16 March 2020

The spread of a novel coronavirus (SARS-CoV-2), which causes the disease COVID-19, presents UK fertility clinics and patients with a unique set of challenges. Some of this is because we simply don't know enough about the effects of the infection on fertility, fertility treatment and early pregnancy. Early data, summarised in the Royal College of Obstetricians and Gynaecologists guidance, are reassuring, but the number of reported cases is still small.

Clinics could face logistical challenges if large numbers of staff are unable to work due to quarantine requirements, or if elective work in hospitals is shut down to make space for emergencies. Should this prospect impact the advice we give patients? The UK Government, at the time of writing, has held back from the more radical social distancing measures implemented in other countries. This leaves clinics with a dilemma of whether to continue to offer fertility treatment to unaffected patients, or to go beyond current Government advice and suspend services.

Patients' anxieties are understandable and those who wish to delay their treatment should be accommodated. It makes sense for anyone who meets the criteria for self-isolation (which are also evolving as we write) to be advised not to start treatment and indeed to stop active treatment if already commenced.

Some would go further and say that all elective fertility treatment should be delayed. The European Society forHuman Reproduction and Embryology advises that all fertility patients should 'avoid becoming pregnant at this time'. A Twitter poll targeting reproductive medicine clinicians found 45.5 percent support for delaying frozen embryo replacement in patients in areas with a high COVID-19 burden.

The question then arises, for how long should treatment be delayed? It is reported that the UK will see the peak of infections three months from now, with a tail persisting into the autumn and a potential second peak after this. If we were to delay all fertility treatment, UK clinics may struggle with the capacity to cope with demand when treatments re-start. One could easily envisage a delay of six months, which may well harm the chances of conception for some patients. Hence the need for advice to be tailored to each individual patient's situation. Delaying treatment, in effect closing clinics, would have other impacts including financial strain (particularly for smaller stand-alone clinics) and loss of morale among the more vulnerable fertility patients.

Furthermore, Chinese researchers have identified that testicular Leydig cells and seminiferous tubules express the angiotensin-converting enzyme 2 (ACE2) receptor, which is used by the virus to gain entry into cells. This short discussion paper has not been peer-reviewed and there is no evidence to suggest that the virus is found in the testes, as reported in BioNews 1039. However, this paper does alert to the need for further research into whether male fertility may be affected by COVID-19, so that patients can be adequately counselled.

The fact is that this is a fast-moving situation, with facts and knowledge changing daily. This makes it hard for professional bodies to issue meaningful guidance to practitioners and patients. The American Society for Reproductive Medicine even calls its guidance 'suggestions', showing the tentative nature of such advice. As far as UK clinics are concerned, unless restriction of movement is introduced, it is reasonable to continue treatment for those who are well and wish to continue. However, centres must be prepared to terminate or complete treatment (including through cycle cancellation, oocyte or embryo freezing) and cease initiating new treatments as and when 'lock-down' commences.

Clinicians have in their toolbox measures, which can be taken proactively, to reduce the risk to patients who find themselves in a situation where treatment has to stop. A patient may develop symptoms, or fall into a risk group, for COVID-19 after having started ovarian stimulation. Patients on a g onadotropin-releasing hormone (GnRH) antagonist regime could be managed by stopping follicle-stimulating hormone (FSH) administration and continuing antagonist administration until the patient's ovarian response has settled. Data from small case studies indicate that GnRH antagonist continuation after the trigger of final oocyte maturation is effective in reducing the risk of ovarian hyperstimulation syndrome (OHSS). Where concern exists about a high ovarian reserve, consideration should be given to co-treatment with letrozole, keeping oestradiol levels low and reducing concern about the risk of OHSS.

The key is anticipation of problems, both clinical and organisational. All centres should have a contingency plan in place that describes a stepwise reduction in their activities. This allows prioritisation down to a minimal activity if needed. It is unlikely that any licensed fertility clinic can shut down completely; work goes on behind the scenes, in particular around the maintenance of storage banks. There are practical considerations for this maintaining tanks for example but also the regulatory issues around consent expiry and data management. Urgent medical issues will still arise, and it may be appropriate to maintain a fertility preservation service for cancer patients. This prioritisation must take into account national and local pandemic policies, as well as recognition of likely reduced levels of staffing due to illness and isolation. Mitigation policies may include replacing consultations with phone- or video-calls and making sure there is a good communication policy for patients who have treatment-related problems.

We must also bear in mind the anxiety that is generated by how this pandemic is playing out. In our connected world, news, including fake news, travels faster than the virus. It is hard to escape the sense of a storm looming or a tidal wave about to break. In some countries, of course, the storm is now raging and the tide has overwhelmed even well-resourced health systems.

Fittingly for the first pandemic of the social media age, there have been extensive informal discussions on these issues among clinicians across many social media platforms. US colleagues have collated a number of measures, gleaned from social media, that clinics should consider in their response to this challenge.

Things are moving apace, and we must respond in a safe and effective way, but without panic. The British Fertility Society and the Association of Reproductive Clinical Scientists are committed to providing guidance to UK clinics as the situation evolves.

Link:
Keep calm and... stop? Fertility treatment in a pandemic - BioNews