What's the Truth about...

The afternoon sitting of the Progress Educational Trust annual conference 'Reality Check: A Realistic Look at Assisted Reproduction' began with an extended session entitled 'What's the Truth about...'. The session, chaired by Joyce Harper, Professor of Reproductive Science at the Institute for Women's Health, University College London, aimed to examine the controversies and dispel the myths surrounding five key aspects of reproductive medicine.

The first two talks examined the relationship between ovarian stimulation protocols and the clinical outcome of fertility treatment. Professor Geeta Nargund, founder and medical director of CREATE Fertility, which specialises in natural and mild IVF, discussed mild stimulation for IVF. Dr Raj Mathur, consultant gynaecologist at St. Mary's Hospital, Manchester, talked about ovarian hyperstimulation syndrome (OHSS).

Professor Nargund asserted that mild IVF, which uses lower doses of drugs to stimulate follicle development within the ovary, has a number of benefits over conventional IVF. She argued that the stimulation protocols for conventional IVF are more expensive, increase the risk of OHSS, adversely affect the physiology of the endometrium, and alter the metabolism of the ovary, potentially reducing egg quality.

In addition, Professor Nargund presented research data which supported her proposition that mild IVF can produce comparable success rates to conventional IVF cycles, even though fewer eggs are collected. These research findings prompted Professor Nargund to question why high doses of stimulation drugs are still being used for IVF when mild ovarian stimulation can reduce the burden of treatment for fertility patients without compromising IVF success rates.

Dr Mathur dispelled some of the main misconceptions about OHSS, notably that it is a leading cause of maternal mortality. Using data from the UK, the Netherlands and Israel, Dr Mathur was able to demonstrate that OHSS-related deaths are 'extraordinarily rare' and emphasised how clinicians can use specific techniques to reduce the incidence of OHSS among their patients.

Dr Mathur explained that OHSS occurs as a direct result of ovarian stimulation. However, ovarian stimulation increases the number of eggs available for IVF treatment, which improves the likelihood of success. As a result, the risk of OHSS is tolerated, and subsequently managed, by the fertility sector. Professor Nargund's zeal for mild ovarian stimulation was not fully shared by Dr Mathur, who stated that 'egg number is a positive predictor of [IVF] success, so to deliberately aim for a lower egg number seems, to me, to be counterintuitive based on current data'.

The third speaker, Professor Christopher Barratt, Head of the Reproductive Medicine Group at the University of Dundee, presented 'What's the truth about ICSI?' and addressed more specifically whether the technique is being overused.

Professor Barratt described how ICSI is increasingly being used worldwide for non-male factor infertility, despite a lack of evidence demonstrating a clinical benefit. Neither the American Society for Reproductive Medicine (ASRM) nor the National Institute for Health and Care Excellence (NICE) recommend using ICSI as a treatment for non-male factor infertility, unless poor fertilisation has been observed following an IVF cycle. So why has this trend in ICSI use emerged?

Professor Barratt explored whether there is a financial incentive for clinics to offer ICSI to their patients over IVF. He estimated that a clinic which performs 500 cycles of ICSI for non-male factor infertility could generate an additional £700,000 per year in treatment costs. However, Professor Barratt does not believe that it is money driving fertility clinics to perform ICSI in non-indicated situations.

According to Professor Barratt, the inability to accurately predict the occurrence of poor or failed fertilisation following IVF may exert a greater influence on whether a clinic recommends ICSI to a patient or not. The development of commercially available tests that can measure sperm-egg binding and the sperm acrosome reaction may allow clinics to perform IVF with greater confidence. However, this potential resolution would require a significant investment of both time and money.

It is currently unclear whether there is enough motivation to develop these tests. ICSI is undoubtedly being used more frequently to treat non-male factor infertility. However, as Professor Barratt asked the audience at the end of his talk, 'Does it actually matter that we are doing this? Do we care?'

