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Review

Epigenetic changes and assisted reproductive technologies

ORCID Icon, ORCID Icon, , & ORCID Icon
Pages 12-25 | Received 16 Jan 2019, Accepted 16 Jul 2019, Published online: 25 Jul 2019

References

  • Jackson RA, Gibson KA, Wu YW, et al. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol. 2004;103(3):551–563.
  • Schieve LA, Meikle SF, Ferre C, et al. Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med. 2002;346(10):731–737.
  • Chen X-K, Wen SW, Bottomley J, et al. In vitro fertilization is associated with an increased risk for preeclampsia. Hypertens Pregnancy. 2009;28(1):1–12.
  • LB R, PR R, Sunde A, et al. Increased risk of placenta previa in pregnancies following IVF/ICSI; a comparison of ART and non-ART pregnancies in the same mother. Hum Reprod. 2006;21(9):2353–2358.
  • McDonald SD, Han Z, Mulla S, et al. Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol. 2009;146(2):138–148.
  • Romundstad LB, Romundstad PR, Sunde A, et al. Effects of technology or maternal factors on perinatal outcome after assisted fertilisation: a population-based cohort study. Lancet. 2008;372(9640):737–743.
  • Gosden R, Trasler J, Lucifero D, et al. Rare congenital disorders, imprinted genes, and assisted reproductive technology. Lancet. 2003;361(9373):1975–1977.
  • El Hajj N, Haaf T. Epigenetic disturbances in in vitro cultured gametes and embryos: implications for human assisted reproduction. Fertil Steril. 2013;99(3):632–641.
  • de Waal E, Mak W, Calhoun S, et al. In vitro culture increases the frequency of stochastic epigenetic errors at imprinted genes in placental tissues from mouse concepti produced through assisted reproductive technologies. Biol Reprod. 2014;90(2):22.
  • Katari S, Turan N, Bibikova M, et al. DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet. 2009;18(20):3769–3778.
  • Gomes MV, Huber J, Ferriani RA, et al. Abnormal methylation at the KvDMR1 imprinting control region in clinically normal children conceived by assisted reproductive technologies. Mol Hum Reprod. 2009;15(8):471–477.
  • Lazaraviciute G, Kauser M, Bhattacharya S, et al. A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously. Hum Reprod Update. 2014;20(6):840–852.
  • de Waal E, Vrooman LA, Fischer E, et al. The cumulative effect of assisted reproduction procedures on placental development and epigenetic perturbations in a mouse model. Hum Mol Genet. 2015;24(24):6975–6985.
  • Sunderam S, Kissin DM, Crawford SB, et al. Assisted reproductive technology surveillance - United States, 2015. MMWR Surveill Summ. 2018;67(3):1–28.
  • Practice Committee of the American Society for Reproductive M. Multiple pregnancy associated with infertility therapy. Fertil Steril. 2006;86(5 Suppl 1):S106–110.
  • Santana DS, Cecatti JG, Surita FG, et al. Twin pregnancy and severe maternal outcomes: the World Health Organization multicountry survey on maternal and newborn health. Obstet Gynecol. 2016;127(4):631–641.
  • Practice Committee of the American Society for Reproductive Medicine. Electronic address aao, practice committee of the society for assisted reproductive T. Guidance on the limits to the number of embryos to transfer: a committee opinion. Fertil Steril. 2017;107(4):901–903.
  • Kalra SK, Barnhart KT. In vitro fertilization and adverse childhood outcomes: what we know, where we are going, and how we will get there. A glimpse into what lies behind and beckons ahead. Fertil Steril. 2011;95(6):1887–1889.
  • Helmerhorst FM, Perquin DA, Donker D, et al. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ. 2004;328(7434):261.
  • Pandey S, Shetty A, Hamilton M, et al. Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(5):485–503.
  • Zhu L, Zhang Y, Liu Y, et al. Maternal and live-birth outcomes of pregnancies following assisted reproductive technology: a retrospective cohort study. Sci Rep. 2016;6:35141.
  • Halliday J. Outcomes of IVF conceptions: are they different? Best Pract Res Clin Obstet Gynaecol. 2007;21(1):67–81.
