01 August 2016
A number of media outlets recently reported a piece of research that offered the prospect of 'reversing the menopause'. Scientists in Greece had announced that they had rejuvenated ovaries after injecting eight perimenopausal women with the exotically named 'autologous platelet-rich-plasma' (PRP), leading to the restoration of menstruation and successful oocyte retrieval (see also BioNews 861). These oocytes were then successfully fertilised and cryopreserved.
The research was presented as a meeting abstract – a short communication, typically of less than 400 words – at the European Society of Human Reproduction and Embryology's annual meeting, although the authors now claim to have treated more than 30 women between the ages of 46 and 49. The team reports that this procedure 'works in two-thirds of cases'.
At first glance, this appears to be a significant breakthrough; women who were experiencing menopausal symptoms resumed menstrual cycles and were able to produce eggs. Undoubtedly, this is potentially very exciting and would have a major impact on the lives of a great many women. However, the key word in that sentence is potentially since there remain significant unknowns about this research.
Importantly the work, as reported, lacked any detailed control groups against which the observations could be compared. Moreover, in such a small number of women (eight reported) it is entirely possible that menstruation and egg development temporarily resumed naturally since these women were perimenopausal – a time signified by irregular cycles. A more fundamental question though is: 'Did this actually work?' Theoretically, it could have – PRP has been shown to cause stem cells to differentiate in laboratory experiments. In addition, there is growing evidence that the ovary contains a latent population of egg progenitor (stem) cells, so in theory the PRP could have caused the potential egg progenitors to differentiate into follicles containing eggs. However, just because something could happen, does not mean that it did. So, while the work has potential, it is much too early to consider this as a treatment option. In addition, we have no data to indicate whether the putative eggs that have been produced are genetically and metabolically normal and able to produce healthy embryos – and ultimately children.
It is well known that reproductive capacity for women is time limited – the dreadfully named 'biological clock' has entered into common vocabulary. Yet still, plenty of young women do not seemingly understand the importance of time-limited reproductive capacity. Recent data from the UK's Office for National Statistics showed that more children in the UK were born to women over 40 than to women under 20. Despite this, fertility falls as age advances – and there is a need for greater awareness of this, as concluded by the recent summit of the Fertility Health Task Force, and summarised excellently by the chair of the British Fertility Society, Professor Adam Balen.
Assisted reproductive technologies – including IVF, cryopreservation of gametes and embryos, and the banking of ovarian tissue – offer possibilities for extending the reproductive lifespan. A breakthrough into ovarian rejuvenation would be a very welcome addition to this for many, notably those women who suffer from premature ovarian failure, but also for the increasing number of young couples who feel that they have to wait until having a family – 'wait to finish Uni; wait to be in a stable job; wait until you can buy your first home; wait until the right moment in your career'. With such significant pressures, options to prolong the reproductive lifespan are appealing. While reproductive choice is essential, it must be balanced against the fact that delaying childbearing often results in the medicalisation of what for many is a natural process.
We must also ensure that future procedures are safe. In the case of autologous PRP, plasma from the patients themselves is used so there are no rejection issues, as there can be in conventional transplants or transfusions. However, PRP would not normally find its way into the ovary and so the effects of this need to be investigated in detail before subjecting women to such a procedure. Furthermore, we have no idea what effects PRP might be having on other actively developing cells in the body, e.g. blood cells, so safety is of paramount importance.
Moreover, there is a need to prove that it actually does work. Reproductive medicine is very special, and our patients are very well informed about the latest breakthroughs. As a consequence of a deep desire to have children, couples will go to extraordinary lengths to get pregnant. So new options are often met with excitement, and people are willing to try anything in the hope that it would work for them. This opens up the prospect for new treatment options to find a way to clinics, sometimes without being tested fully.
As researchers, we have a duty to ensure that any treatments that we offer women have, first and foremost, been shown to be safe and then effective. However, we need to be cautious – intervention in the creation of human life is an incredible feat of scientific endeavour and has transformed the lives of millions of people. But we must be mindful of the possible consequences and intervene in only safe, proven, reliable ways. Experimental discovery is necessary, but it must be robustly investigated before trials on humans are conducted.