Increased risk of metabolic dysfunction in children conceived by assisted reproductive technology



Assisted reproductive technology (ART) is the most widely used treatment for infertility and has resulted in millions of births worldwide. The safety of the offspring has been of the utmost concern. Previous studies suggested an increase in metabolic disorders in offspring later in life. The aim of the present study was to investigate metabolic changes at age 6–10 years in offspring conceived as a result of in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI).


A total of 380 children born from IVF/ICSI and a matched control group of 380 naturally conceived children, all aged 6–10 years, were recruited. Anthropometric measures, ultrasound and serum tests were performed for body mass, glucose metabolism and lipid profiles, and examination of vasculature structure.


The children conceived by ART showed significantly higher fasting blood glucose and serum insulin levels and HOMA-IR (adjusted β [95% CI]: fasting blood glucose 0.49 [0.42, 0.55]; loge-transformed insulin 0.28 [0.20, 0.35]; loge-transformed HOMA-IR 0.38 [0.30, 0.46]), as well as a lower HOMA-B and serum apolipoprotein A (ApoA) levels (adjusted β [95% CI]: loge-transformed HOMA-B −0.19 [−0.27, −0.11]; ApoA −0.17 [−0.21, −0.13]), when compared with the control group. Furthermore, the ultrasound scan indicated elevated carotid intima–media thickness in children conceived by ART (β 0.13 [95% CI 0.12, 0.13]).


Children conceived by IVF/ICSI have a less favourable glucose and cardiovascular metabolic profile in childhood when compared with naturally conceived children. The underlying mechanisms and potential long-term consequences need to be elucidated in future studies.

Graphical abstract

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Fig. 1

Data availability

The data are available from the corresponding author on reasonable request.



Apolipoprotein A


Carotid intima–media thickness


Fasting blood glucose


Intracytoplasmic sperm injection


In vitro fertilisation


Polycystic ovary syndrome


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Authors’ relationships and activities

The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

Contribution statement

LC, BX and Z-JC were involved in the design of the study. WZ conducted the data analysis. All authors were involved in the recruitment of participants and blood sample collection. LC and WZ completed the first draft of the manuscript. All authors were involved in critical revision of the manuscript. All authors read and approved the final manuscript. LC, WZ and Z-J C guarantee this work and take responsibility for the integrity of the data.


This study was supported by The National Key Research and Development Program of China (2017YFC1001000, 2018YFC1004301, 2016YFC10000202) and Shandong Provincial Key Research and Development Program (2018YFJH0504, 2017G006036). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Correspondence to Zi-Jiang Chen.

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Linlin Cui and Wei Zhou are joint first authors.

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Cui, L., Zhou, W., Xi, B. et al. Increased risk of metabolic dysfunction in children conceived by assisted reproductive technology. Diabetologia 63, 2150–2157 (2020).

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  • Assisted reproductive technology
  • Children
  • Metabolic dysfunction