Tag Archives: Mel McDowall

New technique to aid IVF embryo selection

28 August 2017:

Researchers at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) have successfully developed an advanced new imaging technique, which can help assess the quality of early-stage embryos.

The research, reported in the journal ‘Human Reproduction’ has the potential to significantly benefit the IVF industry of the future, improving assisted reproduction outcomes for women.

“We use a special type of imaging to show differences in the metabolism and chemical make-up of embryos before they’ve been implanted,” says lead author Dr Mel Sutton-McDowall (pictured).

“This technique can give us an objective measure of which embryo to choose as part of the IVF process.”

This ‘hyperspectral imaging’ measures light that cells naturally produce during their normal activities. The light or ‘autoflorescence’ produced changes according to the chemical reactions or metabolism going on in the cell.

Being able to measure embryo metabolism is viewed by many researchers as one of the most important factors as to whether a particular IVF program will be successful.

However, says Dr Sutton-McDowall, fertility specialists take a largely subjective approach in deciding which embryos should be used.

“Pre-implantation screening of embryos generally takes place under a normal optical microscope. Although it’s quite easy to discern poor embryos (due to differences in uniformity), it is far harder for the clinician to determine objectively, the viability of the other embryos,” she says.

“The challenge is how to choose the single healthiest embryo out of this group to maximise the chances of pregnancy.”

Dr Sutton-McDowall sees the use of hyperspectral imaging as a new tool that can be combined with other diagnostic methods to provide a more accurate and objective embryo viability assessment.

“The benefit of hyperspectral imaging is that it can capture information-rich content of inspected objects. It analyses every pixel in an image for its light intensity at differing wavelengths,” she says

“This lets us drill down and analyse the hyperspectral signature of each individual embryo, looking for known or anomalous characteristics. It lets us discriminate between embryos, but also measuring metabolic differences within individual embryos. We predict that embryos that have cells with homogeneous (uniform) metabolic profiles are the healthier ones.”

To date, this imaging technology has only been tested on cattle embryos but Dr Sutton-McDowall notes that the technique is extremely promising.

“It offers benefits of being a non-invasive imaging approach that provides real-time information to the clinician,” she says.

The paper is accessible online.

Journal: Human Reproduction.

Publication title: Hyperspectral microscopy can detect metabolic heterogeneity within bovine post-compaction embryos incubated under two oxygen concentrations (7% versus 20%).

Authors: Melanie L. Sutton-McDowall, Martin Gosnell, Ayad G. Anwer, Melissa White, Malcolm Purdey, Andrew D. Abell, Ewa M. Goldys, Jeremy G. Thompson.

Abstract: 

STUDY QUESTION
Can we separate embryos cultured under either 7% or 20% oxygen atmospheres by measuring their metabolic heterogeneity?

SUMMARY ANSWER
Metabolic heterogeneity and changes in metabolic profiles in morula exposed to two different oxygen concentrations were not detectable using traditional fluorophore and two-channel autofluorescence but were detectable using hyperspectral microscopy.

WHAT IS KNOWN ALREADY
Increased genetic and morphological blastomere heterogeneity is associated with compromised developmental competence of embryos and currently forms the basis for embryo scoring within the clinic. However, there remains uncertainty over the accuracy of current techniques, such as PGS and time-lapse microscopy, to predict subsequent pregnancy establishment.

STUDY DESIGN, SIZE, DURATION
The impact of two oxygen concentrations (7% = optimal and 20% = stressed) during post-fertilisation embryo culture was assessed. Cattle embryos were exposed to the different oxygen concentrations for 8 days (D8; embryo developmental competence) or 5 days (D5; metabolism measurements). Between 3 and 4 experimental replicates were performed, with 40–50 embryos per replicate used for the developmental competency experiment, 10–20 embryos per replicate for the fluorophore and two-channel autofluorescence experiments and a total of 21–22 embryos used for the hyperspectral microscopy study.

PARTICIPANTS/MATERIALS, SETTING, METHODS
In-vitro produced (IVP) cattle embryos were utilised for this study. Post-fertilisation, embryos were exposed to 7% or 20% oxygen. To determine impact of oxygen concentrations on embryo viability, blastocyst development was assessed on D8. On D5, metabolic heterogeneity was assessed in morula (on-time) embryos using fluorophores probes (active mitochondria, hydrogen peroxide and reduced glutathione), two-channel autofluorescence (FAD and NAD(P)H) and 18-channel hyperspectral microscopy.

MAIN RESULTS AND THE ROLE OF CHANCE
Exposure to 20% oxygen following fertilisation significantly reduced total blastocyst, expanded and hatched blastocyst rates by 1.4-, 1.9- and 2.8-fold, respectively, compared to 7% oxygen (P < 0.05), demonstrating that atmospheric oxygen was a viable model for studying mild metabolic stress. The metabolic profiles of D5 embryos was determined and although metabolic heterogeneity was evident within the cleavage stage (i.e. arrested) embryos exposed to fluorophores, there were no detectable difference in fluorescence intensity and pattern localisation in morula exposed to the two different oxygen concentrations (P > 0.05). While there were no significant differences in two-channel autofluorescent profiles of morula exposed to 7% and 20% oxygen (main effect, P > 0.05), morula that subsequently progressed to the blastocyst stage had significantly higher levels of FAD and NAD(P)H fluorescence compared to arrested morula (P < 0.05), with no change in the redox ratio. Hyperspectral autofluorescence imaging (in 18-spectral channels) of the D5 morula revealed highly significant differences in four features of the metabolic profiles of morula exposed to the two different oxygen concentrations (P < 0.001). These four features were weighted and their linear combination revealed clear discrimination between the two treatment groups.

