I am a perinatal physiologist who specializes in determining the factors that cause fetal and neonatal brain damage, and in devising treatments to prevent this for application in pregnant women and the neonate.
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
The Role Of Placental Transcription Factors In The Pathogenesis Of Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$601,582.00
Summary
We must understand the role of growth control genes in the growth of the human placenta. The reason is that in several significant placental disorders, placental formation is abnormal and prevents the placenta from functioning efficiently. This in turn, impacts on the growth of the developning fetus. A variety of established and innovative methods described in this project will determine the functions of the placental growth control genes and may lead to novel therapeutic targets.
Mechanisms Of Escape From Progesterone-induced Suppression: Role In Normal And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Prematurity caused by preterm birth is the leading cause of death and disease among newborns in Australia. Here we will define how the length of pregnancy is determined by the opposing actions of progesterone, which maintains pregnancy, and prostaglandins, which induce labour. We will demonstrate the mechanism by which the actions of the two hormones are balanced in normal pregnancy and disrupted in preterm labour. We will show that preterm birth can be prevented by correcting the disorder.
A novel microtubule severing protein involved in male germ cell biology. The project aims to better understand the cellular and biochemical mechanisms underlying a key component of male fertility. Microtubules are a fundamental component of all cells. A mechanism that is increasingly recognised as essential for microtubules regulation is severing. It has been discovered that an uncharacterised microtubule severing protein, KATNAL2, has a key role in male germ cell development. This project aims ....A novel microtubule severing protein involved in male germ cell biology. The project aims to better understand the cellular and biochemical mechanisms underlying a key component of male fertility. Microtubules are a fundamental component of all cells. A mechanism that is increasingly recognised as essential for microtubules regulation is severing. It has been discovered that an uncharacterised microtubule severing protein, KATNAL2, has a key role in male germ cell development. This project aims to define the mechanisms underlying KATNAL2 function in the male germ line. It is expected that these data will generate a comprehensive picture of KATNAL2 function and provide foundation data of relevance across multiple species and tissues. In the longer term, it may also reveal a rational strategy for fertility enhancement or suppression.Read moreRead less
The control of meiosis in mammalian oocytes. This study will elucidate how the egg undergoes its final steps in preparation for fertilisation and early development. This will produce greater knowledge about how eggs develop, which may reveal new approaches to modulating reproductive capacity.
Decoding microtubule remodelling in sperm production. All eukaryotic cells possess a dynamic microtubule (MT) cytoskeleton, which requires constant remodelling to satisfy its many essential cellular roles. Emerging data suggests modifications to the MT surface (the tubulin code) may act as instructional signposts for remodelling. This project aims to define a fundamental component of the tubulin code, glutamylation, and define how this directs MT severing. It also aims to define the cellular fun ....Decoding microtubule remodelling in sperm production. All eukaryotic cells possess a dynamic microtubule (MT) cytoskeleton, which requires constant remodelling to satisfy its many essential cellular roles. Emerging data suggests modifications to the MT surface (the tubulin code) may act as instructional signposts for remodelling. This project aims to define a fundamental component of the tubulin code, glutamylation, and define how this directs MT severing. It also aims to define the cellular functions of MT-severing enzyme FIGNL1 and key MT glutamylation enzymes (CCP1, CCP5 and TTLL1). Insights will be generated using sperm production as a model system and will thus inform the mechanisms by which fertile sperm are built, in addition to being relevant to cell biology across eukaryotic species. Read moreRead less
Functional Genomic Analysis Of The Role Of P53 In Early Embryo Death After Assisted Reproductive Technologies (ART).
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. ART are expensive therapies and much of this cost is related to the relative inefficiency of the technology. 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. Consequently the chance of any individual embryo resulting in a successful birth is not high. There has been only ....Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. ART are expensive therapies and much of this cost is related to the relative inefficiency of the technology. 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. Consequently the chance of any individual embryo resulting in a successful birth is not high. There has been only modest increments in embryo survival in recent years. The low cahnce of individual embryos resulting in a baby means that: (1) generally several treatment cycles are required; (2) superovulation is used to maximise the number of embryos produced giving an accumulation of unwanted cryopreserved embryos; (3) more than one embryo is generally transferred resulting in a significant incidence of multiple pregancies. The high mortality of the early embryo seems to be a general feature of IVF but its causes and effectors are not known. It has recently been established that it largely occurs due to a form of cell 'suicide' known as apoptosis. This form of cell death has important normal functions: its activation allows for cells that are no longer required to be removed, allowing the remodelling of tissues and it also serves to remove cells that are irreversibly damaged. p53 is a protein that has the ability to 'sense' cell stress and damage and to direct the cell to undergo apoptosis if the stress is severe. This project will examine if ART cause increased expression of p53 and whether this elevation of p53 causes embryonic cell death. We will examine the factirs that control p53 expression in the embryo. using mice with mutations that stop the function of p53 and several of its regulatory proteins. Experiments will determine the susceptibility of embryos possessing these mutations and will therefore allow us to define the proteins causing apoptosis after ART.Read moreRead less