تأثير تعدد الأشكال الجيني لمستقبلات الهرمون المحفز للجريبات في الاستجابة للعلاج بعقار FSH عند النساء العراقيات المصابات بالعقم

Effect of Follicle Stimulating Hormone Receptor Gene Polymorphisms on Response of FSH Therapy in Iraqi Infertile Women

Background: Female infertility is a multifactorial condition constituting a worldwide public health problem. Follicle-stimulating hormone (FSH) is produced in the pituitary gland and is essential for reproduction. It specifically binds to a membrane receptor (FSHR) expressed in somatic cells of the gonads. The FSH/FSHR system presents many features compared to classical G protein-coupled receptors (GPCRs). Polymorphisms at codons 307 and 680 are the most commonly encountered allelic variants of the follicle-stimulating hormone receptor (FSHR) gene.
Aims of study: The aims of this study are to detect the genetic polymorphisms of FSHR rs6166 (C> T) and rs6165 (C> T) gene particularly that associated with the response to FSH treatment and their effects on the pathogenesis of infertility in Iraqi women.
Subjects and methods: In this prospective observational study, two hundred sixty women were selected to participate in this study all of them have no differences in age, BMI, age of menarche, fifty of enrolled women apparently healthy that considered as control group and the rest 210 were recently diagnosed infertile women in which they divided into three groups according to ovarian response to treatment into poor responder (70 infertile women), moderate responder (61 infertile women), and high responder (79 infertile women). All the participants had signed informed consent before enrolled in this study, blood samples were obtained from all groups on second day of the menstrual cycle for genetic, hormonal (follicle stimulating hormone , luteinizing hormone, anti-mullerian hormone, thyroid stimulating hormone, prolactin, and estradiol) analysis, all infertile women included in the study were subjected to routine ultrasonography for measurement of antral follicle count, blood sample drawn again for measurement of E2 after six days of treatment by FSH and ultrasonography also done for measurement of size and number of graafian follicles. This study used Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS PCR) for detection of FSHR SNPs, rs6166(C>T) and rs6165 (C>T).
Results: The findings of this study in infertile women, clearly indicates that multiple genotypes of FSHR gene particularly (rs6166) (C>T) and (rs6165) (C>T), that include the homozygous wild genotype (CC), homozygous mutant (TT) and heterozygous (CT) genotype. The T allele was significantly increased (P<0.05) in poor responder infertile women for both rs6166 and rs6165 in FSHR which associated significantly with poor response to FSH in Iraqi infertile women.
Conclusion: Polymorphisms in FSHR gene may be associated with decrease in response to FSH treatment and it was associated with pathogenesis of infertility in Iraqi women/ Kerbala province.