Endometrial injury in women undergoing in vitro fertilisation (IVF)

Review question

To assess whether it is safe and effective to perform endometrial injury (also known as endometrial scratching), in women undergoing in vitro fertilisation (IVF), including intracytoplasmic sperm injection (ICSI) and frozen embryo transfer.

Background

Couples who have trouble getting pregnant may seek fertility treatments to help them conceive, such as IVF. In an IVF cycle, eggs are collected from the woman and are combined with sperm in the laboratory to create embryos. Embryos are transferred into the womb in the hope that they will implant and establish a pregnancy. Implantation is the process by which an embryo embeds itself into the lining of the womb; it is the first step toward establishing a successful pregnancy. It has been suggested that the chances of implantation are increased if endometrial injury is performed before replacement of the embryo into the womb.

Study characteristics

We included 38 clinical trials (8915 women) which had tested the effects of endometrial injury on the outcomes of IVF. The studies were conducted in different populations of women, and the way the endometrial injury was conducted also differed between studies in terms of the instrument used and the timing of the procedure in relation to the IVF cycle. Many of the studies were poor quality and at high risk of bias, and therefore we performed the main analyses only including studies that were not at high risk of bias. Of the 38 included studies, only eight were included in the primary analyses.

Key results

It is unclear whether endometrial injury affects the chance having a baby from IVF. The results suggest that, if the chance of having a baby from IVF is usually about 27%, then the chance of having a baby when using endometrial injury before IVF would be somewhere between less than 27% and 32%. Similarly, for the outcome of pregnancy, if the chance of getting pregnant from IVF is assumed to be about 32%, then the chance of pregnancy when using endometrial injury before IVF is somewhere between 31% and 37%.

Endometrial injury does not appear to affect the chance of having a miscarriage from IVF. The endometrial injury procedure causes mild to moderate pain and a small amount of vaginal bleeding, although this is short-lived. This evidence does not support the routine use of endometrial injury for women undergoing IVF.

One small study compared endometrial injury using two different instruments in the cycle prior to the IVF cycle. All outcomes reported for this study were graded as very-low certainty due to risk of bias, and as such we were not able to interpret the study results.

Certainty of the evidence

For the primary analyses, the evidence is of moderate certainty. The evidence was reduced because the results were imprecise, and consistent with endometrial injury having no effect, being beneficial, and being harmful to the chance of getting pregnant or having a baby.

Authors' conclusions: 

The effect of endometrial injury on live birth and clinical pregnancy among women undergoing IVF is unclear. The results of the meta-analyses are consistent with an increased chance, no effect and a small reduction in these outcomes. We are therefore uncertain whether endometrial injury improves the chance of live birth or clinical pregnancy in women undergoing IVF. Endometrial injury does not appear to affect the chance of miscarriage. It is a somewhat painful procedure associated with a small amount of bleeding. In conclusion, current evidence does not support the routine use of endometrial injury for women undergoing IVF.

Read the full abstract...
Background: 

Implantation of an embryo within the endometrial cavity is a critical step in the process of in vitro fertilisation (IVF). Previous research has suggested that endometrial injury (also known as endometrial scratching), defined as intentional damage to the endometrium, can increase the chance of pregnancy in women undergoing IVF.

Objectives: 

To assess the effectiveness and safety of endometrial injury performed before embryo transfer in women undergoing in vitro fertilisation (IVF) including intracytoplasmic sperm injection (ICSI) and frozen embryo transfer.

Search strategy: 

In June 2020 we searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, LILACS, DARE and two trial registries. We also checked the reference sections of relevant studies and contacted experts in the field for any additional trials.

Selection criteria: 

Randomised controlled trials comparing intentional endometrial injury before embryo transfer in women undergoing IVF, versus no intervention or a sham procedure.

Data collection and analysis: 

We used standard methodological procedures recommended by Cochrane. Two independent review authors screened studies, evaluated risk of bias and assessed the certainty of the evidence by using GRADE (Grading of Recommendation, Assessment, Development and Evaluation) criteria. We contacted and corresponded with study investigators as required. Due to the high risk of bias associated with many of the studies, the primary analyses of all review outcomes were restricted to studies at a low risk of bias for selection bias and other bias. Sensitivity analysis was then performed including all studies. The primary review outcomes were live birth and miscarriage.

Main results: 

Endometrial injury versus control (no procedure or a sham procedure)

A total of 37 studies (8786 women) were included in this comparison. Most studies performed endometrial injury by pipelle biopsy in the luteal phase of the cycle before the IVF cycle. The primary analysis was restricted to studies at low risk of bias, and included eight studies. The effect of endometrial injury on live birth is unclear as the result is consistent with no effect, or a small reduction, or an improvement (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.98 to 1.28; participants = 4402; studies = 8; I2 = 15%, moderate-certainty evidence). This suggests that if the chance of live birth with IVF is usually 27%, then the chance when using endometrial injury would be somewhere between < 27% and 32%.

Similarly, the effect of endometrial injury on clinical pregnancy is unclear (OR 1.08, 95% CI 0.95 to 1.23; participants = 4402; studies = 8; I2 = 0%, moderate-certainty evidence). This suggests that if the chance of clinical pregnancy from IVF is normally 32%, then the chance when using endometrial injury before IVF is between 31% and 37%. When all studies were included in the sensitivity analysis, we were unable to conduct meta-analysis for the outcomes of live birth and clinical pregnancy due to high risk of bias and statistical heterogeneity.

Endometrial injury probably results in little to no difference in chance of miscarriage (OR 0.88, 95% CI 0.68 to 1.13; participants = 4402; studies = 8; I2 = 0%, moderate-certainty evidence), and this result was similar in the sensitivity analysis that included all studies. The result suggests that if the chance of miscarriage with IVF is usually 6.0%, then when using endometrial injury it would be somewhere between 4.2% and 6.8%.

Endometrial injury was associated with mild to moderate pain (approximately 4 out of 10), and was generally associated with some minimal bleeding.

The evidence was downgraded for imprecision due to wide confidence intervals and therefore all primary analyses were graded as moderate certainty.

Higher versus lower degree of injury

Only one small study was included in this comparison (participants = 129), which compared endometrial injury using two different instruments in the cycle prior to the IVF cycle: a pipelle catheter and a Shepard catheter. This trial was excluded from the primary analysis due to risk of bias. In the sensitivity analysis, all outcomes reported for this study were graded as very-low certainty due to risk of bias, and as such we were not able to interpret the study results.

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