Review question
We reviewed the evidence on the effectiveness and safety of intrauterine insemination (IUI) compared to intracervical insemination (ICI) in women who started donor sperm treatment.
Background
The first-line treatment in donor sperm treatment consists of inseminations that can be done by placing sperm inside a woman's uterus to facilitate fertilisation (IUI) or by inserting sperm into the vagina using a small, needleless syringe or a cervical cap (ICI). Both IUI and ICI can be performed in natural cycles or following ovarian stimulation.
Ovarian stimulation can be performed with gonadotrophins, which are injected, or clomiphene citrate, which is available as a tablet. One of the risks of ovarian stimulation is multiple pregnancies. Therefore, the first few cycles of IUI and ICI are usually performed without ovarian stimulation.
It is important that IUI and ICI are performed at a specific time in the woman's menstrual cycle (as close to ovulation as possible). Various techniques of determining the best timing for IUI and ICI in natural cycles are available, such as keeping basal temperature charts, checking cervical mucus scores, testing blood or urine levels of luteinising hormone (LH), or monitoring with ultrasounds.
We compared IUI and ICI with each other, and also compared different types of each technique.
Study characteristics
We found six randomised controlled trials, including 708 women. Two studies compared IUI and ICI in natural cycles. Two studies compared IUI and ICI in gonadotrophin-stimulated cycles. Two studies compared the timing of IUI and ICI. The evidence is current to December 2017.
Key results
There was insufficient evidence to determine whether there was any clear difference between IUI and ICI in live birth rates, in either natural cycles or in gonadotrophin-stimulated cycles. As there was only one live birth in the small study using natural cycles, we could not make any meaningful comparison between the groups. The evidence on gonadotrophin-stimulated cycles suggested that if the live birth rate following ICI was assumed to be 30%, the chance of live birth rate following IUI in gonadotrophin-stimulated cycles would be between 24% and 80%. For IUI and ICI in natural cycles, no multiple pregnancies were reported. In gonadotrophin-stimulated cycles, IUI was associated with higher multiple pregnancy rates than ICI. The evidence suggested that if the risk of multiple pregnancy following ICI in gonadotrophin-stimulated cycles was assumed to be 10%, the risk of multiple pregnancy following IUI would be between 10% and 46%.
We concluded that the evidence was too limited to encourage or discourage either IUI or ICI, in natural cycles or with ovarian stimulation in donor sperm treatment.
Quality of the evidence
Following GRADE assessment, we found that the evidence for all outcomes was of very low quality. The main limitations were risk of bias, due to poor reporting of study methods, and serious imprecision, due to the limited number of studies and small study sizes.
There was insufficient evidence to determine whether there was a clear difference in live birth rates between IUI and ICI in natural or gonadotrophin-stimulated cycles in women who started with donor sperm treatment. There was insufficient evidence available for the effect of timing of IUI or ICI on live birth rates. Very low-quality data suggested that in gonadotrophin-stimulated cycles, IUI may be associated with a higher clinical pregnancy rate than ICI, but also with a higher risk of multiple pregnancy rate. We concluded that the current evidence was too limited to choose between IUI or ICI, in natural cycles or with ovarian stimulation, in donor sperm treatment.
The first-line treatment in donor sperm treatment consists of inseminations that can be done by intrauterine insemination (IUI) or by intracervical insemination (ICI).
To compare the effectiveness and safety of intrauterine insemination (IUI) and intracervical insemination (ICI) in women who start donor sperm treatment.
We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL in October 2016, checked references of relevant studies, and contacted study authors and experts in the field to identify additional studies. We searched PubMed, Google Scholar, the Grey literature, and five trials registers on 15 December 2017.
We included randomised controlled trials (RCTs) reporting on IUI versus ICI in natural cycles or with ovarian stimulation, and RCTs comparing different cointerventions in IUI and ICI. We included cross-over studies if pre-cross-over data were available.
We used standard methodological procedures recommended by Cochrane. We collected data on primary outcomes of live birth and multiple pregnancy rates, and on secondary outcomes of clinical pregnancy, miscarriage, and cancellation rates.
We included six RCTs (708 women analysed) on ICI and IUI in donor sperm treatment. Two studies compared IUI and ICI in natural cycles, two studies compared IUI and ICI in gonadotrophin-stimulated cycles, and two studies compared timing of IUI and ICI. There was very low-quality evidence; the main limitations were risk of bias due to poor reporting of study methods, and serious imprecision.
IUI versus ICI in natural cycles
There was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in natural cycles (odds ratio (OR) 3.24, 95% confidence interval (CI) 0.12 to 87.13; 1 RCT, 26 women; very low-quality evidence). There was only one live birth in this study (in the IUI group). IUI resulted in higher clinical pregnancy rates (OR 6.18, 95% CI 1.91 to 20.03; 2 RCTs, 76 women; I² = 48%; very low-quality evidence).
No multiple pregnancies or miscarriages occurred in this study.
IUI versus ICI in gonadotrophin-stimulated cycles
There was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in gonadotrophin-stimulated cycles (OR 2.55, 95% CI 0.72 to 8.96; 1 RCT, 43 women; very low-quality evidence). This suggested that if the chance of a live birth following ICI in gonadotrophin-stimulated cycles was assumed to be 30%, the chance following IUI in gonadotrophin-stimulated cycles would be between 24% and 80%. IUI may result in higher clinical pregnancy rates than ICI (OR 2.83, 95% CI 1.38 to 5.78; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). IUI may be associated with higher multiple pregnancy rates than ICI (OR 2.77, 95% CI 1.00 to 7.69; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). This suggested that if the risk of multiple pregnancy following ICI in gonadotrophin-stimulated cycles was assumed to be 10%, the risk following IUI would be between 10% and 46%.
We found insufficient evidence to determine whether there was any clear difference between the groups in miscarriage rates in gonadotrophin-stimulated cycles (OR 1.97, 95% CI 0.43 to 9.04; 2 RCTs, overall 67 pregnancies; I² = 50%; very low-quality evidence).
Timing of IUI and ICI
We found no studies that reported on live birth rates.
We found a higher clinical pregnancy rate when IUI was timed one day after a rise in blood levels of luteinising hormone (LH) compared to IUI two days after a rise in blood levels of LH (OR 2.00, 95% CI 1.14 to 3.53; 1 RCT, 351 women; low-quality evidence). We found insufficient evidence to determine whether there was any clear difference in clinical pregnancy rates between ICI timed after a rise in urinary levels of LH versus a rise in basal temperature plus cervical mucus scores (OR 1.31, 95% CI 0.42 to 4.11; 1 RCT, 56 women; very low-quality evidence).
Neither of these studies reported multiple pregnancy or miscarriage rates as outcomes.