Assisted reproductive technology alters deoxyribonucleic acid methylation profiles in bloodspots of newborn infants.
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.
['Estill|Molly S|MS|', 'Bolnick|Jay M|JM|', 'Waterland|Robert A|RA|', 'Bolnick|Alan D|AD|', 'Diamond|Michael P|MP|', 'Krawetz|Stephen A|SA|']
D016022:Case-Control Studies D004247:DNA D019175:DNA Methylation D059788:Dried Blood Spot Testing D004624:Embryo Transfer D005260:Female D005298:Fertility D005307:Fertilization in Vitro D006801:Humans D007231:Infant, Newborn D007246:Infertility D007315:Insemination, Artificial D008297:Male D015997:Neonatal Screening D020411:Oligonucleotide Array Sequence Analysis D011247:Pregnancy D020554:Sperm Injections, Intracytoplasmic D016896:Treatment Outcome
ICSI epigenetics epialleles 450k ART