The Role Of Male Chromosomal Polymorphism And AZF Microdeletion Played In Spermatogenesis And The Outcome Of IVF/ICSI-ET Treatment

Chromosomal polymorphisms are heritable variations located in heterochromatic regions in the genome. They usually occur in the pericentric heterochromatin on the long arms of chromosome1,9,16, and Y, and also in heterochromatin on the short arms, satellites or stalks of chromosome13,14,15,21and22. Given that heterochromatin consists of tandemly organized and highly repeated DNA, chromosomal polymorphic variations have been traditionally considered as normal variants (polymorphisms) without proved impact on phenotype. However, there are more and more reports about increased incidence of chromosomal polymorphisms in infertile couples. Chromosomal polymorphic variations have also been reported to correlate with recurrent spontaneous abortions (RSA), idiopathic infertility and poor obstetric history. Modern Molecular Biologists demonstrate that non-coding regions have functions even if seemingly in "gene-desert" regions. Any change in a specific region of heterochromatin might inhibit pivotal gene expression, hamper meiosis and disturb normal gametogenesis. The heterochromatin, located in centromere, plays an essential role in spindle attachment and any alteration in this region could disturb chromosome movement or sister chromatid cohesion during mitosis and meiosis.Infertility management will be sought by～10%of reproductive age couples, the male factor being present in40%～50%. Approximately90%of infertile males subject bad spermatogenesis, which caused by various factors, such as inflammation, endocrine disturbance, lack of nutrition, genetic and environmental agent. The frequency of chromosomal polymorphism in general population is approximate1.77%, in infertile males up to7.9%, noteworthy, it tends to occur more frequently in male partners than female partners within infertile couples. In some research chromosomal polymorphism has seemed to have adverse affect on spermatogenesis and sperm quality, leading male infertility.There were many spermatogenetic genes located in the azoospermia factor region (AZF), which located in Yq11, and subdivided into AZF a, AZFb, AZFc and AZFd regions. The microdeletion in these regions played a critical role in the male infertility. Although advanced assisted reproductive technique (ART), artificial insemination with husband’s semen (AIH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have been widely used for severe male infertility, the effect of male chromosomal polymorphism and AZF microdeletion on the outcome of IVF/ICSI is still unclear. The objective of the present study is evaluate the role of male chromosomal polymorphism and AZF microdeletion played in spermatogenesis and its impact on IVF/ICSI-ET outcome.Section1The Role of Male Chromosomal Polymorphism Played in Spermatogenesis and the Outcome of IVF/ICSI-ET TreatmentObjectiveTo evaluate the role of male chromosomal polymorphism played in spermatogenesis and its impact on IVF/ICSI-ET outcome.Material and methodsThe retrospective analysis was conducted with281infertile couples requesting IVF or ICSI treatments. They were placed in2groups, one in which the male partner had a chromosomal polymorphism (n=132) and the other in which there were no polymorphisms (n=149). The sperm quality and outcome of IVF/ICSI treatment were compared between the two groups. Measures included fertilization rate, implantation rate, pregnancy rate, chemical pregnancy rate, clinical pregnancy rate, early miscarriage rate, ongoing pregnancy rate, and preterm delivery rate. Besides that, we analysed the distribution of chromosomal polymorphism in infertile males according to sperm parameter and the sex ratio of offspring in pregnancies of couples with or without Y chromosomal variation. SPSS19.0computer software was used for data analysis.ResultMales with chromosomal polymorphism had significantly higher frequencies of severe oligozoospermia and azoospermia than those without (37.12%vs.16.11%, P<0.001;27.27%vs.10.74%, P<0.001; respectively). A significantly decreased fertilization rate was observed in polymorphism carriers with normozoospermia than non-carriers with normozoospermia (65.19%vs.72.07%, P=0.005). In males with severe oligozoospermia, fertilization rate and clinical pregnancy rate were statistically lower in polymorphism cases than those without (68.02%vs.78.00%, P<0.001;45.00%vs.66.67%, P=0.031; respectively). We found Y chromosomal polymorphism was the most prevalent polymorphism (65.16%), among which Yqh+(56.06%) was the commonest type. The gender of offspring in couples with Y chromosome variations and those without is not significantly different (54.84%vs.48.44%, P>0.05).ConclusionIn our study, male chromosomal polymorphism was observed to have adverse effect on spermatogenesis, and negatively influenced the outcome of IVF/ICSI-ET treatment in patients with severe oligozoospermia. Y chromosomal polymorphisms have been found to be the most prevalent polymorphism in infertile males, and most frequently occurred in severe oligozoospermia. Section2The Role of AZF Microdeletion Played in Spermatogenesis and the Outcome of IVF/ICSI-ET TreatmentObjectiveTo evaluate the role of AZF microdeletion played in spermatogenesis and its impact on IVF/ICSI-ET outcome.Material and methodsThe retrospective analysis was conducted with98infertile couples requesting IVF or ICSI treatments. All the males were oligozoospermia or severe oligozoospermia. Multiplex polymerase chain reaction(M-PCR) were used to identify the microdeletions in AZF regions. The outcome of ICSI treatment were compared between the AZF microdeletion carriers and noncarriers with severe oligozoospermia or azoospermia.ResultAmong the98males with oligozoospermia or severe oligozoospermia, one (4.00%,1/25) with oligozoospermia and four (5.48%,4/73) with severe oligozoospermia were detected to carry microdeletions in AZFc and AZFd. Among them, three carriers with severe oligozoospermia have resulted in term delivery babies, three female offspring and one male offspring. Another two carriers failed to get pregnancy after ICSI-ET. The fertilization rate, implantation rate and clinical pregnancy rate were similar between AZF microdeletion group and control group.ConclusionIn our study, the microdeletions in AZFc and AZFd regions may not have adverse effect on the outcome of ICSI-ET treatment for infertile males with oligozoospermia or severe oligozoospermia.