Iranian Society of Gynecology Oncology

Document Type : Review Article


1 Legal Medicine Research Center, Legal Medicine Organization, Ahvaz, Iran.

2 Department of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran

3 Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran.

4 Legal Medicine Research Center, Legal Medicine Organization, Ahvaz, Iran

5 Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

6 Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran

7 Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran


Surrogacy is an assisted reproductive technology in which the intended parents allocate the gestation and birth to another woman named the surrogate mother. From this view of surrogacy, although there is no genetic relationship between surrogate mother and fetus, this approach is faced with some issues such as the epigenetic effect, which is the environmental influence on gene expression. Epigenetics plays a critical role in ovulation, spermatogenesis, and embryonic growth, development, and health. DNA methylation, histone modification, and non-coding RNAs activity are the major epigenetic mechanisms. In this mini-review, we focus on the possibility of epigenetic alterations during in vivo embryo culture and intrauterine life.


Main Subjects

1. Soderstrom-Anttila V, Wennerholm UB, Loft A, Pinborg A, Aittomaki K, Romundstad LB, et al. Surrogacy: outcomes for surrogate mothers, children and the resulting families-a systematic review. Hum Reprod Update. 2016;22(2):260-76. [DOI:10.1093/humupd/dmv046] [PMID]
2. Simopoulou M, Sfakianoudis K, Tsioulou P, Rapani A, Anifandis G, Pantou A, et al. Risks in Surrogacy Considering the Embryo: From the Preimplantation to the Gestational and Neonatal Period. Biomed Res Int. 2018;2018:6287507. [DOI:10.1155/2018/6287507] [PMID] [PMCID]
3. Rezaei Z, Adabi K, Sadjadi A. A Comparison of Endometrial Thickness and Pregnancy Outcomes in Two Methods of Intrauterine Injection and Subcutaneous Injection of GCSF in Infertile Women Candidates for IVF. J Obstet Gynecol Cancer Res. 2020;5(2):39-43. [DOI:10.30699/jogcr.5.2.39]
4. Zademodares S, Abbaspour M, Anbarluei M, Rahmati N, Fathi M, Naeiji Z. In vitro Fertilization outcome in Patients with Polycystic Ovary Syndrome: Role of Age and Maternal Body Weight. J Obstet Gynecol Cancer Res. 2022;6(4):161-6. [DOI:10.30699/jogcr.6.4.161]
5. Beale JM, Creighton SM. Long-term health issues related to disorders or differences in sex development/intersex. Maturitas. 2016;94:143-8. [DOI:10.1016/j.maturitas.2016.10.003] [PMID]
6. Dar S, Lazer T, Swanson S, Silverman J, Wasser C, Moskovtsev SI, et al. Assisted reproduction involving gestational surrogacy: an analysis of the medical, psychosocial and legal issues: experience from a large surrogacy program. Human Reproduction. 2015;30(2):345-52. [DOI:10.1093/humrep/deu333] [PMID]
7. Chen J, Wang Y, Wang C, Hu J-F, Li W. LncRNA functions as a new emerging epigenetic factor in determining the fate of stem cells. Front Genet. 2020;11:277. [DOI:10.3389/fgene.2020.00277] [PMID] [PMCID]
8. Yang X, Liu M, Li M, Zhang S, Hiju H, Sun J, et al. Epigenetic modulations of noncoding RNA: a novel dimension of Cancer biology. Mol Cancer. 2020;19(1):64. [DOI:10.1186/s12943-020-01159-9] [PMID] [PMCID]
9. Ge SQ, Lin SL, Zhao ZH, Sun QY. Epigenetic dynamics and interplay during spermatogenesis and embryogenesis: implications for male fertility and offspring health. Oncotarget. 2017;8(32):53804-18. [DOI:10.18632/oncotarget.17479] [PMID] [PMCID]
