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The health of children conceived by ART: 'the chicken or the egg?'

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Harvard

Berntsen, S, Söderström-Anttila, V, Wennerholm, U-B, Laivuori, H, Loft, A, Oldereid, NB, Romundstad, LB, Bergh, C & Pinborg, A 2019, 'The health of children conceived by ART: 'the chicken or the egg?'', Human Reproduction Update, vol. 25, no. 2, pp. 137-158. https://doi.org/10.1093/humupd/dmz001

APA

Berntsen, S., Söderström-Anttila, V., Wennerholm, U-B., Laivuori, H., Loft, A., Oldereid, N. B., Romundstad, L. B., Bergh, C., & Pinborg, A. (2019). The health of children conceived by ART: 'the chicken or the egg?'. Human Reproduction Update, 25(2), 137-158. https://doi.org/10.1093/humupd/dmz001

CBE

Berntsen S, Söderström-Anttila V, Wennerholm U-B, Laivuori H, Loft A, Oldereid NB, Romundstad LB, Bergh C, Pinborg A. 2019. The health of children conceived by ART: 'the chicken or the egg?'. Human Reproduction Update. 25(2):137-158. https://doi.org/10.1093/humupd/dmz001

MLA

Vancouver

Berntsen S, Söderström-Anttila V, Wennerholm U-B, Laivuori H, Loft A, Oldereid NB et al. The health of children conceived by ART: 'the chicken or the egg?'. Human Reproduction Update. 2019 Mar 1;25(2):137-158. https://doi.org/10.1093/humupd/dmz001

Author

Berntsen, Sine ; Söderström-Anttila, Viveca ; Wennerholm, Ulla-Britt ; Laivuori, Hannele ; Loft, Anne ; Oldereid, Nan B ; Romundstad, Liv Bente ; Bergh, Christina ; Pinborg, Anja. / The health of children conceived by ART: 'the chicken or the egg?'. In: Human Reproduction Update. 2019 ; Vol. 25, No. 2. pp. 137-158.

Bibtex

@article{02ba1b4000d54d8ba25ba8f165331cc0,
title = "The health of children conceived by ART: 'the chicken or the egg?'",
abstract = "Worldwide, more than 7 million children have now been born after ART: these delivery rates are steadily rising and now comprise 2-6% of births in the European countries. To achieve higher pregnancy rates, the transfer of two or more embryos was previously the gold standard in ART. However, recently the practise has moved towards a single embryo transfer policy to avoid multiple births. The positive consequences of the declining multiple birth rates after ART are decreasing perinatal risks and overall improved health for the ART progeny. In this review we summarize the risks for short- and long-term health in ART singletons and discuss if the increased health risks are associated with intrinsic maternal or paternal factors related to subfertility or to the ART treatments per se. Although the risks are modest, singletons born after ART are more likely to have adverse perinatal outcomes compared to spontaneously conceived (SC) singletons dependent on the ART method. Fresh embryo transfer is associated with a higher risk of small for gestational age babies (SGA), low birthweight and preterm birth (PTB), while frozen embryo transfer is associated with large-for-gestational age babies and pre-eclampsia. ICSI may be associated with a higher risk of birth defects and transferral of the poor semen quality to male progeny, while oocyte donation is associated with increased risk of SGA and pre-eclampsia. Concerning long-term health risks, the current evidence is limited but suggests an increased risk of altered blood pressure and cardiovascular function in ART children. The data that are available for malignancies seem reassuring, while results on neurodevelopmental health are more equivocal with a possible association between ART and cerebral palsy. The laboratory techniques used in ART may also play a role, as different embryo culture media give rise to different birthweights and growth patterns in children, while culture to blastocyst stage is associated with PTB. In addition, children born after ART have altered epigenetic profiles, and these alterations may be one of the key areas to explore to improve our understanding of adverse child outcomes after ART. A major challenge for research into adverse perinatal outcomes is the difficulty in separating the contribution of infertility per se from the ART treatment (i.e. 'the chicken or the egg'?). Choosing and having access to the appropriate control groups for the ART children in order to eliminate the influence of subfertility per se (thereby exploring the pure association between ART and child outcomes) is in itself challenging. However, studies including children of subfertile couples or of couples treated with milder fertility treatments, such as IUI, as controls show that perinatal risks in these cohorts are lower than for ART children but still higher than for SC indicating that both subfertility and ART influence the future outcome. Sibling studies, where a mother gave birth to both an ART and a SC child, support this theory as ART singletons had slightly poorer outcomes. The conclusion we can reach from the well designed studies aimed at disentangling the influence on child health of parental and ART factors is that both the chicken and the egg matter.",
keywords = "Adverse child outcomes, ART, Culture media, Epigenetics, Frozen embryo transfer, ICSI, Infertility, IVF, Oocyte donation, Sibling studies",
author = "Sine Berntsen and Viveca S{\"o}derstr{\"o}m-Anttila and Ulla-Britt Wennerholm and Hannele Laivuori and Anne Loft and Oldereid, {Nan B} and Romundstad, {Liv Bente} and Christina Bergh and Anja Pinborg",
note = "{\textcopyright} The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.",
year = "2019",
month = mar,
day = "1",
doi = "10.1093/humupd/dmz001",
language = "English",
volume = "25",
pages = "137--158",
journal = "Human Reproduction Update",
issn = "1355-4786",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - The health of children conceived by ART: 'the chicken or the egg?'

