Study Of The Relationship Between Chromosome Polymorphism And Male Infertility, Spouse Spontaneous Abortion

Objectives：By studying of the relationship between chromosome polymorphism andthe clinical phenotype of infertility and spouse miscarriage, and for the patients withchromosome polymorphism, do the pidegree research and follow-up theirreproductive outcomes, provide a theoretical basis and experimental evidence for theclinical genetic counseling and treatment of such patients.Methods：The study population came from4147patients with male infertility or spousespontaneous abortion attending genetic consultancy in the Cell Biology Department,Clinical Hospital of Jilin University during2008.01-2013.10. By karyotype analysisidentified134cases of chromosomal polymorphism in patients aged22to43yearsold. Control group1:602cases of general population (sperm doners from the spermbank); Control group2:50males with normal fertility and normal karyotype aged22to41years; Control group3:50cases of azoospermia men with normal karyotypeaged21to39years; Control group4:40cases of oligozoospermia men with normalkaryotype aged23to44years old. Analysis for Sperm conentration, vitality andmotion parameters, spermatogenic cells, reproductive hormone, Y chromosomemicrodeletions on infertility males. Detected sperm aneuploidy rates by fluorescencein situ hybridization, High-throughput sequencing technology for duplications ordeletions of chromosome fragments, conducted a questionnaire survey on Pedigreeinvestigation, telephone follow-up on reproductive outcomes, using SPSS statisticalsoftware for data analysis.Results：1. The incidence of Chromosomal polymorphism in patients with male infertility andcontrol group1(sperm doners from sperm bank) is3.25%and3.16%respectively. There is no significant difference between the two groups of data, but theconstituent ratio of various types of polymorphisms has a statistically significantdifference. In infertile group, Y chromosome polymorphism accounted for thelargest proportion,53.6%, but in the control group1, various types ofpolymorphisms evenly distributed.2. In the134cases of chromosomal polymorphism patients, there are43cases ofazoospermia,37cases of oligozoospermia,54cases of normal sperm concentration.The constituent ratio of Y chromosome polymorphism in azoospermia group,oligozoospermia group, and normal sperm concentration group is69.8%vs40.5%vs20.4%. The constituent ratio of autosomal polymorphism in the three groups is30.2%vs59.5%vs79.6%. Compared the three groups, P <0.05. With the spermconcentration decreased, the constituent ratio of Y chromosome polymorphismincreased, and autosomal polymorphism constitute decreased.16cases ofazoospermia detected the semen cytological analysis, and5cases found of sperms,2cases found of spermatogenic cells,9cases found of100%other cells.3. The FSH, LH levels in patients of azoospermia with chromosomal polymorphismhave no significant difference compared with the levels in patients ofazoospermia with normal karyotype, P>0.05, and the levels were significantlyhigher compared with the fertility people with normal karyotype, P <0.05; TheFSH, LH levels in patients of oligozoospermia with chromosomal polymorphismhave no significant difference compared with the levels in patients ofoligozoospermiawith with normal karyotype, P>0.05, and the levels weresignificantly higher compared with the fertility people with normal karyotype, P<0.05; There was no statistically significant difference in the T levels among thethree groups, P>0.05. Prompted that the hormone levels changed in patients withchromosome polymorphism is related to azoospermia and oligozoospermia, but notto polymorphism.4. In28cases of infertility patients with Y chromosome polymorphism,9patientspresented with AZF microdeletions, and1case karyotype is46, XY, Yqh+, the other8cases are46, XY, Yqh-, the incidence of deletion is32.1%.5. The incidence of Chromosomal polymorphism in patients with spouse spontaneousabortion and control group1(the general population group) is3.20%and3.16%respectively. There is no significant difference between the two groups of data.6. The chromosome polymorphism detection rate in the patients whose spouseexperienced one time of miscarriage is3.31%(20/604). The detection rate is3.37%(22/652) in patients whose spouse experienced two times of miscarriage. The rate is2.89%(7/242) in patients experienced three times of miscarriage. The rate is1.92%(1/52) in patients experienced four times of miscarriage and in patients experiencedmore than four times of miscarriage the rate is0%(0/13). The polymorphismdetection rate does not increased with the frequency of abortion.7. Visit35cases of polymorphic pedigrees, autosomal polymorphism inherited fromthe mother in15cases,7cases inherited from the father, de novo mutations in1case. Y chromosome polymorphism inherited in8cases,4cases of de novomutation. De novo mutation karyotypes were46, XY,15pstk+and46, XY, Yqh-.Follow-up of reproductive outcomes in infertile group,30.2%(16/53) in patientshad a healthy reproductive offspring. In spouse abortion group,55.6%(20/36) ofpatients had their health next generations. The patients with chromosomepolymorphism can normal reproduction.8. The incidence of sperm aneuploidy rate was no statistical difference between thepatients with chromosome polymorphism and patients with normal karyotype.Detected of High-throughput sequencing technology, the patient with46, XY,16qh+karyotype found200kb CNVs deletions on the chromosome14and100kbCNVs deletions on the chromosome15; the patient with46, XY,21pstk-karyotypefound360kb deletion on the chromosome22.Conclusions:1. The infertility patients with Y chromosome polymorphism have a high incidence ofAZF microdeletion, recommended that such patients should do further genetictesting.1/9/16qh±, D/G group variation, inv(9) does not cause phenotypic changes, suggesting that they are not the direct cause of male infertility, and recommendedsuch patients can choose their reproductive way just like the people with normalkaryotype.2.The detection rate of chromosome polymorphism in the patients with spousespontaneous abortion and the general population has no statistically significant, andthe detection rate has nothing to do with the number of abortion, suggesting that thepolymorphism is not the direct cause of spontaneous abortion, and recommendedsuch patients can choose their reproductive way just like the people with normalkaryotype.