Research in context
Evidence before this study
Before starting this study, we searched the Cochrane Library and PubMed for relevant studies published in English from database inception up to Dec 3, 2012. We used the following search terms: “unexplained infertility”, “unexplained subfertility”, “intrauterine insemination”, “intrautero tuboperitoneal insemination”, “IUI”, “artificial insemination by partner”, and “artificial insemination”. We identified one high quality Cochrane systematic review and no additional trials. The Cochrane systematic review reported two randomised controlled trials comparing intrauterine insemination (IUI) with expectant management. Neither study reported benefit. One randomised controlled trial compared IUI with gonadotropin therapy versus expectant management in women with intermediate prognosis for natural conception. The relative risk for livebirth was 0·86 (95% CI 0·54–1·4). The second study compared six cycles of IUI only versus expectant management; however, only 37 (19%) of 193 women in the IUI group completed all six cycles and 26 (13%) received none. Compared with expectant management, the odds ratio for a livebirth was 1·46 (95% CI 0·88–2·43) after unstimulated IUI. The 2013 National Institute for Health and Care Excellence guidelines for people with fertility problems recommend “that intrauterine insemination with or without ovarian stimulation should not be routinely offered to couples with unexplained infertility”.
Added value of this study
This study is a well powered, randomised controlled trial comparing IUI with clomifene citrate versus expectant management in women with poor prognosis for natural conception within the next 12 months. It differs from previous randomised controlled trials in this field in that the prognosis is less favourable and that ovulation induction with clomifene citrate was used. This is the first study to report benefit with IUI with ovarian stimulation compared with expectant management.
Implications of all the available evidence
Our study provides the first reliable evidence that IUI with ovarian stimulation can be offered to women with a poor prognosis for natural conception. However, further randomised controlled trials would be welcome to test our findings in other settings and provide additional evidence to support a change in the present recommendations. One such study (NTR5599) is currently recruiting in the Netherlands.