October 20, 2015

expert reaction to conference presentation (unpublished work) on mitochondrial DNA content and embryo implantation

Unpublished work presented at the 2015 American Society for Reproductive Medicine conference has reported associations between the mitochondrial DNA content of early stage embryos and their success at implantation in the womb following IVF.

Prof. Tina Buchholz, Scientific Director of the International Federation of Fertility Societies, said:

“The study from Fragouli et al offers a very interesting approach and it is certainly important to follow this up. So far however, this is a small study (with only 65 blastocysts used), and doesn’t provide sufficient evidence to implement in clinical practice. Certainly, mitochondria, as the powerstation of the cell, will play a role in implantation. But to measure the amount of mtDNA you need to perform an invasive approach, and futhermore it is not certain whether the result in one or a few cells is reflected throughout the whole embryo. We definitively need more research on this, and at this stage, I would be cautious in predicting this as a new biomarker.”

Prof. Daniel Brison, Professor of Clinical Embryology, University of Manchester, said:

“The work presented here is scientifically very interesting from a well know group with access to state of the art technologies.  Their work will improve our understanding of early human embryo development, understanding which is desperately needed to improve IVF success rates as the authors say, and also to increase the safety of IVF treatments.  I have not seen the full details of the study so cannot comment on the success rates claimed for this particular method of detected mitochondrial DNA in embryos, but we should remember that many IVF cycles fail because the woman is not receptive, so that embryo selection no matter how careful will not help.  Also this technique is only likely to be useful  in a small proportion of cycles in which embryos are cultured to the blastocyst stage and multiple embryos are then available for selection.  Finally the fact that these embryos have to be cultured for longer in the laboratory to use this test might in itself be causing the stress which the test then detects, which could in the end be counterproductive. So like all new developments in science we should be both excited but also cautious about what it might mean in the real world.”

Prof. Adam Balen, Chair of the British Fertility Society and Professor of Reproductive Medicine and Surgery, Leeds Centre for Reproductive Medicine, said:

“There is a lot of interest in mitochondrial activity within eggs and developing embryos and this study presents a fascinating insight into the potential relationship between  mitochondrial activity in genetically normal embryos and their potential for developing into a viable pregnancy. It is still early days and the proposed test requires much more work and validation before application into clinical practice. There is no doubt this is a very important line of research and Dr Wells and his team are to be congratulated for what they have achieved to date.”

Prof. Simon Fishel, Founder and President of CARE Fertility Group, and Professor of Human Reproduction at CARE Fertility Group, said:

“This is an area gaining interest, not least because we know that ageing cells, and the eggs from older women, have less functional mitochondria. But to be used as a meaningful assay (test), mtDNA (mitochondrial DNA) levels need to be directly related to function. At the moment we don’t know that just measuring mtDNA levels relates meaningfully to different energy (ATP) production – the main function of mitochondria – and therefore reduced cell viability.  Secondly, the level of mitochondrial DNA will be related to the number of cells being analysed – this has yet to be clarified in assays. So it is very early days in this interesting lab research but we can’t yet consider it as a functional clinical test.”

Prof. Alison Murdoch, Head of Newcastle Fertility Centre at Life, Newcastle University, said:

“Women who carry major mitochondrial abnormalities are still able to produce embryos that develop well and make babies. Thus great caution is needed before this data from women with normal mitochondria can be related to potential fertility.”

Abstract title: ‘The biological and clinical impact of mitochondrial genome variation in human embryos’ by E Fragouli et al. presented at the 2015 American Society for Reproductive Medicine conference.

Declared interests

Prof. Tina Buchholz declares that she has no relevant interests.

Prof. Daniel Brison: Grant funding – current grant from Diabetes UK including some work on embryo metabolism. Voluntary appointments – HFEA Scientific and Clinical Advances Advisory Committee. Other financial interest – minor shareholder in Novocellus Ltd, University of York spinout working on assays of embryo metabolism.

Prof. Adam Balen declares that he has no relevant interests.

Prof. Simon Fishel: “I hold shares in CARE Fertility.”

Prof. Alison Murdoch declares that she has no relevant interests.