Infertility remains a devastating disease for many couples, despite the success of IVF, as treatment is often unsuccessful, or remains out-of-reach for both health and/or financial reasons. My fellowship aims to improve our understanding of some of the causes of infertility in women. This will translate to a new infertility treatment that is safer for their health and provides for improved long-term health outcomes for their children.
Identification Of Factors Essential For Oocyte Viability
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
Approximately 2% Australia children are now conceived using in vitro fertilisation technologies, allowing infertile couples to bear their own children. However, a major consequence of IVF techniques is multiple pregnancies (i.e. twins and triplets) which is a major health risk to mothers and their infants. Furthemore, IVF increases birth defects, which are mostly attributed to the increased multiple pregnancies, but is also observed in pregnancies involving a single infant. It is essential that ....Approximately 2% Australia children are now conceived using in vitro fertilisation technologies, allowing infertile couples to bear their own children. However, a major consequence of IVF techniques is multiple pregnancies (i.e. twins and triplets) which is a major health risk to mothers and their infants. Furthemore, IVF increases birth defects, which are mostly attributed to the increased multiple pregnancies, but is also observed in pregnancies involving a single infant. It is essential that IVF techniques are developed that enables the transfer of a single embryo to the mother resulting in the birth of a single healthy baby, without the ethical concerns of surplus embryo disposal. Women receiving IVF are required to adminster hormones that stimulate the eggs in their ovaries to mature to the point where they can be fertilised by their partner's sperm. These hormones, called gonadotrophins, override the body's own ovarian stimulating system and cause many eggs to mature and be collected for fertilisation, instead of normally just one. In this way, the best embryo(s) can be selected for transfer back to the mother, and other embryos can be frozen and stored for later use. However, large doses of gonadotrophins has consequences. They can be dangerous to some patients who are sensitive to their potency, and stimulate a massive response. They also reduce the quality of eggs and subsequent embryos, which reduces the chances of a pregnancy. All this can be avoided if eggs can be collected from ovaries in an immature state and maturation achieved in the laboratory. However, although attempted, this has not been a successful technique, primarily because we don't understand the process of human egg maturation. Our research will investigate the biochemistry, physiology and genetics of non-human eggs and embryos resulting from eggs that are grown and matured in the laboratory, to develop techniques for the successful maturation of human eggs in the laboratory.Read moreRead less
Development Of Engineered Novel Growth Factors For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$410,439.00
Summary
Infertility comes at an enormous social and financial cost to Australian society. The aim of this proposal is to improve the success rate of an innovative technology that matures eggs in the laboratory and so eliminates the need for the hormones normally used in IVF. To achieve this a newly discovered egg-secreted protein first has to be produced in the laboratory.
Physical Determinants Of Lung Development Before And After Birth
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Survival at birth is critically dependent upon the ability of the lungs to take on the role of exchanging gases; a role previously performed by the placenta. The lungs must, therefore, have grown and matured sufficiently during fetal life, before they are required at the time of birth. Inadequate development of the lungs during fetal life is the most common cause of death and disease in newborn babies. This may be due to premature birth, when the lungs have had insufficient time to develop, or i ....Survival at birth is critically dependent upon the ability of the lungs to take on the role of exchanging gases; a role previously performed by the placenta. The lungs must, therefore, have grown and matured sufficiently during fetal life, before they are required at the time of birth. Inadequate development of the lungs during fetal life is the most common cause of death and disease in newborn babies. This may be due to premature birth, when the lungs have had insufficient time to develop, or it may be due to inappropriate lung development during fetal life. It is important therefore, to understand the mechanisms that control growth and development of the lung both before and after birth. During fetal life the lungs are filled with liquid which expands the lungs and provides a stretch stimulus causing them to grow. Previously we have shown that a reduction in the degree of fetal lung expansion causes lung growth to cease. Likewise, if we increase the degree of lung expansion in the fetus, we induce a rapid increase in fetal lung growth and maturation. This stimulus is so potent that it can reverse an existing lung growth deficit, thus enabling survival of the newborn. In this application we will investigate the mechanisms by which alterations in lung expansion induce growth and maturation of the lung. Specifically we will investigate the role of calmodulin in fetal lung growth, because the genes that encode it are activated when the lung cells are growing most rapidly. In addition, we will identify other genes that are turned on or off during rapid growth of the lung because those genes are likely to play important roles in the regulation of fetal lung growth and development. We will also investigate the underlying differences in the control of lung growth at different stages of gestation, as well as investigate factors that regulate lung growth after birth, particularly in prematurely born animals.Read moreRead less
A small number of babies die unexpectedly while still in the womb: the numbers are much higher than those dying from Sudden Infant Death Syndrome (SIDS). Some of these babies slow their movements down in the days before death. It would be very helpful to be able to accurately monitor babies' movements in the womb so that we could help the few babies who need it, and so prevent poor outcomes. Mothers feel their babies moving, but it's often hard for them to pick up all the movements that do occur ....A small number of babies die unexpectedly while still in the womb: the numbers are much higher than those dying from Sudden Infant Death Syndrome (SIDS). Some of these babies slow their movements down in the days before death. It would be very helpful to be able to accurately monitor babies' movements in the womb so that we could help the few babies who need it, and so prevent poor outcomes. Mothers feel their babies moving, but it's often hard for them to pick up all the movements that do occur. The best way of measuring babies' movements is during an ultrasound. However, that's expensive and means that the pregnant mother needs to lie still for about half an hour to have this testing done. We are developing a way of recording babies' movements, which still lets the pregnant woman continue with her normal activities. We will do this using an AMBULATORY FETAL ACTIVITY MONITOR, which is an accelerometer, like an advanced pedometer. The ambulatory fetal activity monitor will measure the activity of the unborn baby during pregnancy, looking at the number of times s-he moves and how simple or complex the movements are. We expect that the unborn baby who is not getting enough nutrition during the pregnancy will have fewer movements than other unborn babies. This project involves checking that movements picked up by the ambulatory fetal activity monitor are the same as movements seen on an ultrasound. We will then monitor a large number of pregnant women with healthy and possibly unhealthy babies, to help identify the babies who need help. Once we have this information, we will be able to use it in the future to possibly prevent poor outcomes in those babies who do need help.Read moreRead less
Characterisation Of Cumulus Cell Molecular Mediators Of Oocyte Health
Funder
National Health and Medical Research Council
Funding Amount
$451,896.00
Summary
Many women are poorly fertile because of poor egg quality due to age, disease and lifestyle. IVF can assist, but requires large doses of hormone, which can lead to significant health risks. IVM is an alternative lab technique to IVF, but has very poor success. We discovered that synthetic proteins copied from recently discovered egg proteins can be added to the egg and substantially increase IVM success. Answering why will further will aid treatment for infertile women
Re-energising The Preimplantation Embryo To Extend Lifetime Health
Funder
National Health and Medical Research Council
Funding Amount
$1,156,936.00
Summary
Diseases of aging are associated with shortening at the ends of chromosomes called telomeres. The length of an individual’s telomeres is established during embryo development, and in situations where embryo development is compromised such as with maternal obesity the normal process of telomere lengthening may not occur. We will determine how such disruptions in embryo telomere lengthening contribute to poor health in adulthood and test ways to restore the natural process.