Male Infertility And Defective Sperm-oocyte Interaction
Funder
National Health and Medical Research Council
Funding Amount
$244,614.00
Summary
Infertility affects 15% of people and although not usually ill, they are extremely distressed by the condition. In vitro fertilisation (IVF) with normal sperm and intracytoplasmic sperm injection for sperm defects, can assist such patients have a family, but these treatments are expensive and not always successful. The causes of male infertility are largely unknown, diagnostic methods are crude and there is usually no treatment to promote natural conception. Conventional semen analysis provides ....Infertility affects 15% of people and although not usually ill, they are extremely distressed by the condition. In vitro fertilisation (IVF) with normal sperm and intracytoplasmic sperm injection for sperm defects, can assist such patients have a family, but these treatments are expensive and not always successful. The causes of male infertility are largely unknown, diagnostic methods are crude and there is usually no treatment to promote natural conception. Conventional semen analysis provides limited information on fertilising ability. Our work over 15 years has shown that many patients go undiagnosed, particularly those with defects impairing fertilisation. During human fertilisation, sperm bind to the zona pellucida, a coat around the egg, via the membrane over a cap like structure on the sperm head called the acrosome. Binding of a sperm triggers the acrosome reaction, the process by which the membranes covering the acrosome fuse and the acrosomal contents are released. The sperm then penetrates the zona pellucida, binds to the membrane of the egg and is taken into the cytoplasm. We have developed tests to assess sperm binding to the zona pellucida and the acrosome reaction using eggs that failed to fertilise during clinical IVF. These tests show defects of sperm binding to the zona pellucida and the zona pellucida induced acrosome reaction are present in over 25% of patients without other obvious causes for their infertility. The men are severely infertile but have normal sperm by conventional tests. In this project we will determine if there are changes in membrane proteins in sperm which do not bind to the zona pellucida or undergo the acrosome reaction. We will categorise patients on the responses of their sperm to activation of key enzymes and other regulatory molecules involved in the fertilisation process. This will allow us to select subjects for further examination of protein abnormalities and genetic causes of the conditions.Read moreRead less
Facilitating Endometrial Receptivity To Improve Pregnancy Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$734,252.00
Summary
The womb prepares itself in each menstrual cycle for pregnancy and the implantation of an embryo. In some women, the endometrium may not prepare itself adequately and this can lead to infertility. We have identified small RNA that may be useful in predicting which women are not adequately prepared for implantation and may be used to develop treatments for infertile women, for which there are currently no treatments.
Mechanisms And Utilisation Of IFN-epsilon-mediated Protection Against Chlamydia Reproductive Tract Infection
Funder
National Health and Medical Research Council
Funding Amount
$750,486.00
Summary
Chlamydia is a common cause of sexually transmitted diseases resulting in pelvic inflammatory disease, infertility and ectopic pregnancy. There are no vaccines that prevent infection or disease. We have discovered a new factor in the immune system (interferon-epsilon) that only occurs in the reproductive tract. If this factor is absent then Chlamydia infections are more severe. We will investigate how this factor protects against infection and if we can use it as a new agent against Chlamydia ST ....Chlamydia is a common cause of sexually transmitted diseases resulting in pelvic inflammatory disease, infertility and ectopic pregnancy. There are no vaccines that prevent infection or disease. We have discovered a new factor in the immune system (interferon-epsilon) that only occurs in the reproductive tract. If this factor is absent then Chlamydia infections are more severe. We will investigate how this factor protects against infection and if we can use it as a new agent against Chlamydia STDs.Read moreRead less
A Novel Reproductive Tract Factor That Protects Against Chlamydia
Funder
National Health and Medical Research Council
Funding Amount
$541,133.00
Summary
Chlamydia is a common cause of sexually transmitted diseases resulting in pelvic inflammatory disease, infertility and ectopic pregnancy. There are no vaccines that prevent infection or disease. We have discovered a new factor in the immune system (interferon-epsilon) that only occurs in the reproductive tract. If this factor is absent then Chlamydia infections are more severe. We will investigate how this factor protects against infection and if we can use it as a new agent against Chlamydia ST ....Chlamydia is a common cause of sexually transmitted diseases resulting in pelvic inflammatory disease, infertility and ectopic pregnancy. There are no vaccines that prevent infection or disease. We have discovered a new factor in the immune system (interferon-epsilon) that only occurs in the reproductive tract. If this factor is absent then Chlamydia infections are more severe. We will investigate how this factor protects against infection and if we can use it as a new agent against Chlamydia STDs.Read moreRead less
