisms G919A and A2039G of FSHR in Males with Severe Forms of Infertility

The responsibility of male factor in couple's infertility has been exponentially raised recently due to comprehensive evaluation of reproductive male function and improved diagnostic equipment. Despite this improvement in diagnosis, azoospermia is always the most challenging topic associated with infertility treatment. Several conditions that interfere with spermatogenesis and reduce sperm production and quality can lead to azoospermia. Azoospermia may also occur because of a reproductive tract obstruction. Optimal management of patients with azoospermia requires a full understanding of the disease etiology. Chromosomal disorders are encountered at a higher frequency in the infertile compared with the fertile population. These chromosome alterations can currently be diagnosed in 15% of azoospermic and 5% of oligospermic men and represent one of the most common genetic defects in infertile men. Therefore, it is important that these men undergo genetic testing prior to the use of their sperm for ART. The aim of the research was to investigate of polymorphic links of G919A and A2039G of FSHR with azoospermia in men. Materials and methods. During 2012-2016 information and biological samples of 1637 men with decreased infertility were analyzed. Microscopic analysis of ejaculate with parameters of fertility according to WHO from 2010 was done. Results. Analysis of genetic characteristics of men with various forms of azoospermia showed that 7.3% of patients were heterozygous for the CFTR gene mutations delF508 and all of them have obstructive form. Abnormalities in karyotype – 45, XY, rob(13; 21)(q10; q10), 46,XX, 47,XXY [18] / 46,XY [2]; 47,XXY – were found in 12.2% of patients. In the form of non-obstructive azoospermia the frequency of homozygotes GGAA, GGGG, AAAA is in 1.8-3.2 times higher than theoretically expected. The frequency of homozygous with wild type alleles GGAA is in 2.6 times higher than in controls. In men with non-obstructive azoospermia a direct correlation between the number of polymorphic alleles for the SNP G919A of FSHR gene and levels of follicle-stimulating hormone was found out, as rs = 0,49. The level of FSH in some patients with non-obstructive form is on the upper limit or higher comparing with normal values -19,07-33,42 mIU/mL, and in obstructive form FSH level is in the normal range. For obstructive azoospermia the actual frequency of heterozygotes GGGG, GAAG, AAAA is in 2-5,1, times higher than expected. GGAA homozygotes were not found in group of men with obstructive azoospermia. Conclusion. Thus, a precise diagnosis of azoospermia and systematic evaluation of the patient to establish the disease etiology is necessary to establish appropriate management options and to determine the associated cost benefits, risks and prognosis for treatment success. Clinicians should also provide adequate counseling for the couple and generous support for patients with severe male factor infertility.