Jan Grace, clinical director of gynaecology services and consultant gynaecologist at Guy's and St. Thomas' Hospital, continued the afternoon session by considering whether preimplantation genetic screening (PGS) can improve IVF success rates. In her talk, 'What's the truth about aneuploidy screening?', Grace explained how it has been difficult to establish whether PGS is clinically useful in the IVF clinic due to a plethora of contradictory research studies.

The STAR trial, a prospective, multi-centre, randomised control trial, indicated that PGS may improve IVF success rates for older women. Nevertheless, this finding has been met with some scepticism as the study had not been specifically designed to assess PGS effectiveness in relation to patient age.

Grace did not feel that there was enough evidence, at present, to indicate that PGS improves IVF outcome. She stated, 'It's a screening test which hasn't been shown to be particularly effective or efficient; until it is non- or minimally invasive, accurate, straightforward, and of low cost, it is difficult to justify it as a routine test.'

The final talk of the session was given by Professor Robin Lovell-Badge, Head of the Laboratory of Stem Cell Biology and Developmental Genetics at the Francis Crick Institute, and Chair of Trustees at PET. Professor Lovell-Badge used his presentation to explore a more theoretical concern, namely, the implications of genome editing for Down's Syndrome.

Professor Lovell-Badge addressed the fear that genome editing could exacerbate the stigmatisation of people with Down's syndrome. He expanded on his earlier discussion of this issue in BioNews (see BioNews 963), explaining that while it might be possible in theory to edit the germline genome of an early embryo to address Down's, in practice it is not possible to predict which embryos will have an extra copy of chromosome 21.

By contrast, Professor Lovell-Badge said that by editing the genome of somatic cells at a later stage in life, it may in the future be possible to ameliorate some of the health complications associated with Down's syndrome. However, this is only a hypothetical possibility at present, and it would require many years of research and development to become a reality.

Professor Harper invited audience contributions, saying: 'I don't know if there is any other medical field that has quite as much controversy as we do'. A lively conversation followed, which incorporated both the professional and lay perspectives. Much of the discussion focused on the pattern of ICSI use, and on how fertility treatment options are communicated to patients.

The discussion highlighted that IVF is used more frequently than ICSI in China. Participants attributed this to the fact that some Chinese fertility clinics perform 'rescue-ICSI' on eggs that fail to show early signs of fertilisation shortly after the IVF insemination procedure, thereby reducing the risk of a failed fertilisation event. While thought-provoking, this practice is not currently available in the UK due to the potential risk of creating embryos that have been fertilised by more than one sperm.

The lack of effective therapeutic treatments for reduced sperm quality was criticised by one audience member. Indeed, until such restorative forms of treatment have been developed, patients who experience male-factor infertility will have to rely on ICSI to have their own genetic child. The general safety of ICSI was also questioned. It was felt that there was not enough evidence to comment on the safety aspect of the procedure at present. Nevertheless, it is clearly an important issue that needs to be resolved.

The panel of speakers were asked to discuss how complex scientific information relating to fertility treatment options can be communicated to patients more clearly. Professor Barratt felt that patients often experience confusion because some fertility clinics offer treatment options that are not recommended by professional bodies. These mixed messages were cited to be the root of patient uncertainty rather than the complexity of the scientific information.

Jan Grace acknowledged that fertility specialists are often faced with 'very emotive, distressed patients' who are willing to try anything to have a child, however, it seems that some clinicians are currently finding it difficult to balance professional responsibility with patient desire in these emotionally charged situations.

The session, which was sponsored by the Anne McLaren Memorial Trust Fund, was brought to a close by Professor Harper who aptly wondered what Professor McLaren's views on the session would have been. As one of the pioneering scientists in the reproductive medicine field, with a wealth of experience in both research and bioethics, her perspective on the session topics would have been dearly welcomed.

The Progress Educational Trust (PET) would like to thank the sponsors of its conference - the Anne McLaren Memorial Trust Fund, Edwards and Steptoe Research Trust Fund, CooperSurgical, the European Sperm Bank, Ferring Pharmaceuticals, the London Women's Clinic, NGA Law and the Institute of Medical Ethics.