Assisted reproductive technology alters deoxyribonucleic acid methylation profiles in bloodspots of newborn infants

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Abstract

OBJECTIVE: To evaluate the effect of infertility and intracytoplasmic sperm injection (ICSI) on DNA methylation of offspring.

DESIGN: Microarray analysis of DNA methylation in archived neonatal bloodspots of in vitro fertilization (IVF)/ICSI-conceived children compared with controls born to fertile and infertile parents.

SETTING: Academic research laboratory.

PATIENT(S): Neonatal blood spots of 137 newborns conceived spontaneously, through intrauterine insemination (IUI), or through ICSI using fresh or cryopreserved (frozen) embryo transfer.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): The Illumina Infinium HumanMethylation450k BeadChip assay determined genome-wide DNA methylation. Methylation differences between conception groups were detected using a Bioconductor package, ChAMP, in conjunction with Adjacent Site Clustering (A-clustering).

RESULT(S): The methylation profiles of assisted reproductive technology and IUI newborns were dramatically different from those of naturally (in vivo) conceived newborns. Interestingly, the profiles of ICSI-frozen (FET) and IUI infants were strikingly similar, suggesting that cryopreservation may temper some of the epigenetic aberrations induced by IVF or ICSI. The DNA methylation changes associated with IVF/ICSI culture conditions and/or parental infertility were detected at metastable epialleles, suggesting a lasting impact on a child's epigenome.

CONCLUSION(S): Both infertility and ICSI alter DNA methylation at specific genomic loci, an effect that is mitigated to some extent by FET. The impact of assisted reproductive technology and/or fertility status on metastable epialleles in humans was uncovered. This study provides an expanded set of loci for future investigations on IVF populations.

Original languageEnglish (US)
JournalFertility and Sterility
DOIs
StatePublished - Jun 8 2016

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Assisted Reproductive Techniques
Intracytoplasmic Sperm Injections
Methylation
DNA Methylation
Fertilization in Vitro
DNA
Insemination
Infertility
Newborn Infant
Embryo Transfer
Cryopreservation
Microarray Analysis
Epigenomics
Fertility
Cluster Analysis
Parents
Genome
Research
Population

Cite this

@article{264761cb60c84c62a3d219e6cb4fe583,
title = "Assisted reproductive technology alters deoxyribonucleic acid methylation profiles in bloodspots of newborn infants",
abstract = "OBJECTIVE: To evaluate the effect of infertility and intracytoplasmic sperm injection (ICSI) on DNA methylation of offspring.DESIGN: Microarray analysis of DNA methylation in archived neonatal bloodspots of in vitro fertilization (IVF)/ICSI-conceived children compared with controls born to fertile and infertile parents.SETTING: Academic research laboratory.PATIENT(S): Neonatal blood spots of 137 newborns conceived spontaneously, through intrauterine insemination (IUI), or through ICSI using fresh or cryopreserved (frozen) embryo transfer.INTERVENTION(S): None.MAIN OUTCOME MEASURE(S): The Illumina Infinium HumanMethylation450k BeadChip assay determined genome-wide DNA methylation. Methylation differences between conception groups were detected using a Bioconductor package, ChAMP, in conjunction with Adjacent Site Clustering (A-clustering).RESULT(S): The methylation profiles of assisted reproductive technology and IUI newborns were dramatically different from those of naturally (in vivo) conceived newborns. Interestingly, the profiles of ICSI-frozen (FET) and IUI infants were strikingly similar, suggesting that cryopreservation may temper some of the epigenetic aberrations induced by IVF or ICSI. The DNA methylation changes associated with IVF/ICSI culture conditions and/or parental infertility were detected at metastable epialleles, suggesting a lasting impact on a child's epigenome.CONCLUSION(S): Both infertility and ICSI alter DNA methylation at specific genomic loci, an effect that is mitigated to some extent by FET. The impact of assisted reproductive technology and/or fertility status on metastable epialleles in humans was uncovered. This study provides an expanded set of loci for future investigations on IVF populations.",
author = "Diamond, {Michael P}",
note = "Copyright {\circledC} 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.",
year = "2016",
month = "6",
day = "8",
doi = "10.1016/j.fertnstert.2016.05.006",
language = "English (US)",
journal = "Fertility and Sterility",
issn = "0015-0282",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Assisted reproductive technology alters deoxyribonucleic acid methylation profiles in bloodspots of newborn infants

