Current Research

Clinical Trials

Introducing Mitochondrial Donation into Australia: The mitoHOPE (Healthy Outcomes Pilot and Evaluation) Program

Prof John Carroll, Dr Deepak Adhikari, Dr Meenakshi Choudhary, Prof John Christodoulou, Prof David Coman, Prof Martin Delatycki, A/Prof Carolyn Ellaway, Prof Michael Fahey, A/Prof Ilias Goranitis, Dr Christopher Gyngell, Dr Karin Hammarberg, Dr Tristan Hardy, Prof Mary Herbert, A/Prof Ryan Hodges, A/Prof Lisa Hui, Dr Louise Hyslop, Dr Benjamin Kamien, Dr Janet Long, A/Prof Karinne Ludlow, Prof David Mackey, Prof Andrew Mallett, Prof Jeffrey Mann, Prof Catherine Mills, Prof Rebecca Robker, Prof Luk Rombauts, Prof Michael Ryan, Dr Suzanne Sallevelt, Prof Christopher Semsarian, Prof Robert Sparrow, Dr Michel Tchan, Prof David Thorburn, Dr Meaghan Wall, Dr Mathew Wallis, Dr Narelle Warren, Dr Wai Yan Yau, Prof Deirdre Zander-Fox, Prof Sophia Zoungas
Monash University, Monash IVF, Murdoch Children’s Research Institute, The University of Adelaide, Newcastle University, Mito Foundation

Every week in Australia, it’s estimated one child is born with a severe form of mitochondrial disease, which can lead to premature death or a lifetime of debilitating illness and disability. There is no cure for mitochondrial disease. Current treatments aim to decrease the impact of symptoms, but they do not change the course of the disease. Monash IVF researchers, in collaboration with Monash University and Murdoch Children’s Research Institute, are establishing an Australian-first clinical program to investigate a lifesaving technique known as mitochondrial donation or ‘three-person IVF’. Mitochondrial donation aims to ensure only healthy mitochondria, the powerhouses of our cells that are vital to our survival, are passed on to an embryo by minimising the risk of prospective mothers passing on devastating mitochondrial disease to their children. Used in conjunction with IVF, mitochondrial donation techniques allow an embryo to be created that contains the nuclear DNA from a man and a woman (the prospective mother) and mitochondria in an egg donated by another woman (the mitochondrial donor).

The mitoHOPE Program is a mitochondrial pilot program to test the safety, efficacy, and feasibility of mitochondrial donation to help determine whether mitochondrial donation could be introduced into clinical practice in Australia. The program includes a clinical trial for at-risk individuals. For more information go to the mitoHOPE Program website. The mitoHOPE Program is funded by a $15 million Medical Research Future Fund (MRFF) grant, as well as contributions from program partners.

ANZCTR Trial ID: TBA

Felix-Method for Separating DNA intact sperm to improve IVF Outcomes

Prof Rob McLachlan, A/Prof Hassan Bakos, Prof Deidre Zander-Fox, Dr Leanne-Pacella-Ince
Monash IVF Group, University of Newcastle and Memphasys Ltd

Current semen preparation methods in Assisted Reproductive Technology (ART) do not assess the molecular integrity of sperm. The selection of sperm for ICSI is usually based on morphological suitability which is determined by low magnification screening. Sperm with high levels of DNA damage are known to result in reduced fertilisation rates, poorer embryo development, reduced pregnancy rates, and increased levels of miscarriage. The Felix^TM System, manufactured by Memphasys Ltd, uses electrophoresis and size-exclusion membranes to separate DNA intact sperm. The Monash IVF Group has partnered with Memphasys to undertake a clinical study to evaluate this new technology. Density Gradient Centrifugation (DGC) and Swim-up (SU) are two globally established methods for the preparation of sperm for assisted reproductive technologies. This project was designed to assess the safety and performance of the Felix™ System in comparison to the DGC and SU method.