AU - Berntsen, Sine

AU - Söderström-Anttila, Viveca

AU - Wennerholm, Ulla-Britt

AU - Laivuori, Hannele

AU - Loft, Anne

AU - Oldereid, Nan B

AU - Romundstad, Liv Bente

AU - Bergh, Christina

AU - Pinborg, Anja

N1 - © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Worldwide, more than 7 million children have now been born after ART: these delivery rates are steadily rising and now comprise 2-6% of births in the European countries. To achieve higher pregnancy rates, the transfer of two or more embryos was previously the gold standard in ART. However, recently the practise has moved towards a single embryo transfer policy to avoid multiple births. The positive consequences of the declining multiple birth rates after ART are decreasing perinatal risks and overall improved health for the ART progeny. In this review we summarize the risks for short- and long-term health in ART singletons and discuss if the increased health risks are associated with intrinsic maternal or paternal factors related to subfertility or to the ART treatments per se. Although the risks are modest, singletons born after ART are more likely to have adverse perinatal outcomes compared to spontaneously conceived (SC) singletons dependent on the ART method. Fresh embryo transfer is associated with a higher risk of small for gestational age babies (SGA), low birthweight and preterm birth (PTB), while frozen embryo transfer is associated with large-for-gestational age babies and pre-eclampsia. ICSI may be associated with a higher risk of birth defects and transferral of the poor semen quality to male progeny, while oocyte donation is associated with increased risk of SGA and pre-eclampsia. Concerning long-term health risks, the current evidence is limited but suggests an increased risk of altered blood pressure and cardiovascular function in ART children. The data that are available for malignancies seem reassuring, while results on neurodevelopmental health are more equivocal with a possible association between ART and cerebral palsy. The laboratory techniques used in ART may also play a role, as different embryo culture media give rise to different birthweights and growth patterns in children, while culture to blastocyst stage is associated with PTB. In addition, children born after ART have altered epigenetic profiles, and these alterations may be one of the key areas to explore to improve our understanding of adverse child outcomes after ART. A major challenge for research into adverse perinatal outcomes is the difficulty in separating the contribution of infertility per se from the ART treatment (i.e. 'the chicken or the egg'?). Choosing and having access to the appropriate control groups for the ART children in order to eliminate the influence of subfertility per se (thereby exploring the pure association between ART and child outcomes) is in itself challenging. However, studies including children of subfertile couples or of couples treated with milder fertility treatments, such as IUI, as controls show that perinatal risks in these cohorts are lower than for ART children but still higher than for SC indicating that both subfertility and ART influence the future outcome. Sibling studies, where a mother gave birth to both an ART and a SC child, support this theory as ART singletons had slightly poorer outcomes. The conclusion we can reach from the well designed studies aimed at disentangling the influence on child health of parental and ART factors is that both the chicken and the egg matter.

AB - Worldwide, more than 7 million children have now been born after ART: these delivery rates are steadily rising and now comprise 2-6% of births in the European countries. To achieve higher pregnancy rates, the transfer of two or more embryos was previously the gold standard in ART. However, recently the practise has moved towards a single embryo transfer policy to avoid multiple births. The positive consequences of the declining multiple birth rates after ART are decreasing perinatal risks and overall improved health for the ART progeny. In this review we summarize the risks for short- and long-term health in ART singletons and discuss if the increased health risks are associated with intrinsic maternal or paternal factors related to subfertility or to the ART treatments per se. Although the risks are modest, singletons born after ART are more likely to have adverse perinatal outcomes compared to spontaneously conceived (SC) singletons dependent on the ART method. Fresh embryo transfer is associated with a higher risk of small for gestational age babies (SGA), low birthweight and preterm birth (PTB), while frozen embryo transfer is associated with large-for-gestational age babies and pre-eclampsia. ICSI may be associated with a higher risk of birth defects and transferral of the poor semen quality to male progeny, while oocyte donation is associated with increased risk of SGA and pre-eclampsia. Concerning long-term health risks, the current evidence is limited but suggests an increased risk of altered blood pressure and cardiovascular function in ART children. The data that are available for malignancies seem reassuring, while results on neurodevelopmental health are more equivocal with a possible association between ART and cerebral palsy. The laboratory techniques used in ART may also play a role, as different embryo culture media give rise to different birthweights and growth patterns in children, while culture to blastocyst stage is associated with PTB. In addition, children born after ART have altered epigenetic profiles, and these alterations may be one of the key areas to explore to improve our understanding of adverse child outcomes after ART. A major challenge for research into adverse perinatal outcomes is the difficulty in separating the contribution of infertility per se from the ART treatment (i.e. 'the chicken or the egg'?). Choosing and having access to the appropriate control groups for the ART children in order to eliminate the influence of subfertility per se (thereby exploring the pure association between ART and child outcomes) is in itself challenging. However, studies including children of subfertile couples or of couples treated with milder fertility treatments, such as IUI, as controls show that perinatal risks in these cohorts are lower than for ART children but still higher than for SC indicating that both subfertility and ART influence the future outcome. Sibling studies, where a mother gave birth to both an ART and a SC child, support this theory as ART singletons had slightly poorer outcomes. The conclusion we can reach from the well designed studies aimed at disentangling the influence on child health of parental and ART factors is that both the chicken and the egg matter.

KW - Adverse child outcomes

KW - ART

KW - Culture media

KW - Epigenetics

KW - Frozen embryo transfer

KW - ICSI

KW - Infertility

KW - IVF

KW - Oocyte donation

KW - Sibling studies

UR - http://www.scopus.com/inward/record.url?scp=85062179650&partnerID=8YFLogxK

U2 - 10.1093/humupd/dmz001

DO - 10.1093/humupd/dmz001

M3 - Journal article

C2 - 30753453

VL - 25

SP - 137

EP - 158

JO - Human Reproduction Update

JF - Human Reproduction Update

SN - 1355-4786

IS - 2

ER -

ID: 56520263