Unexplained infertility - inexplicable guidelines

The National Institute for Health and Care Excellence (NICE) guideline (2013), when referring to unexplained infertility, recommends expectant treatment for up to two years and then, if unsuccessful, proceeding to IVF, blatantly ruling out the possibility of using intra-uterine insemination (IUI) as a possible intermediate treatment. In our hospital's hinterland, the clinical commissioning groups gleefully jumped at the opportunity to stop all funding for IUI for both unexplained and mild male infertility by quoting NICE guidance (while at the same time conveniently ignoring the NICE recommendation that they should provide three cycles of IVF for each eligible couple).

The recommendation to exclude IUI as a treatment option has been met mainly with disdain by fertility professionals as it is based on flimsy, and sometimes mistakenly interpreted, evidence. Much of the evidence that was taken into account was based on the use of IUI together with clomifene. It has long been known that this form of treatment is little better than doing nothing and waiting. However, when IUI is performed with stimulation by gonadotrophins (FSH, follicle stimulating hormone, or FSH + LH, luteinising hormone) it is a completely different story, with success rates over three cycles of treatment quoted in the 20 to 30 percent range.

A survey of 136 IVF practitioners (all members of the British Fertility Society) that we published in Human Fertility (2014) revealed that, for unexplained infertility, only 16 percent recommended IVF as first-line treatment, that 30 percent would not change their practice to accord with the guidelines and that the rest were awaiting evidence. Further evidence has come to light refuting NICE's main objection to stimulated IUI cycles — that they result in ten times the multiple-birth rate and include many high-order-multiple pregnancies. However, a Cochrane review (2012) and a very large randomised controlled trial from the Netherlands (2015) completely contradicted these statistics, revealing multiple pregnancy rates the same or lower than in IVF. Similarly, in this latter trial, six cycles of stimulated IUI produced the same number of live births (47 percent) as six cycles of so-called modified natural cycle IVF (43 percent) and three cycles of IVF with single-embryo transfer (52 percent). For couples with unexplained or mild male infertility, IUI is the least burdensome treatment, associated with the lowest costs and is neither invasive nor dangerous if performed correctly in properly selected patients. So, by excluding IUI and going straight to IVF, in many cases we are using a sledgehammer to crack a nut — or, rather, amputating an arm to get rid of a boil on the finger!

We are now faced with an extraordinary situation working as NHS fertility doctors in our area. Take, for example, the case of a woman aged 24 who wants to conceive but has polycystic ovary syndrome. She is not ovulating, the obvious cause of her infertility, but cannot afford private treatment. She has not conceived on clomifene treatment, which she had to pay for but is at least affordable. The next logical step is to treat with low-dose FSH treatment, with or without IUI, neither of which is funded. She is therefore shunted straight to IVF, which is the only funded treatment left open to her. All this when, with the universally accepted normal chain of treatment sequence before resorting to IVF, she would stand a well over 70 percent chance of having a live birth.

There is something rotten in the state of fertility treatment when it is driven by such illogical thinking and management. As well as being more expensive for the NHS, this patient is exposed to far more invasive, exhausting and potentially dangerous treatment than is needed, and which produces no better results than the conventionally accepted treatment throughout the world.

The NICE consultation revealed 284 sets of concerns about the fertility recommendations, which were dismissed in the final guidance but show that we are not alone in finding its recommendations contentious. Particularly worrying is its encouragement to perform an even greater number of IVF treatments despite an estimated one-third of patients probably undergoing IVF unnecessarily. A dignified way out of the hole that NICE has dug for itself would be to reverse its IUI decision on the basis of 'new evidence'. It would be the correct step and would enable a return to good clinical common sense.