Subfertility and assisted reproduction techniques are associated with poorer cardiometabolic profiles in childhood

Pontesilli, Martina; Painter, Rebecca C.; Grooten, Iris J.; Post, Joris A. M. van der; Mol, Ben Willem J.; Vrijkotte, Tanja G. M.; Repping, Sjoerd; Roseboom, Tessa J.

doi:10.1016/j.rbmo.2014.11.006

Cited by 74 publications

(54 citation statements)

References 23 publications

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“…Children conceived through artificial reproduction techniques have higher glucose levels compared to controls (64). At the age of 5–6 years, glucose levels were increased by 0.4 mmol/l (95% CI 0.2–0.6) and 0.2 mmol/l (95% CI 0.0–0.5), respectively.…”

Section: Resultsmentioning

confidence: 99%

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Pregnancy: An Underutilized Window of Opportunity to Improve Long-term Maternal and Infant Health—An Appeal for Continuous Family Care and Interdisciplinary Communication

2017

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Physiologic adaptations during pregnancy unmask a woman’s predisposition to diseases. Complications are increasingly predicted by first-trimester algorithms, amplify a pre-existing maternal phenotype and accelerate risks for chronic diseases in the offspring up to adulthood (Barker hypothesis). Recent evidence suggests that vice versa, pregnancy diseases also indicate maternal and even grandparent’s risks for chronic diseases (reverse Barker hypothesis). Pub-Med and Embase were reviewed for Mesh terms “fetal programming” and “pregnancy complications combined with maternal disease” until January 2017. Studies linking pregnancy complications to future cardiovascular, metabolic, and thrombotic risks for mother and offspring were reviewed. Women with a history of miscarriage, fetal growth restriction, preeclampsia, preterm delivery, obesity, excessive gestational weight gain, gestational diabetes, subfertility, and thrombophilia more frequently demonstrate with echocardiographic abnormalities, higher fasting insulin, deviating lipids or clotting factors and show defective endothelial function. Thrombophilia hints to thrombotic risks in later life. Pregnancy abnormalities correlate with future cardiovascular and metabolic complications and earlier mortality. Conversely, women with a normal pregnancy have lower rates of subsequent diseases than the general female population creating the term: “Pregnancy as a window for future health.” Although the placenta works as a gatekeeper, many pregnancy complications may lead to sickness and earlier death in later life when the child becomes an adult. The epigenetic mechanisms and the mismatch between pre- and postnatal life have created the term “fetal origin of adult disease.” Up to now, the impact of cardiovascular, metabolic, or thrombotic risk profiles has been investigated separately for mother and child. In this manuscript, we strive to illustrate the consequences for both, fetus and mother within a cohesive perspective and thus try to demonstrate the complex interrelationship of genetics and epigenetics for long-term health of societies and future generations. Maternal–fetal medicine specialists should have a key role in the prevention of non-communicable diseases by implementing a framework for patient consultation and interdisciplinary networks. Health-care providers and policy makers should increasingly invest in a stratified primary prevention and follow-up to reduce the increasing number of manifest cardiovascular and metabolic diseases and to prevent waste of health-care resources.

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Section: Resultsmentioning

confidence: 99%

“…Similarly, systolic and diastolic BP was elevated by 0.8 mmHg (95% CI −0.2 to 1.8) and 1.4 mmHg (95% CI 0.6–2.3). Since the duration of infertility correlates with BP in the offspring and with PE in the pregnant women, epigenetic and genetic factors have been implied (64). …”

Section: Resultsmentioning

confidence: 99%

Pregnancy: An Underutilized Window of Opportunity to Improve Long-term Maternal and Infant Health—An Appeal for Continuous Family Care and Interdisciplinary Communication