LIMITATIONS, REASONS FOR CAUTION
Metabolic profiles were assessed at a single time point (morula), and as such further investigation is required to determine if differences in hyperspectral signatures can be detected in pre-compaction embryos and oocytes, using both cattle and subsequently human models. Furthermore, embryo transfers should be performed to determine the relationship between metabolic profiles and pregnancy success.

WIDER IMPLICATIONS OF THE FINDINGS
Advanced autofluorescence imaging techniques, such as hyperspectral microscopy, may provide clinics with additional tools to improve the assessment of embryos prior to transfer.

Failure to launch: aberrant cumulus gene expression during oocyte in vitro maturation

22 November 2016:

Failure to launch: aberrant cumulus gene expression during oocyte in vitro maturation

http://m.reproduction-online.org/content/153/3/R109.abstract
Hannah M Brown, Kylie R Dunning, Melanie Sutton-McDowall, Robert B Gilchrist,
Jeremy G Thompson and Darryl L Russell

Abstract
In vitro maturation (IVM) offers significant benefits for human infertility treatment and animal breeding, but this potential is yet to be
fully realised due to reduced oocyte developmental competence in comparison with in vivo matured oocytes. Cumulus cells occupy
an essential position in determining oocyte developmental competence. Here we have examined the areas of deficient gene
expression, as determined within microarrays primarily from cumulus cells of mouse COCs, but also other species, between in vivo
matured and in vitro matured oocytes. By retrospectively analysing the literature, directed by focussing on downregulated genes, we
provide an insight as to why the in vitro cumulus cells fail to support full oocyte potential and dissect molecular pathways that have
important roles in oocyte competence. We conclude that the roles of epidermal growth factor signalling, the expanded extracellular
matrix, cumulus cell metabolism and the immune system are critical deficiencies in cumulus cells of IVM COCs.

eChallenge success!

echallenge3sq18 November 2016:

Team ‘Life Whisperers’, composed of CNBP researchers from the University of Adelaide, Melanie McDowall and Jonathan Hall, together with their mentor Michelle Perugini have won first prize in both the Medical Innovations and Research Commercialisation categories of the ‘Australian eChallenge’ competition.

Run by the Entrepreneurship, Commercialisation and Innovation Centre (ECIC) at the University of Adelaide, the eChallenge is a competition based learning experience that develops strategic business thinking for early-stage entrepreneurial ventures. Participants pitch their venture concepts to potential investors from the local business community. This year it attracted 152 teams across a number of categories.

The successful ‘Life Whisperers’ team proposed and pitched to judges, a new non-invasive diagnostic product to help improve embryo selection and ultimately improve positive IVF outcomes. In winning both categories, the team won $20,000 ($10,000 per category) with the money able to be used to help support future startup activity.

 Below – Entrepreneur Steven Fang presents Jonathan and Mel with one of their winning cheques.

echallenge1-edit

Coverage: Barbara Kidman Fellowships

Barbara-Kidman10 December 2015:

University of Adelaide and CNBP researchers Dr Sabrina Heng and Dr Melanie McDowall are recipients of the Barbara Kidman Women’s Fellowship for 2016.

The Fellowship supports  female academics in enhancing and promoting their career, following time out of the workplace due to carer’s or family leave. The Fellowship is for 12 months and can be used for research support, overseas travel or professional development.

Both Sabrina and Mel were interviewed about the award, their science and their experiences in academia more generally on Radio Adelaide’s ‘Sound of Sciene’ program.

The full interview can be heard online here.

A win for trans-disciplinary and trans node research

Mel McDowall High Res Edit 0040

12 June 2015:

It just goes to show that collaborations work! CNBP researcher Mel McDowall has won the “International Award for Best Abstract (Australia/New Zealand)” at the Study of Reproduction (SSR) annual conference that will be held in San Juan, Puerto Rico 18–22 of June. Based in the USA, SSR is one of the largest reproductive societies in the world.

The study, titled “Non-invasive detection of metabolic heterogeneity in cow embryos as a predictor of developmental competence” aimed at investigating patterns of different metabolism within embryos cultured in optimal or stressed conditions and stems from a collaboration between Ewa Goldys, Martin Gosnell and Ayad Anwer (Macquarie University); Andrew Abell and Malcolm Purdey (University of Adelaide) and Jeremy Thompson.

In the final experimental stages, this study is already making a big impact on the reproductive biology world!

A picture says a 1000 words

Mel McDowall High Res Edit 004001 May 2015 :

A recently published article by Mel Sutton-McDowall and collaborators (Jeremy Thompson, Malcolm Purdey, Ewa Goldys, Hannah Brown and Andrew Abell) has made the front cover of the Molecular Reproduction and Development Journal. The paper examined the influence of an oocyte specific growth factor BMP15  follicle stimulating hormone (FSH) on oocyte metabolism. The study was the result of CNBP cross nodal and transdisciplinary collaboration.

The cover can be found : http://onlinelibrary.wiley.com/doi/10.1002/mrd.22394/abstract;jsessionid=5318322C961EE49865D8E3C683A2E7EE.f01t01

and the paper is available here: http://onlinelibrary.wiley.com/doi/10.1002/mrd.22470/abstract