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First Published: September 24: 2015
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New Research Sheds Light on the Effects of In-Vitro Fertilisation on Embryonic Growth

|| June 24: 2018: University of Helsinki News: Päivi Lehtinen Writing || ά. In vitro fertilisation affects the regulatory region of genes, essential for placental and embryonic growth, as well as, the birth weight. This new study suggests that the effects depend on genetic variation inherited from the parents. This information could be useful in development of assisted reproduction technologies. It is known that in vitro fertilisation:IVF, can affect the size of the new-borns. Children derived from fresh embryo transfer have smaller birth weight and, surprisingly, children derived from frozen embryo transfer have, subtly, higher birth weight in average.

In the study conducted by University of Helsinki, Helsinki University Hospital and University of Tartu, the researchers looked for mechanisms by how the IVF can alter the embryonic growth. More than three percent of new-borns are derived from IVF treatments currently in Finland. 86 couples with IVF derived pregnancies and 157 couples with spontaneous pregnancies as controls were recruited for this study. IVF samples were divided in two groups depending on whether the embryos were transferred in utero fresh after fertilisation or after they were frozen and thawed before the transfer.

The regulation region of two growth genes, insulin-like growth factor two and H19, was examined. A common genetic variation in this region has been associated with different amount of epigenetic marks depending on which variants an individual has inherited from the parents.

DNA methylation, the most well-known epigenetic mark, was investigated in this study. These methyl groups bind to the DNA strand and affect the gene function.

“We divided the placentas in genotypes according to the variants, which the new-borns had inherited and we observed that the effect of IVF on the epigenetic marks depends on the genotype.” Says Adjunct Professor Nina Kaminen-Ahola, the Leader of the research team at the University of Helsinki.

Furthermore, the birth weight and placental weight, as well as, the head circumference of new-borns, which were derived from fresh embryo transfer, were smaller only in one particular genotype. Also, the new-borns with this genotype, who were derived from frozen embryo transfer, were significantly heavier.

“This work together with our previous work about the effects of prenatal alcohol exposure on embryonic development, reveals a genotype-specific effects of environmental factors.” Says Professor Kaminen-Ahola. “As far as I know, this is the first genetic factor, which has been associated with the phenotype of IVF-derived new-borns.

This single nucleotide polymorphism locates in the binding site of a regulatory protein and, thus, could affect the binding of the protein, as well as, gene function in altered environmental conditions. However, the effect of this variation on the regulation of these growth genes should be examined by functional studies.”

Professor Kaminen-Ahola emphasizes that these changes are not dangerous and IVF treatments are safe. “Low birth weight has been associated with increased risk for heart and vascular diseases and, therefore, it is necessary to understand the mechanisms underlying it to develop the IVF methods.

In the future, this could be a part of personalised medicine and help to target the sources of health care system more specifically.”
Research Group of Environmental Epigenetics: Children born with the help of fertility treatments are, generally, healthy. Comparisons with children conceived spontaneously without treatments indicate that they have a slightly higher risk of premature birth and low birth weight.

Several studies have connected fertility treatment methods to changes in the epigenome that regulates gene function in the placenta or cord blood. However, the results have been conflicting, and no extensive follow-up studies have been conducted.

In order to investigate the potential effects of fertility treatments, Dr Nina Kaminen-Ahola has launched an extensive study based on samples gathered at birth and follow-up data.

“The purpose of our study is to find whether fertility treatment methods alter the epigenome and whether such changes can affect the health and development of the individual.” Professor Kaminen-Ahola says. “In addition, we study whether there are differences between various fertility treatment methods and how these methods could be developed further.”

For more information, contact: Dr. Nina Kaminen-Ahola, PhD, University of Helsinki: Tel. +358 50 4482768: email: nina.kaminen at helsinki.fi
The Paper: rs10732516 polymorphism at the IGF2/H19 locus associates with genotype-specific effects on placental DNA methylation and birth weight of newborns conceived by assisted reproductive technology: Heidi Marjonen, Pauliina Auvinen, Hanna Kahila, Olga Tšuiko, Sulev Kõks, Airi Tiirats, Triin Viltrop, Timo Tuuri, Viveca Söderström-Anttila, Anne-Maria Suikkari, Andres Salumets, Aila Tiitinen and Nina Kaminen-Ahola: Clinical Epigenetics:::ω.

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