AU - Diamond, Michael P

N1 - Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

PY - 2016/6/8

Y1 - 2016/6/8

N2 - OBJECTIVE: To evaluate the effect of infertility and intracytoplasmic sperm injection (ICSI) on DNA methylation of offspring.DESIGN: Microarray analysis of DNA methylation in archived neonatal bloodspots of in vitro fertilization (IVF)/ICSI-conceived children compared with controls born to fertile and infertile parents.SETTING: Academic research laboratory.PATIENT(S): Neonatal blood spots of 137 newborns conceived spontaneously, through intrauterine insemination (IUI), or through ICSI using fresh or cryopreserved (frozen) embryo transfer.INTERVENTION(S): None.MAIN OUTCOME MEASURE(S): The Illumina Infinium HumanMethylation450k BeadChip assay determined genome-wide DNA methylation. Methylation differences between conception groups were detected using a Bioconductor package, ChAMP, in conjunction with Adjacent Site Clustering (A-clustering).RESULT(S): The methylation profiles of assisted reproductive technology and IUI newborns were dramatically different from those of naturally (in vivo) conceived newborns. Interestingly, the profiles of ICSI-frozen (FET) and IUI infants were strikingly similar, suggesting that cryopreservation may temper some of the epigenetic aberrations induced by IVF or ICSI. The DNA methylation changes associated with IVF/ICSI culture conditions and/or parental infertility were detected at metastable epialleles, suggesting a lasting impact on a child's epigenome.CONCLUSION(S): Both infertility and ICSI alter DNA methylation at specific genomic loci, an effect that is mitigated to some extent by FET. The impact of assisted reproductive technology and/or fertility status on metastable epialleles in humans was uncovered. This study provides an expanded set of loci for future investigations on IVF populations.

AB - OBJECTIVE: To evaluate the effect of infertility and intracytoplasmic sperm injection (ICSI) on DNA methylation of offspring.DESIGN: Microarray analysis of DNA methylation in archived neonatal bloodspots of in vitro fertilization (IVF)/ICSI-conceived children compared with controls born to fertile and infertile parents.SETTING: Academic research laboratory.PATIENT(S): Neonatal blood spots of 137 newborns conceived spontaneously, through intrauterine insemination (IUI), or through ICSI using fresh or cryopreserved (frozen) embryo transfer.INTERVENTION(S): None.MAIN OUTCOME MEASURE(S): The Illumina Infinium HumanMethylation450k BeadChip assay determined genome-wide DNA methylation. Methylation differences between conception groups were detected using a Bioconductor package, ChAMP, in conjunction with Adjacent Site Clustering (A-clustering).RESULT(S): The methylation profiles of assisted reproductive technology and IUI newborns were dramatically different from those of naturally (in vivo) conceived newborns. Interestingly, the profiles of ICSI-frozen (FET) and IUI infants were strikingly similar, suggesting that cryopreservation may temper some of the epigenetic aberrations induced by IVF or ICSI. The DNA methylation changes associated with IVF/ICSI culture conditions and/or parental infertility were detected at metastable epialleles, suggesting a lasting impact on a child's epigenome.CONCLUSION(S): Both infertility and ICSI alter DNA methylation at specific genomic loci, an effect that is mitigated to some extent by FET. The impact of assisted reproductive technology and/or fertility status on metastable epialleles in humans was uncovered. This study provides an expanded set of loci for future investigations on IVF populations.

U2 - 10.1016/j.fertnstert.2016.05.006

DO - 10.1016/j.fertnstert.2016.05.006

M3 - Article

C2 - 27288894

JO - Fertility and Sterility

JF - Fertility and Sterility

SN - 0015-0282

ER -