ANZCTR Trial ID: ACTRN12622000439741

NuLIFE: A prospective placebo-controlled trial investigating the ability of uterine application of a copper chloride containing gel to modulate endometrial cytokine production in healthy women

Prof Kelton Tremellen, Dr Erin Morton
Monash IVF Group, Flinders University and NuLIFE B.V., Netherlands

IVF treatment. Even when a high-quality genetically normal embryo is transferred to the uterus, only 50% of these embryos successfully implant. As such, inefficient implantation rates are the “Achilles’ heel” of IVF treatment, resulting in significant psychological distress to patients and costs. Therefore, new therapies that augment successful implantation are urgently required. Successful implantation of the embryo requires appropriate development of the adjacent endometrium to assist embryo cell division, attachment, and invasion. Several cytokines and growth factors have been identified whose expression in the endometrium occurs at the time of implantation and have been suggested as biomarkers for uterine receptivity. Two of these growth factors, Leukaemia Inhibitory Factor (LIF) and Vascular Endothelial Growth Factor (VEGF) have been consistently reported to be essential to implantation, with endometrial and uterine fluid levels of LIF and VEGF being significantly higher in fertile women compared to those experiencing recurrent IVF implantation failure. We propose a proof-of-concept study in which we will investigate the possibility that application of an investigational gel to the endometrium will also up-regulate endometrial LIF and VEGF production in vivo, similar to our in vitro results.

ANZCTR Trial ID: ACTRN12621001666819

Clomiphene in male infertility (CIMI) trial: A double-blind randomised placebo-controlled trial of clomiphene in normogonadotrophic idiopathic male infertility

Dr Sarah Catford, Prof Robert McLachlan, Prof Luk Rombauts, Dr Ie-Wen Sim, A/Professor Darren Katz, Dr Tristan Hardy, A/Professor Kate Stern
Monash IVF Group, Hudson Institute of Medical Research, Men’s Health Melbourne, and The Royal Women’s Hospital

Male infertility affects 2.5-12% of men worldwide and contributes to 30-50% of couple infertility. Studies suggest that medical therapies including clomiphene may be a therapeutic option in idiopathic male infertility with normal levels of gonadotrophins. Clomiphene has been used to treat male infertility since the 1960s with some studies showing its use can improve semen parameters, sperm retrieval rates, and pregnancy rates. However, existing data are conflicting and of poor quality with no clear evidence of benefit. Due to limited data, Clomiphene has not been approved by regulatory authorities for this indication. This study will evaluate whether Clomiphene improves sperm quantity and quality in men with idiopathic oligozoospermia and normal gonadotrophins. Eligible men will be recruited from fertility clinics in Melbourne and consenting participants will be randomised to clomiphene or placebo for 6 months. During the study, participants will complete online surveys, and undergo clinical reviews, blood, and semen testing to monitor hormone levels, semen parameters, and any side effects.

ANZCTR Trial ID: ACTRN12623000329662

Research Studies

Establishment and validation of the ‘exposome’ as a prognostic predictor of female fertility

A/Prof Mark Green, Dr Bradley Clarke, Prof Deidre Zander-Fox, Prof Luk Rombauts
Monash IVF Group and University of Melbourne

There is now an increasing reliance on Assisted Reproductive Technology (ART) in order to conceive. It is postulated that the rising trend in infertility can be partially attributed to exposure to man-made environmental toxicants, such as endocrine disrupting chemicals (EDCs), found in many everyday household items and personal care products. The aims of this project are to firstly, establish and validate methodologies to quantify the ‘exposome’, and secondly, the accurate quantification of EDCs in the blood, urine and follicular fluid of patients. EDC concentrations will then be analysed with respect to clinical measurements of fertility to determine whether a negative correlation exists between EDCs and patient outcomes measures (i.e. number of eggs, as well as fertilisation, blastocyst and utilisation rates). The findings of this study will provide preliminary data to determine whether the exposome can be used as a reliable prognostic marker for egg quality and thus fertility. The project outcomes have substantial scope for understanding how exposure to chemicals can influence clinical success rates.

Development of a non-invasive test to screen IVF endometrial receptivity - iREST (IVF Receptivity Endometrium Screening Test)

Prof Kelton Tremellen, Dr Tristan Hardy, Dr Joachim Alfer
Monash IVF Group, Institute of Pathology, Ravensburg, Germany and Pronacera, Seville, Spain

The process of implantation of an embryo is a complex cascade of events. Following ovulation there is a rise in reproductive hormones and epithelial cells transform into highly active secretory cells that synthesise various substances (nutrients, growth factors, cytokines) known to enhance embryo development and alter endometrial function to facilitate implantation - opening of the “window of implantation” (WOI). This study proposes that a non-invasive, inexpensive test, independent of menstrual cycle stage, the iREST assay (Receptivity Endometrium Screening Test), can be performed on a peripheral blood sample to predict whether the endometrium is receptive and adequately mature for successful implantation.

