Beyond Red, Yellow, and Green: The HFEA's Evolving Stance on IVF Add-Ons

In this Newsletter, I will be revealing some of my inner - and occasionally heretic - thoughts about Infertility and IVF, which have matured over the years of working as a fertility specialist and also as the CEO and Medical Director of Bourn Hall, the world's 1st IVF clinic.

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The Human Fertilisation and Embryology Authority (HFEA) (HFEA), the UK regulator for #IVF clinics, has recently updated their guidance around #IVF #add-ons. An add-on is a test or intervention that can be performed in addition to routine IVF treatment, for which there is no strong evidence of improving live birth rates in most cases. The HFEA had previously developed a traffic light system to describe the evidence behind each proposed add-on. For example, an add-on with some evidence of effectiveness would be given a ‘yellow’ light, with the ‘red’ light reserved for the more controversial add-ons.

The recently revised version of this traffic light system has introduced some useful changes, which, in my opinion, render this guidance a bit fairer. The previous ‘red’ category used to include add-ons with various traits and risks; it has now expanded into three separate categories: the ‘grey’, where the evidence is insufficient to determine if an add-on is beneficial; the ‘black’ where the evidence indicates it does not help at all; and the new ‘red’, where the evidence suggests it may pose some risk to health or may actually decrease the success of IVF. That’s great because these new categories indeed describe three completely separate entities that should be judged individually. If I were a patient, I would be much more open to considering an add-on where the evidence is not enough yet - and my doctor says they have had some good experience with it - rather than an add-on that could jeopardize my future health.

Another significant step in the right direction for the updated traffic light system is the exploration of outcomes other than #livebirth. We, the IVF professional community, have had a longstanding obsession with ‘live birth,’ and while it is probably the single most important outcome of IVF, it is by far not the only one that should matter. Patients certainly want the best chances of having a baby, but they also want to have a #baby as soon as possible or avoid the traumatic event of a miscarriage. They also want treatments that work for them and their unique circumstances, not just for everyone. The HFEA has humbly taken this message on board. In the example of #PGT-A (the genetic screening of #embryos before transfer), they have given a ‘green’ light that it could prevent miscarriage, even though they still call it ‘red’ for live birth.

I still find that the way the evidence for individual add-ons is evaluated is rather strict. For an add-on to achieve a ‘green’ light, the HFEA requires at least two high-quality #randomizedcontrolledtrials (RCTs - the gold standard of experimental clinical research) that originate from different research groups and both confirm improvement in live birth. RCTs in Reproductive Medicine are notoriously difficult to deliver, mainly because IVF patients are unwilling to be randomized to a placebo group, particularly if they are funding their IVF treatment privately. Recent attempts at conducting large, multi-centre RCTs in IVF have been discontinued before reaching the intended sample size. This means that what the HFEA demands based on evidence is probably unachievable for the majority of add-ons.

A typical example of how strictly the HFEA evaluates the evidence behind an add-on is their allocation of a ‘yellow’ light to Embryoglue (this involves a chemical called hyaluronic acid that is added around the embryo before transfer, which could help with the implantation of this embryo). For Embryoglue, there is accumulative evidence that it works, so much so, that the European Society of Human Reproduction and Embryology (ESHRE) is now recommending it for IVF. One has to assume that the HFEA interprets the same evidence in a somewhat more cautious way, since it still resisted giving Embryoglue a ‘green’ light.

My strongest concern about the revised traffic light system is that, in an effort to become more precise and fair in classifying add-ons, the system has become more complex and convoluted than before. It is no longer a straightforward traffic light system (with green, yellow, and red), but an elaborate concoction of colour codes. I wonder…if it were a real traffic light, would it lead to more road traffic accidents?

Let’s not forget that the ultimate recipient of this piece of HFEA guidance is the patient, not fertility specialists like myself. As a specialist, I have the benefit of substantial background knowledge and experience that helps me, after significant reflection, grasp the meaning of this traffic light system. Will the average patient be able to read through this guidance and truly understand what it means? I have my doubts. Of course, the main message for most of the add-ons is that one should be cautious and, ideally, avoid them altogether. However, everyone working in the field of IVF knows well that patients are interested in many of the add-ons and will likely continue to request add-on interventions, in an attempt to shorten their journey to parenthood.

Any tool that empowers patients to make better choices is certainly welcome from patients and professionals alike. It is important that any new tools are retrospectively evaluated by real patients to ensure that they are doing what they were destined to do. Clinics have an important role in this by encouraging the receipt of feedback from their patients and feeding this onwards to the HFEA.

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