At least 1 in 6 Australian couples experience infertility and now 4% of children are conceived by IVF – and this number is on the rise. Age is the largest cause of infertility and increasingly women are having children later in life, and turning to IVF. However, IVF is not a magic solution that works for all women. Only 17% of IVF cycles are successful and result in a live birth. Why is the success rate so low? This is a complicated question and the full answer is unknown. However, Dr Melanie McDowall, a Senior Post-Doc in the Early Development Research Group has focused her research on increasing IVF success and hopes to gain clinical acceptance for her new and uncomplicated approach.
Once an egg is successfully fertilised it begins dividing – first into two cells, then four, then eight and so on. Each cell is called a blastomere. When particular stressors are introduced, individual blastomeres may behave differently within a single embryo – the higher the stress, the more variability. For an embryo to successfully implant and continue to develop, uniformity is required between blastomeres.
When selecting ideal embryos for IVF, clinical embryologists use morphology – that is determining quality through appearance, and benchmarking embryos against expected milestones and dates. However, differences between blastomeres are not always seen using morphology, which partially explains why the best quality embryos can be hard to identify and 83% of IVF cycles do not result in a live birth.
Melanie’s embryo research is taking a new approach using the technique of autofluorescence, which takes advantage of a cells natural emission of fluorescent light under UV illumination. All cells naturally have a level of autofluroescence and can be put under a microscope, imaged and put back into the culture undisturbed. The resulting images highlight differences in blastomeres without using toxic dyes, and poor quality embryos are more easily recognisable.
“IVF is currently an expensive and time-consuming process which puts huge restraints financially, emotionally and economically on not only the parents, but society at large,” said Melanie.
“The exciting thing about autofluorescence is that it is non-invasive, takes five minutes, uses technology which currently exists in most labs, and embryos continue to grow with no negative effects on development.”
“This would limit the number of poor quality embryos used in IVF which will increase the number of successful pregnancies.”
Using autofluroescence, Melanie compared embryos exposed to two different concentration levels of oxygen. Once an egg is fertilised and enters the oviduct in the uterus the oxygen concentration decreases to 7%. She found that culturing embryos at 7% led to more successfully developed embryos than culturing at the atmospheric oxygen level of 20%.
“When we culture embryos we try to provide conditions similar to those seen in the body. Through autofluroescence techniques, we found significantly fewer differences between blastomeres in embryos cultured at 7% oxygen than we did in stressed embryos cultured at 20% oxygen,” said Melanie.
“You simply cannot pick up these differences using traditional morphology techniques.”
While Melanie’s work has significant implications for human reproduction, her research has utilised bovine embryos and the results have the potential to change the cattle industry.
“There is a world-wide sub fertility problem in dairy cattle with a 1% decrease in fertility in high performance animals every year, costing the industry $5 million dollars per year. This is due to high levels of genetic selection for milk production, causing stress to the animals,” said Melanie.
“We know that stressed embryos are more likely to fail, so if we can non-invasively test cattle embryos from high performance animals using autofluroescence, we can then create large numbers of these embryos and ship them around the world to transplant in sub-quality cows.”
The next step towards clinical acceptance in humans is for Melanie to undertake toxicity studies on a mouse model, to prove there are no negative effects of UV illumination.
“With short gestation periods of 21 days, and 3 weeks growth until mice are adults, I expect we will be able to quickly demonstrate the successful use of autofluoroescence as a non-invasive testing technique,” said Melanie.
“In the future I believe this technique also will have the ability to demonstrate incorrect number of chromosomes in an embryo – this currently cannot be tested without embryo biopsy.”
Despite the continual increases in IVF technology and the improvements her research will likely bring to the field, Melanie is an advocate for getting the message out there that women need to plan for children earlier in life.
“Women think IVF is a band aid and regardless of age, if you are healthy you will be able to have a child through IVF using your own eggs,” says Melanie.
“Unfortunately this isn’t the case as demonstrated in the low success rates of IVF, especially in older women, and all women should plan in their 20’s when they want to have children to ensure they don’t leave it too late.”
Unlike males who continue to produce sperm throughout life, women are born with all their eggs. Genetics is the main factor that determines when egg numbers and quality decreases, which contributes to infertility. As a rule, fertility starts to decrease at age 32 and substantially decreases at 35, and women in their forties have a 1-2% chance of having a live birth per cycle of IVF.
“During 2013, I worked with Your Fertility to develop a case study video discussing women, age and fertility, and I have written articles for The Conversation. If your eggs have aged (or have a low numbers of eggs in your ovaries) IVF is not going to help you have a child with your own DNA.”
Melanie will present her findings in the finals of the Meat and Livestock Australia New Scientist award at the Society for Reproductive Biology annual conference held in August in Melbourne and then the following week at the World Congress of Reproductive Biology in Edinburgh.
“I’m really excited to present my results and to receive feedback from researchers who I collaborate with in Australia and internationally. I believe this technique will have implications not just for embryo evaluation, but for researchers focusing on other areas of the human body.”
Melanie’s research is funded by the ARC Centre of Excellence for Nanoscale BioPhotonics.
Melanie’s articles & case study video