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Fish analysis of chromosomal aneuploidies in spermatozoa from severely infertile men undergoing intracytoplasmic sperm injection (ICSI)

University of British Columbia

BACKGROUND: The association between subsets of male infertility, oligoasthenoteratozoospermia (OAT), obstructive azoospermic (OA), non-obstructive azoospermia (NOA), and increased risk of having chromosomal abnormalities in the sperm has not been investigated. Chromosomal aneuploidy in sperm will be systematically investigated by standard methods with large sample sizes required to present significance. METHODS: Triple colour FISH analysis of chromosomes 18, X and Y and dual colour FISH analysis of chromosomes 13 and 21 were performed on spermatozoa retrieved from OAT patients, OA patients and NOA and control. RESULTS: 101,490 spermatozoa retrieved from OAT patients, 101,435 from OA patients, 12,200 from NOA patients and 101,486 from normal fertile men were examined. The three infertile patient groups had significantly increased rates of chromosomal aneuploidies (13.61% in OAT, 5.23% in OA, and 15.00% in NOA), compared with that in control group (1.50%; P< 0.0001). All the differences among the three infertile groups reached a significant level (P< 0.0001). The rates of nullisomy for sex chromosomes, and chromosomes 13,18 and 21 in three infertile groups were significantly higher than that in control group (P<0.05). The rates of disomy for sex chromosomes in three infertile groups were significantly higher than that in control group (P< 0.0001), with X Y disomy predominating. The incidences of disomy for all autosomes in the three infertile groups were significantly higher than that in control group (P<0.05). All chromosomes investigated had obvious differences in the incidence of disomy in three infertile groups and could mean they were differently prone to meiotic non-disjunction. There were individual differences among infertile men, and patients who had extremely high rates of aneuploidies largely contribute to the overall rate of aneuploidies of the group. CONCLUSIONS: Severely infertile men have a higher incidence of chromosomal abnormalities in their spermatozoa, of which sex chromosome aneuploidy is the most predominant. Interchromosomal variations in chromosomal aneuploidies exist in severely infertile men. Most paternal non-disjunction for sex chromosome occurs in meiosis I. There are individual differences in incidence of sperm chromosome aneuploidies among infertile patients.

Thesis/Dissertation

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2009-12-02

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http://hdl.handle.net/2429/16195

Reproductive and Developmental Sciences

University of British Columbia

UBCV

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