• PMID: 26361204
• Gene Name: EEF1A2
• Condition: Male infertility, Embryo quality
• Association: Associated
• Population size: 181
• Population details: 181 (127 men undergoing IVF treatment, 54 normozoospermic, fertile men)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: Microarray

Aberrant sperm DNA methylation predicts male fertility status and embryo quality

Aston KI, Uren PJ, Jenkins TG, Horsager A, Cairns BR, Smith AD, Carrell DT.

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. CI - Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. FAU - Aston, Kenneth I AU - Aston KI AD - Department of Surgery, University of Utah Andrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah. FAU - Uren, Philip J AU - Uren PJ AD - Molecular and Computational Biology, University of Southern California, Los Angeles, California. FAU - Jenkins, Timothy G AU - Jenkins TG AD - Department of Surgery, University of Utah Andrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah. FAU - Horsager, Alan AU - Horsager A AD - Episona, Inc, Glendale, California. FAU - Cairns, Bradley R AU - Cairns BR AD - Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah; Howard Hughes Medical Institute, Chevy Chase, Maryland. FAU - Smith, Andrew D AU - Smith AD AD - Molecular and Computational Biology, University of Southern California, Los Angeles, California.