Effect of IVF culture medium on health of IVF children

From animal studies it is known that embryo culture leads to growth, behavioral
and cardio-metabolic alterations in the offspring. Embryo culture effects on
human offspring have long been uninvestigated, until a few years ago when we
found that the medium used to culture embryos in an IVF treatment has a
significant effect on the incidence of low birth weight (LBW) and on birth
weight. As this was the first randomized trial on embryo culture effects in
human, nothing is known abouth health effects at later stages of development.
Since a lower birth weight is related to an increased risk for (adult) chronic
diseases belonging to metabolic syndrome (Barker theory), our findings raises
concern for the IVF progeny. In advance of diseases at adult age, we
hypothesize that IVF culture medium affects parameters of metabolic syndrome at
childhood stage.

The primary objective is to elucidate whether there is a difference in the
outcome of health parameters between IVF children who as an embryo were
cultured in two different culture media. As secondary objectives we will
investigate how the health parameters of the IVF children (singletons) from the
primary objective compare with those of non-IVF children and we will map
differences in DNA methylation profile between the children of the two culture
media groups and between IVF and spontaneously conceived children.

In this observational study, all children born in our culture medium trial and
spontaneously conceived control children will be called up for physiological
(blood pressure, endothelial function (via iontophoresis and glycocalyx),
stress response), metabolic (lipid profile, glucose), cognitive (Cito scores)
and anthropometric (length, weight, skin fold thickness) examinations.

Consenting children from the IVF group and the IVF-siblings group (Control3),
together with one or both parents, are asked to come to the MUMC (or a hospital
closer to their home) once, for the following examinations: height, weight,
skinfold thickness, blood pressure, endothelial function, lipid, glucose and
insulin level in blood (3 sample of 5ml), cortisol level in hair and saliva
collection (2ml) for DNA methylation analysis. The investigations will be
performed by a researcher/physician under supervision of a qualified
pediatrician. The investigations include regular medical examinations, which
belong to *the risk of everyday life* that is seen as a negligible risk. The
burden is reduced to a minimum by using anesthetic cream before the vena
puncture (1 venapuncture of 15ml), and paying attention to resistance of the
child. It is not possible to test our hypothesis in another (adult) study
population since adult IVF progeny is scarce and since these IVF children are
the first (worldwide) to be born after a randomized usage of two different
culture media.
The parent(s) is/are asked to fill in a questionnaire regarding medical issues,
lifestyle and demographic variables.
The anthropometric and physiological examinations in the children from Control
1 will be done at school. For control blood values we will use the surplus
blood of children who had their blood samples taken for disorders that do not
affect lipid profile like fractures or allergy Control 2.