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
Uptake of fertility preservation procedures (eg. egg and embryo freezing) prior to cancer treatment is increasing and women will return to use these to try to conceive. Radiation may damage the uterus and there is insufficient evidence to guide the management of those exposed to intermediate doses. The aim is to improve understanding of radiation effects on the uterus which will assist clinicians with deciding whether it can support a pregnancy, or if surrogacy should be advised.
Seminal Plasma Cytokines As Novel Fertility Diagnostics In Men
Funder
National Health and Medical Research Council
Funding Amount
$101,000.00
Summary
Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Current IVF therapy is not successful when the underlying reason for infertility is failure of the maternal tissues to support embryo implantation. We have discovered signaling proteins present in male semen that act in the female reproductive tissues to prepare for embryo implantation and healthy pregnancy. Recently we have identified those proteins and have shown that some men ha ....Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Current IVF therapy is not successful when the underlying reason for infertility is failure of the maternal tissues to support embryo implantation. We have discovered signaling proteins present in male semen that act in the female reproductive tissues to prepare for embryo implantation and healthy pregnancy. Recently we have identified those proteins and have shown that some men have an imbalance in seminal proteins that leads to immune rejection of the embryo in the female partner. This project aims to develop a new test for male fertility that is based on seminal plasma proteins and independent of existing sperm count tests. Furthermore we will determine whether seminal protein imbalance can result from the �silent� presence of male reproductive tract infection.Read moreRead less
The aim of this project is to determine whether melatonin supplementation has an effect on cumulative pregnancy and delivery rates, allowing for the use of frozen embryos obtained during a melatonin treatment cycle. This will be achieved by a series of experiments designed to investigate the effect of melatonin on follicular fluid and culture media as well as assessing clinical pregnancy rates and delivery rates.
Comparison Of Pregnancy Outcomes Following Transferring One Or Two Embryos In A Selected Group Of Infertility Patients.
Funder
National Health and Medical Research Council
Funding Amount
$120,302.00
Summary
Assisted reproductive technology (ART) deals with issues of fundamental importance to individuals involved, and society as a whole. Despite major advances, ART continues to be very costly in many regards. A major reason for this is the relatively low rate of pregnancy, which averages 25% per procedure. The common response to the problem of low pregnancy rates is to return several embryos to uterus. A dilemma associated with this strategy is the high risk of multiple pregnancy, which is associate ....Assisted reproductive technology (ART) deals with issues of fundamental importance to individuals involved, and society as a whole. Despite major advances, ART continues to be very costly in many regards. A major reason for this is the relatively low rate of pregnancy, which averages 25% per procedure. The common response to the problem of low pregnancy rates is to return several embryos to uterus. A dilemma associated with this strategy is the high risk of multiple pregnancy, which is associated with adverse consequences for mother and fetus(es). Compared to singleton births; fetal, neonatal, and perinatal mortality rates are 3-6 times higher in twins, and 5-15 times higher in multiple births of a higher order. Cerebral palsy rates among survivors are six times higher in twins and twenty times higher in triplets. The increase in the incidence of adverse outcomes related to multiple pregnancy has been well documented in ART. We propose a randomised controlled study to assess single embryo transfer (SET) compared to double embryo transfer (DET). Infertility women with a high risk of multiple pregnancy will be randomly allocated to receive one or two embryos, which is the usual treatment at present. We shall then examine the rates of single and multiple pregnancies, and the success of those pregnancies in this group of patients. Potential benefits to the community from this project are very substantial, as it has the capacity to substantially reduce the number of multiple births. Patients will also benefit by having more accurate information with which to make an informed choice during treatment.Read moreRead less
Oxygen, Oxidative Phosphorylation And Regulation Of Embryo Development.
Funder
National Health and Medical Research Council
Funding Amount
$141,096.00
Summary
There is concern that human infertility treatment requiring the growth of embryos in the laboratory, as applied in human IVF, may cause problems during fetal development or even possibly lead to health problems much later in life as an adult. In particular, many clinics are now growing human embryos outside the body for several days longer (to select the best embryos for transfer) than what occurred a decade ago. This concern is based on the evidence that the environment in which an embryo grows ....There is concern that human infertility treatment requiring the growth of embryos in the laboratory, as applied in human IVF, may cause problems during fetal development or even possibly lead to health problems much later in life as an adult. In particular, many clinics are now growing human embryos outside the body for several days longer (to select the best embryos for transfer) than what occurred a decade ago. This concern is based on the evidence that the environment in which an embryo grows in has an impact on the way in which some genes are switched on and off. Normal on-off switching at appropriate times during early development should lead to healthy offspring. Failure to turn off or on, or inappropriate timing, may lead to consequences that manifest themselves later in development. We believe that oxygen concentration and the activity of mitochondria, the organelles of cells that converts oxygen into energy, are key regulators in turning on and off genes during early embryo development. This is because we have shown that, in embryos of a species that is metabolically similar to the human embryo, oxygen concentration and mitochondria activity need to change as the embryo grows for optimal development in the laboratory. In other mammalian cells, oxygen and mitochondria activity are known to turn on or off several particular genes, known as transcription factors. Transcription factors are genes which regulate other genes. Therefore, transcription factors are good candidates as regulators of early embryo development. The present project aims to determine if factors such as changing oxygen concentration and mitochondria activity during laboratory growth of embryos affects the way in which these transcription factors turn on and off. If we find this is true, the way in which human embryos are grown in the laboratory needs to be examined carefully to minimize the risk of possible long-term consequences to the resulting fetus.Read moreRead less
Cohesin: Role In Germ Cell Chromosomal Segregation
Funder
National Health and Medical Research Council
Funding Amount
$435,526.00
Summary
At least 10 to 25% of all human fetuses have the wrong number of chromosomes (aneuploidy). Most of these abormal fetuses perish in utero, making it the leading known cause of early pregnancy loss. Aneuploidy is the leading genetic cause of developmental disabilities and mental retardation. Abundant evidence suggests that most of these chromosome abnormalities originate during unequal partitioning of genetic material (chromosomes) in eggs and sperm. The proposed project focuses on two related gen ....At least 10 to 25% of all human fetuses have the wrong number of chromosomes (aneuploidy). Most of these abormal fetuses perish in utero, making it the leading known cause of early pregnancy loss. Aneuploidy is the leading genetic cause of developmental disabilities and mental retardation. Abundant evidence suggests that most of these chromosome abnormalities originate during unequal partitioning of genetic material (chromosomes) in eggs and sperm. The proposed project focuses on two related genes, called Rec8 and Rad21, which we recently discovered in humans and mice. Due to that these genes are essential for chromosome separation in other species and they exists in species as diverse as yeast and humans, they may be responsible for accurate separation of chromosomes in germ cells in mammals. In this proposal, we will determine the role(s) of these molecules in controlling proper chromosome segregation by loss-of-function studies in genetically engineered mice lacking Rec8 and Rad21 genes. By analyzing the chromosomal abnormalities of the cells from these animals, we will gain critical information about the nature of chromosome partitioning disorders in humans.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
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
Interleukin 11 And Leukemia Inhibitory Factor: Pivotal Regulators Of Uterine Receptivity And Placental Function
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Infertility, spontaneous abortion and pre-eclampsia are major clinical problems. Interleukin (IL)-11 and leukemia inhibitory factor (LIF) are critical for embryo implantation in mice but their mechanisms of action in women are not well defined. We will define their roles in the establishment of pregnancy and provide new critical information on their potential as targets for diagnostic and therapeutic tools for infertility and major diseases associated with pregnancy.