  • Maccani MA, Marsit CJ. Epigenetics in the placenta. Am J Reprod Immunol. 2009;62(2):78–89.
  • Nelissen EC, van Montfoort AP, Dumoulin JC, et al. Epigenetics and the placenta. Hum Reprod Update. 2011;17(3):397–417.
  • Kohan-Ghadr HR, Kadam L, Jain C, et al. Potential role of epigenetic mechanisms in regulation of trophoblast differentiation, migration, and invasion in the human placenta. Cell Adh Migr. 2016;10(1–2):126–135.
  • Odom LN, Segars J. Imprinting disorders and assisted reproductive technology. Curr Opin Endocrinol Diabetes Obes. 2010;17(6):517–522.
  • Gosden R, Trasler J, Lucifero D, et al. Rare congenital disorders, imprinted genes, and assisted reproductive technology. Lancet. 2003;361(9373):1975–1977.
  • Le Bouc Y, Rossignol S, Azzi S, et al. Epigenetics, genomic imprinting and assisted reproductive technology. Ann Endocrinol. 2010;71(3):237–238.
  • Cortessis VK, Azadian M, Buxbaum J, et al. Comprehensive meta-analysis reveals association between multiple imprinting disorders and conception by assisted reproductive technology. J Assist Reprod Genet. 2018;35(6):943–952.
  • Ceelen M, van Weissenbruch MM, Prein J, et al. Growth during infancy and early childhood in relation to blood pressure and body fat measures at age 8-18 years of IVF children and spontaneously conceived controls born to subfertile parents. Hum Reprod. 2009;24(11):2788–2795.
  • Ceelen M, van Weissenbruch MM, Vermeiden JP, et al. Cardiometabolic differences in children born after in vitro fertilization: follow-up study. J Clin Endocrinol Metab. 2008;93(5):1682–1688.
  • Chen M, Wu L, Zhao J, et al. Altered glucose metabolism in mouse and humans conceived by in-vitro fertilization (IVF). Diabetes. 2014.
  • Sakka SD, Loutradis D, Kanaka-Gantenbein C, et al. Absence of insulin resistance and low-grade inflammation despite early metabolic syndrome manifestations in children born after in vitro fertilization. Fertil Steril. 2010;94(5):1693–1699.
  • Ashworth A. Effects of intrauterine growth retardation on mortality and morbidity in infants and young children. Eur J Clin Nutr. 1998;52(Suppl 1):S34–41. discussion S41-32
  • Ravelli GP, Stein ZA, Susser MW. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 1976;295(7):349–353.
  • Arends NJ, Boonstra VH, Duivenvoorden HJ, et al. Reduced insulin sensitivity and the presence of cardiovascular risk factors in short prepubertal children born small for gestational age (SGA). Clin Endocrinol (Oxf). 2005;62(1):44–50.
  • Jaquet D, Gaboriau A, Czernichow P, et al. Insulin resistance early in adulthood in subjects born with intrauterine growth retardation. J Clin Endocrinol Metab. 2000;85(4):1401–1406.
  • Valdez R, Athens MA, Thompson GH, et al. Birthweight and adult health outcomes in a biethnic population in the USA. Diabetologia. 1994;37(6):624–631.
  • Hart R, Norman RJ. The longer-term health outcomes for children born as a result of IVF treatment: part I–general health outcomes. Hum Reprod Update. 2013;19(3):232–243.
  • Ceelen M, van Weissenbruch MM, Roos JC, et al. Body composition in children and adolescents born after in vitro fertilization or spontaneous conception. J Clin Endocrinol Metab. 2007;92(9):3417–3423.
  • Knoester M, Helmerhorst FM, van der Westerlaken LA, et al. Matched follow-up study of 5 8-year-old ICSI singletons: child behaviour, parenting stress and child (health-related) quality of life. Hum Reprod. 2007;22(12):3098–3107.
  • Morgan HD, Santos F, Green K, et al. Epigenetic reprogramming in mammals. Hum Mol Genet. 2005;14: R47–58. Spec No 1.
  • Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science. 2001;293(5532):1089–1093.