10. Huntriss J, Balen AH, Sinclair KD, Brison DR, Picton HM. Epigenetics and Reproductive Medicine (Scientific Impact Paper No. 57). BJOG. 2018;125(13):e43-e54. [DOI:10.1111/1471-0528.15240] [PMID]
11. Tavalaee M, Razavi S, Nasr-Esfahani MH. Influence of sperm chromatin anomalies on assisted reproductive technology outcome. Fertil Steril. 2009;91(4):1119-26. [DOI:10.1016/j.fertnstert.2008.01.063] [PMID]
12. Maunakea AK, Chepelev I, Cui K, Zhao K. Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition. Cell Res. 2013;23(11):1256-69. [DOI:10.1038/cr.2013.110] [PMID] [PMCID]
13. Nematollahi A, Rezaeian A, Nasr Esfahani MH, Department of Animal Biotechnology M, Reproductive Biomedicine Research Center, Tavalaee RIf. The role and importance of DNA methylation in spermatogenesis process. Med Sci J Islamic Azad Univ. 2021;31(1):1-13.
14. Iannello A, Rolla S, Maglione A, Ferrero G, Bardina V, Inaudi I, et al. Pregnancy Epigenetic Signature in T Helper 17 and T Regulatory Cells in Multiple Sclerosis. Front Immunol. 2018;9:3075. [DOI:10.3389/fimmu.2018.03075] [PMID] [PMCID]
15. Green BB, Marsit CJ. Select Prenatal Environmental Exposures and Subsequent Alterations of Gene-Specific and Repetitive Element DNA Methylation in Fetal Tissues. Curr Environ Health Rep. 2015;2(2):126-36. [DOI:10.1007/s40572-015-0045-0] [PMID] [PMCID]
16. Breton-Larrivee M, Elder E, McGraw S. DNA methylation, environmental exposures and early embryo development. Anim Reprod. 2019;16(3):465-74. [DOI:10.21451/1984-3143-AR2019-0062] [PMID] [PMCID]
17. Rashidi M, Tavalaee M, Abbasi H, Nomikos M, Nasr-Esfahani MH. Increased de novo DNA methylation enzymes in sperm of individuals with varicocele. Cell J. 2021;23(4):389.
18. Niemitz EL, Feinberg AP. Epigenetics and assisted reproductive technology: a call for investigation. Am J Hum Genet. 2004;74(4):599-609. [DOI:10.1086/382897] [PMID] [PMCID]
19. Gokbuget D, Blelloch R. Epigenetic control of transcriptional regulation in pluripotency and early differentiation. Development. 2019;146(19). [DOI:10.1242/dev.164772] [PMID] [PMCID]
20. La Rovere M, Franzago M, Stuppia L. Epigenetics and Neurological Disorders in ART. Int J Mol Sci. 2019;20(17). [DOI:10.3390/ijms20174169] [PMID] [PMCID]
21. Bowdin S, Allen C, Kirby G, Brueton L, Afnan M, Barratt C, et al. A survey of assisted reproductive technology births and imprinting disorders. Hum Reprod. 2007;22(12):3237-40. [DOI:10.1093/humrep/dem268] [PMID]
22. 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. [DOI:10.1530/REP-12-0237] [PMID]
23. Ventura-Junca P, Irarrazaval I, Rolle AJ, Gutierrez JI, Moreno RD, Santos MJ. In vitro fertilization (IVF) in mammals: epigenetic and developmental alterations. Scientific and bioethical implications for IVF in humans. Biol Res. 2015;48:68. [DOI:10.1186/s40659-015-0059-y] [PMID] [PMCID]
24. Arnaud P. Genomic imprinting in germ cells: imprints are under control. Reproduction. 2010;140(3):411-23. [DOI:10.1530/REP-10-0173] [PMID]
25. Sanchez-Delgado M, Court F, Vidal E, Medrano J, Monteagudo-Sanchez A, Martin-Trujillo A, et al. Human Oocyte-Derived Methylation Differences Persist in the Placenta Revealing Widespread Transient Imprinting. PLoS Genet. 2016;12(11):e1006427. [DOI:10.1371/journal.pgen.1006427] [PMID] [PMCID]
26. Ivanova E, Canovas S, Garcia-Martinez S, Romar R, Lopes JS, Rizos D, et al. Correction to: DNA methylation changes during preimplantation development reveal interspecies differences and reprogramming events at imprinted genes. Clin Epigenetics. 2020;12(1):96. [DOI:10.1186/s13148-020-00887-5] [DOI:10.1186/s13148-020-00857-x]