Implantation of an embryo into the uterus & development of a functional placenta are critical to initiate & continue a pregnancy. Implantation failure causes infertility and is a major bottle-neck in IVF. Placental insufficiency leads to pregnancy loss, under-developed fetuses & a life-threatening pregnancy-specific disease preeclampsia. This application will investigate how a woman’s uterus works for implantation and placental development, how to increase IVF success and diagnose & potentially ....Implantation of an embryo into the uterus & development of a functional placenta are critical to initiate & continue a pregnancy. Implantation failure causes infertility and is a major bottle-neck in IVF. Placental insufficiency leads to pregnancy loss, under-developed fetuses & a life-threatening pregnancy-specific disease preeclampsia. This application will investigate how a woman’s uterus works for implantation and placental development, how to increase IVF success and diagnose & potentially treat preeclampsia.Read moreRead less
Interferon Epsilon, A Key Cytokine In The Pathophysiology Of The Female Reproductive Tract Mucosa
Funder
National Health and Medical Research Council
Funding Amount
$793,303.00
Summary
The female reproductive tract is a complex environment, which permits pregnancy but protects against infections, all under the influence of hormones and the resident microbial flora. We have discovered a novel protein called interferon epsilon that acts on cells in the female reproductive tract to regulate protection against infections. We aim to discover how this new protein works and will determine its therapeutic potential in infections and inflammatory diseases affecting women's health.
BH3-only Proteins Are Critical For The Developmentally Programmed Death Of Oocytes: Impact On Ooctye Quality And The Fertile Lifespan
Funder
National Health and Medical Research Council
Funding Amount
$273,537.00
Summary
The ability of women to have healthy children, and the age at which menopause occurs, are largely dependent on the number and quality of the eggs stored in their ovaries. For unknown reasons, around two-thirds of all eggs die very shortly after they are made. We are unraveling the genes involved in determining whether an egg will live or die, and are investigating the role of these genes as _quality control sentinels", responsible for ensuring that only the highest quality eggs are ovulated.
Translating Oocyte Biology Discoveries To New Clinical Practices
Funder
National Health and Medical Research Council
Funding Amount
$772,605.00
Summary
A/Professor Gilchrist is a reproductive biologist studying factors that regulate the intrinsic quality of unfertilised eggs. He has produced and patented the use of unique growth factors produced by the egg that enhance egg quality in women. Bringing together industry and a world-leading clinic, he is developing new forms of hormone-free infertility treatment which he will take to clinical practice over the next 5 years.
Reproductive health critically impacts a woman’s wellbeing, irrespective of her choice to have children. The ovary and its hormones govern physiological events regulating health at puberty, across the menstrual cycle, during the establishment and maintenance of pregnancy, and in parturition, lactation and menopause. The major health burdens concerning ovaries that we are studying include polycystic ovarian syndrome and assisted reproductive technologies used to treat infertility.
Exploitation Of Unique Growth Factors To Develop New Products For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$132,525.00
Summary
Infertility comes at an enormous social and financial cost to Australian society; infertility is a major psychological burden on young couples and the technologies used to treat infertility, such as in vitro fertilisation (IVF), require expensive drugs to stimulate the ovary. The cost of these drugs to Medicare is expected to exceed $100 million p.a. over the next decade. A reproductive technology, which has always shown great potential to elevate some of this burden, is oocyte (egg) in vitro ma ....Infertility comes at an enormous social and financial cost to Australian society; infertility is a major psychological burden on young couples and the technologies used to treat infertility, such as in vitro fertilisation (IVF), require expensive drugs to stimulate the ovary. The cost of these drugs to Medicare is expected to exceed $100 million p.a. over the next decade. A reproductive technology, which has always shown great potential to elevate some of this burden, is oocyte (egg) in vitro maturation (IVM), which drastically reduces the use-cost of drugs and the stress to patients. However, oocyte IVM has been slow to live up to its potential and the technology is still not in widespread clinical practice, mainly due to disappointing success rates in women. We have been studying oocyte IVM in animals for many years, and have recently made a significant technological breakthrough, improving success rates by ~50%. In this field, a 50% increase in efficiency is substantial and has significant clinical and commercial application. Currently, we are the only group worldwide with this technology. Over the course of this 2-year project we will conduct follow-up experiments to refine this discovery and investigate the feasibility of using this approach to treat human infertility. We are already in negotiations with two medical device manufacturers to licence this technology. We expect that this project will lead to a series of products and technologies that will enter a clinical trial for the treatment of infertility within 2-3 years.Read moreRead less