  • von Meyenn F, Reik W. Forget the Parents: epigenetic Reprogramming in Human Germ Cells. Cell. 2015;161(6):1248–1251.
  • Smith ZD, Chan MM, Humm KC, et al. DNA methylation dynamics of the human preimplantation embryo. Nature. 2014;511(7511):611–615.
  • Reik W, Epigenetics: KG. Cellular memory erased in human embryos. Nature. 2014;511(7511):540–541.
  • Okae H, Chiba H, Hiura H, et al. Genome-wide analysis of DNA methylation dynamics during early human development. PLoS Genet. 2014;10(12):e1004868.
  • Guo H, Zhu P, Yan L, et al. The DNA methylation landscape of human early embryos. Nature. 2014;511(7511):606–610.
  • Market-Velker BA, Zhang L, Magri LS, et al. Dual effects of superovulation: loss of maternal and paternal imprinted methylation in a dose-dependent manner. Hum Mol Genet. 2010;19(1):36–51.
  • de Waal E, Yamazaki Y, Ingale P, et al. Gonadotropin stimulation contributes to an increased incidence of epimutations in ICSI-derived mice. Hum Mol Genet. 2012;21(20):4460–4472.
  • Weinerman R, Ord T, Bartolomei MS, et al. The superovulated environment, independent of embryo vitrification, results in low birthweight in a mouse model. Biol Reprod. 2017;97(1):133–142.
  • Sato C, Shimada M, Mori T, et al. Assessment of human oocyte developmental competence by cumulus cell morphology and circulating hormone profile. Reprod Biomed Online. 2007;14(1):49–56.
  • Khoueiry R, Mery L, Mery L, et al. Dynamic CpG methylation of the KCNQ1OT1 gene during maturation of human oocytes. J Med Genet. 2008;45(9):583–588.
  • Geuns E, Hilven P, Van Steirteghem A, et al. Methylation analysis of KvDMR1 in human oocytes. J Med Genet. 2007;44(2):144–147.
  • Xin F, Susiarjo M, Bartolomei MS. Multigenerational and transgenerational effects of endocrine disrupting chemicals: A role for altered epigenetic regulation?. Semin Cell Dev Biol. 2015;43:66–75.
  • Kobayashi H, Hiura H, John RM, et al. DNA methylation errors at imprinted loci after assisted conception originate in the parental sperm. Eur J Hum Genet. 2009;17(12):1582–1591.
  • Hiura H, Hattori H, Kobayashi N, et al. Genome-wide microRNA expression profiling in placentae from frozen-thawed blastocyst transfer. Clin Epigenetics. 2017;9:79.
  • Tierling S, Souren NY, Gries J, et al. Assisted reproductive technologies do not enhance the variability of DNA methylation imprints in human. J Med Genet. 2010;47(6):371–376.
  • Kanber D, Buiting K, Zeschnigk M, et al. Low frequency of imprinting defects in ICSI children born small for gestational age. Eur J Hum Genet. 2009;17(1):22–29.
  • Li L, Wang L, Le F, et al. Evaluation of DNA methylation status at differentially methylated regions in IVF-conceived newborn twins. Fertil Steril. 2011;95(6):1975–1979.
  • Zechner U, Pliushch G, Schneider E, et al. Quantitative methylation analysis of developmentally important genes in human pregnancy losses after ART and spontaneous conception. Mol Hum Reprod. 2010;16(9):704–713.
  • Feng C, Tian S, Zhang Y, et al. General imprinting status is stable in assisted reproduction-conceived offspring. Fertil Steril. 2011;96(6):1417–1423.e1419.
  • Shi X, Ni Y, Zheng H, et al. Abnormal methylation patterns at the IGF2/H19 imprinting control region in phenotypically normal babies conceived by assisted reproductive technologies. Eur J Obstet Gynecol Reprod Biol. 2011;158(1):52–55.
  • Zheng HY, Shi XY, Wu FR, et al. Assisted reproductive technologies do not increase risk of abnormal methylation of PEG1/MEST in human early pregnancy loss. Fertil Steril. 2011;96(1):84–89.e82.
