By Jordana Bell, Senior Lecturer, King’s College London; Jeffrey Craig, Principal Research Fellow, Murdoch Childrens Research Institute, and Juan Castillo-Fernandez, PhD candidate, King’s College London
The rate of IVF births has risen dramatically in recent years as fertility rates continue to fall worldwide. To date, over 5m babies have been born with the help of these technologies.
However, there have been concerns about potential health problems in children conceived by IVF. Our latest study shows that those fears are largely unfounded.
Since the first IVF baby was born in 1978, scientists have raised concerns about potential birth defects and health problems in children conceived by IVF.
Most of the children appear healthy, but a small increase in health problems, such as low birth weight, premature birth and birth defects, has been reported.
Since IVF has only been available for about 40 years, the long-term health effects of this technology have not yet been fully explored.
There is growing evidence that certain risk factors, such as poor maternal nutrition, at the time of conception and pregnancy can influence a person’s health in later life. Recent studies have shown that some of these long-term health effects may be encoded by epigenetics.
Epigenetics are the biological mechanisms that regulate genes. Epigenetic switches control whether genes are activated or silenced. Events that occur in early development, including the time between conception and birth, can influence health in later life and epigenetics plays an important role in this process.
Previous research has studied the link between epigenetics and IVF, but the results have been inconsistent. One reason for this is that fertility treatment is often associated with common risk factors, aside from the IVF technology itself, such as being older mums or having twins or triplets, which are more likely to be delivered prematurely and have a lower birth weight.
The twin approach
In our study, we examined epigenetic changes in IVF and naturally conceived newborn twins. We only considered babies born from twin pregnancies to avoid finding epigenetic differences attributed to single and multiple births.
Most of the previous epigenetic studies in IVF focused on selected regions of the genome that regulate genes known to cause developmental disorders due to epigenetic alterations, but we investigated the entire genome to ask if there were differences in genes that had not been previously implicated in epigenetic disorders.
We found no major epigenetic differences in IVF-conceived twins, but we did find epigenetic changes with small impacts. Two genes related to male and female infertility showed small but significant differences in IVF-conceived twins, which suggests that the newborn twin epigenetic profile may contain markers of parental infertility, to a small extent. But it is unclear if the small changes that we saw were a result of infertility or the IVF treatment itself.
Twins provide a natural unique study design that allows us to separate the importance of genes and environment on human traits. Environment exposures can be shared by both twins in a pair, for example in the womb, or exposures can also be specific to each twin. Using this twin-based approach we found that environmental factors specific to each twin were most likely to influence the top IVF-associated epigenetic changes. One explanation for these results could be that the IVF procedure introduces slight variability in epigenetic marks.
Epigenetic differences have been identified in common chronic diseases such as cancer, psychiatric disorders and diabetes. We found no such major epigenetic differences in babies conceived by IVF, although future studies are needed to see if the small epigenetic changes we observed remain over time. Our results are reassuring for parents who used IVF and children conceived by IVF as our research suggests that IVF technology has little impact on epigenetic changes, and potentially future health.