27. Melamed N, Choufani S, Wilkins-Haug LE, Koren G, Weksberg R. Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies. Epigenetics. 2015;10(6):474-83. [DOI:10.4161/15592294.2014.988041] [PMID] [PMCID]
28. Hiura H, Okae H, Chiba H, Miyauchi N, Sato F, Sato A, et al. Imprinting methylation errors in ART. Reprod Med Biol. 2014;13(4):193-202. [DOI:10.1007/s12522-014-0183-3] [PMID] [PMCID]
29. Krzyzewska IM, Alders M, Maas SM, Bliek J, Venema A, Henneman P, et al. Genome-wide methylation profiling of Beckwith-Wiedemann syndrome patients without molecular confirmation after routine diagnostics. Clin Epigenetics. 2019;11(1):53. [DOI:10.1186/s13148-019-0649-6] [PMID] [PMCID]
30. El Hajj N, Haaf T. Epigenetic disturbances in in vitro cultured gametes and embryos: implications for human assisted reproduction. Fertil Steril. 2013;99(3):632-41. [DOI:10.1016/j.fertnstert.2012.12.044] [PMID]
31. Pinborg A, Loft A, Romundstad LB, Wennerholm UB, Soderstrom-Anttila V, Bergh C, et al. Epigenetics and assisted reproductive technologies. Acta Obstet Gynecol Scand. 2016;95(1):10-5. [DOI:10.1111/aogs.12799] [PMID]
32. Kobayashi N, Miyauchi N, Tatsuta N, Kitamura A, Okae H, Hiura H, et al. Factors associated with aberrant imprint methylation and oligozoospermia. Sci Rep. 2017;7. [DOI:10.1038/srep42336] [PMID] [PMCID]
33. Nomura Y, Lambertini L, Rialdi A, Lee M, Mystal EY, Grabie M, et al. Global methylation in the placenta and umbilical cord blood from pregnancies with maternal gestational diabetes, preeclampsia, and obesity. Reprod Sci. 2014;21(1):131-7. [DOI:10.1177/1933719113492206] [PMID] [PMCID]
34. Singh G, Singh V, Schneider JS. Post-translational histone modifications and their interaction with sex influence normal brain development and elaboration of neuropsychiatric disorders. Biochim Biophys Acta Mol Basis Dis. 2019;1865(8):1968-81. [DOI:10.1016/j.bbadis.2018.10.016] [PMID]
35. Ma P, Schultz RM. HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation. Cell Death Differ. 2016;23(7):1119-27. [DOI:10.1038/cdd.2016.31] [PMID] [PMCID]
36. Gioia L, Barboni B, Turriani M, Capacchietti G, Pistilli MG, Berardinelli P, et al. The capability of reprogramming the male chromatin after fertilization is dependent on the quality of oocyte maturation. Reproduction. 2005;130(1):29-39. [DOI:10.1530/rep.1.00550] [PMID]
37. Jahangiri M, Shahhoseini M, Movaghar B. The Effect of Vitrification on Expression and Histone Marks of Igf2 and Oct4 in Blastocysts Cultured from Two-Cell Mouse Embryos. Cell J. 2018;19(4):607-13.
38. Jahangiri M, Shahhoseini M, Movaghar B. H19 and MEST gene expression and histone modification in blastocysts cultured from vitrified and fresh two-cell mouse embryos. Reprod Biomed Online. 2014;29(5):559-66. [DOI:10.1016/j.rbmo.2014.07.006] [PMID]
39. Huang Y, Shen XJ, Zou Q, Wang SP, Tang SM, Zhang GZ. Biological functions of microRNAs: a review. J Physiol Biochem. 2011;67(1):129-39. [DOI:10.1007/s13105-010-0050-6] [PMID]
40. Arfat Y, Chang H, Gao Y. Stress-responsive microRNAs are involved in re-programming of metabolic functions in hibernators. J Cell Physiol. 2018;233(4):2695-704. [DOI:10.1002/jcp.26034] [PMID]
41. Zhang J, Li H, Fan B, Xu W, Zhang X. Extracellular vesicles in normal pregnancy and pregnancy-related diseases. J Cell Mol Med. 2020;24(8):4377-88. [DOI:10.1111/jcmm.15144] [PMID] [PMCID]
42. Sills ES, Anderson RE, McCaffrey M, Li X, Arrach N, Wood SH. Gestational surrogacy and the role of routine embryo screening: Current challenges and future directions for preimplantation genetic testing. Birth Defects Res C Embryo Today. 2016;108(1):98-102. [DOI:10.1002/bdrc.21112] [PMID]
