Risk Of Birth Defects In Children Born Following Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$191,962.00
Summary
The development of assisted reproductive technology (ART) for infertility treatment has advanced at a tremendous pace since late 1970's. The use of ART is becoming increasingly frequent, with Australia having one of the highest rates of use internationally. Over 4,000 births result from ART annually in Australia. At the same time, minimally invasive infertility treatment-ovulation induction and insemination, remains a main option for some infertile couples and also generates several thousand bir ....The development of assisted reproductive technology (ART) for infertility treatment has advanced at a tremendous pace since late 1970's. The use of ART is becoming increasingly frequent, with Australia having one of the highest rates of use internationally. Over 4,000 births result from ART annually in Australia. At the same time, minimally invasive infertility treatment-ovulation induction and insemination, remains a main option for some infertile couples and also generates several thousand births annually. A fundamental concern for those involved in infertility treatment is the health of the children born following the treatment. Evidence from many studies indicates that compared to the general population, ART babies are more likely to be a twin or triplet, have a low birth weight, be born premature, and suffer higher rates of perinatal death and cerebral palsy. These issues are gradually being addressed by transferring a single embryo in a cycle. Of greater concern is the recent reporting by a Western Australian team that the risk of major birth defects is doubled in ART children. This is a highly significant finding that has raised concern in patients and clinicians. It is imperative to verify the findings through replication in a larger study. It is equally important to identify whether the increased risk is due to potentially modifiable treatment factors or patient factors related to their infertility. This innovative study will therefore also separate patient characteristics and type of treatment, and partition the risk attributable to various factors. The health of children from infertility treatments is of fundamental concern and has become an important public health issue. This study will direct future basic research in embryology and clinical services where there is a continual need to balance technical innovation and efficacy with treatment safety. The long-term benefit will be improvement of the health status of Australian families.Read moreRead less
I am a developmental biologist who identifies and characterises genes required for normal embryonic development in mouse. I translate this information into the genetic diagnosis and developmental understanding of congenital malformations in humans.
Improving Respiratory Transition And Outcomes Of Newborn Infants
Funder
National Health and Medical Research Council
Funding Amount
$262,251.00
Summary
Effective mask ventilation is the most important intervention at birth that can reduce mortality and disability in term and preterm infants. I will develop strategies to help clinicians improve their resuscitation skills. I will also study new ways to better support babies’ transition after birth, to improve their short and long term outcomes. The results of this research will change the way newly born babies are cared for around the world.
Defining The Genetic And Environmental Factors That Cause Abnormal Vertebral Segmentation During Embryogenesis
Funder
National Health and Medical Research Council
Funding Amount
$724,147.00
Summary
Many birth defects cause vertebral malformations along the spinal column. They originate as the fetus forms, and may be caused by gene mutation or environmental factors. Whilst studying one type of vertebral malformation we have found a genetic cause for 30% of cases. We will investigate the genetic and environmental cause of the remainder. We will look for new genes causing this disease, and use a mouse model to learn how low oxygen levels during pregnancy causes such malformations
Functional Screening Of Novel Genes In Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Our faces are central to our ability to communicate, feed, breath and interact with each other. Birth defects that impact on the normal development of the face are common and affect not only the child but have a dramatic impact on the child's family as well. The genetic causes of most facial birth defects are unknown. This project will develop a method for determining how development of the face is controlled and will help identify genes that are responsible for facial birth defects.
Defining The Genetic Causes Of The Abnormal Vertebral Segmentation Syndrome, Spondylocostal Dysostosis
Funder
National Health and Medical Research Council
Funding Amount
$476,523.00
Summary
There are many birth defects that cause vertebral malformations along the spinal column. These occur as the embryo develops in utero, during the formation of structures known as somites. Somites also form the ribs, muscle, tendons and dermis. We are studying an example of this type of birth defect called spondylocostal dysostosis (SCD). We have shown that mutations in three different genes cause some cases of this inherited disease in humans. These genes are called DLL3, MESP2 and LFNG. However, ....There are many birth defects that cause vertebral malformations along the spinal column. These occur as the embryo develops in utero, during the formation of structures known as somites. Somites also form the ribs, muscle, tendons and dermis. We are studying an example of this type of birth defect called spondylocostal dysostosis (SCD). We have shown that mutations in three different genes cause some cases of this inherited disease in humans. These genes are called DLL3, MESP2 and LFNG. However, 80% of SCD patients do not have a mutation in any of these genes. Thus we need to discover how these other cases occur. This project uses two strategies in parallel. Firstly, we will analyse large families that have a history of SCD, and use this information to find causative gene mutations. However, a significant proportion of cases occur without family history. To find out what genes are involved in these cases is more difficult. We have created a mutant mouse by specifically deleting the DLL3 gene. This mouse has very similar vertebral malformations to SCD. We will compare embryos from normal and mutant mice to find genes that do not operate normally in the mutant. These genes are candidates for causing SCD, and thus we will screen these genes in human patients for mutations. However, simply finding a change in a candidate gene does not necessarily mean that this is the cause of SCD. To prove this, we have developed several tests to determine if the mutation alters the normal function of the protein encoded by the mutated gene. This work will greatly benefit the future genetic assessment of SCD patients. In addition, by studying our mouse model of SCD, we will gain a greater understanding of how DLL3 functions. This knowledge may be useful in developing stem cell-based therapies that involve the production of specific cell types.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
I am an epidemiologist using record linkage to investigate the causes and consequences of developmental disabilities such as birth defects, intellectual disability and autism and to identify possibilities for their prevention and amelioration.