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• W2975269619 abstract "Epidemiological studies suggest that the disease state of infertility may play a role in the observed increased incidence of rare imprinting disorders in children born following infertility treatment. Imprinting disorders frequently arise from epigenetic dysregulation at imprinting control regions (ICRs). Examples include loss of imprinted DNA methylation at the KvDMR ICR in ∼50% of children with Beckwith-Wiedemann Syndrome, and loss of methylation at the H19 ICR in ∼45% of children with Russell-Silver Syndrome. The purpose of this study was to examine the association between duration of infertility and DNA methylation at four ICRs in euploid blastocysts. Research study. Surplus cryopreserved euploid blastocysts of transferrable quality (grade ≥3BB; n=58) were donated with IRB approval and patient consent. Blastocysts were subdivided into four groups based on duration of infertility, classified as number of months of reported primary infertility prior to the oocyte retrieval that resulted in a live birth [Fertile Control: 0 months, donor oocyte/donor sperm (n=14); Infertile Short: 12-24 months (n=14); Infertile Intermediate: 36-48 months (n=14); Infertile Long: ≥60 months (n=16)]. Female age was restricted to ≤39 years. Infertility diagnoses were equally varied among the test groups. Euploid blastocyst DNA was isolated (QIAamp DNA Micro Kit; Qiagen) and bisulfite converted (EZ DNA Methylation-Direct Kit; Zymo Research) prior to PCR amplification and pyrosequencing (PyroMark Q24 Advanced system; Qiagen). Statistical analysis included Student’s t-test and one-way ANOVA where appropriate, with significance at p<0.05. Extended durations of infertility ≥36 months (Infertile Intermediate + Infertile Long; mean=65 months) showed significant alterations in blastocyst imprinted DNA methylation, with a decrease in methylation marks when compared to short durations ≤24 months (Fertile Control + Infertile Short; mean=10 months). The ICRs for KvDMR (39% Extended Infertility vs. 48% Short Infertility; p<0.05), H19 (29% Extended Infertility vs. 41% Short Infertility; p<0.05), and MEST (40% Extended Infertility vs. 49% Short Infertility; p<0.05) showed significant hypomethylation, while SNRPN trended downward without significance. Infertility diagnoses, blastocyst grades, and total doses of recombinant follicle stimulating hormone during ovarian stimulation where comparable across the groups. This novel study is the first to report evidence that altered blastocyst imprinted methylation correlates with prolonged infertility. The prevalence of ICR hypomethylation was significant in euploid blastocysts derived from patients with an extended duration of infertility ≥36 months. Ongoing studies will investigate whether the underlying infertility leads to epigenetic errors, or if the methylation alterations themselves are perpetuating the duration of infertility? Our results contribute towards the identification of a mechanistic link between imprinted epigenetic dysregulation and infertility as a prolonged disease." @default.
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• W2975269619 date "2019-09-01" @default.
• W2975269619 modified "2023-10-18" @default.
• W2975269619 title "The prolonged disease state of infertility is associated with blastocyst imprinted epigenetic dysregulation" @default.
• W2975269619 doi "https://doi.org/10.1016/j.fertnstert.2019.07.782" @default.
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