In the decades since the world's first IVF baby was born in the UK in 1978, fertility treatment has changed from being experimental to routine. Around 10 million IVF babies have so far been born worldwide. However, all medical treatments come with some risk, and fertility treatments are no exception. The Progress Educational Trust's event 'Prioritising Patient Safety: How to Minimise Risk in Fertility Treatment' explored what is known about risks, and what can be done to minimise them, in the context of IVF.
The event was chaired by Sarah Norcross, with speakers Professor Abha Maheshwari (clinical director of Aberdeen Fertility and lead clinician at Fertility Scotland), Dr Michael Rimmer (specialist registrar in obstetrics and gynaecology and clinical research training fellow at the University of Edinburgh), Professor Ashley Moffett (emeritus professor of reproductive immunology at Cambridge University), Professor Marian Knight (professor of maternal and child population health at the University of Oxford), and Rachel Cutting (director of compliance and information at the Human Fertilisation and Embryology Authority, or HFEA).
Professor Maheshwari spoke about increased risks to women associated with IVF. Maternal risks increase for certain women because of a range of pre-existing factors (some of which lead to increased risk in pregnancy with natural conception too), including having had previous cancer treatment, polycystic ovary syndrome (PCOS), renal transplant or Turner's syndrome. Various factors associated with IVF may also increase some of the risks – for example, both extended embryo culture and frozen embryo transfer increase the risk of having larger babies, associated with increased likelihood of caesarean sections. Professor Maheshwari's take away suggestion was that patient care should be individualised as far as possible, and clinicians should look at individual patients' risk – and, crucially, try to modify it – by taking into account a matrix of factors prior to them attempting to conceive. As she concluded: 'One size doesn't fit all.'
Dr Rimmer spoke about ovarian hyperstimulation syndrome (OHSS) – its causes and consequences, how it presents, and how it might be prevented. He explained that it is difficult to predict which patients might suffer from OHSS, or how severely, when their ovaries are stimulated to produce multiple eggs for IVF treatment (or egg donation). Symptoms range from 'mild' abdominal pain and distension caused by fluid leaking from blood vessels to nausea and vomiting in 'moderate' conditions, and risk of blood clots, respiratory distress and/or pulmonary embolism in 'severe' cases. Mild OHSS is experienced by around 33 percent of patients, while severe OHSS affects just 1-2 percent. Risk factors include being younger, having a high follicle count, PCOS, previous OHSS, the number of eggs retrieved, and becoming pregnant following a stimulated cycle. Patients are driven to want to have as many eggs retrieved as possible in one attempt, as they don't want to undergo multiple stimulated cycles at additional cost and risk. Clinicians must strike a balance between accommodating this, and reducing the risk to patients. This can be done by taking an individualised patient-focused approach, adapting the stimulation protocol and/or the time of embryo transfer.
Professor Moffett began by saying that the idea that the maternal immune system is a threat to the embryo or fetus is wrong, and cannot justify the provision of 'immune' treatments as an 'add-on' to fertility treatment. Uterine natural killer (NK) cells are not actually 'killers' (see BioNews 1128). The cells from the mother and the baby are kept separate, and the NK cells are thought to be important in maintaining this barrier. Professor Moffett said that although the functions of NK cells are still not clearly understood, there is no evidence to show that they are in any way harmful during pregnancy. Clinicians should not use immunosuppressants as an adjunct to IVF, especially not during a virus pandemic (!).
Speaking of the pandemic, Professor Knight presented on what is known about COVID-19 in relation to pregnancy, as well as the effects of vaccinations. Sadly, there have been both maternal and infant deaths that have been attributed to COVID-19, and it has become clear that not being vaccinated makes pregnant mothers more vulnerable. Professor Knight explained that women were more likely to be admitted to hospital with COVID-19 during pregnancy if they were older, had a high BMI, or were from certain ethic groups. Comorbidities such as diabetes or hypertension increased the risk, and all of these indicators also increased the likely severity of an infection.
It has been shown (in data that encompasses studies up to and including the Delta variant) that vaccination is highly protective. The data also showed that women were less likely to have pre-term birth if they had received one or more doses of the vaccine. Though not included in the data presented, Professor Knight remarked that in relation to the Omicron variant, there have as yet been no reports of fully vaccinated pregnant women experiencing severe COVID-19. Crucially, it has also been established that COVID-19 vaccines do not affect fertility (beyond a transient effect on male fertility) or IVF outcomes.
Rachel Cutting spoke about the HFEA's recent publication containing data on multiple births (see BioNews 1132). She started by showing the reduction in multiple births that followed the 'one at a time' campaign, launched in 2007, which encouraged clinics to transfer only one embryo in IVF treatments in all but a few situations. Since that campaign, the multiple birth rate has decreased to a record low of 6 percent (from a high of near 30 percent) of all IVF births. However, the recent report showed that the multiple birth rate remains slightly higher for patients of black ethnicities and for younger, privately funded patients.
Questions from the audience included whether better public funding of IVF could help to reduce some of the risks discussed. Panellists agreed this could be the case – Professor Maheshwari said that in Scotland, where IVF is better funded, there is a lower multiple birth rate. In fact, Scotland has the lowest multiple birth rate of the UK (at 4.7 percent) together with the highest IVF success rates. Rachel Cutting added that part of the evidence supporting the 'One at a Time' campaign had come from Belgium, where multiple births were low and there was generous state funding for treatment. Overall, the panellists agreed that more individualised care and pre-conception optimisation of treatment, and better data collection, could help to minimise risks to patients. All speakers wanted to see patient safety addressed in the next iteration of the NICE guideline on fertility treatment.
PET is grateful to the Scottish Government for supporting this event.
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