• S M Verhulst, B J Cohlen, E Hughes, E Te Velde, and M J Heineman.
• Rijksuniversiteit Groningen, Vijverlaan 4, Rotterdam, Netherlands. s.verhulst@wherever.nl
• Cochrane Db Syst Rev. 2006 Oct 18 (4): CD001838.

BackgroundIntra-uterine insemination (IUI) is a widely used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive than in vitro fertilisation (IVF), the safety of IUI in combination with ovarian hyperstimulation (OH) is debated. The main concern about IUI treatment with OH is the increase in multiple pregnancy rates.ObjectivesTo determine whether for couples with unexplained subfertility IUI improves the live birth rate compared with timed intercourse (TI), both with and without ovarian hyperstimulation.Search StrategyWe searched the Cochrane Menstrual Disorder and Subfertility Group Trials Register (searched March 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to November 2005), EMBASE (1980 to November 2005), SCIsearch and reference lists of articles. Authors of identified studies were contacted for missing or unpublished data.Selection CriteriaTruly randomised controlled trials (RCTs) with at least one of the following comparisons were included: --IUI versus TI, both in a natural cycle; --IUI versus TI, both in a stimulated cycle; --IUI in a natural cycle versus IUI in a stimulated cycle; --IUI with OH versus TI in natural cycle; --IUI in a natural cycle versus TI with OH. Only couples with unexplained subfertility were included.Data Collection And AnalysisQuality assessment and data extraction were performed independently by two review authors. Outcomes were extracted and the data were pooled. Subgroup analyses and sensitivity analyses were done where possible.Main ResultsIn the six trials where IUI was compared with TI, both in stimulated cycles, there was evidence of an increased chance of pregnancy (six RCTs, 517 women: OR 1.68, 95% CI 1.13 to 2.50). A significant increase in pregnancy rate was also found for women where IUI with OH was compared with IUI in a natural cycle (three RCTs, 415 women: OR 2.33, 95% CI 1.46 to 3.71). However, the trials provided insufficient data to investigate the impact of IUI with or without OH on several important outcomes including live birth, multiple pregnancies, miscarriage and risk of ovarian hyperstimulation. There was no evidence of a difference in pregnancy rate for IUI with OH compared with TI in a natural cycle (one RCT, 51 women: OR 4.05, 95% CI 0.39 to 41.87). No RCTs were found for the other two comparisons.Authors' ConclusionsThere is evidence that IUI with OH increases the live birth rate compared to IUI alone. The likelihood of pregnancy was also increased for treatment with IUI compared to TI both in stimulated cycles. There is insufficient data on multiple pregnancies and other adverse events for treatment with OH. Therefore, couples should be fully informed about the risks of IUI and OH as well as alternative treatment options.

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