  • Zheng HY, Shi XY, Wang LL, et al. Study of DNA methylation patterns of imprinted genes in children born after assisted reproductive technologies reveals no imprinting errors: A pilot study. Exp Ther Med. 2011;2(4):751–755.
  • Zheng HY, Tang Y, Niu J, et al. Aberrant DNA methylation of imprinted loci in human spontaneous abortions after assisted reproduction techniques and natural conception. Hum Reprod. 2013;28(1):265–273.
  • Oliver VF, Miles HL, Cutfield WS, et al. Defects in imprinting and genome-wide DNA methylation are not common in the in vitro fertilization population. Fertil Steril. 2012;97(1):147–153.e147.
  • Sakian S, Louie K, Wong EC, et al. Altered gene expression of H19 and IGF2 in placentas from ART pregnancies. Placenta. 2015;36(10):1100–1105.
  • Vincent RN, Gooding LD, Louie K, et al. Altered DNA methylation and expression of PLAGL1 in cord blood from assisted reproductive technology pregnancies compared with natural conceptions. Fertil Steril. 2016;106(3):739–748.e733.
  • Wong EC, Hatakeyama C, Robinson WP, et al. DNA methylation at H19/IGF2 ICR1 in the placenta of pregnancies conceived by in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril. 2011;95(8):2524–2526.e2521-2523.
  • Rancourt RC, Harris HR, Michels KB. Methylation levels at imprinting control regions are not altered with ovulation induction or in vitro fertilization in a birth cohort. Hum Reprod. 2012;27(7):2208–2216.
  • Puumala SE, Nelson HH, Ross JA, et al. Similar DNA methylation levels in specific imprinting control regions in children conceived with and without assisted reproductive technology: a cross-sectional study. BMC Pediatr. 2012;12:33.
  • Camprubí C, Iglesias-Platas I, Martin-Trujillo A, et al. Stability of genomic imprinting and gestational-age dynamic methylation in complicated pregnancies conceived following assisted reproductive technologies. Biol Reprod. 2013;89(3):50.
  • Loke YJ, Galati JC, Saffery R, et al. Association of in vitro fertilization with global and IGF2/H19 methylation variation in newborn twins. J Dev Orig Health Dis. 2015;6(2):115–124.
  • Whitelaw N, Bhattacharya S, Hoad G, et al. Epigenetic status in the offspring of spontaneous and assisted conception. Hum Reprod. 2014;29(7):1452–1458.
  • Choux C, Binquet C, Carmignac V, et al. The epigenetic control of transposable elements and imprinted genes in newborns is affected by the mode of conception: ART versus spontaneous conception without underlying infertility. Hum Reprod. 2018;33(2):331–340.
  • Dimitriadou E, Noutsopoulos D, Markopoulos G, et al. Abnormal DLK1/MEG3 imprinting correlates with decreased HERV-K methylation after assisted reproduction and preimplantation genetic diagnosis. Stress. 2013;16(6):689–697.
  • Liu Y, Tang Y, Ye D, et al. Impact of abnormal DNA methylation of imprinted loci on human spontaneous abortion. Reprod Sci. 2018;25(1):131–139.
  • Chen XJ, Chen F, Lv PP, et al. Maternal high estradiol exposure alters CDKN1C and IGF2 expression in human placenta. Placenta. 2018;61:72–79.
  • Tang L, Liu Z, Zhang R, et al. Imprinting alterations in sperm may not significantly influence ART outcomes and imprinting patterns in the cord blood of offspring. PLoS One. 2017;12(11):e0187869.
  • Turan N, Katari S, Gerson LF, et al. Inter- and intra-individual variation in allele-specific DNA methylation and gene expression in children conceived using assisted reproductive technology. PLoS Genet. 2010;6(7):e1001033.
  • Nelissen EC, Dumoulin JC, Daunay A, et al. Placentas from pregnancies conceived by IVF/ICSI have a reduced DNA methylation level at the H19 and MEST differentially methylated regions. Hum Reprod. 2013;28(4):1117–1126.
  • Lou H, Le F, Hu M, et al. Aberrant DNA methylation of IGF2-H19 locus in human fetus and in spermatozoa from assisted reproductive technologies. Reprod Sci. 2019;26(7):997–1004.
