12 December 2011
ByAppeared in BioNews 637
The third session of the Progress Educational Trust's annual conference 'The Best Possible Start in Life: The Robust and Responsive Embryo boasted a redoubtable roll-call of eminent clinicians and researchers as speakers. This being the case, I couldn't help wondering if the decision to limit such luminaries to ten minutes apiece was a wise one.
But I was wrong. The decision to allow as much time as possible for questions from the floor bore fruit and this session's lively Q&A fuelled an atmosphere of debate that was to continue into the afternoon. This pre-lunch back-and-forth was, I'd argue, where the conference, sponsored by Merck Serono, came alive.
Perhaps this was thanks to the excellent, engaging presentations that had gone before. The session's title was 'Making the grade' and as Mr Anthony Rutherford, chair of the British Fertility Society, who chaired the session, explained, the theme here was diagnostic testing in fertility treatment and IVF. A central question was how embryologists can best determine which of the embryos produced during IVF have the greatest chance of healthy development and therefore should be transferred to the patient's uterus. This is a particularly vexed question – many IVF cycles will fail precisely because we are currently unable to answer it reliably.
The first speaker, Dr Simon Fishel, managing director of CARE Fertility, is perhaps one of the best-placed scientists in the world to tackle this thorny issue. His many career firsts include the successful implementation of a screening technique called array comparative genomic hybridisation (aCGH), which led to the birth of baby Oliver, born to a mother whose 13 previous attempts at IVF had failed.
Dr Fishel's presentation was an accessible and concise introduction to the whole topic. He began his talk by noting that assessment of embryo viability has come a long way over the last decade: 'For years what we've done is we've taken a single point in time, we've looked down the microscope, we've worked out the morphological score and we've based the potential viability on that. We now know things are very different'.
Of course, embryo imaging has also come of age and embryologists now, said Dr Fishel, have access to 'a whole range of phenotypic images'. Thus they can now better evaluate the speed and evenness with which the cells in the early embryo divide (or, more accurately, 'cleave') and make judgments based on such observations.
Dr Fishel also introduced the newer DNA tests which may help scientists select the most viable embryos. This topic was developed more fully in the next talk, 'From personal genomics to embryomics – how far should we go?' by Professor Alan Handyside, consultant in preimplantation genetics and screening at the London Bridge Fertility, Gynaecology and Genetics Centre.
Again, Professor Handyside is almost uniquely well-placed to discuss this, having led the team at Hammersmith Hospital which reported the first unaffected child born after PGD (preimplantation genetic diagnosis). That child turned 21 this year.
Professor Handyside began discussing the implications of whole genome sequencing, reminding the audience that, while the cost and time of sequencing were reducing at an alarming rate, 'it may be 20 or 30 years before we can interpret much of the information [from a fully sequenced genome] in a meaningful way'. Would whole genome sequencing be used on IVF embryos in the future? Professor Handyside said that his 'feeling is that what is going to happen – and what is happening already – is that prospective parents are going to be the ones that are going to have their genomes sequenced'.
He concluded his talk with an outline of the new techniques (aCGH was included) which enable embryologists to diagnose aneuploidies – the absence of chromosomes or the presence of extra chromosomes – which would otherwise lead to the failure of IVF treatment.
Next to the stand was Mr Luciano Nardo, a consultant gynaecologist and reproductive surgeon, and director of GyneHealth, Northwest Fertility and Conceive International. His talk on 'Periconceptual [the time before and after conception] assessment of female reproductive performance and individualisation of IVF treatment' was something of a break from the embryology-focused presentations that preceded it.
Such a break was perhaps necessary as a reminder that successful IVF requires more than 'just' the implantation of a viable embryo to result in a successful pregnancy. The focus for much of Nardo's talk was anti-Müllerian hormone (AMH). The concentration of AMH in the blood relative to the optimum level has recently been shown to be a good predictor of the success of IVF.
The final talk in the session, by Professor Helen Picton, professor of reproduction and early development at the University of Leeds and scientific director of Leeds Teaching Hospitals NHS Trust's Reproductive Medicine Unit, returned to the theme of embryonic assessment. Professor Picton began by reminding us that aneuploidy screening and other techniques, though extremely promising, were also currently too expensive for widespread use. This meant that most embryologists were reliant on embryo morphology scores and cleavage rates when assessing which embryos to implant. These techniques, Professor Picton told us (using the graphical aids of embryo images and mawkish baby photos) are far from perfect.
Professor Picton went on to discuss a growing body of work in the field of metabolomics, where embryos' metabolic turnover is assessed by measuring the concentrations of metabolites – amino acids in particular – present in the embryo culture medium. Much of this work builds on the 'quiet embryo hypothesis' of Professor Henry Leese of the University of York. In Professor Picton's analogy this hypothesis postulates that the most viable embryos are the marathon runners of the embryo world, they are 'primed to be efficient, they don't burn up their fuel too fast'.
Professor Picton presented some of the evidence supporting the quiet embryo hypothesis before the Q&A session began. Several hands were raised immediately and Professor Marilyn Monk, the speaker for the opening session; Simon House, chair of the McCarrison Society for Nutrition and Health; and Dr Joyce Harper, reader in genetics and human embryology all asked probing questions.
But it was a question – or rather a series of questions – from Professor Peter Braude of King's College London which really fired the debate. He began by asking: 'How should new technologies be introduced in IVF practice? How do we know that they work? And why is it that currently when we introduce a new technology there's a lesser standard than if we're bringing in new drugs?' After expressing the view that many IVF patients had been let down by the promises of PGS (preimplantation genetic screening) he asked: 'What are scientists going to do to demonstrate that before they implement it that [such technologies] really work and it's not a con?'
Professor Handyside replied first, countering that while PGS 'was pushed as improving pregnancy rates' its advantages are in fact other – the technology, if properly used, could rather prevent the implantation of unviable embryos. He said that it was a 'scandal' that so many of these were implanted each year.
Professor Picton followed on, saying that due to the constraints placed on scientists in this field researchers were confined to working predominantly with mouse embryos. This placed them at a distinct disadvantage compared with those working in other areas.
Finally, Dr Fishel gave a spirited defence of the use of technologies before they've been fully validated in clinical trials.
'When you are faced with a situation where you're trying to improve an individual patient's lot', he said, 'if your underlying science shows that factor 'A' is a problem and process 'B' might eliminate factor 'A'...should you be allowed to use that with patient consent? That is a whole debate. I would be possibly abusing some of the advances that we've had in IVF over the years if I said that the only way we can move forward ever in this field is to get randomised controlled trials undertaken and finished. I actually think that's not going to be done in many situations'.
Such talk fed into the conference's final session, 'Should assisted conception always be evidence based?' which will be reported by BioNews, alongside a review of the fourth session, next week.