GM-CSF Regulation Of Preimplantation Embryo Development
Funder
National Health and Medical Research Council
Funding Amount
$481,320.00
Summary
Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be ov ....Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be overcome simply by the transfer of a single embryo. However, patient and clinical expectations are that single embryo transfer should be achieved with little to no reduction in pregnancy rate, and currently this is not possible because our methods for culturing embryos are inadequate. Studies in animals suggest that laboratory growth of mammalian embryos can lead to small-for-gestational age babies (even when the effect of multiple births is taken into consideration). This backed by recent studies which agree that babies born from IVF are smaller than expected. This might lead to health problems in later life, as smallness at birth is associated with higher risks of cardiovascular disease and diabetes, especially as age progresses beyond 40 years. However, the oldest IVF child is currently 23 years of age. Previously we have shown that a protein growth factor, called granulocyte-macrophage colony-stimulating factor (GM-CSF), found normally in the reproductive tract, has dramatic beneficial effects on human and mouse embryos grown in the laboratory. Furthermore, we have shown in mice that embryo exposure to GM-CSF alleviates the detrimental side effects of in vitro culture on foetal growth and body structure after birth. Our research is now focussed on understanding why this protein is beneficial to embryo growth and to test if we can increase pregnancy rates and produce normal healthy infants from the transfer of single embryos treated with GM-CSF.Read moreRead less
Compound Culture Media To Improve Human IVF Pregnancies
Funder
National Health and Medical Research Council
Funding Amount
$254,340.00
Summary
In Australia 1 in 6 couples require IVF to conceive. Although pregnancy rates have improved over the last 10 years the live birth rate in Australia per cycle is only 17%. This project will assess a new method for the culture of embryos for the ability to maintain embryo vitality and produce healthy babies.
Reappraisal Of The Mechanisms Underlying Implantation Success Or Failure
Funder
National Health and Medical Research Council
Funding Amount
$750,755.00
Summary
Infertility affects 1:6 Australian couples; these seek help. However, for each IVF cycle, there is only ~18.5% chance of a live birth, significantly due to failure of embryo implantation. We discovered nano-vesicles in the uterine cavity, that are released from the womb lining and taken up by the pre-implantation embryo to improve its implantation potential. We will determine how this extracellular environment can enhance implantation success and circumvent/management of infertility.
Role Of Tumour Suppressor Genes In Early Embryopathy
Funder
National Health and Medical Research Council
Funding Amount
$408,000.00
Summary
Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. Much of this is due to the high mortality of the resulting embryos. Typically, 45-80% of embryos produced by ART do not survive the first week. The high mortality of the early embryo seems to be a general feature of ART but its causes and effectors are incompletely defined. It has been established that this high mortality is largely due to a marked retardation in ....Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. Much of this is due to the high mortality of the resulting embryos. Typically, 45-80% of embryos produced by ART do not survive the first week. The high mortality of the early embryo seems to be a general feature of ART but its causes and effectors are incompletely defined. It has been established that this high mortality is largely due to a marked retardation in the rate of cell cycle progression by embryo cells, and commonly is associated with a form of cell 'suicide', known as apoptosis. In non-embryonic cells a group of genes known as the tumour suppressor genes (TSGs) are responsible for slowing cell-cycle progression and are commonly involved in inducing apoptosis following cell stress. The role of TSGs in the early embryo is not well studied. We have recently shown that the most important of the TSGs, P53, is normally kept at very low levels in the early embryo but that ART causes up-regulation of its expression. This upregulation is a major cause of the embryopathy associated with ART in an animal model but that genetic mutations that prevent P53 expression favours increased embryo development and viability. This project will examine whether ART also causes up-regulation other important TSGs and whether this occurs in human embryos. We will examine the hypothesis that ART increases the survival of embryos with mutations to the P53 gene (creating a postive genetic selection pressure in favour of these mutations); and which aspects of ART cause this positive selection. The project will demonstarte whether changes in the ART procedures have the potential to mitigate against selection of embryos bearing deletrious mutations.Read moreRead less
I am a reproductive biologist, studying how the environment, both in vivo and in vitro, interacts with oocytes and early embryos in determining both their short and long-term development, with specific interests in application to clinical infertility treatment.
Metabolic And Molecular Determinants Of Embryo Viability
Funder
National Health and Medical Research Council
Funding Amount
$551,321.00
Summary
We know that our health as adults is influenced by the lifestyle of our mothers during pregnancy. In particular, increased risk of adult-onset diseases such as diabetes and cardiovascular disease occurs when small and lean infants at birth are raised in conditions where nutrient intake is not restricted and obesity occurs. This concept of fetal programming is now widely accepted. Our laboratory is leading research in a new concept, that of embryonic programming. We have extensive animal data dem ....We know that our health as adults is influenced by the lifestyle of our mothers during pregnancy. In particular, increased risk of adult-onset diseases such as diabetes and cardiovascular disease occurs when small and lean infants at birth are raised in conditions where nutrient intake is not restricted and obesity occurs. This concept of fetal programming is now widely accepted. Our laboratory is leading research in a new concept, that of embryonic programming. We have extensive animal data demonstrating that exposure of embryos to physiological perturbations alters fetal development, similarly to that occurring in nutrient restriction during pregnancy. Furthermore, there is data from IVF-derived children that their birth-weight is lower than expected, possibly due to the conditions used for conception in the laboratory. How does the response by eggs and embryos, at the time of conception, affect subsequent development? There has been some focus on changes to DNA that are not related to mutations, but structural changes in the DNA that alters gene expression. We call this epigenetics and epigenetic changes are found in embryos, including human embryos following IVF. However, no one knows how such epigenetic changes occur as a result of this stress response by the egg or embryo. Our proposal is to determine the mechanism of how epigenetic alterations take place in eggs and embryos. Our theory is that the mitochondria, the energy producing packages within all cells, are sending signals to the embryo's nucleus. When the egg or embryo finds itself in adverse conditions, the signals change as a result of changes in the energy balance. This in turn changes the activity of enzymes in the nucleus that regulates DNA structure. If we can prove that this relationship occurs, then we can assess these changes in human embryos that are excess to a patient's requirements and learn if programming takes place in human embryos.Read moreRead less
I am a reproductive biologist whose research is focussed around understanding how the early events of conception and embryo development are controlled. Critical aspects of my research are to determine the consequences to pregnancy and adult health if the