Injury to the lining of the womb to improve pregnancy rates in couples having sexual intercourse or placement of sperm into the womb

Review question

To assess the effect of performing an intentional injury to the lining of the womb (such as taking a biopsy or sample) on the chance of achieving a pregnancy and having a baby in women who are trying to conceive via sexual intercourse or with placement of sperm into the womb (intrauterine insemination: IUI).

Background

To have a successful pregnancy, sperm and egg need to meet and fertilise to create an embryo, and this embryo needs to implant into the lining of the womb. It has been suggested that the chances of implantation are increased by intentionally injuring or damaging the lining of the womb in a minor way. This injury can be done by taking a small biopsy from the lining of the womb with a small flexible plastic device such as a pipelle.

Study characteristics

Nine randomised controlled trials met the inclusion criteria of this review, and included a total of 1512 women. The women in seven studies were trying to get pregnant from IUI, and from intercourse in two studies. Most women had a type of subfertility known as unexplained subfertility, which means that after having all routine tests done there is no obvious explanation for why the couple has not become pregnant so far. Eight trials compared intentional endometrial injury with no injury/placebo procedure; of these two trials also compared intentional endometrial injury in the cycle prior to IUI with intentional endometrial injury in the IUI cycle. One trial compared higher vs. lower degree of intentional endometrial injury. The evidence is current to 31 October 2015.

Key results

The results from the included studies suggest a beneficial effect of endometrial injury on the chance of getting pregnant, but the studies are associated with many significant limitations. Therefore, it is not possible to say with any confidence whether endometrial injury can increase the probability of pregnancy. We are uncertain whether endometrial injury increases the probability of a live birth or a pregnancy beyond 12 weeks.

The endometrial injury procedure is a common procedure and is known to cause a degree of temporary pain or discomfort. Only one included study reported on whether the women experienced pain during the procedure, and the average pain experienced was six out of 10 on a visual scale from zero to 10. Endometrial injury does not seem to have an effect on miscarriage, ectopic pregnancy or multiple pregnancy. No studies reported bleeding after the procedure.

Quality of the evidence

The quality of the evidence was low or very low as assessed using GRADE criteria. In general, the studies included in this review were not very well designed and did not recruit a high enough number of women to provide meaningful results. This means the results must be treated cautiously, and further studies are needed to confirm the findings. There remains uncertainty about whether or not the endometrial injury procedure increases the probability of having a baby.

Authors' conclusions: 

It is uncertain whether endometrial injury improves the probability of pregnancy and live birth/ongoing pregnancy in women undergoing IUI or attempting to conceive via sexual intercourse. The pooled results should be interpreted with caution as we graded the quality of the evidence as either low or very low. The main reasons we downgraded the quality of the evidence were most included studies were at a high risk of bias and had an overall low level of precision. Further well-conducted RCTs that recruit large numbers of participants and minimise internal bias are required to confirm or refute these findings.

Read the full abstract...
Background: 

Intentional endometrial injury is currently being proposed as a technique to improve the probability of pregnancy in women undergoing assisted reproductive technologies (ART) such as in vitro fertilisation (IVF). Endometrial injury is often performed by pipelle biopsy or a similar technique, and is a common, simple, gynaecological procedure that has an established safety profile. However, it is also known to be associated with a moderate degree of discomfort/pain and requires an additional pelvic examination. The effectiveness of this procedure outside of ART, in women or couples attempting to conceive via sexual intercourse or with low complexity fertility treatments such as intrauterine insemination (IUI) and ovulation induction (OI), remains unclear.

Objectives: 

To evaluate the effectiveness and safety of intentional endometrial injury in subfertile women and couples attempting to conceive through sexual intercourse or intrauterine insemination (IUI).

Search strategy: 

We searched the Cochrane Gyanecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, DARE, ISI Web of Knowledge and ClinicalTrials.gov; as well as reference lists of relevant reviews and included studies. We performed the searches from inception to 31 October 2015.

Selection criteria: 

We included randomised controlled trials (RCTs) that evaluated any kind of intentional endometrial injury in women planning to undergo IUI or attempting to conceive spontaneously (with or without OI) compared to no intervention, a mock intervention or intentional endometrial injury performed at a different time or to a higher/lower degree.

Data collection and analysis: 

Two review authors independently selected trials, extracted data and assessed trial quality using GRADE methodology. The primary outcomes were live birth/ongoing pregnancy and pain experienced during the procedure. Secondary outcomes were clinical pregnancy, miscarriage, ectopic pregnancy, multiple pregnancy and bleeding secondary to the procedure. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I2 statistic.

Main results: 

Nine trials, which included a total of 1512 women, met the inclusion criteria of this Cochrane review. Most of these studies included women with unexplained infertility. In seven studies the women were undergoing IUI and in two studies the women were trying to conceive from sexual intercourse. Eight trials compared intentional endometrial injury with no injury/placebo procedure; of these two trials also compared intentional endometrial injury in the cycle prior to IUI with intentional endometrial injury in the IUI cycle. One trial compared higher vs. lower degree of intentional endometrial injury.

Intentional endometrial injury vs. either no intervention or a sham procedure

We are uncertain whether endometrial injury improves live birth/ongoing pregnancy as the quality of the evidence has been assessed as very low (risk ratio (RR) 2.22, 95% confidence interval (CI) 1.56 to 3.15; six RCTs, 950 participants; I² statistic = 0%, very low quality evidence). When we restricted the analysis to only studies at low risk of bias the effect was imprecise and the evidence remained of very low quality (RR 2.64, 95% CI 1.03 to 6.82; one RCT, 105 participants; very low quality evidence). Endometrial injury may improve clinical pregnancy rates however the evidence is of low quality (RR 1.98, 95% CI 1.51 to 2.58; eight RCTs, 1180 participants; I² statistic = 0%, low quality evidence).

The average pain experienced by participants undergoing endometrial injury was 6/10 on a zero-10 visual analogue scale (VAS)(standard deviation = 1.5). However, only one study reported this outcome.

Higher vs. lower degree of intentional endometrial injury

When we compared hysteroscopy with endometrial injury to hysteroscopy alone, there was no evidence of a difference in ongoing pregnancy rate (RR 1.29, 95% CI 0.71 to 2.35; one RCT, 332 participants; low quality evidence) or clinical pregnancy rate (RR 1.15, 95% CI 0.66 to 2.01; one RCT, 332 participants, low quality evidence). This study did not report the primary outcome of pain during the procedure.

Timing of intentional endometrial injury

When endometrial injury was performed in the cycle prior to IUI compared to the same cycle as the IUI, there was no evidence of a difference in ongoing pregnancy rate (RR 0.65, 95% CI 0.37 to 1.16, one RCT, 176 participants; very low quality evidence) or clinical pregnancy rate (RR 0.82, 95% CI 0.50 to 1.36; two RCTs, 276 participants; very low quality evidence). Neither of these studies reported the primary outcome of pain during the procedure.

In all three comparisons there was no evidence of an effect on miscarriage, ectopic pregnancy or multiple pregnancy. No studies reported bleeding secondary to the procedure.

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