• Susanne M Veltman-Verhulst, Ben J Cohlen, Edward Hughes, and Maas Jan Heineman.
• University Medical Center Utrecht, Department of Reproductive Medicine and Gynecology, Utrecht, Netherlands. veltmanverhulst@gmail.com.
• Cochrane Db Syst Rev. 2012 Jan 1 (9): 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 rate.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 (OH).Search MethodsWe searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 7), MEDLINE (1966 to July 2011), EMBASE (1980 to July 2011), PsycINFO (1806 to July 2011), 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 Authors of identified studies were contacted for missing or unpublished data.Selection CriteriaTruly randomised controlled trials (RCTs) with at least one of the following comparisons were included: IUI versus TI, both in a natural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 a 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 and sensitivity analyses were done where possible.Main ResultsOne trial compared IUI in a natural cycle with expectant management and showed no evidence of increased live births (334 women: odds ratio (OR) 1.60, 95% confidence interval (CI) 0.92 to 2.8). In the six trials where IUI was compared with TI, both in stimulated cycles, there was evidence of an increased chance of pregnancy after IUI (six RCTs, 517 women: OR 1.68, 95% CI 1.13 to 2.50). A significant increase in live birth rate was found for women where IUI with OH was compared with IUI in a natural cycle (four RCTs, 396 women: OR 2.07, 95% CI 1.22 to 3.50). However the trials provided insufficient data to investigate the impact of IUI with or without OH on several important outcomes including live births, 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 (two RCTs, total 304 women: data not pooled). The final comparison of IUI in natural cycle to TI with OH showed a marginal, significant increase in live births for IUI (one RCT, 342 women: OR 1.95, 95% CI 1.10 to 3.44).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 in stimulated cycles. One adequately powered multicentre trial showed no evidence of effect of IUI in natural cycles compared with expectant management. 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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