The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health—Follow-up of a randomized clinical trial

S. Mintjens; M. D. Menting; R. J.B.J. Gemke; M. N.M. van Poppel; M. van Wely; A. J. Bensdorp; R. I. Tjon Kon Fat; B. W.J. Mol; R. C. Painter; C. van de Beek; T. J. Roseboom

doi:10.1016/j.ejogrb.2019.09.026

The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health—Follow-up of a randomized clinical trial

S. Mintjens^*, M. D. Menting, R. J.B.J. Gemke, M. N.M. van Poppel, M. van Wely, A. J. Bensdorp, R. I. Tjon Kon Fat, B. W.J. Mol, R. C. Painter, C. van de Beek, T. J. Roseboom

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Objective: Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring? Study design: Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4–7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance. Results: We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0–7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences. Conclusions: Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have hampered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive.

Original language	English
Pages (from-to)	131-138
Number of pages	8
Journal	European Journal of Obstetrics and Gynecology and Reproductive Biology
Volume	242
Early online date	26 Sept 2019
DOIs	https://doi.org/10.1016/j.ejogrb.2019.09.026
Publication status	Published - Nov 2019

Bibliographical note

Funding
This work was supported by a grant of the Dutch Heart Foundation (2013T085). The initial trial was supported by a grant from ZonMW, the Dutch Organization for Health Research and Development (120620027) and a grant from Zorgverzekeraars Nederland, the Dutch association of healthcare insurers (09-003). The funders had no role in the design, conduct and interpretation of the study. The authors declare no conflict of interest.

Stijn Mintjens, Malou Menting, Reinoud Gemke, Mireille van Poppel, Madelon van Wely, Alexandra Bensdorp, Raïssa Tjon Kon Fat, Ben Willem Mol, Rebecca Painter, Cornelieke van de Beek and Tessa Roseboom declare no conflicts of interest relevant to this study. Outside the work submitted, Ben Willem Mol is supported by a NHMRC practitioner Fellowship and reports consultancy for ObsEva, Merck, Merck KGaA and Guerbet. Rebecca Painter reports board membership for the Dutch Gezondheidsraad and NVVH guideline committees, and travel expenses reimbursement for ESHRE meeting Barcelona 2018 (June).

Acknowledgements
We thank all the women and children who participated in this study. We are grateful to all who contributed to the follow-up study; with special thanks to our colleague PhD students, post-docs, research assistants and students. This follow-up study would not have been possible without the original INeS trial; therefore, we thank all participating hospitals for their contribution to this study, and the gynecologists, research nurses, research midwives and office members of the Dutch Consortium (www.studies-obsgyn.nl) for their hard work and dedication.

Keywords

Assisted reproductive techniques
Cardiometabolic health
Follow-up
Hormone stimulation
In vitro fertilization
Neurodevelopment

Access to Document

10.1016/j.ejogrb.2019.09.026

Cite this

Mintjens, S., Menting, M. D., Gemke, R. J. B. J., van Poppel, M. N. M., van Wely, M., Bensdorp, A. J., Tjon Kon Fat, R. I., Mol, B. W. J., Painter, R. C., van de Beek, C., & Roseboom, T. J. (2019). The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health—Follow-up of a randomized clinical trial. European Journal of Obstetrics and Gynecology and Reproductive Biology, 242, 131-138. https://doi.org/10.1016/j.ejogrb.2019.09.026

The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health—Follow-up of a randomized clinical trial. / Mintjens, S.; Menting, M. D.; Gemke, R. J.B.J. et al.
In: European Journal of Obstetrics and Gynecology and Reproductive Biology, Vol. 242, 11.2019, p. 131-138.

Research output: Contribution to journal › Article › peer-review

Mintjens, S, Menting, MD, Gemke, RJBJ, van Poppel, MNM, van Wely, M, Bensdorp, AJ, Tjon Kon Fat, RI, Mol, BWJ, Painter, RC, van de Beek, C & Roseboom, TJ 2019, 'The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health—Follow-up of a randomized clinical trial', European Journal of Obstetrics and Gynecology and Reproductive Biology, vol. 242, pp. 131-138. https://doi.org/10.1016/j.ejogrb.2019.09.026

Mintjens S, Menting MD, Gemke RJBJ, van Poppel MNM, van Wely M, Bensdorp AJ et al. The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health—Follow-up of a randomized clinical trial. European Journal of Obstetrics and Gynecology and Reproductive Biology. 2019 Nov;242:131-138. Epub 2019 Sept 26. doi: 10.1016/j.ejogrb.2019.09.026

