In-vitro fertilisation (IVF) has helped infertile couples start families for more than 35 years. But while the technology has evolved, it remains an expensive, invasive process that can have significant side-effects.
Our team of Australian and Belgian medical scientists have developed an infertility treatment that could result in a simpler, cheaper infertility treatment using fewer drugs. Our findings will be presented today at the Annual Scientific Meeting of the Society for Reproductive Biology.
It’s early days – and the treatment won’t be offered any time soon – but it represents an important advance in fertility research.
The IVF process
IVF requires women to take fertility drugs such as follicle stimulating hormone (FSH), to stimulate the growth of eggs (oocytes) before they are removed from the ovary. Women must give themselves daily injections two to four weeks before egg collection.
Women need to be closely monitored during this period with repeated blood tests and ultrasounds to ensure that their ovaries are responding as expected.
Taking IVF fertility drugs can cause significant discomfort, including pain from repeated injections, bloating, mood swings, nausea, vomiting and breast tenderness. In rare cases, the ovaries can over-respond, leading to emergency hospitalisation.
The fertility drugs are also expensive for patients and/or health care providers, including Medicare.
Early forms of in-vitro maturation
In-vitro maturation (IVM) of oocytes is a related infertility technique but importantly, it uses minimal or no hormone stimulation. Using IVM, eggs are retrieved while they are still at the immature stage, without the need for prolonged medication use.
IVM brings the eggs to maturity in cell culture in the laboratory. They are then fertilised and grown in the lab as in IVF.
Currently, IVM patients typically receive three days of hormones. But even this may not be needed. In advanced farm animal breeding, where IVM has been successfully applied for decades, animals receive no drugs.
As women receive less drugs for IVM, they also need less monitoring, meaning fewer blood tests and ultrasounds.
However, the significant downside of IVM compared to IVF has been lower pregnancy rates, so patients and doctors have preferred IVF.
Since the introduction of IVF in the 1970s, scientists have made major strides in our understanding of how an egg cell can support the earliest stages of life. We knew the ovary and egg benefited from the FSH given to women undergoing IVF. So researchers set out to treat the egg in the lab instead of treating the women.
The aim of this approach was to restore, as far as possible in the lab, the natural processes that occur during egg maturation in the ovary. Around ten years ago, we assembled a multi-disciplinary, multi-national team to tackle this challenge.
Egg cells send minute growth factor signals to their neighbouring nurse cells, instructing these cells how to nurture the egg in the ovary. We discovered that adding these growth factors to eggs during IVM improves egg quality leading to more and better quality embryos.
A protein biochemist in our team in Adelaide, David Mottershead, discovered and then made a key egg cell growth factor called cumulin.
In initial experiments treating pig eggs in the lab, we enhanced the IVM process by adding a combination of cumulin and a small signalling molecule called cAMP.
We showed an improvement in egg quality and a doubling in embryo yield (the proportion of eggs that survive to the embryo stage) compared to the existing IVM method.
Testing these ideas on human eggs is inherently difficult, as eggs from young women are scarce and valuable. To do this we turned to the institute that pioneered many of the major advances in IVF: Vrije Universiteit Brussel’s (VUB) university hospital, UZ Brussel, in Belgium.
In a pre-clinical trial, Belgian researchers Johan Smitz and Michel De Vos found that adding cumulin and cAMP to IVM led to an improvement in human egg quality and a 50% increase in embryo yield.
We don’t yet know how this will compare to IVF success rates. The chance of having a baby per egg collection is 55% with IVF compared with 41% from standard IVM. By improving the IVM process, we might expect advanced IVM to approach the effectiveness of IVF, but importantly, with the use of minimal drugs.
Reducing the need for drugs, blood tests and ultrasounds during fertility treatment will result in cost-savings, especially to Medicare, which currently foots most of the bill for these.
Our advanced IVM results are an early “proof of principal” in humans. But much work is still to be done before this advanced form of IVM is available.
Safety studies are needed to ensure that altering the conditions of egg maturation does not affect the long-term health of offspring.
Such innovations also need to pass regulatory approval from agencies such as the US Food and Drug Administration and the Therapeutic Goods Administration (TGA) in Australia, before they can proceed to full clinical trials. This can be a lengthy process.
This innovation, and other recent advances in IVM, bring hope that maybe one day we may be able to treat infertility without the need for a woman to inject herself with high doses of hormones for several weeks. This would make treating infertility simpler, cheaper, less invasive and with less medical risk.
IVM is also an important technology for fertility preservation for cancer patients. Young women or girls facing cancer treatment and who wish to preserve their fertility but often don’t have time to freeze their eggs, will also benefit from IVM innovations.
Robert B. Gilchrist is an inventor on a patent family owned by the University of Adelaide related to this technology. A/Prof Gilchrist’s research program has received funding from the National Health and Medical Research Council of Australia, the Australian Research Council and from Cook Medical. Gilchrist has previously acted as a consultant to Cook Medical.
Jeremy Thompson is an inventor on a patent family owned by the University of Adelaide related to this technology. A/Prof Thompson’s research program has received funding from the National Health and Medical Research Council of Australia, the Australian Research Council and from Cook Medical. Thompson is a consultant to Cook Medical.
William L. Ledger Prof Ledger’s research program has received funding from the National Health and Medical Research Council of Australia, Ferring Pharmaceuticals, MSD and Swiss Precision Diagnostics. Ledger is a minority shareholder in Virtus Health and a fertility specialist with IVF-Australia.
Authors: Robert Gilchrist, Associate Professor in Reproductive Biology; Head, Oocyte Biology Research Unit, UNSW Australia