Weight Loss Programs And Subsequent Fertility Rates In An In Vitro Fertilisation (IVF) Program
Funder
National Health and Medical Research Council
Funding Amount
$28,067.00
Summary
Compared with normal weight women, obese women have lower fertility both in natural and IVF cycles. Obesity is a risk factor for many maternal and fetal morbidities. This study will be the first randomised controlled trial aimed at demonstrating the effect on pregnancy rates of a prior weight loss program for obese women undertaking IVF treatment. A 12 week weight loss program including dietary, exercise, education and psychological factors will be initiated in the treatment arm.
The Importance Of ADAMTS Proteases In Ovulation And Fertility.
Funder
National Health and Medical Research Council
Funding Amount
$205,500.00
Summary
In the ovary eggs are matured within a specialised organ called a follicle. Female fertility is dependent on the efficient release of eggs from the follicle as well as transport of the egg to the site of fertilization. During these processes the egg is encased within a mucous-like cushion made of cells, proteins and complex carbohydrates. This cushion or matrix plays an active role in egg release, transport and fertilization. Proper formation of this cushion just before egg release is therefore ....In the ovary eggs are matured within a specialised organ called a follicle. Female fertility is dependent on the efficient release of eggs from the follicle as well as transport of the egg to the site of fertilization. During these processes the egg is encased within a mucous-like cushion made of cells, proteins and complex carbohydrates. This cushion or matrix plays an active role in egg release, transport and fertilization. Proper formation of this cushion just before egg release is therefore essential for efficient female fertility. This project examines the role of newly identified proteins and protease enzymes that are involved in the formation and function of the matrix cushion around eggs. This has important implications for the causes of infertility in women as well as improving the efficacy of IVF techniques.Read moreRead less
Understanding The Determinants Of Human Oocyte And Embryo Health
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
This project will address key questions involving how the human egg and embryo maintain their ability to develop into a healthy fetus. In recent years there have been significant advances in our understanding of how animal oocytes grow and become competent as well as an increased understanding of how the animal embryo maintains its viability in culture. Currently there is little information as to how the human oocyte and embryo develops. This study will address the current lack of knowledge by e ....This project will address key questions involving how the human egg and embryo maintain their ability to develop into a healthy fetus. In recent years there have been significant advances in our understanding of how animal oocytes grow and become competent as well as an increased understanding of how the animal embryo maintains its viability in culture. Currently there is little information as to how the human oocyte and embryo develops. This study will address the current lack of knowledge by extending the information gathered in animal models to establish how the human oocyte communicates with its surrounding cells and how this communication is important for development. We will also study how the developing embryo maintains its physiology and metabolism and the relationship between the ability to control metabolic balance and viability will be established. All of the questions outlined in this proposal can be performed without disturbing the oocyte and developing embryo by analysing the surrounding cells and the spent media. Therefore, all of these questions can be answered non-invasively. The outcome of this proposal will be an increased understanding of how the physiology and development of the human oocyte and embryo is maintained. However, importantly this data will then provide information as to the relationship of these parameters to developmental competence. Therefore, it will be possible to establish a range of markers that can be used to predict the developmental competence of a human embryo. Currently multiple embryos are routinely transferred in an IVF cycle resulting in an increase in multiple gestation pregnancies and their associated complications. The information generated in this study will provide information enabling markers to be used to identify the most viable embryo from a cohort, which is essential if single embryo transfer is to be universally adopted in an IVF program.Read moreRead less
Characterisation Of A Signal Transduction Pathway In The Early Embryo
Funder
National Health and Medical Research Council
Funding Amount
$208,500.00
Summary
The creation of embryos in the lab is important in assisted reproductive technology (ART) and potentially in cell therapies using embryonic stem cells. Yet, the development of the early embryo is not well understood. Creation of embryos in the lab is expensive and much of this cost is related to the relative inefficiency of the technology due to the high mortality of the resulting embryos. Typically, 45 - 80% of embryos produced by ART do not survive the first week. Hormones are essential chemic ....The creation of embryos in the lab is important in assisted reproductive technology (ART) and potentially in cell therapies using embryonic stem cells. Yet, the development of the early embryo is not well understood. Creation of embryos in the lab is expensive and much of this cost is related to the relative inefficiency of the technology due to the high mortality of the resulting embryos. Typically, 45 - 80% of embryos produced by ART do not survive the first week. Hormones are essential chemical messengers that regulate the normal functions of the body. Early embryo development is dependent on the action of special hormones that are produced by the embryonic cells themselves. The actions of these hormones are necessary for their normal survival. ART compromises the production and action of several of these hormones. Currently, there is not a detailed picture of how these embryonic hormones act on the embryo to promote their survival. Cells respond to outside hormones by changing the activity of a number intracellular proteins that act as on-off switches. The combinatorial pattern of 'switch' settings is modified by hormones, which in turn can act to change the pattern of gene expression. This project will extend our extensive studies on the nature of action of the well-described embryonic hormone known as PAF. The mechanism by which this hormone acts to signal changes in the pattern of the embryo's gene expression will be investigated. An understanding of how these embryonic hormones work will in the future allow for significant improvements in embryo viability.Read moreRead less
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
Characterisation Of The Pathways Leading To DNA Demethylation In The Embryo.
Funder
National Health and Medical Research Council
Funding Amount
$634,573.00
Summary
Complex living creatures like humans have specialised cells that co-operate to form important organs like brains and reproductive organs. Specialised cells have specific genes locked on or off. When a sperm fertilises an egg, all the switches of the genes that are locked on or off get reset to neutral so that the fertilised egg can divide and grow into all cell types in the body. We do not know how this resetting happens in the egg. This project seeks to discover the mechanism involved.
Characterization Of The Molecular Basis Of Human Sperm-oocyte Interaction
Funder
National Health and Medical Research Council
Funding Amount
$492,956.00
Summary
In this proposal, we shall exploit our expertise in gamete biology and innovative proteomic technologies to elucidate the molecular mechanisms that underpin human sperm-oocyte interaction. This exquisitely cell- and species-specific event constitutes one of the most strategically important cellular interactions. Our research will provide the foundation for diagnosis and treatment of male infertility and identify a range of targets for the development of novel contraceptive technology.
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
Generation Of Human Intestinal Stem Cells By Direct Reprogramming
Funder
National Health and Medical Research Council
Funding Amount
$630,391.00
Summary
Intestinal stem cells (ISCs) can give rise to mini guts in vitro with exciting applications for drug screening and cell based regenerative medicine. However, currently the establishment of mini gut cultures requires an invasive procedure. By taking advantage of a revolutionary new predictive algorithm (Mogrify) we will generate ISC directly from somatic and pluripotent cell sources.