43. Kennedy EM, Hermetz K, Burt A, Everson TM, Deyssenroth M, Hao K, et al. Placental microRNA expression associates with birthweight through control of adipokines: results from two independent cohorts. Epigenetics. 2021;16(7):770-82. [DOI:10.1080/15592294.2020.1827704] [PMID] [PMCID]
44. Franzago M, Santurbano D, Vitacolonna E, Stuppia L. Genes and Diet in the Prevention of Chronic Diseases in Future Generations. Int J Mol Sci. 2020;21(7). [DOI:10.3390/ijms21072633] [PMID] [PMCID]
45. Rauschert S, Melton PE, Burdge G, Craig JM, Godfrey KM, Holbrook JD, et al. Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk. Front Genet. 2019;10:770. [DOI:10.3389/fgene.2019.00770] [PMID] [PMCID]
46. Zakarya R, Adcock I, Oliver BG. Epigenetic impacts of maternal tobacco and e-vapour exposure on the offspring lung. Clin Epigenetics. 2019;11(1):32. [DOI:10.1186/s13148-019-0631-3] [PMID] [PMCID]
47. Maccani MA, Padbury JF, Marsit CJ. miR-16 and miR-21 expression in the placenta is associated with fetal growth. PLoS One. 2011;6(6):e21210. [DOI:10.1371/journal.pone.0021210] [PMID] [PMCID]
48. Herberth G, Bauer M, Gasch M, Hinz D, Roder S, Olek S, et al. Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers. J Allergy Clin Immunol. 2014;133(2):543-50. [DOI:10.1016/j.jaci.2013.06.036] [PMID]
49. Barker DJ. In utero programming of chronic disease. Clin Sci. 1998;95(2):115-28. [DOI:10.1042/CS19980019]
50. Mason S, Zhou FC. Editorial: Genetics and epigenetics of fetal alcohol spectrum disorders. Front Genet. 2015;6:146. [DOI:10.3389/fgene.2015.00146] [PMID] [PMCID]
51. Palma-Gudiel H, Cordova-Palomera A, Leza JC, Fananas L. Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review. Neurosci Biobehav Rev. 2015;55:520-35. [DOI:10.1016/j.neubiorev.2015.05.016] [PMID]
52. Pizzorusso T, Tognini P. Interplay between Metabolism, Nutrition and Epigenetics in Shaping Brain DNA Methylation, Neural Function and Behavior. Genes (Basel). 2020;11(7). [DOI:10.3390/genes11070742] [PMID] [PMCID]
53. Alejandro EU, Mamerto TP, Chung G, Villavieja A, Gaus NL, Morgan E, et al. Gestational Diabetes Mellitus: A Harbinger of the Vicious Cycle of Diabetes. Int J Mol Sci. 2020;21(14). [DOI:10.3390/ijms21145003] [PMID] [PMCID]
54. Ruchat SM, Houde AA, Voisin G, St-Pierre J, Perron P, Baillargeon JP, et al. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases. Epigenetics. 2013;8(9):935-43. [DOI:10.4161/epi.25578] [PMID] [PMCID]
55. Zhang J, Ma X, Wang H, Ma D, Huang G. Elevated methylation of the RXRA promoter region may be responsible for its downregulated expression in the myocardium of patients with TOF. Pediatr Res. 2014;75(5):588-94. [DOI:10.1038/pr.2014.17] [PMID]
56. Lesseur C, Armstrong DA, Paquette AG, Li Z, Padbury JF, Marsit CJ. Maternal obesity and gestational diabetes are associated with placental leptin DNA methylation. Am J Obstet Gynecol. 2014;211(6):654 e1-9. [DOI:10.1016/j.ajog.2014.06.037] [PMID] [PMCID]
57. Zeisel SH. Importance of methyl donors during reproduction. Am J Clin Nutr. 2009;89(2):673S-7S. [DOI:10.3945/ajcn.2008.26811D] [PMID] [PMCID]
58. Li Y. Epigenetic Mechanisms Link Maternal Diets and Gut Microbiome to Obesity in the Offspring. Front Genet. 2018;9:342. [DOI:10.3389/fgene.2018.00342] [PMID] [PMCID]
59. Tserga A, Binder AM, Michels KB. Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1-carbon metabolism. FASEB J. 2017;31(12):5149-58. [DOI:10.1096/fj.201601214RR] [PMID] [PMCID]
