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Intra‐uterine insemination for unexplained subfertility

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Abstract

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Background

Intra‐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.

Objectives

To 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 methods

We 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 Authors of identified studies were contacted for missing or unpublished data.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 criteria

Truly 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 analysis

Quality 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 results

One 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' conclusions

There 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.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

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Intra‐uterine insemination for unexplained subfertility

There is evidence that intra‐uterine insemination (IUI) improves the odds of becoming pregnant for couples with unexplained subfertility when combined with fertility drugs to induce ovulation.

IUI is a treatment often used for couples with unexplained subfertility. In an IUI cycle, the male partner's sperm is prepared and placed directly in the uterus at the time of ovulation. IUI cycles can be used in combination with fertility drugs to stimulate the ovaries and increase the number of available eggs. However, these drugs can have adverse effects and also increase the risk of multiple pregnancies. The review of trials found some evidence that IUI increases the chance of pregnancy compared to correct timing of intercourse. There was also evidence of an increased live birth rate in women who underwent IUI and who were also given fertility drugs to stimulate the ovaries. However, increased multiple pregnancy rates are concerning and further studies are needed to assess the magnitude of this problem.