  • JL K, Yang B, AE S, et al. Skewed X inactivation and IVF-conceived infants. Reprod Biomed Online. 2010;20(5):660–663.
  • Wu EX, Stanar P, Ma S. X-chromosome inactivation in female newborns conceived by assisted reproductive technologies. Fertil Steril. 2014;101(6):1718–1723.
  • Melamed N, Choufani S, Wilkins-Haug LE, et al. Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies. Epigenetics. 2015;10(6):474–483.
  • Estill MS, Bolnick JM, Waterland RA, et al. Assisted reproductive technology alters deoxyribonucleic acid methylation profiles in bloodspots of newborn infants. Fertil Steril. 2016;106(3):629–639.e610.
  • El Hajj N, Haertle L, Dittrich M, et al. DNA methylation signatures in cord blood of ICSI children. Hum Reprod. 2017;32(8):1761–1769.
  • Litzky JF, Deyssenroth MA, Everson TM, et al. Placental imprinting variation associated with assisted reproductive technologies and subfertility. Epigenetics. 2017;12(8):653–661.
  • Choufani S, Turinsky AL, Melamed N, et al. Impact of assisted reproduction, infertility, sex, and paternal factors on the placental DNA methylome. Hum Mol Genet. 2018;28(3):372–385.
  • Castillo-Fernandez JE, Loke YJ, Bass-Stringer S, et al. DNA methylation changes at infertility genes in newborn twins conceived by in vitro fertilisation. Genome Med. 2017;9(1):28.
  • Ghosh J, Coutifaris C, Sapienza C, et al. Global DNA methylation levels are altered by modifiable clinical manipulations in assisted reproductive technologies. Clin Epigenetics. 2017;9:14.
  • Ball MP, Li JB, Gao Y, et al. Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol. 2009;27(4):361–368.
  • Ghosh J, Mainigi M, Coutifaris C, et al. Outlier DNA methylation levels as an indicator of environmental exposure and risk of undesirable birth outcome. Hum Mol Genet. 2016;25(1):123–129.
  • Xu N, Barlow GM, Cui J, et al. Comparison of genome-wide and gene-specific DNA methylation profiling in first-trimester chorionic villi from pregnancies conceived with infertility treatments. Reprod Sci. 2017;24(7):996–1004.
  • Lou H, Le F, Zheng Y, et al. Assisted reproductive technologies impair the expression and methylation of insulin-induced gene 1 and sterol regulatory element-binding factor 1 in the fetus and placenta. Fertil Steril. 2014;101(4):974–980.e972.
  • El Hajj N, Haaf T. Epigenetic disturbances in in vitro cultured gametes and embryos: implications for human assisted reproduction. Fertil Steril. 2013;99(3):632–641.
  • Lazaraviciute G, Kauser M, Bhattacharya S, et al. A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously. Hum Reprod Update. 2014;20(6):840–852.
  • Song S, Ghosh J, Mainigi M, et al. DNA methylation differences between in vitro- and in vivo-conceived children are associated with ART procedures rather than infertility. Clin Epigenetics. 2015;7(1):41.
  • Mainigi M, Rosenzweig JM, Lei J, et al. Peri-implantation hormonal milieu: elucidating mechanisms of adverse neurodevelopmental outcomes. Reprod Sci. 2016;23(6):785–794.
  • Mainigi MA, Weinerman R, Ord T, et al. Low birthweight during fresh IVF cycles is due to altered placental vasculogenesis: evidence from a mouse model. Paper presented at: American Society of Reproductive Medicine2016; 2016.
  • Doherty AS, Mann MR, Tremblay KD, et al. Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo. Biol Reprod. 2000;62(6):1526–1535.
  • Rivera RM, Stein P, Weaver JR, et al. Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development. Hum Mol Genet. 2008;17(1):1–14.
  • Lucifero D, Mann MRW, Bartolomei MS, et al. Gene-specific timing and epigenetic memory in oocyte imprinting. Hum Mol Genet. 2004;13(8):839–849.