60. Haggarty P, Hoad G, Campbell DM, Horgan GW, Piyathilake C, McNeill G. Folate in pregnancy and imprinted gene and repeat element methylation in the offspring. Am J Clin Nutr. 2013;97(1):94-9. [DOI:10.3945/ajcn.112.042572] [PMID]
61. Stsepetova J, Baranova J, Simm J, Parm U, Roop T, Sokmann S, et al. The complex microbiome from native semen to embryo culture environment in human in vitro fertilization procedure. Reprod Biol Endocrinol. 2020;18(1):3. [DOI:10.1186/s12958-019-0562-z] [PMID] [PMCID]
62. Donkin I, Barres R. Sperm epigenetics and influence of environmental factors. Mol Metab. 2018;14:1-11. [DOI:10.1016/j.molmet.2018.02.006] [PMID] [PMCID]
63. Theis KR, Romero R, Winters AD, Greenberg JM, Gomez-Lopez N, Alhousseini A, et al. Does the human placenta delivered at term have a microbiota? Results of cultivation, quantitative real-time PCR, 16S rRNA gene sequencing, and metagenomics. Am J Obstet Gynecol. 2019;220(3):267 e1- e39. [DOI:10.1016/j.ajog.2018.10.018] [PMID] [PMCID]
64. Lelu K, Laffont S, Delpy L, Paulet PE, Perinat T, Tschanz SA, et al. Estrogen receptor alpha signaling in T lymphocytes is required for estradiol-mediated inhibition of Th1 and Th17 cell differentiation and protection against experimental autoimmune encephalomyelitis. J Immunol. 2011;187(5):2386-93. [DOI:10.4049/jimmunol.1101578] [PMID]
65. Surace AEA, Hedrich CM. The Role of Epigenetics in Autoimmune/Inflammatory Disease. Front Immunol. 2019;10:1525. [DOI:10.3389/fimmu.2019.01525] [PMID] [PMCID]
66. Richetto J, Meyer U. Epigenetic Modifications in Schizophrenia and Related Disorders: Molecular Scars of Environmental Exposures and Source of Phenotypic Variability. Biol Psychiatry. 2021;89(3):215-26. [DOI:10.1016/j.biopsych.2020.03.008] [PMID]
67. Ruiz-Hernandez A, Kuo CC, Rentero-Garrido P, Tang WY, Redon J, Ordovas JM, et al. Environmental chemicals and DNA methylation in adults: a systematic review of the epidemiologic evidence. Clin Epigenetics. 2015;7:55. [DOI:10.1186/s13148-015-0055-7] [PMID] [PMCID]
68. Alahmar AT. Role of Oxidative Stress in Male Infertility: An Updated Review. J Hum Reprod Sci. 2019;12(1):4-18. [DOI:10.4103/jhrs.JHRS_150_18] [PMID] [PMCID]
69. Chen Z, Gong L, Zhang P, Li Y, Liu B, Zhang L, et al. Epigenetic Down-Regulation of Sirt 1 via DNA Methylation and Oxidative Stress Signaling Contributes to the Gestational Diabetes Mellitus-Induced Fetal Programming of Heart Ischemia-Sensitive Phenotype in Late Life. Int J Biol Sci. 2019;15(6):1240-51. [DOI:10.7150/ijbs.33044] [PMID] [PMCID]
70. Menezo YJ, Silvestris E, Dale B, Elder K. Oxidative stress and alterations in DNA methylation: two sides of the same coin in reproduction. Reprod Biomed Online. 2016;33(6):668-83. [DOI:10.1016/j.rbmo.2016.09.006] [PMID]
71. Cao-Lei L, Veru F, Elgbeili G, Szyf M, Laplante DP, King S. DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13(1/2) years: Project Ice Storm. Clin Epigenetics. 2016;8:54. [DOI:10.1186/s13148-016-0219-0] [PMID] [PMCID]
72. DeSocio JE. Epigenetics, maternal prenatal psychosocial stress, and infant mental health. Arch Psychiatr Nurs. 2018;32(6):901-6. [DOI:10.1016/j.apnu.2018.09.001] [PMID]
73. Barha CK, Salvante KG, Jones MJ, Farre P, Blais J, Kobor MS, et al. Early post-conception maternal cortisol, children's HPAA activity and DNA methylation profiles. J Dev Orig Health Dis. 2019;10(1):73-87. [DOI:10.1017/S2040174418000880] [PMID]
74. Glover V, O'Connor TG, O'Donnell K. Prenatal stress and the programming of the HPA axis. Neurosci Biobehav Rev. 2010;35(1):17-22. [DOI:10.1016/j.neubiorev.2009.11.008] [PMID]
