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Aberrant sperm DNA methylation predicts male fertility status and embryo quality

Fertility and sterility, 2015-12, Vol.104 (6), p.1388-1397.e5 [Peer Reviewed Journal]

American Society for Reproductive Medicine ;2015 American Society for Reproductive Medicine ;Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. ;ISSN: 0015-0282 ;EISSN: 1556-5653 ;DOI: 10.1016/j.fertnstert.2015.08.019 ;PMID: 26361204

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Title:
Aberrant sperm DNA methylation predicts male fertility status and embryo quality
Author: Aston, Kenneth I., Ph.D ; Uren, Philip J., Ph.D ; Jenkins, Timothy G., Ph.D ; Horsager, Alan, Ph.D ; Cairns, Bradley R., Ph.D ; Smith, Andrew D., Ph.D ; Carrell, Douglas T., Ph.D
Subjects: Blastocyst - pathology ; Cluster Analysis ; CpG Islands ; DNA Methylation ; embryo ; Female ; Fertility - genetics ; Fertilization in Vitro ; Genetic Testing - methods ; genomewide ; Humans ; Infertility, Male - diagnosis ; Infertility, Male - genetics ; Infertility, Male - physiopathology ; Infertility, Male - therapy ; Internal Medicine ; IVF outcome ; Male ; male infertility ; microarray ; Obstetrics and Gynecology ; Oligonucleotide Array Sequence Analysis ; Predictive Value of Tests ; Pregnancy ; Pregnancy Rate ; Promoter Regions, Genetic ; Retrospective Studies ; Risk Factors ; Sperm DNA ; Spermatozoa - pathology ; Treatment Outcome
Is Part Of: Fertility and sterility, 2015-12, Vol.104 (6), p.1388-1397.e5
Description: Objective To evaluate whether male fertility status and/or embryo quality during in vitro fertilization (IVF) therapy can be predicted based on genomewide sperm deoxyribonucleic acid (DNA) methylation patterns. Design Retrospective cohort study. Setting University-based fertility center. Patient(s) Participants were 127 men undergoing IVF treatment (where any major female factor cause of infertility had been ruled out), and 54 normozoospermic, fertile men. The IVF patients were stratified into 2 groups: patients who had generally good embryogenesis and a positive pregnancy (n = 55), and patients with generally poor embryogenesis (n = 72; 42 positive and 30 negative pregnancies) after IVF. Intervention(s) Genomewide sperm DNA methylation analysis was performed to measure methylation at >485,000 sites across the genome. Main Outcome Measure(s) A comparison was made of DNA methylation patterns of IVF patients vs. normozoospermic, fertile men. Result(s) Predictive models proved to be highly accurate in classifying male fertility status (fertile or infertile), with 82% sensitivity, and 99% positive predictive value. Hierarchic clustering identified clusters enriched for IVF patient samples and for poor-quality–embryo samples. Models built to identify samples within these groups, from neat samples, achieved positive predictive value ≥94% while identifying >one fifth of all IVF patient and poor-quality–embryo samples in each case. Using density gradient prepared samples, the same approach recovered 46% of poor-quality–embryo samples with no false positives. Conclusion(s) Sperm DNA methylation patterns differ significantly and consistently for infertile vs. fertile, normozoospermic men. In addition, DNA methylation patterns may be predictive of embryo quality during IVF.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 0015-0282
EISSN: 1556-5653
DOI: 10.1016/j.fertnstert.2015.08.019
PMID: 26361204
Source: MEDLINE
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Aberrant sperm DNA methylation predicts male fertility status and embryo quality

American Society for Reproductive Medicine ;2015 American Society for Reproductive Medicine ;Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. ;ISSN: 0015-0282 ;EISSN: 1556-5653 ;DOI: 10.1016/j.fertnstert.2015.08.019 ;PMID: 26361204

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