Experts urge caution over study linking IVF technique to increased risk of intellectual disability
A new study from the Telethon Kids Institute in Australia has revealed a possible association between intellectual disability and some specific forms of Assisted Reproductive Technology (ART). Experts are urging caution when interpreting these results, as it is unclear exactly what may be causing the increased rates of intellectual disability.
The study tracked over 200,000 live births between 1994 and 2002. A little over one percent of those births were conceived using an ART technique. Overall, the results showed only a small increase in intellectual disability relating to ART (1 in 48 for ART versus 1 in 59 for non-ART). However, a specific technique called intracytoplasmic sperm injection (ICSI), showed a more significant increase in risk for intellectual disability (1 in 32).
From a distance this is an undeniably concerning conclusion, but the research comes with a number of caveats suggesting prospective parents considering ART should not be significantly worried. Michele Hanson, lead author on the Telethon study, is first to assuage concerns regarding her findings, primarily suggesting, "it is important to note our findings relate to births from 1994 to 2002 and there have been major shifts in ART clinical practice in Australia since that time."
One of the big shifts in ART practice that Hanson is referring to is the move from more commonly performing multiple embryo transfers in the 1990s, to general recommendations for single embryo transfers today. Multiple embryo transfers are known to increase rates of multiple births, preterm births and lower birth weights – all major factors that raise a child's risk of developing an intellectual disability. Peter Illingworth, from IVF Australia, suggests that modern best-practice procedures for IVF today should certainly reduce these risk factors that the study has highlighted.
"One critical factor in this study is that almost all the transfers in the 1990s were multiple embryo transfers," says Illingworth. "It is now well-known that following multiple embryo transfer, even singleton pregnancies are at higher risk of complications."
Hansen affirms this shift in best practice for modern ART treatments by pointing out that, in Australia at least, around 88 percent of all treatment cycles as of 2016 consisted of a single embryo transfer, subsequently lowering rates of multiple and preterm births.
As the study revealed, the highest risk of intellectual disability came via treatments using an ICSI technique, and questions have rightly been raised asking whether the technique itself is causing this increased risk. Again, this is frustratingly unclear at this stage, although Gino Pecoraro from the University of Queensland suggests a variety of reasons could explain the increases in intellectual disability associated with the technique.
"It may be related to the technique of puncturing the egg to insert the sperm directly inside or it might be that the sperm itself is of a low quality which was why the technique was needed in the first place," explains Pecoraro. "Also older fathers are more likely to need ICSI to help have a family and age is also a factor associated with increased risk of sperm having genetic mutations."
Jane Halliday from the Murdoch Children's Research Institute has specifically studied outcomes for children conceived using ICSI techniques. Her expansive work has only found very limited evidence to suggest the method increases risk of neurodevelopment issues in children.
"We have recently published a review of outcomes for ICSI-conceived children compared with spontaneously conceived children and the section on neurodevelopment summarized 24 studies of mostly good quality showing these children are comparable in neurodevelopment," says Halliday. "Seven studies did report some clinically insignificant differences while others had methodological limitations. We also reviewed ICSI-conceived compared with IVF-conceived offspring and only five of 24 studies reported ICSI children faring worse in terms of neurodevelopment."
Perhaps the primary consideration to come out of this research is that individuals, and fertility specialists, should be fundamentally aware of the potential extra risks surrounding ICSI techniques. It's noted that ICSI use has increased over time, currently encompassing 63 percent of all ART cycles in Australia, and above 90 percent in some other parts of the world.
Further study is undoubtedly necessary to bring further clarity to this research, however it is important to remember that this is just one study that sits alongside several others that have found no significant differences between IVF-conceived children and naturally-conceived children. The general consensus at this point is that prospective parents examine all their ART options before undergoing fertility treatments.
"More research needs to be done but until the answer is clear, it is worthwhile for couples undergoing fertility treatment to be aware, ask their specialist what type of ART they will be receiving and whether ICSI is the only option or if an alternative available," suggests Gino Pecoraro.
The new research was published in the journal Pediatrics.