In Defence of Women

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12 November 2018 - by Dr Geeta Nargund, Professor Stuart Campbell, Dr Svend Lindenberg, Dr Pasquale Patrizio, Professor Rene Frydman
Over the last ten years, the International Society for Mild Approaches in Assisted Reproduction (ISMAAR) has campaigned worldwide to put the welfare of women at the heart of fertility treatment.
IVF has been transformed over the last 40 years. One of the most startling changes is that a treatment which was originally intended to address the problem of tubal infertility is now regularly used to treat women who are both healthy and fertile. From male factor infertility, to elective egg freezing or same-sex couples wishing to start a family, the contexts of our practice have been irreversibly changed. These should rightly be regarded as advances, but with every step forward, we have an increasing responsibility to ensure that no healthy woman is made ill from fertility treatment.
Women undergoing IVF can experience a wide range of side effects, the most serious of which is Ovarian Hyperstimulation Syndrome (OHSS). In its mild form this affects as many as one third of cycles, with 3.1 to 8 percent being moderately or severely affected, according to the Royal College of Obstetricians and Gynaecologists.
Research has shown that if more than 15 eggs are collected during one cycle, women are at increased risk of OHSS without any increase in IVF success rates. The data from the Human Fertilisation and Embryology Authority (HFEA), released in response to parliamentary questions by MP Siobhain McDonagh between April to June 2018, revealed that between 2013 and 2017, 20 or more eggs were collected in 21,244 cycles, approximately 6.5 percent of total cycles in that period. Further, in 1860 cycles, more than 30 eggs and in some cases more than 50 eggs were collected in a single cycle.
At the same time, NHS data has recorded 836 emergency hospital admissions as a result of OHSS in a single year; a stark difference to the 60 cases reported directly to the HFEA. The true picture about hospital admissions can only be obtained if we link the HFEA registry with that of the NHS registry as is done in Scandinavia, Australia, USA and many other countries.
OHSS is often presented to women as a 'no pain, no gain' reality, yet it must be at least presented to patients that OHSS is a largely preventable condition and that the mild stimulation IVF treatment strategy delivers equivalent success rates per cycle while significantly reducing the risk of OHSS.
The aim of conventional IVF is to stimulate the ovaries to maximise the egg numbers, while in mild IVF, the aim is to obtain a mild response that will produce an adequate number of quality eggs to produce equivalent success rates. If the ideal number of eggs per live birth with conventional IVF in women with normal ovarian reserve is 15, with mild IVF it is about half that number and can be as few as five. The battle lines are drawn squarely between quantity and quality.
Statements that there is 'little doubt' that the conventional approach gives a woman a 'significantly better chance' must be challenged (see BioNews 973). The classic paper by Valerie Baker and colleagues who studied over 650,000 consecutive cycles from the American Society of Reproductive Medicine database demonstrated that there was an inverse relationship between the stimulating dose of follicle stimulating hormone and live birth throughout all age groups, including among women under the age of 35.
There are numerous papers confirming that mild IVF gives comparable success rates in terms of live births as conventional IVF. At present there is no large randomised study directly comparing the two methods, but that does not justify defenestrating the significant body of evidence demonstrating equivalence of success rates. This is not to mention the significant benefits that mild IVF brings in relation to health outcomes for women and children, and reduction in the burden of both treatment and the total cost.
The number of eggs collected per cycle in the UK is increasing annually with the risk of OHSS contained by the use of agonist trigger and 'freeze-all embryos' in the case of high oestradiol levels. While this strategy is an important emergency tool in reducing OHSS complications, it is not prevention and it should not be taken as a licence to ignore the dangers of ovarian stimulation, nor subjecting women to the concomitant side effects. True prevention is not placing women at OHSS risk in the first place by avoiding aggressive protocols of ovarian stimulation.
It must always be remembered that the protection of the welfare of women in IVF is a wider concept beyond OHSS prevention. There are additional treatments, such as the administration of intravenous immunology drugs, which may have potentially harmful effects and are in desperate need of more oversight. At present, lack of data collection and database linkage restrictions are obscuring our ability to determine the size of problem.
Instead of large-scale, rigorous analysis, we are often given bland reassurances that all is well with the state of IVF in the UK. Sensible proposals to protect the welfare of women are currently being put forward in Parliament by McDonagh and should be supported whatever one's view on the best stimulation strategy.
We surely all agree that the aim of IVF treatment should be to achieve a singleton, healthy, full term, normal weight baby, without putting a woman's health at risk in the short or long term. With the additional oversight and data, we will be able to speak confidently as one voice that we are protecting the welfare of women during IVF treatment.