Please wait a minute...
Journal of ZheJiang University(Medical Science)  2017, Vol. 46 Issue (3): 279-284    DOI: 10.3785/j.issn.1008-9292.2017.06.09
Research progress on the safety of offsprings conceived by assisted reproductive technology
WANG Liya, QIAN Yeqing, JIN Fan
Department of Reproductive Genetics, Women's Hospital, Zhejiang University School of Medicine, Key Laboratory of Reproductive Genetics, Ministry of Education, Hangzhou 310006, China
Download:   PDF(977KB)
Export: BibTeX | EndNote (RIS)      


Assisted reproductive technology (ART) employs superovulation, in vitro culture and other micromanipulation to complete oocyte maturation, fertilization and early embryo development. Although these techniques have been successfully applied to solve infertility problems, the process may interfere in cell proliferation, differentiation and growth. The clinical and laboratory studies on the safety issue of ART are reviewed in this article. Studies found that the incidence of birth defects increased in ART offspring. Superovulation, in vitro culture and intracytoplasmic sperm injection may induce epigenetic aberrations during embryo development, which would influence the development of ART conceived children. The epigenetic susceptibility related to ART might be transmitted to subsequent generations, and the potential impact on ART offspring still need further investigation. In addition, ART treatments may also increase the risk of genetic diseases.

Key wordsEmbryonic development/genetics      Child development/genetics      Parent-child relations      Reproductive techniques, assisted/adverse effects      Genetics      Safety      Review     
Received: 15 February 2017      Published: 25 June 2017
CLC:  R714  
Cite this article:

WANG Liya, QIAN Yeqing, JIN Fan. Research progress on the safety of offsprings conceived by assisted reproductive technology. Journal of ZheJiang University(Medical Science), 2017, 46(3): 279-284.