2017

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“…12–14,67 However, independent of birthweight, there is evidence that at least some IVF-conceived children may be at increased risk for cardiometabolic disorders including insulin resistance, higher blood pressure, and higher body fat percentage compared to children conceived without medical assistance. 68 Most children conceived through IVF are still in their first three decades of life and, thus, limited data exists regarding long-term morbidity and mortality. Surrogate measures of cardiometabolic health, including body mass index (BMI), body fat, blood pressure, serum lipids, inflammatory factors, and glucose tolerance, have been used to predict the risks in IVF-conceived children and young adults.…”

Section: Long-term Cardiometabolic Outcomes In Ivf/icsi-conceived Chimentioning

confidence: 99%

In Vitro fertilization and adverse obstetric and perinatal outcomes

Sullivan-Pyke

Senapati

Mainigi

et al. 2017

Seminars in Perinatology

105

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Most IVF-conceived children are healthy, but IVF has also been associated with adverse obstetric and perinatal outcomes as well as congenital anomalies. There is also literature suggesting an association between IVF and neurodevelopmental disorders as well as potentially long-term metabolic outcomes. The main driver for adverse outcomes is the higher risk of multiple gestations in IVF, but as the field moves toward single embryo transfer, the rate of multiple gestations is decreasing. Studies have shown that singleton IVF pregnancies still have a higher incidence of adverse outcomes compared to unassisted singleton pregnancies. Infertility itself may be an independent risk factor. Animal models suggest that epigenetic changes in genes involved in growth and development are altered in IVF during the hormonal stimulation and embryo culture. Further animal research and prospective human data is needed to elucidate the mechanisms by which IVF may contribute to adverse outcomes and to decrease risks.

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“…Blood pressure was assessed in five to six year-old children, conceived by IVF/ICSI, ovulation induction, artificial insemination, or conceived after more than 12 months (subfertile) or conceived naturally within 12 months (fertile). Children in the ovulation induction or subfertile group had significantly higher systemic blood pressure than children from the fertile group, while IVF/ICSI and artificial insemination groups were not different from the fertile group [37]. Subgroups were small in this study-- 28, 51, 34, and 220 children in the IVF/ICSI, ovulation induction, artificial insemination, or subfertile group, respectively, by comparison to over 2,000 children assessed for blood pressure in the fertile group.…”

Section: Evidence That Art Can Increase the Risk Of Cardiometabolimentioning

confidence: 99%

“…Young children conceived through IVF/ICSI or by ovulation induction had significantly higher fasting glucose levels by comparison with fertile controls [37]. Similarly, pubertal children conceived through IVF also had higher fasting glucose levels than their control counterparts.…”

Section: Evidence That Art Can Increase the Risk Of Cardiometabolimentioning

confidence: 99%

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

Vrooman

Bartolomei

2017

Reproductive Toxicology

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Millions of children have been born worldwide though assisted reproductive technologies (ART). Consistent with the Developmental Origins of Health and Disease hypothesis, there is concern that ART can induce adverse effects, especially because procedures coincide with epigenetic reprogramming events. Although the majority of studies investigating the effects of ART have focused on perinatal outcomes, more recent studies demonstrate that ART-conceived children may be at increased risk for postnatal effects. Here, we present the current epidemiological evidence that ART-conceived children have detectable differences in blood pressure, body composition, and glucose homeostasis. Similar effects are observed in the ART mouse model, which have no underlying infertility, suggesting that cardiometabolic effects are likely caused by ART procedures and not due to reasons related to infertility. We propose that the mouse system can, consequently, be used to adequately study, modify, and improve outcomes for ART children.

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Subfertility and assisted reproduction techniques are associated with poorer cardiometabolic profiles in childhood

Cited by 74 publications

References 23 publications

Pregnancy: An Underutilized Window of Opportunity to Improve Long-term Maternal and Infant Health—An Appeal for Continuous Family Care and Interdisciplinary Communication

Pregnancy: An Underutilized Window of Opportunity to Improve Long-term Maternal and Infant Health—An Appeal for Continuous Family Care and Interdisciplinary Communication

In Vitro fertilization and adverse obstetric and perinatal outcomes

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

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