75. Hogg K, Blair JD, McFadden DE, von Dadelszen P, Robinson WP. Early onset pre-eclampsia is associated with altered DNA methylation of cortisol-signalling and steroidogenic genes in the placenta. PLoS One. 2013;8(5):e62969. [DOI:10.1371/journal.pone.0062969] [PMID] [PMCID]
76. Oberlander TF, Weinberg J, Papsdorf M, Grunau R, Misri S, Devlin AM. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics. 2008;3(2):97-106. [DOI:10.4161/epi.3.2.6034] [PMID]
77. Hompes T, Izzi B, Gellens E, Morreels M, Fieuws S, Pexsters A, et al. Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood. J Psychiatr Res. 2013;47(7):880-91. [DOI:10.1016/j.jpsychires.2013.03.009] [PMID]
78. Simopoulou M, Sfakianoudis K, Rapani A, Giannelou P, Anifandis G, Bolaris S, et al. Considerations Regarding Embryo Culture Conditions: From Media to Epigenetics. In Vivo. 2018;32(3):451-60. [DOI:10.21873/invivo.11261]
79. Chen HF, Chen SU, Ma GC, Hsieh ST, Tsai HD, Yang YS, et al. Preimplantation genetic diagnosis and screening: Current status and future challenges. J Formos Med Assoc. 2018;117(2):94-100. [DOI:10.1016/j.jfma.2017.08.006]
80. Swain JE, Carrell D, Cobo A, Meseguer M, Rubio C, Smith GD. Optimizing the culture environment and embryo manipulation to help maintain embryo developmental potential. Fertil Steril. 2016;105(3):571-87. [DOI:10.1016/j.fertnstert.2016.01.035] [PMID]
81. Lindgren KE, Gulen Yaldir F, Hreinsson J, Holte J, Karehed K, Sundstrom-Poromaa I, et al. Differences in secretome in culture media when comparing blastocysts and arrested embryos using multiplex proximity assay. Ups J Med Sci. 2018;123(3):143-52. [DOI:10.1080/03009734.2018.1490830] [PMID] [PMCID]
82. Schwarzer C, Esteves TC, Arauzo-Bravo MJ, Le Gac S, Nordhoff V, Schlatt S, et al. ART culture conditions change the probability of mouse embryo gestation through defined cellular and molecular responses. Hum Reprod. 2012;27(9):2627-40. [DOI:10.1093/humrep/des223] [PMID]
83. Gad A, Schellander K, Hoelker M, Tesfaye D. Transcriptome profile of early mammalian embryos in response to culture environment. Anim Reprod Sci. 2012;134(1-2):76-83. [DOI:10.1016/j.anireprosci.2012.08.014] [PMID]
84. Armstrong S, MacKenzie J, Woodward B, Pacey A, Farquhar C. GM-CSF (granulocyte macrophage colony-stimulating factor) supplementation in culture media for women undergoing assisted reproduction. Cochrane Database Syst Rev. 2020;7:CD013497. [DOI:10.1002/14651858.CD013497.pub2] [PMID] [PMCID]
85. Hemkemeyer SA, Schwarzer C, Boiani M, Ehmcke J, Le Gac S, Schlatt S, et al. Effects of embryo culture media do not persist after implantation: a histological study in mice. Hum Reprod. 2014;29(2):220-33. [DOI:10.1093/humrep/det411] [PMID]
86. Van Montfoort APA, Arts E, Wijnandts L, Sluijmer A, Pelinck MJ, Land JA, et al. Reduced oxygen concentration during human IVF culture improves embryo utilization and cumulative pregnancy rates per cycle. Hum Reprod Open. 2020;2020(1):hoz036. [DOI:10.1093/hropen/hoz036] [PMID] [PMCID]
87. Karagenc L, Sertkaya Z, Ciray N, Ulug U, Bahceci M. Impact of oxygen concentration on embryonic development of mouse zygotes. Reprod Biomed Online. 2004;9(4):409-17. [DOI:10.1016/S1472-6483(10)61276-X] [PMID]
88. Oliveira JB. Does embryo culture at low oxygen tension improve ART outcomes? JBRA Assist Reprod. 2017;21(1):1. [DOI:10.5935/1518-0557.20170001] [PMID] [PMCID]
89. Morin SJ. Oxygen tension in embryo culture: does a shift to 2% O2 in extended culture represent the most physiologic system? J Assist Reprod Genet. 2017;34(3):309-14. [DOI:10.1007/s10815-017-0880-z] [PMID] [PMCID]