URL:     OR



关键词: 胚胎发育/遗传学,  儿童发育/遗传学,  亲子关系,  生殖技术,  辅助/副作用,  遗传学,  安全,  综述 

[1] OOKI S. Maternal age and birth defects after the use of assisted reproductive technology in Japan, 2004-2010[J]. Int J Womens Health,2013,5:65-77.
[2] REEFHUIS J, HONEIN M A, SCHIEVE L A, et al. Assisted reproductive technology and major structural birth defects in the United States[J]. Hum Reprod,2009,24(2):360-366.
[3] YIN L, HANG F, GU L J, et al. Analysis of birth defects among children 3 years after conception through assisted reproductive technology in China[J]. Birth Defects Res A Clin Mol Teratol,2013,97(11):744-749.
[4] HANSEN M, KURINCZUK J J, MILNE E, et al. Assisted reproductive technology and birth defects:a systematic review and meta-analysis[J]. Hum Reprod Update,2013,19(4):330-353.
[5] LEDFORD H. Language:disputed definitions[J]. Nature,2008,455(7216):1023-1028.
[6] GUO F, YAN L, GUO H, et al. The transcriptome and DNA methylome landscapes of human primordial germ cells[J]. Cell,2015,161(6):1437-1452.
[7] GUO H, ZHU P, YAN L, et al. The DNA methylation landscape of human early embryos[J]. Nature,2014,511(7511):606-610.
[8] AMOR D J, HALLIDAY J. A review of known imprinting syndromes and their association with assisted reproduction technologies[J]. Hum Reprod,2008,23(12):2826-2834.
[9] RIVERA R M, STEIN P, WEAVER J R, et al. Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development[J]. Hum Mol Genet,2008,17(1):1-14.
[10] PIEDRAHITA J A. The role of imprinted genes in fetal growth abnormalities[J]. Birth Defects Res A Clin Mol Teratol,2011,91(8):682-692.
[11] KERJEAN A, COUVERT P, HEAMS T, et al. In vitro follicular growth affects oocyte imprinting establishment in mice[J]. Eur J Hum Genet,2003,11(7):493-496.
[12] BORGHOL N, LORNAGE J, BLACHERE T, et al. Epigenetic status of the H19 locus in human oocytes following in vitro maturation[J]. Genomics,2006,87(3):417-426.
[13] LIU X, ZHAO D, ZHENG Y, et al. Expression of histone acetyltransferase GCN5 and histone deacetylase 1 in the cultured mouse preimplantation embryos[J]. Curr Pharm Des,2014,20(11):1772-1777.
[14] HALLIDAY J, OKE K, BREHENY S, et al. Beckwith-Wiedemann syndrome and IVF:a case-control study[J]. Am J Hum Genet,2004,75(3):526-528.
[15] BELTRAND J, NICOLESCU R, KAGUELIDOU F, et al. Catch-up growth following fetal growth restriction promotes rapid restoration of fat mass but without metabolic consequences at one year of age[J/OL]. PLoS One,2009,4(4):e5343.
[16] BARKER D J. The fetal and infant origins of adult disease[J]. BMJ,1990,301(6761):1111.
[17] GOSDEN R, TRASLER J, LUCIFERO D, et al. Rare congenital disorders, imprinted genes, and assisted reproductive technology[J]. Lancet,2003,361(9373):1975-1977.
[18] WANG N, REN C E, LOU Y Y, et al. Inter-generational effects of the in vitro maturation technique on pregnancy outcomes, early development, and cognition of offspring in mouse model[J]. Clin Chim Acta,2017,473:218-227.
[19] LI L, LE F, WANG L Y, et al. Normal epigenetic inheritance in mice conceived by in vitro fertilization and embryo transfer[J]. J Zhejiang Univ Sci B,2011,12(10):796-804.
[20] LE F, WANG L Y, WANG N, et al. In vitro fertilization alters growth and expression of Igf2/H19 and their epigenetic mechanisms in the liver and skeletal muscle of newborn and elder mice[J]. Biol Reprod,2013,88(3):75.
[21] WANG N, WANG L, LE F, et al. Altered expression of Armet and Mrlp51 in the oocyte, preimplantation embryo, and brain of mice following oocyte in vitro maturation but postnatal brain development and cognitive function are normal[J]. Reproduction,2011,142(3):401-408.
[22] WANG L Y, WANG N, LE F, et al. Persistence and intergenerational transmission of differentially expressed genes in the testes of intracytoplasmic sperm injection conceived mice[J]. J Zhejiang Univ Sci B,2013,14(5):372-381.
[23] XU X R, FU R G, WANG L Y, et al. Epigenetic inheritance of paternally expressed imprinted genes in the testes of ICSI mice[J]. Curr Pharm Des,2014,20(11):1764-1771.
[24] LI L, WANG L, XU X, et al. Genome-wide DNA methylation patterns in IVF-conceived mice and their progeny:a putative model for ART-conceived humans[J]. Reprod Toxicol,2011,32(1):98-105.
[25] WANG N, FANG L, LIU X, et al. Altered expressions and DNA methylation of imprinted genes in chromosome 7 in brain of mouse offspring conceived from in vitro maturation[J]. Reprod Toxicol,2012,34(3):420-428.
[26] CLEMENTINI E, PALKA C, IEZZI I, et al. Prevalence of chromosomal abnormalities in 2078 infertile couples referred for assisted reproductive techniques[J]. Hum Reprod,2005,20(2):437-442.
[27] BONDUELLE M, CAMUS M, DE VOS A, et al. Seven years of intracytoplasmic sperm injection and follow-up of 1987 subsequent children[J]. Hum Reprod,1999,14 Suppl 1:243-264.
[28] BONDUELLE M, LIEBAERS I, DEKETELAERE V, et al. Neonatal data on a cohort of 2889 infants born after ICSI (1991-1999) and of 2995 infants born after IVF (1983-1999)[J]. Hum Reprod,2002,17(3):671-694.
[29] FUJIMOTO S, PAHLAVAN N, DUKELOW W R. Chromosome abnormalities in rabbit preimplantation blastocysts induced by superovulation[J]. J Reprod Fertil,1974,40(1):177-181.
[30] IMREH M P, GERTOW K, CEDERVALL J, et al. In vitro culture conditions favoring selection of chromosomal abnormalities in human ES cells[J]. J Cell Biochem,2006,99(2):508-516.
[31] FORSYTH N R, MUSIO A, VEZZONI P, et al. Physiologic oxygen enhances human embryonic stem cell clonal recovery and reduces chromosomal abnormalities[J]. Cloning Stem Cells,2006,8(1):16-23.
[32] TATENO H. Chromosome aberrations in mouse embryos and fetuses produced by assisted reproductive technology[J]. Mutat Res,2008,657(1):26-31.
[33] WANG W H, MENG L, HACKETT R J, et al. Limited recovery of meiotic spindles in living human oocytes after cooling-rewarming observed using polarized light microscopy[J]. Hum Reprod,2001,16(11):2374-2378.
[34] HASTINGS P J, LUPSKI J R, ROSENBERG S M, et al. Mechanisms of change in gene copy number[J]. Nat Rev Genet,2009,10(8):551-564.
[35] ZHENG Y M, LI L, ZHOU L M, et al. Alterations in the frequency of trinucleotide repeat dynamic mutations in offspring conceived through assisted reproductive technology[J]. Hum Reprod,2013,28(9):2570-2580.

