Women were eligible for inclusion in this study if they were <42 years of age, with BMI <35 kg/m2 and unexplained infertility, which was defined as normal ovulation (or normal with ovarian stimulation), bilateral patent fallopian tubes, normal semen analysis, and a prediction score of natural conception leading to livebirth in the next year of less than 30% (determined using the validated Hunault prediction model). Women with mild endometriosis, polycystic ovarian syndrome (providing ovulation was confirmed with or without ovarian stimulation for at least six cycles) were included, as were those who had previous intrauterine insemination (IUI) or in vitro fertilisation (IVF) cycles.
The treatment consisted of three cycles of IUI with ovarian stimulation (either clomifene 50-150mg or letrozole 2.5-7.5mg on days 2-6; choice made by the clinic) or three cycles of expectant management (couples advised to be sexually active around the likely time of ovulation).
The authors of a related editorial note that the diagnosis of unexplained subfertility is given to up to 40% of couples seeking fertility treatment, and that the treatment course for these patients remains unclear. Although expectant management remains an option for young couples with a sort duration of conception delay, others prefer a more proactive approach; the two options then are IUI with ovarian stimulation or IVF. Only two trials to date have compared IUI to expectant management in this setting and neither was able to demonstrate superiority of IUI, and the NICE fertility guideline (CG156; Feb 2013) therefore does not recommend its use (except in certain circumstances). Numerous CCGs have since withdrawn funding for IUI, leaving IVF as the only option.
The current study, which suggests that five women (95% CI 3–9) would need to have three cycles of stimulated IUI to result in one additional livebirth, is the first to their knowledge to show a significant benefit of stimulated IUI over expectant management. They call for a trial comparing the cumulative livebirth rate after three stimulated IUI cycles versus one full IVF cycle to determine the best first-line approach for the treatment of unexplained subfertility, but until such becomes available they suggest “it is reasonable to offer young couples with a low predicted chance of natural conception, the option of starting three cycles of stimulated IUI before embarking on the more invasive IVF treatment.”