Intra-uterine insemination for unexplained subfertility

Review question

Does intra-uterine insemination (IUI) treatment (with or without fertility drugs) lead to higher live birth rates in couples with unexplained subfertility as compared to timed intercourse or expectant management?

Background

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. Expectant management and timed intercourse have also been shown to result in high pregnancy rates resulting in live birth. With this review we would like to enhance decision-making for starting treatment for couples with unexplained subfertility.

Study characteristics

Cochrane authors included 14 randomised controlled trials (1867 women) in this review, comparing women with unexplained subfertility undergoing fertility treatment with IUI with or without ovarian stimulation drugs. Women who underwent IUI treatment were compared to women who received ovarian stimulation drugs along with timed intercourse or couples who were randomised to expectant management. The main outcome of interest was live birth rate, but pregnancy rate, miscarriage rate and other adverse effects were also recorded. The evidence is current to December 2015.

Key results

There was no conclusive evidence of a difference between most treatment groups in cumulative live birth rates (i.e. rates at conclusion of a course of treatment), multiple pregnancy rates and other adverse effects for couples with unexplained subfertility undergoing intra-uterine insemination (IUI) when compared with timed intercourse (TI), both with and without ovarian hyperstimulation (OH).

Quality of the evidence

The evidence was of moderate quality for live birth and low to moderate quality for multiple pregnancy. The main limitation of the evidence was lack of precision in the findings for both live birth and multiple pregnancy.

Authors' conclusions: 

This systematic review did not find conclusive evidence of a difference in live birth or multiple pregnancy in most of the comparisons for couples with unexplained subfertility treated with intra-uterine insemination (IUI) when compared with timed intercourse (TI), both with and without ovarian hyperstimulation (OH). There were insufficient studies to allow for pooling of data on the important outcome measures for each of the comparisons.

Read the full abstract...
Background: 

Intra-uterine insemination (IUI) is a widely used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive thAppendixan 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. This is an update of a Cochrane review (Veltman-Verhulst 2012) originally published in 2006 and updated in 2012.

Objectives: 

To determine whether, for couples with unexplained subfertility, IUI improves the live birth rate compared with timed intercourse (TI), or expectant management, both with and without ovarian hyperstimulation (OH).

Search strategy: 

We searched the Cochrane Gynaecology and Fertility (formerly Cochrane Menstrual Disorders and Subfertility Group) Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, inception to Issue 11, 2015), Ovid MEDLINE, Ovid EMBASE, PsycINFO and trial registers, all from inception to December 2015 and reference lists of articles. Authors of identified studies were contacted for missing or unpublished data. The evidence is current to December 2015.

Selection criteria: 

Truly randomised controlled trial (RCT) comparisons of IUI versus TI, in natural or stimulated cycles. Only couples with unexplained subfertility were included.

Data collection and analysis: 

Two review authors independently performed study selection, quality assessment and data extraction. We extracted outcomes, and pooled data and, where possible, we carried out subgroup and sensitivity analyses.

Main results: 

We included 14 trials including 1867 women.

IUI versus TI or expectant management both in natural cycle

Live birth rate (all cycles)

There was no evidence of a difference in cumulative live births between the two groups (Odds Ratio (OR) 1.60, 95% confidence interval (CI) 0.92 to 2.78; 1 RCT; n = 334; moderate quality evidence). The evidence suggested that if the chance of a live birth in TI was assumed to be 16%, that of IUI would be between 15% and 34%.

Multiple pregnancy rate

There was no evidence of a difference in multiple pregnancy rate between the two treatment groups (OR 0.50, 95% CI 0.04 to 5.53; 1 RCT; n = 334; moderate quality evidence).

IUI versus TI or expectant management both in stimulated cycle

Live birth rate (all cycles)

There was no evidence of a difference between the two treatment groups (OR 1.59, 95% CI 0.88 to 2.88; 2 RCTs; n = 208; I2 = 72%; moderate quality evidence). The evidence suggested that if the chance of achieving a live birth in TI was assumed to be 26%, the chance of a live birth with IUI would be between 23% and 50%.

Multiple pregnancy rate

There was no evidence of a difference in multiple pregnancy rates between the two treatment groups (OR 1.46, 95% CI 0.55 to 3.87; 4 RCTs, n = 316; I2 = 0%; low quality evidence).

IUI in a natural cycle versus IUI in a stimulated cycle

Live birth rate (all cycles)

An increase in live birth rate was found for women who were treated with IUI in a stimulated cycle compared with those who underwent IUI in natural cycle (OR 0.48, 95% CI 0.29 to 0.82; 4 RCTs, n = 396; I2 = 0%; moderate quality evidence). The evidence suggested that if the chance of a live birth in IUI in a stimulated cycle was assumed to be 25%, the chance of a live birth in IUI in a natural cycle would be between 9% and 21%.

Multiple pregnancy rate

There was no evidence of a difference in multiple pregnancy rate between the two treatment groups (OR 0.33, 95% CI 0.01 to 8.70; 2 RCTs; n = 65; low quality evidence).

IUI in a stimulated cycle versus TI or expectant management in a natural cycle

Live birth rate (all cycles)

There was no evidence of a difference in live birth rate between the two treatment groups (OR 0.82, 95% CI 0.45 to 1.49; 1 RCT; n = 253; moderate quality evidence). The evidence suggested that if the chance of a live birth in TI or expectant management in a natural cycle was assumed to be 24%, the chance of a live birth in IUI in a stimulated cycle would be between 12% and 32%.

Multiple pregnancy rate

There was no evidence of a difference in multiple pregnancy rate between the two treatment groups (OR 2.00, 95% CI 0.18 to 22.34; 2 RCTs; n = 304; moderate quality evidence).

IUI in natural cycle versus TI or expectant management in stimulated cycle

Live birth rate (all cycles)

There was evidence of an increase in live births for IUI (OR 1.95, 95% CI 1.10 to 3.44; 1 RCT, n = 342; moderate quality evidence). The evidence suggested that if the chance of a live birth in TI in a stimulated cycle was assumed to be 13%, the chance of a live birth in IUI in a natural cycle would be between 14% and 34%.

Multiple pregnancy rate

There was no evidence of a difference in multiple pregnancy rate between the groups (OR 1.05, 95% CI 0.07 to 16.90; 1 RCT; n = 342; moderate quality evidence).

The quality of the evidence was assessed using GRADE methods. Quality ranged from low to moderate, the main limitation being imprecision in the findings for both live birth and multiple pregnancy..

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