Intrauterine insemination practice and the UK NICE guidelines

Sir, Involuntary childlessness affects more than 70 million couples worldwide and has a large impact on quality of life, leading to lasting psychosocial effects (Boivin et al., 2007; Wirtberg et al., 2007). For couples with mild and unexplained male infertility, intrauterine insemination (IUI) is the least burdensome treatment, associated with the lowest costs in both time and other expenses. IUI should be encouraged as a first choice, regardless of national funding strategy (Romundstad et al., 2015). The IVF results with single embryo transfer and IVF in a modified natural cycle were the same as IUI with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates (Bensdorp et al., 2015). In the UK, National Institute for Health and Care Excellence (NICE) recommends against the use of IUI in most circumstances; arguments based on a single randomized controlled trial (Bhattacharya et al., 2008) that yielded an IUI pregnancy rate of 6% per cycle compared with the mean pregnancy rate of 13% per IUI cycle reported in the UK for the same time period (NICE guidelines, 2013; HFEA website, 2015). A major assumption within NICE was that stimulated IUI cycles increased multiple births using pregnancy rates as a proxy for live birth rates; therefore, the data on actual multiple births was missing. The risk of multiple pregnancies after stimulation of two, three and four follicles are estimated to increase by 6, 14 and 10%. The absolute rate of multiple pregnancies is 0.3% after monofollicular, and 2.8% after multifollicular, growth (van Rumste et al., 2008). While the risk for multiple births for IUI with two to three follicles has to be much less than if two or three embryos were transferred in an IVF cycle, no comparative study exists to answer this question of relative risk between matched follicles and embryos during treatment (van Rumste et al., 2008). Shifting from a unifollicular to bifollicular IUI cycles will potentially increase the chance of achieving an IUI pregnancy by 3.4-fold (Tomlinson et al., 1996). The average UK clinic in 2011 had an IUI pregnancy rate of 13.7% per cycle over 4174 IUI cycles in females younger than 37 years of age. In 2012, UK clinics performing IUI achieved a pregnancy rate of 13.65% per cycle in women younger than 37 (4657 cycles) compared with a pregnancy rate of 12.35% per cycle in all women treated (5943 cycles). To put these IUI figures into perspective, for UK IVF/ICSI in 2011, a total of 13 703 pregnancies were reported resulting in pregnancy rates of 27.2% per woman treated (48 141 women), 22.1% per IVF cycle (61 726 cycles) and as 15.3% per embryo transferred (89 648 embryos transferred) (HFEA website, 2015; NICE Costing Report, 2013). Following continuous improvements over 5 years we submitted our 2014 IUI data to the HFEA, wherein 184 cycles with 109 women gave a pregnancy rate of 20.1% per cycle, such that 34% of women could expect a pregnancy. Furthermore, of women aged ≤35 years, 39% of the cohort became pregnant. Application of the NICE guidelines in our clinic would have denied IUI treatment from 34% of our pregnant cohort who would have instead have undergone unnecessary IVF procedures. Our experience, along with recent robust evidence on risks of treatments (Bensdorp et al., 2015; Romundstad et al., 2015), demands an urgent review of the NICE guidelines, which have so far failed and been neglected on matters of utmost clinical importance.