Whole Genome Sequencing of Embryos for Preimplantation Genetic Testing

Dr Tristan Hardy, Dr Jan Liebelt, Prof Deirdre Zander-Fox, Dr. Leanne Pacella-Ince,Prof Kelton Tremellen, Dr Emily Button
Monash IVF Group

The purpose of this study is to improve the current form of embryo genetic testing by using sequencing technology. Our group is exploring novel ways to use sequencing data to analyse the DNA fingerprint of embryos and provide an assessment of the likelihood of aneuploidy (PGT-A), structural rearrangements (PGT-SR), and single gene conditions (PGT-M). The workflow is designed to improve the patient experience and reduce the need for additional samples from family members prior to having PGT, easing the transition from test design to embryo testing.

Impact of Early Pregnancy Screening on Perinatal and Childhood Welfare – a Fourteen Year Review. Understanding antenatal ultrasound findings and their impact on pregnancy, newborn, and childhood outcomes: A population-based linkage study

Dr Andrew McLennan, Dr Kata Kraljevic, Dr Jonathan Morris, Dr Jillian Patterson
Monash IVF Group, The University of Sydney, Kolling Institute of Medical Research

This project will examine 17 years of early prenatal screening for genetic abnormalities and adverse pregnancy outcome (2006‐2022) from approximately 220,000 obstetric patients with over 600,000 ultrasound examinations conducted at Sydney Ultrasound for Women. Pregnancy, perinatal and childhood outcomes for this cohort will be identified through linkage with multiple NSW Health databases covering both short‐term pregnancy outcomes and longer‐term childhood development. In conjunction with the Women and Babies Research Group at the Kolling Institute, this research will provide an assessment of screening accuracy and long‐term outcomes for chromosomal and genetic anomalies, adverse pregnancy outcome risk prediction, fetal structural abnormality diagnostic accuracy, pre‐term birth prediction using cervical length screening, fetal growth restriction assessment, and adverse twin pregnancy outcome prediction. This is a unique opportunity to highlight the benefits of innovative clinical research in private practice and to assess the potential for translation into improved perinatal and childhood development outcomes.

Defining the male contribution to pregnancy immune tolerance deficit in women

Dr David Sharkey, Prof Sarah Robertson, Prof Kelton Tremellen
Monash IVF Group and Robinson Research Institute, University of Adelaide

This project will generate new knowledge and understanding of factors in male partner seminal fluid that influence a couple’s fertility and reproductive success by identifying novel agents in human seminal plasma and sperm that are associated with promoting immune adaptation in women and determining links in couples between composition of seminal fluid, immune tolerance, and fertility. Advancing knowledge on this novel paternal contribution to reproductive success will enable the identification of pivotal bioactive compounds in seminal fluid that promote immune tolerance in women. The outcomes have the potential to change practise in pre-conception planning, provide new diagnostic tests for unexplained male subfertility, and inform the development of new immune therapies for infertility. There is an urgent demand for improved tests for male factor infertility and this research is well-positioned to deliver a simple, microbead-based test that is expected to have widespread utility and uptake. The intellectual property to be generated from this work has potential for commercialisation and clinical translation.

Genetic studies on male infertility and the trans-generational health of children conceived through ART

Prof Moira O’Bryan, Dr Sarah Catford, Prof Robert McLachlan, Dr Gideon Blecher, Dr Ie-Wen Sim, Dr Darren Katz, Prof Luk Rombauts
Monash IVF Group, University of Melbourne, and Hudson Institute of Medical Research

Infertility affects 1 in 20 Australian men and male factors are involved in about half of all assisted reproductive technology (ART) treatments. Most often there is an unexplained failure of the testicular sperm tubules to produce adequate numbers of motile sperm capable of fertilisation. Genetic factors are suspected to be causal in many cases. Understanding such genetic factors may result in new diagnostic tests and ultimately specific treatments. Such research may also address uncertainties around the possible transmission of infertility to ART-conceived offspring. This ongoing complex study uses samples from the Monash Male Infertility data set, and in collaboration with the leading overseas investigators, as a part of the International Male Infertility Genetics Consortium, will forge ahead until the extent and impact of genetic variants in male factor infertility, including for the general and reproductive health of the man and his offspring, is resolved.

For more information on a research study or to participate in a clinical trial, please send all enquiries to mivfgresearch@monashivfgroup.com.