The following describes the 2006 fertility and infertility research activities of the Royal Women's Hospital. This page is under development.
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The Women’s provides reproductive services in collaboration with Melbourne IVF.
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Female reproductive biology
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Integration of fundamental research and clinical application is the hallmark of scientific research in the area of human reproductive biology at the Women’s Reproductive Services and Melbourne IVF. One focus in the in vitro fertilisation (IVF) laboratories has been on identifying the embryonic factors associated with successful implantation. The knowledge we have gained from careful observations on early stages of development has led to improved selection of the embryo which is most likely to implant. This, in turn, has helped facilitate the move towards transferring only single embryos in many cases.
A consequence of the above trend is that we now find ourselves in a position where we cryopreserve approximately twice as many embryos as we transfer fresh. Analysis of the factors associated with successful embryo cryopreservation has long been a major interest in our laboratories and much of our published work is in this area.
Our interest in and, close identification with, cryopreservation in reproductive medicine is also reflected in the work of Dr Debra Gook, who carried out much of the pioneering work in oocyte cryopreservation. This work continues and our first births from this approach have recently been confirmed. Work in this area also includes the cryopreservation of ovarian tissue as a route to potential fertility preservation in young women with cancer and many of our publications represent significant milestones in the development of this technology. This work also extends to fundamental studies of human follicular development in a xenografting model. More recent work has explored the genesis of the zona pellucida during follicular development and has uncovered previously unknown facts in relation to this structure in both adult and fetal ovarian follicles.
Finally, the legislative changes which have allowed carefully regulated research on human IVF embryos which are no longer required for treatment purposes led to a collaborative project involving Melbourne IVF and a prominent stem cell group, Stem Cell Sciences. This work, which is still ongoing, has led in turn to the derivation of the first human embryonic stem cell lines in Victoria.
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Male reproductive biology
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Male factors contribute to infertility as much as do female factors. We have for many years been investigating how sperm interact with oocytes, how sperm function, the variables that affect semen quality, how to automate semen analysis, the causes and management of male infertility, and the outcomes for both women and their children after assisted reproductive techniques. We have also been involved in many clinical trials of different reproductive techniques.
Defects of sperm-oocyte interaction account for about 25% of patients with infertility of unknown causes. If diagnosed before IVF is attempted, patients with defects of sperm-oocyte interaction would be treated by ICSI and avoid an IVF cycle with low or zero fertilisation. In the future, simpler alternative tests of sperm functional capacity that correlate with sperm-oocyte interaction will be developed that should assist in the prognosis for natural conception of couples with mild abnormalities of semen analysis.
Our research has shown that semen quality does not seem to be low in Australia, in contrast with some other parts of the world. In fact fertile women may be conceiving more quickly than reported in the past. The current information about pregnancy rates and the ranges of semen analysis results in fertile couples provides useful reference data for clinical counselling of infertile couples.
In a recently completed trial, the pregnancy rate with IVF was significantly higher than for intrauterine insemination and therefore was not preferable to IVF.
A male infertility database and classification of diagnoses has been developed that has been useful for a number of studies on causes and outcomes of treatment. A method of fine needle tissue aspiration biopsy of the testis was developed for diagnosis of defects of spermatogenesis and collection of sperm for ICSI. The role of screening investigations for genetic conditions has been successful. Therapeutic trials have included multicentre studies of hormonal methods of male contraception, effectiveness of recombinant gonadotrophin treatment for hypogonadotrophic hypogonadism and heparin and aspirin treatment for IVF implantation failure.
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Genetic and molecular research
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The work of the Genetic and Molecular Research Laboratory is directed towards the diagnosis and understanding of genetic anomalies in embryos. A key focus is the development of genetic testing of single cells and this requires sophisticated molecular techniques. The work underpins the clinical Preimplantation Genetic Diagnosis (PGD) service at Melbourne IVF where genetically healthy embryos are identified by testing a single cell biopsied from an embryo. Many Victorian couples have directly benefited from this work and delivered healthy babies. Some IVF couples are at high risk of chromosomal abnormalities in their embryos which prevent them from achieving a successful pregnancy. Other couples have a serious genetic disease in their family and utilise the PGD program to have a healthy baby.
Chromosome translocations can be diagnosed in early embryos using fluorescent in situ hybridisation (FISH). The Genetic and Molecular Research Laboratory holds a National Health and Medical Research Council (NHMRC) of Australia embryo research licence to develop novel FISH tests for couples who carry translocations. Some of these translocations have been extremely complex and required sophisticated strategies of molecular testing. Many couples have benefited from this work, avoiding miscarriage and having healthy children.
Some serious diseases, including cystic fibrosis and haemophilia, are caused by a genetic error in a single gene. These diseases can be diagnosed in single cells from embryos by amplifying the small fragments of DNA using the polymerase chain reaction (PCR).
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Clinical reproductive research
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Reproductive Services at the Women’s, in collaboration with Melbourne IVF, has an active research program in the important area of fertility protection and preservation. This research focuses on measures to help protect and preserve fertility for young patients who are having therapy that is potentially toxic to their gonads as part of their cancer treatment.
We recently completed and are planning studies evaluating the use of a GnRH antagonist and agonists in protecting ovarian function during chemotherapy. Our interim results suggest that a GnRH antagonist given during cyclophosphamide treatment may exert a protective effect on ovarian function in women receiving toxic chemotherapy doses.
We have commenced an ovarian tissue grafting program to preserve fertility for patients who have had ovarian tissue frozen with us prior to their chemotherapy or radiotherapy. For this group of patients the cancer treatment has resulted in ovarian failure, and this program focuses on restoring ovarian function. In appropriate patients, the frozen ovarian tissue is thawed and grafted back to the patient in a painstaking laparoscopic procedure with ovarian slices being put into the inactive ovary and the pelvic side wall. Once there is evidence of ovarian activity, the tissue will be stimulated to produce mature eggs which can be retrieved and fertilised with IVF.
The endocrine metabolic field of research concentrates on improving the gynaecological, reproductive and general health for women with polycystic ovarian syndrome (PCOS). The program particularly focuses on the development of permanent lifestyle changes for patients with endocrine metabolic disorders.
The Big Girls Group (BGG) is a four-month weight management and lifestyle modification program for women requiring either fertility treatment, regulation of menstruation or weight loss (particularly in women with PCOS).
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Other reproductive research
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We have recently collaborated in clinical trials assessing a sustained release and thus long-acting follicle stimulating hormone (FSH), aimed to develop a treatment procedure requiring fewer injections for patients.
We are in the final stages of a randomised pilot to assess intrauterine insemination (IUI) versus in vitro fertilisation (IVF).
The social and emotional needs of people attending the Women’s Reproductive Services and Melbourne IVF have always been considered to be very important, and we have a strong focus on providing an easily accessible counselling service.
The donor programs comprise a large part of the focus for counsellors and many research studies have been undertaken with the aim of gaining a better understanding of the needs of donors and recipients.
A case-control study looking at the relationship between IVF conception and Beckwith-Weideman syndrome (BWS) indicated that there was a small but significant increase in BWS in the IVF group, similar to overseas studies.
In a major longitudinal study questionnaires were completed by 150 women who had conceived via treatment at the Women’s/Melbourne IVF.
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