Successful establishment of pregnancy requires a viable embryo and a receptive uterus. The contribution that reduced uterine receptivity makes to human infertility is unknown. IVF patients with implantation failure will be investigated using different approaches to identify gene pathways that are altered in reduced uterine receptivity. This study could lead to a clinical test for uterine receptivity and help to improve fertility treatment options for women with repeated implantation failure.
Changes In Protein Glycosylation Promote Endometrial Receptivity Leading To Successful Implantation
Funder
National Health and Medical Research Council
Funding Amount
$489,198.00
Summary
~15% of couples are unable to have children. Their reliance on reproductive technologies (eg, IVF) has increased 4 fold over the past decade. One reason for infertility is that the lining of the uterus (endometrium) is not able to allow an embryo to attach – a key event in establishing healthy pregnancy. There is no test to assess whether the endometrium is ‘receptive’ to an embryo. We will develop special assays for a test and provide a basis for treatment without recourse to IVF.
Targeted Disruption Of Lipoxygenase Enzymes To Prevent Oxidative Stress-mediated Pathologies In The Male Germline
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
An estimated 80 million individuals suffer from infertility globally with at least 50% of these cases due to defects in sperm function. Unfortunately, due to a severe lack of knowledge surrounding sperm biology and dysfunction, no successful curative or preventative measures have been established. My project will study why sperm cells die and investigate new ways to limit cellular stress so we can develop new therapeutic strategies to mitigate the growing problems in male reproductive health.
Why Is There An Increased Risk Of Severe Adverse Perinatal Outcomes After The Use Of Clomiphene Citrate For Infertility Treatment?
Funder
National Health and Medical Research Council
Funding Amount
$570,065.00
Summary
Clomiphene citrate (CC) has been a first line treatment for female infertility internationally since the 1960’s. However, safety studies using routine prescribing practices were never performed, and numerous data sources now indicate that CC is associated with major adverse outcomes if the fetus is inadvertently exposed. We are linking prescription data to perinatal outcomes to confirm how CC is associated with adverse events so as to inform prescriber and practice change.
Identifying Strategies To Improve Perinatal Outcomes After Assisted Conception
Funder
National Health and Medical Research Council
Funding Amount
$724,799.00
Summary
Around 20% of young women express concern with being able to conceive, 16% experience clinical infertility, and ~8% use invasive therapies for which there can be limited safety data. We, and others, have reported adverse events for mother and child after infertility treatment, including neonatal death and birth defects. This project will provide urgently needed, robust evidence to guide patient and clinical decision making so as to optimise health of mother and baby.
Kisspeptin And Its Receptor Mastermind Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$601,979.00
Summary
Reproduction is controlled by the brain and gonadotropin releasing hormone (GnRH) is the primary stimulatory factor. Finding critical regulators of GnRH has remained the most important goal for reproductive endocrinologists for over 30 years. The brain peptide hormone called kisspeptin and its receptor Kiss1R appear vital in the control of reproduction. This project will detail the role kisspeptin and Kiss1R play in controlling hormones from the brain that govern puberty and reproduction.
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.
Mechanisms Of DNA Damage-induced Oocyte Apoptosis And Infertility: Examination Of The Role Of BH3-only Proteins.
Funder
National Health and Medical Research Council
Funding Amount
$495,755.00
Summary
Our ability to prevent or postpone menopause following cancer treatment, is of great importance for female fertility, health and quality of life. We will demonstrate that the death gene of the Bcl-2 family of life and death genes, Puma, is responsible for killing female germ cells after damaging treatment. When Puma is absent, sufficient high quality germ cells are able to survive damaging treatment, allowing normal fertility in mice. The quality of these rescued germ cells will be analysed in d ....Our ability to prevent or postpone menopause following cancer treatment, is of great importance for female fertility, health and quality of life. We will demonstrate that the death gene of the Bcl-2 family of life and death genes, Puma, is responsible for killing female germ cells after damaging treatment. When Puma is absent, sufficient high quality germ cells are able to survive damaging treatment, allowing normal fertility in mice. The quality of these rescued germ cells will be analysed in detail.Read moreRead less
Role Of Mouse Rad21 And Rec8 Genes In Recombination And Ionising Radiation Response
Funder
National Health and Medical Research Council
Funding Amount
$403,750.00
Summary
We have created a line of mice and are creating a second mouse line which lack two specific genes known as Mrec8 and Mrad21. These genes have a number of roles in mammals. These roles include acting as a glue to hold chromosomes together and allowing exchange of DNA between separate DNA molecules. The latter is important in physiological processes such as genetic exchange during meiosis, but also in the response of the cell to DNA damage, specifically, breakages in both strands of the DNA helix. ....We have created a line of mice and are creating a second mouse line which lack two specific genes known as Mrec8 and Mrad21. These genes have a number of roles in mammals. These roles include acting as a glue to hold chromosomes together and allowing exchange of DNA between separate DNA molecules. The latter is important in physiological processes such as genetic exchange during meiosis, but also in the response of the cell to DNA damage, specifically, breakages in both strands of the DNA helix. In the studies proposed here, we will breed these mice both with each other and with other mice that have specific, single gene defects which lead to abnormal responses to DNA strand breakages. We shall assess the effects of the different genes on response to DNA strand breaking agents in the animals, as well as in cells which have been derived from the animals. These experiments are expected to shed light onto the consequences of defects in DNA repair for the stability of cells and animals, and may provide information which ultimately benefits cancer patients, especially those having radiotherapy.Read moreRead less
Medically Assisted Fertility Treatment And Infant Outcomes: The Role Of IVF (in Vitro Fertilisation), Ovulation Induction And Subfertility
Funder
National Health and Medical Research Council
Funding Amount
$463,001.00
Summary
Medically assisted fertility treatment such as IVF and fertility medications account for the birth of at least one in 25 children born in Australia. While the health outcomes of these children are reassuring there is a lack of conclusive findings on the clinical role of IVF and non-IVF treatments and on their safety, particularly the newer forms of IVF. This research will fill this evidence gap, informing patients and clinicians on the safety and effectiveness of fertility treatments.