الفهرس 
MALE INFERTILLITYOnly 14 pages are availabe for public view
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Abstract
Infertility is a common disease, affecting between 17 and 25% of all couples and is defined as the inability of a couple in reproductive age to conceive following 12 months of unprotected intercourse.
Several studies have shown an increased incidence of chromosomal abnormalities in infertile males. In patients with sperm counts below 10 × 106/ml, the rate of chromosomal aberrations is estimated to be 5–7%, with the percentage of cytogenetically abnormal cases increasing up to 10–15% in patients with azoospermia. Most frequently, sex chromosome aneuploidies are reported. Nevertheless, any incidence of chromosomal abnormality in the female partner could influence the outcome of intracytoplasmic sperm injection (ICSI).
Spermatogenesis requires a normal X and Y recombination to proceed properly. A defect in the mechanism of recombination in the XY pairing in the pseudoautosomal region could lead to defect in spermatogenesis and subsequent oligozoospermia.
The association between infertility and sperm disomy is well documented. Results vary but most report that men with severely compromised semen parameters have a significantly elevated proportion of disomic sperm. Recently, many studies have found a relationship between the decrease in semen quality due to occupational hazards and sperm disomy.
There is growing evidence that aspects of a man’s environment and lifestyle can affect sperm DNA integrity through a variety of physical, chemical and biological factors. Several occupational and environmental exposures and toxins have known or suspected deleterious actions to male reproductive function. For some specific agents, such as smoking, addiction, heat, ionizing radiation, inorganic lead, dibromochloropropane (DBCP), ethylene dibromide (EDB), some ethylene glycol ethers, carbon disulfide and welding operations, the evidence is strongly supported in well-designed epidemiological studies.
In our work:
- We estimated the frequency and type of chromosomal aberrations in peripheral blood of patients with idiopathic infertile men who exposed to various environmental hazardous factors, physical factors such as heat, chemical factors such as pesticides, paints, chemical solvents and heavy metals and personal habits such as smoking and addiction to some drugs like Tramadol.
- Evaluation and comparison of sperm DNA fragmentation in idiopathic infertile men and fertile control was done.
- Determination of the incidence of sperm disomy in cases of idiopathic male infertility has been evaluated.
This was done as follows:
- The study included fifty male with age ranged from (20 - 40) year, twenty of infertile men with severe idiopathic Oligo-Atheno-Terato-Zoospermia (iOAT) as group I, twenty of idiopathic infertile men with normal semen parameters as groupII.They were recruited from the andrology outpatient clinic, National Research Center. The participants of both groups (group I and group II) were exposed to various hazardous environmental factors, physical factors such as heat, chemical factors such as pesticides, paints, chemical solvents and heavy metals and personal habits such as smoking and addiction to some drugs like Tramadol. Ten fertile healthy males were enrolled as controls represented by group (C). The donors gave informed written consent to participate in the study.
- Chromosomal analysis (G-banding technique) on metaphase chromosome was processed according to standard protocols.
- Alkaline Comet Assay to sperm DNA fragmentation was performed according to standard method.
- Standard Fluorescent In Stiu Hybridization (FISH) was carried out to detect disomy XY using XY cocktail centeromric probe.
- Statistical analysis was performed to evaluate the results and to correlate the results together.
The results of the study were as follows:
A. Chromosomal analysis (G-banding technique):
Cytogenetic investigations revealed chromosomal anomalies in two out of fourty patients, one patient of group I had structure chromosomal abnormality (translocation 9p,13q) and one patient in group II had sex chromosome abnormalities: mosaic forms (46, XY/47, XXY). While the remaining individuals were found to have normal Karyotype (46, XY).
B. Fluorescent In Stiu Hybridization (FISH):
- A highly significant direct relationship between age and percentage of total disomy was observed in both groups I and II.
- There was highly significant inverse correlation between total disomy percent and semen parameters among the three studied groups. Moreover, a positive correlation between DNA damage and total disomy percent
- Total disomy percentage showed a higher increase in the spermatozoa of men with severe iOAT (group I) than in those of idiopathic infertile men with high semen quality (group II), compared to group (C).
- Also, there was highly significant negative correlation as the number of environmental factors increases and percentage of total disomic percent.
C. Alkaline Comet Assay to sperm DNA fragmentation:
- Our results revealed highly significant direct relationship between age and percentage of sperm DNA damage in group I and II.
- Highly significant inverse correlation between sperm DNA damage percent and semen parameters.
- Sperm DNA fragmentation percentage increased in idiopathic infertile men (group II) more than severe iOAT patients (group I).
- In addition, there was highly significant negative correlation as the number of environmental factors increases and percentage of total disomic percent.
from the study and the results obtained, we concluded that:
A comprehensive testing of DNA damage in adequately infertile men with normal semen standards can have a critical impact to overcome the primary pathology in pre-assisted reproductive technique assessment.
Based on the results of our study, it is possible that sperm DNA damage analysis may be better in discriminating between infertile men and fertile men than standard semen analysis. Other recent independent studies have also suggested that sperm DNA damage analysis is an independent test of sperm quality that may have better diagnostic capabilities than standard sperm parameters.
The results of the present study also indicated that men with severe oligozoospermia tended to be at greater risk for XX disomy in their spermatozoa. Such an increase in XX disomy could lead to a slight increase in 47,XXX conception after ICSI.
Our study provides robust evidence to show that the sperm DNA fragmentation is a useful biomarker of both male infertility and predicted IVF outcome. Measurement of sperm DNA fragmentation in native semen using the alkaline Comet assay provides the sensitivity and specificity needed to determine IVF success. The testing of sperm DNA damage can be a hope both as a diagnostic test for male infertility and a prognostic test for the outcome of Assisted Reproductive Technologies.
It is also concluded that the comet assay can detect, high degrees of sperm DNA damage are accompanied by significant impair¬ment in all seminal parameters. At present, comet assay in sperm, used in reproductive toxicology studies, seems to provide the necessary sensitivity, accuracy and flexibility for becoming a reliable test system for the biomonitoring of genotoxins and reprotoxins.
Sperm from infertile men with normal standard sperm parameters may have significant levels of DNA damage that are comparable with infertile men with abnormal sperm parameters.
Clearly, therefore, there is value in understanding the environmental and lifestyle factors that may lead to damage of the paternal genome in the hope that if hazards can be identified we might be able to devise protective measures.
Recommendations and suggestions:
- Our results suggest that sperm DNA integrity assessment may help to differentiate men with fertility problems and can therefore be of help in counseling of infertile couples.
- When men with low sperm concentrations of 5 X106/ml undergo ICSI, even if they have a normal karyotype, it is important to inform them and their partners of the possible risks of aneuploidy in their fetus.
- Infertile men with normal standard semen parameters on repeated analysis should be evaluated for sperm DNA damage. This test may reveal a hidden abnormality of sperm nuclear DNA in infertile men classified as idiopathic, based on apparently normal standard sperm parameters. Men with abnormal semen parameters should be given a genetic counseling.