Infertility, assisted reproduction technologies and imprinting disturbances: a Dutch study

Doornbos, M.; Maas, Saskia M.; McDonnell, Joseph; Vermeiden, Jan P.W.; Hennekam, Raoul C. M.

doi:10.1093/humrep/dem172

Cited by 199 publications

(173 citation statements)

References 18 publications

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“…A study conducted by Doornbos et al found that an increased incidence of imprinting diseases was associated with increased fertility problems of the parents but not ART (39). Particularly, the intrinsic imprinting defects of spermatozoa appeared to be responsible for the increased incidence of imprinting disorders (37).…”

Section: Discussionmentioning

confidence: 97%

Study of DNA methylation patterns of imprinted genes in children born after assisted reproductive technologies reveals no imprinting errors: A pilot study

Zheng

Shi

Wang

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Assisted reproductive technology (ART) includingin vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have been shown to be associated with abnormal genomic imprinting, thus increasing the incidence of imprinting disorders such as Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS) in ART-conceived children. Furthermore, a recent study described abnormal DNA methylation in clinically normal children conceived by ART. However, data from different studies are conflicting or inconclusive. This study examined DNA methylation patterns of multiple imprinted genes in children born after ART to primarily evaluate the impact of ART on genomic imprinting. A total of 101 newborns conceived by ART (40 ICSI and 61 IVF) and 60 naturally conceived newborns were involved in our study. After obtaining the approval of the Institutional Ethics Committee, umbilical cord blood was collected from each infant. Genomic DNA was isolated from each blood sample and treated using sodium bisulfite. Subsequently, using methylation-specific PCR (MS-PCR), we analyzed six differentially methylated regions (DMRs) including KvDMR1, SNRPN, MEST, MEG3, TNDM and XIST. Meanwhile, information regarding twin pregnancies, gestational age, and birth weight of the neonates was documented. None of the cases presented with phenotypic abnormalities. Children conceived by ART were more likely to have low birth weight and to be born before term, compared with children conceived spontaneously. However, 7 months to 3 years of clinical follow-up showed that none of the children had clinical symptoms of any imprinting diseases. Furthermore, the MS-PCR results showed that all 161 children had normal DNA methylation patterns at six DMRs despite the different mode of conception. Our data did not indicate a higher risk of DNA-methylation defects in children born after ART. However, further studies using quantitative methods are needed to confirm these results.

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Section: Discussionmentioning

confidence: 97%

Study of DNA methylation patterns of imprinted genes in children born after assisted reproductive technologies reveals no imprinting errors: A pilot study

Zheng

Shi

Wang

et al. 2011

Experimental and Therapeutic Medicine

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“…Advanced maternal age (O35 years) is directly related to a decline in fertility with a reduced oocyte reserve and poor oocyte quality (Liu & Case 2011). In a Dutch study evaluating ARTs and parental infertility, 6.3% of AS, 8.5% of BWS, and 2.1% of total children were conceived via ARTs, while 6.3% of AS, 8.5% of BWS, and 3.5% of total children were born to subfertile families without ARTs (Doornbos et al 2007; Table 6). …”

Section: Female Infertility/subfertilitymentioning

confidence: 99%

Genomic imprints as a model for the analysis of epigenetic stability during assisted reproductive technologies

Denomme¹,

Mann²

2012

Reproduction

112

118

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Gamete and early embryo development are important stages when genome-scale epigenetic transitions are orchestrated. The apparent lack of remodeling of differential imprinted DNA methylation during preimplantation development has lead to the argument that epigenetic disruption by assisted reproductive technologies (ARTs) is restricted to imprinted genes. We contend that aberrant imprinted methylation arising from assisted reproduction or infertility may be an indicator of more global epigenetic instability. Here, we review the current literature on the effects of ARTs, including ovarian stimulation, in vitro oocyte maturation, oocyte cryopreservation, IVF, ICSI, embryo culture, and infertility on genomic imprinting as a model for evaluating epigenetic stability. Undoubtedly, the relationship between impaired fertility, ARTs, and epigenetic stability is unquestionably complex. What is clear is that future studies need to be directed at determining the molecular and cellular mechanisms giving rise to epigenetic errors.

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“…A study of sporadic PWS cases found that 9 of the 163 PWS patients were conceived by ART (2 using ICSI and 7 using fertility drugs) and two of the patients were found to have a chromosome deletion (Sutcliffe et al, 2006). Another study showed that 4 of 86 PWS patients were conceived using various forms and 1 using ovulation induction) (Doornbos et al, 2007). On the other hand, Lidegaard et al any cases of PWS in 6,052 children conceived by ART.…”

Section: Art and Birth Defectsmentioning

confidence: 99%

Intrauterine environment-genome interaction and Children's development (3): Assisted reproductive technologies and developmental disorders

Shiota

Yamada²

2009

J. Toxicol. Sci.

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-In vitro fertilization (IVF) and other assisted reproductive technologies (ART) are widely used clinically as infertility treatments. Although ART procedures are generally considered safe, some studies have suggested an increase in the occurrence of major malformations and some other complications in babies conceived by ART. Further, it has recently been suggested that ART are associated with imprinting disorders in the offspring such as Beckwith-Wiedemann syndrome and Angelman syndrome. We review the human and animal studies investigating the outcome of ART pregnancies and discuss the potential risk of ART to pre-and perinatal development.

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Infertility, assisted reproduction technologies and imprinting disturbances: a Dutch study

Abstract: After correction for the increased fertility problems of the parents, there is no increased incidence of ART related birth of AS, PWS or BWS children. ART does not seem to have a direct effect on the increase of imprinted diseases.

Cited by 199 publications

References 18 publications

Study of DNA methylation patterns of imprinted genes in children born after assisted reproductive technologies reveals no imprinting errors: A pilot study

Study of DNA methylation patterns of imprinted genes in children born after assisted reproductive technologies reveals no imprinting errors: A pilot study

Genomic imprints as a model for the analysis of epigenetic stability during assisted reproductive technologies

Intrauterine environment-genome interaction and Children's development (3): Assisted reproductive technologies and developmental disorders

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