Dr Matthew Vermilyea: Studies of IVF tots turn focus to future

Most studies show that overall IVF children are healthy and have no higher risk of childhood cancers or other major illness. Photo / Getty Images

Assisted reproductive technology has advanced significantly since the first healthy IVF baby was born more than 35 years ago.

But debate continues about whether identified risks are attributable to assisted reproductive technology (Art) or to parental characteristics affecting embryo quality and fertility. Further, a few publications are reporting on the incidence of genetic abnormalities and congenital malformation in Art children as against naturally conceived children.

A few years ago, collaborative research from the Liggins Institute and Fertility Associates gained attention when it was found IVF children were a bit taller than expected and had more favourable lipid or cholesterol profiles. This was reassuring, considering the hypothesis that their lower birth weight might be associated with poorer health long term.

Since then, a variety of studies have been done, some showing minor inherited changes but none raising significant concerns.

Fertility Associates and the Liggins Institute have followed up two other groups of children born after assisted reproduction - children from frozen-thawed embryos and children born after their mothers used Clomiphene (an ovulation induction medication). Those conceived from frozen embryos were the closest to children conceived naturally in height and metabolic measurements such as blood lipids. Children conceived after Clomiphene were a little shorter. The differences in height and blood lipids are too small to be of practical concern but the differences may provide clues.

Rather than the culture of embryos in vitro giving rise to the apparent changes in the children's height, it is more likely due to the hormone levels present around conception, and the effect they have on the uterus. Children conceived where there was lots of oestrogen (fresh embryo transfer after IVF) were taller; children conceived with typical amounts of oestrogen were average (thawed embryo transfer); and children conceived after use of Clomiphene, a mild anti-oestrogen, were shorter. This reminds us that there is more to IVF than what happens in the lab.

Data from fertility centres worldwide will help identify the incidence and cause of potential health risks from babies born from IVF, but potential sources of bias must be taken into account. Data may be influenced by selection bias (proper controls), observational bias (missing or inconsistent data), surveillance bias (Art pregnancies monitored more than natural pregnancies) and other compounding factors which must be considered.

It is known environmental cues trigger responses that may alter the heritable traits of embryos. This may occur during the handling and culture of embryos in the laboratory. But the lab could still be important. Improvements to make Art even safer are being applied in labs, particularly, the reduction of potential effects caused by stresses to the embryos.

Fertility Associates has been looking into a "reduced stress" protocol which involves minimal disturbance to embryos grown in the laboratory.

In tandem with time-lapse technology, a true "hands-off" approach to embryo culture can occur.

The goal of any fertility clinic is to give children who are as healthy as possible.

NZ is already a world leader in reducing the biggest risk with IVF - multiple pregnancies.

The rate of twins from IVF has fallen from about 20-30 per cent a decade ago to about 5 per cent, among the lowest in the world.

There is now a lot of attention on the relative merit of freezing all embryos so that embryos are transferred in menstrual cycles with typical levels of oestrogen.

There is also a growing interest in using milder ovarian stimulation for IVF - hopefully with fewer but better eggs. Art has been a great blessing for people experiencing infertility, with more than 15,000 children born from Fertility Associates and more than 5 million children from IVF worldwide.

Most studies show that overall IVF children are healthy and have no higher risk of childhood cancers or other major illness. The focus is now more on any potential long-term effects.

It is likely studying Art children will help show how the circumstances of conception, and parents' health at that time, can affect long-term health, and how that information can be used to optimise lifestyle to help future generations.

• Dr Matthew (Tex) Vermilyea is Fertility Associates' scientific director.