[1] XU Jingjing, TAN Yanbin, ZHANG Minming. Medical imaging in tumor precision medicine: opportunities and challenges[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 455-461.
[2] PAN Jingying, HE Mengye, KE Wei, HU Menglin, WANG Meifang, SHEN Peng. Advances on correlation of PET-CT findings with breast cancer molecular subtypes, treatment response and prognosis[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 473-480.
[3] ZHANG Siying, CHEN Feng. Research progress of CT/MRI parametric response map in precision evaluation of therapeutic response of cancer patients[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 468-472.
[4] PAN Yao, CHEN Jieyu, YU Risheng. Accurate imaging diagnosis and evaluation of pancreatic cancer[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 462-467.
[5] WANG Mengyan, ZHU Biao. Research progress on genes mutations related to sulfa drug resistance in Pneumocystis jirovecii[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 563-569.
[6] WANG Haifeng, CHEN Tiantian, WANG Yueyue, LI Yu, ZHANG Lingyu, DING Yongxing, CHEN Sulian, WANG Wenrui, YANG Qingling, CHEN Changjie. CXC chemokine receptor 4 regulates breast cancer cell cycle through S phase kinase associated protein 2[J]. Journal of ZheJiang University(Medical Science), 2017, 46(4): 357-363.
[7] GE Yumei, CHEN Xuebo, HUANG Yanying, LYU Huoyang, ZHAO Zhao, ZHOU Yonglie. Drug resistance and protoporphyrin ferrochelatase of Ralstonia mannitolilytica[J]. Journal of ZheJiang University(Medical Science), 2017, 46(4): 413-420.
[8] LI Yandie, LU Meiping. Progress on the study of NLRP3 inflammasome in autoinflammatory diseases of children[J]. Journal of ZheJiang University(Medical Science), 2017, 46(4): 449-453.
[9] ZOU Lixia, LU Meiping, GUO Li, TENG Liping, XU Yiping, ZHENG Qi. Efficacy and safety of humanized interleukin-6 receptor antibody in treatment of systemic juvenile idiopathic arthritis[J]. Journal of ZheJiang University(Medical Science), 2017, 46(4): 421-426.
[10] SHEN Dan, WANG Fangfang, JIANG Zhou, QU Fan. Long-term effects of polycystic ovary syndrome on the offspring[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 300-304.
[11] FU Xiaohua, XU Weihai, QIU Shengchun, SHU Jing. Research progress on the relationship of brown adipose tissue with polycystic ovary syndrome[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 315-320.
[12] FU Yanling, ZHU Yimin. Potential clinical application of Kisspeptin in reproductive endocrinology[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 328-333.
[13] QIAN Yeqing, WANG Liya, LUO Yuqin, YAN Kai, DONG Minyue, JIN Fan. Advances in the application of high-throughput sequencing in clinical genetics[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 334-337.
[14] HONG Fang, HUANG Xinwen, ZHANG Yu, YANG Jianbin, TONG Fan, MAO Huaqing, HUANG Xiaolei, ZHOU Xuelian, YANG Rulai, ZHAO Zhengyan. Screening for newborn organic aciduria in Zhejiang province:prevalence, outcome and follow-up[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 240-247.
[15] YAN Kai, JIN Fan. Advances on prenatal diagnosis of birth defects associated with genetic disorders[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 227-232.