  • Mann MRW, Lee SS, Doherty AS, et al. Selective loss of imprinting in the placenta following preimplantation development in culture. Development. 2004;131(15):3727–3735.
  • Rivera R, Stein P, Weaver J, et al. Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development. Hum Mol Genet. 2008;17(1):1–14.
  • Huntriss J, Balen AH, Sinclair KD, et al., Royal College of Obstetricians G. Epigenetics and Reproductive Medicine: scientific Impact Paper No. 57. BJOG. 2018.
  • Tomizawa S, Nowacka-Woszuk J, Kelsey G. DNA methylation establishment during oocyte growth: mechanisms and significance. Int J Dev Biol. 2012;56(10–12):867–875.
  • Fortier AL, Lopes FL, Darricarrère N, et al. Superovulation alters the expression of imprinted genes in the midgestation mouse placenta. Hum Mol Genet. 2008;17(11):1653–1665.
  • Stouder C, Deutsch S, Paoloni-Giacobino A. Superovulation in mice alters the methylation pattern of imprinted genes in the sperm of the offspring. Reprod Toxicol. 2009;28(4):536–541.
  • Weinerman R, Mainigi M. Why we should transfer frozen instead of fresh embryos: the translational rationale. Fertil Steril. 2014;102(1):10–18.
  • Pelkonen S, Koivunen R, Gissler M, et al. Perinatal outcome of children born after frozen and fresh embryo transfer: the Finnish cohort study 1995-2006. Hum Reprod. 2010;25(4):914–923.
  • Ozgur K, Berkkanoglu M, Bulut H, et al. Perinatal outcomes after fresh versus vitrified-warmed blastocyst transfer: retrospective analysis. Fertil Steril. 2015;104(4):899–907.e893.
  • Shapiro BS, Daneshmand ST, Restrepo H, et al. Matched-cohort comparison of single-embryo transfers in fresh and frozen-thawed embryo transfer cycles. Fertil Steril. 2013;99(2):389–392.
  • Zhang W, Xiao X, Zhang J, et al. Clinical outcomes of frozen embryo versus fresh embryo transfer following in vitro fertilization: a meta-analysis of randomized controlled trials. Arch Gynecol Obstet. 2018.
  • Maheshwari A, Pandey S, Amalraj Raja E, et al. Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Hum Reprod Update. 2018;24(1):35–58.
  • Denomme MM, Mann MR. Genomic imprints as a model for the analysis of epigenetic stability during assisted reproductive technologies. Reproduction. 2012;144(4):393–409.
  • Moussa M, Shu J, Zhang X, et al. Cryopreservation of mammalian oocytes and embryos: current problems and future perspectives. Sci China Life Sci. 2014;57(9):903–914.
  • Shaw L, Sneddon SF, Brison DR, et al. Comparison of gene expression in fresh and frozen-thawed human preimplantation embryos. Reproduction. 2012;144(5):569–582.
  • Young LE, Fernandes K, McEvoy TG, et al. Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet. 2001;27(2):153–154.
  • Zaitseva I, Zaitsev S, Alenina N, et al. Dynamics of DNA-demethylation in early mouse and rat embryos developed in vivo and in vitro. Mol Reprod Dev. 2007;74(10):1255–1261.
  • Salilew-Wondim D, Fournier E, Hoelker M, et al. Genome-wide DNA methylation patterns of bovine blastocysts developed in vivo from embryos completed different stages of development in vitro. PLoS One. 2015;10(11):e0140467.
  • Salvaing J, Peynot N, Bedhane MN, et al. Assessment of ‘one-step’ versus ‘sequential’ embryo culture conditions through embryonic genome methylation and hydroxymethylation changes. Hum Reprod. 2016;31(11):2471–2483.
  • Urrego R, Rodriguez-Osorio N, Niemann H. Epigenetic disorders and altered gene expression after use of Assisted Reproductive Technologies in domestic cattle. Epigenetics. 2014;9(6):803–815.
  • Mani S, Ghosh J, Lan Y, et al. Epigenetic changes in preterm birth placenta suggest a role for ADAMTS genes in spontaneous preterm birth. Hum Mol Genet. 2018.

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