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Male infertility: establishing sperm aneuploidy thresholds in the laboratory

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Abstract

Purpose

Fluorescence in situ hybridization (FISH) in spermatozoa provides an estimate of the frequency of chromosomal abnormalities, but there is not a clinical consensus on how to statistically analyze sperm FISH results. We therefore propose a statistical approach to establish sperm aneuploidy thresholds in a fertile population.

Methods

We have determined the distribution and variation of the frequency of nullisomy, disomy, and diploidy for a set of 13 chromosomes (1, 2, 9, 13, 15, 16, 17, 18, 19, 21, 22, X, and Y) in sperm nuclei from 14 fertile men by means of automatized FISH. The dispersion of data has been analyzed by the non-parametric Wilcoxon Rank Sum test. We have established the threshold values for each chromosome and aneuploidy type on the basis of the confidence interval values (99.9%).

Results

Nullisomy thresholds ranged from 0.49% for chromosome 19 to 3.09% for chromosome 22; disomy thresholds ranged from 0.30% for chromosome 21 to 1.47% for chromosome 15; diploidy thresholds ranged from 0.24% for the 9/19 chromosome set to 1.21% for the 13/21 chromosome set.

Conclusions

Applying this approach with clinical purposes will enable us to categorize the patient as altered or normal regarding his sperm aneuploidy. Any result surpassing the cited threshold values indicates a 99.9% probability of being significantly different from fertile controls.

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Authors and Affiliations

  1. Reproductive Genetics Unit, Sistemas Genómicos S.L, Ronda G. Marconi 6, Parque Tecnológico, 46980, Paterna, Valencia, Spain

    Elena García-Mengual, Alba Sáez-Cuevas & Xavier Vendrell

  2. Bioinformatics Department, Sistemas Genómicos S.L, Ronda G. Marconi 6, Parque Tecnológico, 46980, Paterna, Valencia, Spain

    Juan Carlos Triviño

  3. CREA, Assisted Reproduction Medical Center, Carrer de Sant Martí 4, 46003, Valencia, Spain

    Juan Bataller & Miguel Ruíz-Jorro

Authors
  1. Elena García-Mengual
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  2. Juan Carlos Triviño
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  3. Alba Sáez-Cuevas
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  6. Xavier Vendrell
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Corresponding author

Correspondence to Elena García-Mengual.

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An informed consent was signed by all the donors participating in this study. The study was approved by the Institutional Research Ethics Committee.

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García-Mengual, E., Triviño, J.C., Sáez-Cuevas, A. et al. Male infertility: establishing sperm aneuploidy thresholds in the laboratory. J Assist Reprod Genet 36, 371–381 (2019). https://doi.org/10.1007/s10815-018-1385-0

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  • DOI: https://doi.org/10.1007/s10815-018-1385-0

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