@article{c4310b942e2842d5b250793adc69daa8,

title = "The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health—Follow-up of a randomized clinical trial",

abstract = "Objective: Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring? Study design: Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4–7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance. Results: We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0–7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences. Conclusions: Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have hampered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive.",

keywords = "Assisted reproductive techniques, Cardiometabolic health, Follow-up, Hormone stimulation, In vitro fertilization, Neurodevelopment",

author = "S. Mintjens and Menting, {M. D.} and Gemke, {R. J.B.J.} and {van Poppel}, {M. N.M.} and {van Wely}, M. and Bensdorp, {A. J.} and {Tjon Kon Fat}, {R. I.} and Mol, {B. W.J.} and Painter, {R. C.} and {van de Beek}, C. and Roseboom, {T. J.}",

note = "Funding This work was supported by a grant of the Dutch Heart Foundation (2013T085). The initial trial was supported by a grant from ZonMW, the Dutch Organization for Health Research and Development (120620027) and a grant from Zorgverzekeraars Nederland, the Dutch association of healthcare insurers (09-003). The funders had no role in the design, conduct and interpretation of the study. The authors declare no conflict of interest. Stijn Mintjens, Malou Menting, Reinoud Gemke, Mireille van Poppel, Madelon van Wely, Alexandra Bensdorp, Ra{\"i}ssa Tjon Kon Fat, Ben Willem Mol, Rebecca Painter, Cornelieke van de Beek and Tessa Roseboom declare no conflicts of interest relevant to this study. Outside the work submitted, Ben Willem Mol is supported by a NHMRC practitioner Fellowship and reports consultancy for ObsEva, Merck, Merck KGaA and Guerbet. Rebecca Painter reports board membership for the Dutch Gezondheidsraad and NVVH guideline committees, and travel expenses reimbursement for ESHRE meeting Barcelona 2018 (June). Acknowledgements We thank all the women and children who participated in this study. We are grateful to all who contributed to the follow-up study; with special thanks to our colleague PhD students, post-docs, research assistants and students. This follow-up study would not have been possible without the original INeS trial; therefore, we thank all participating hospitals for their contribution to this study, and the gynecologists, research nurses, research midwives and office members of the Dutch Consortium (www.studies-obsgyn.nl) for their hard work and dedication.",

year = "2019",

month = nov,

doi = "10.1016/j.ejogrb.2019.09.026",

language = "English",

volume = "242",

pages = "131--138",

journal = "European Journal of Obstetrics and Gynecology and Reproductive Biology",

issn = "0301-2115",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health—Follow-up of a randomized clinical trial

AU - Mintjens, S.

AU - Menting, M. D.

AU - Gemke, R. J.B.J.

AU - van Poppel, M. N.M.

AU - van Wely, M.

AU - Bensdorp, A. J.

AU - Tjon Kon Fat, R. I.

AU - Mol, B. W.J.

AU - Painter, R. C.

AU - van de Beek, C.

AU - Roseboom, T. J.

N1 - Funding This work was supported by a grant of the Dutch Heart Foundation (2013T085). The initial trial was supported by a grant from ZonMW, the Dutch Organization for Health Research and Development (120620027) and a grant from Zorgverzekeraars Nederland, the Dutch association of healthcare insurers (09-003). The funders had no role in the design, conduct and interpretation of the study. The authors declare no conflict of interest. Stijn Mintjens, Malou Menting, Reinoud Gemke, Mireille van Poppel, Madelon van Wely, Alexandra Bensdorp, Raïssa Tjon Kon Fat, Ben Willem Mol, Rebecca Painter, Cornelieke van de Beek and Tessa Roseboom declare no conflicts of interest relevant to this study. Outside the work submitted, Ben Willem Mol is supported by a NHMRC practitioner Fellowship and reports consultancy for ObsEva, Merck, Merck KGaA and Guerbet. Rebecca Painter reports board membership for the Dutch Gezondheidsraad and NVVH guideline committees, and travel expenses reimbursement for ESHRE meeting Barcelona 2018 (June). Acknowledgements We thank all the women and children who participated in this study. We are grateful to all who contributed to the follow-up study; with special thanks to our colleague PhD students, post-docs, research assistants and students. This follow-up study would not have been possible without the original INeS trial; therefore, we thank all participating hospitals for their contribution to this study, and the gynecologists, research nurses, research midwives and office members of the Dutch Consortium (www.studies-obsgyn.nl) for their hard work and dedication.

PY - 2019/11

Y1 - 2019/11

N2 - Objective: Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring? Study design: Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4–7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance. Results: We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0–7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences. Conclusions: Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have hampered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive.

AB - Objective: Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring? Study design: Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4–7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance. Results: We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0–7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences. Conclusions: Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have hampered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive.

KW - Assisted reproductive techniques

KW - Cardiometabolic health

KW - Follow-up

KW - Hormone stimulation

KW - In vitro fertilization

KW - Neurodevelopment

UR - http://www.scopus.com/inward/record.url?scp=85072779501&partnerID=8YFLogxK

U2 - 10.1016/j.ejogrb.2019.09.026

DO - 10.1016/j.ejogrb.2019.09.026

M3 - Article

C2 - 31586879

AN - SCOPUS:85072779501

SN - 0301-2115

VL - 242

SP - 131

EP - 138

JO - European Journal of Obstetrics and Gynecology and Reproductive Biology

JF - European Journal of Obstetrics and Gynecology and Reproductive Biology

ER -

The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health—Follow-up of a randomized clinical trial

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this