Endometrial injury in women undergoing in vitro fertilisation (IVF)

Sarah F Lensen, Sarah Armstrong, Ahmed Gibreel, Carolina O Nastri, Nick Raine-Fenning, Wellington P Martins, Sarah F Lensen, Sarah Armstrong, Ahmed Gibreel, Carolina O Nastri, Nick Raine-Fenning, Wellington P Martins

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 methods: 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.

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.

Trial registration: ClinicalTrials.gov NCT01340560 NCT00846183 NCT00837733 NCT00796341 NCT01132144 NCT01882842.

Conflict of interest statement

All review authors are investigators or otherwise closely associated with trials included in this review.

Sarah F Lensen is an investigator of one included study (Lensen 2019)

Sarah Armstrong is an investigator of one included study (Lensen 2019)

Ahmed Gibreel is an investigator of one included study (Gibreel 2015)

Carolina O Nastri is an investigator of one included study (Nastri 2013) and two excluded studies (NCT02093442; NCT02180256)

Nick Raine‐Fenning is an investigator of one included study (Polanski 2015). He has received lecture payments from GE Healthcare and is a minority share holder in an IVF unit (Nurture)

Wellington P Martins is an investigator of one included study (Nastri 2013) and two excluded studies (NCT02093442; NCT02180256)