Analysis And Research On Genetic Factors Of Male Infertility

Objective 1.To master the genetic etiology of male infertility through analysis of clinical data and genetic examination;2.To enrich the genetic spectrum of NOA etiology by detecting pathogenic genes/mutations through WES,in order to provide theoretical basis for genetic diagnosis,genetic counseling and individual treatment for NOA patients.Methods In the study,male patients with infertility attending the center for reproductive medicine in General Hospital of Ningxia Medical University from August 2015 to September 2022 were selected,and the diagnosis was clarified by medical history,physical examination,routine semen examination,urological ultrasound and other ancillary examinations.1.311 cases diagnosed with NOA,571 cases with severe oligozoospermia,and671 subjects with normal semen attending for female infertility.We couected the date include of age,BMI,smoking,and years of infertility;karyotype analysis was performed on all subjects,and AZF microdeletion analysis was performed on some subjects,to analyze the detection rates of abnormal karyotypes and AZF microdeletions;2.182 cases of NOA,329 cases of severe oligozoospermia,and 575 cases of normal controls who underwent Assisted Reproductive Technique to were analyzed for pregnancy outcome;3.15 NOA patients with negative karyotype and AZF microdeletion were selected for genetic testing by WES.Results1.The age,smoking,and BMI of male partners in the three groups were statis-tically different(P < 0.05),and all NOA groups were higher than the other two groups;the years of infertility were longer in the NOA group than the other two groups(5.5 ± 4.2 vs 4.8 ± 3.8 vs3.9 ± 2.8,P < 0.05),and the type of infertility accounted for a larger proportion of prim-ary infertility in the NOA group than the other two groups(86.2% vs 71.3% vs 47.2%,P < 0.05).2.A total of 60 karyotype abnormalities were detected in NOA in 882 infertility patients,accounting for 6.8%,of which KS accounted for 78.3%(47/60)of the karyotype abnormalliti-es in NOA,and chromosomal polymorphisms accounted for 3.7%(33/882);27 karyotype abnormalities were detected in severe oligospermia,accounting for 3.1%,and chromosomal polymorphisms accounted for 7.2%(63/882);A total of 8 karyotype abnormalities were detected in control group,accounting for 1.19%,and chromosomal polymorphisms accoun ted for 8.6%(58/671);In 49 patients with NOA,AZF detection revealed abnormalities in 20 cases,accounting for 40.82%,among which AZFc deletion was the most common in 9 cases(45%).3.Among the 182 patients with NOA who underwent ART for fertility,102 cases were treated with sperm donor,accounting for 56.0% of the total number of cases,and KS was the main factor(26.5%,27/102).Comparing the clinical outcomes of the three groups,the clinical pregnancy rate was significantly higher in the NOA group than in the control group(61.2% vs53.8% vs 44.5%,P < 0.05),the live birth rate was significantly higher in the NOA group than in the control group(91.8% vs 80.2% vs 66.8%,P < 0.05).4.WES testing was performed in 15 NOA patients,and a total of 46 variants of 27 NOA-related causative genes were detected,including a total of 8 variants of 6 CHH-related genes,with a higher incidence of PROKR2 and WDR11 variants in CHH.The incidence of CFTR was higher in non-CHH patients by 33.3%(7/21),followed by DNAH17 19.0%(4/21),AR14.3%(3/21)and DNAH9 14.3%(3/21).Conclusion1.The detection rate of abnormal chromosomal karyotype in male infertility patients in the study was 9.86%,and chromosomal abnormalities in NOA were the main genetic factor with a detection rate of 6.8%,Klinefelter syndrome was the most common type.The highest detection rate of AZF microdeletions was AZFc.2.The detection rate of chromosomal abnormalities in severe oligospermia was 3.06%,and the rate of chromosomal polymorphism carriage was similar to that of the normal group.3.In this study,the clinical pregnancy rate and live birth rate of NOA group were higher than those of the other two groups.4.CFTR,DNAH17,AR and DNAH9 were the common genes found in NOA group of our study,with the most genetic variants and polymorphic loci located on chromosome 17;the common genes associated with CHH pathogenesis were PROKR2 and WDR11.5.The tests of Karyotype and AZF microdeletion are important for the clinically diagnosis and treatment of male infertility,most of the mutated loci in NOA testing are determined to be of unknown clinical significance,and functional verification and database search are needed to continuously enrich the pathogenic knowledge of NOA.