The HFEA statement on add-ons in IVF can turn hope into reality

Recently, the Human Fertilisation and Embryology Authority (HFEA) released a statement on adjunct treatments in IVF (see BioNews 983). The regulator had provided clear notice of its publication and both its stated intentions and content were as anticipated. Indeed, from the moment that a BMJ report in 2016 (commissioned by the BBC) claimed there was little evidence of benefit in most of the 27 'add-ons' studied, the HFEA recognised the need to act.

In the press, beneath headlines of 'IVF rip off clinics', the fertility patient was depicted as having been abandoned by a toothless regulator to the shenanigans of a rapacious IVF mafia. The chair of the HFEA announced soon after at a public meeting organised at the Royal College of Obstetricians and Gynaecologists by the Progress Educational Trust (which publishes BioNews), that adjuvant treatments were high on its agenda and a new website would include a traffic-light system to rate them all. And this has now been provided.

The HFEA has responded not just by insisting that all fertility treatments be 'offered ethically' but by seeking to create a culture change among fertility professionals in the UK that protects patients from potential exploitation while still encouraging innovation in clinical practice. The resulting document, endorsed by representatives of the major bodies representing the profession and patient groups, appears to have struck this balance (see BioNews 983).

For many clinics, it will sit comfortably with current practice as we have already taken steps to simplify the menu of treatments and to make pricing more inclusive and transparent. Procedures previously treated as add-ons, such as blastocyst culture, embryo freezing and time-lapse imaging are being increasingly adopted as standard practice, being included in the baseline cost of IVF treatment.

At the same time we perceive a shift away from 'shopping lists' of clinical adjuvant therapies being offered. This is in part being led by growing evidence from randomised clinical trials (RCTs) that blind application of empirical treatments such as endometrial scratching (see BioNews 957) may harm as many as they may help, and a recognition that such adjuvants should be based on a diagnostic rationale.

Simplified approaches, clear costs and readily understood inclusive packages represent one step in the right direction. Reducing our reliance on empirical approaches is another. A third step would be to adopt a responsible but realistic approach to implementing new innovations.

One example of this might be the elective freezing of all embryos. Trials of this approach are ongoing but will be of limited practical value guiding daily practice, because the stimulation regimens employed are designed to protect safety in the event of a fresh transfer rather than generating an optimal number of embryos for freezing.

Given the well-known rationales for adopting this approach, some clinics, including our own, have decided to move ahead of the evidence base and to implement this into routine practice.

Our field enjoys a high rate of innovation and current models for validating their value are no longer fit for purpose. A properly powered RCT takes time to design, achieve regulatory approval and to execute. The more 'definitive' the trial, the more likely it is that the technologies employed are obsolete by the time of publication.

A salutary example can be found in a recently published trial of endometrial preparation methods for frozen thaw cycles. Carefully designed and well-powered, the findings were considered obsolete at publication because practice had moved in the meantime to vitrification rather than slow freezing. The field had moved on. And patients can move the goalposts too.

The pioneers of egg sharing considered it a pragmatic means of increasing access to IVF and to donor oocytes. Despite resistance from the HFEA, it became popular, and ten years later the evidence base eventually caught up to support it. However, in the meantime, our patients' wishes had changed. The transformative impact of oocyte vitrification made donor egg banks a reality, and this source of donor eggs is increasingly perceived as more attractive compared with shared eggs. So now a new evidence base is required, and we will again be playing catch up.

We applaud the HFEA's statement on adjuvant therapies, because it reflects the way our patients and the profession want to go. But it's salutary to see that none of the add-ons so far identified and assessed are sent on their way with a green light. The bottom line is that none of these add-ons have enough evidence yet to confirm their safety and effectiveness as routine treatments.

Relying on RCTs to be the primary arbiter of the colour of a traffic light risks limiting the growth of the evidence base we need. However, we take some encouragement from the acknowledgement made in the statement that considerations of individual patient wellbeing may justify the use of treatments that languish under the ignominy of the red light. With that clinical freedom comes responsibility, and we support the further statement that clinics should collect outcome data prospectively and share this with researchers. The analysis of high quality and big data offers a fruitful way forward and the HFEA is in a strong position to support this.