Abstract

Abstract Study question Does flushing the endometrial cavity improve fertility outcomes in couples with infertility and what are the preferred flushing mediums? Summary answer Flushing the endometrial cavity appears to improve live birth rate, implantation rate and clinical pregnancy rate. There was no difference in miscarriage or complication rate. What is known already Live birth rate was improved in cleavage-stage transfer when the uterus was flushed with human chorionic gonadotropin (hCG) at a dose >500 IU in a Cochrane review (Craciunas L et al 2018). Chemical and clinical pregnancy rates and implantation rate may be improved by endometrial flushing with platelet-rich plasma (PRP) in a meta-analysis by Maleki-Hajiagha A et al 2020. Flushing the cavity with oil-based contrast at hysterosalpingography (HSG) improved pregnancy rates when compared with water-based contrast in a systematic review by Fang F et al 2018. Study design, size, duration Our study was a systematic review and meta-analysis. We searched MEDLINE (1946 to December 2020), Embase (1980 to December 2020), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1961 to 9 December 2020) PsychINFO (1806 to December 2020). We screened the titles of search results to identify studies for inclusion and then screened abstracts and full texts to ensure trials met search criteria. Participants/materials, setting, methods We included in this review all randomised controlled trials (RCTs), quasi-experimental or cohort studies evaluating intrauterine instillation or flushing with any medium, irrespective of timing of intervention and irrespective of language or country of origin. We performed the meta-analyses using a random-effects model and performed subgroup and sensitivity analysis. Two authors independently extracted the data. We calculated the risk ratio or odds ratio with 95% confidence intervals based on intention-to-treat or available data analysis. Main results and the role of chance We included 36 RCTs and 12 non-randomised trials including 12230 participants. The sample size varied from 15 to 1186. We included 11 comparisons. Primary outcomes were healthy baby rate and live birth rate. Healthy baby rate was not reported in any of the trials. Live birth rate favoured oil soluble contrast medium (at HSG) when compared to water based contrast medium (OR 0.64, 95% CI 0.52 to 0.78, 2 RCTs and 1 cohort study, 2050 participants, I2 = 86%) or no intervention (OR 3.53, 95% CI 1.64 to 7.60, 2 RCTs, 192 participants, I2 = 0%). With regards to our secondary outcomes: CSF instillation, HCG instillation, PRP instillation and oil-soluble contrast medium at HSG (over water-soluble contrast medium) were favoured for implantation rate and clinical pregnancy rate. There was no statistically significant difference in miscarriage or complication rate for any of the comparisons. All trials were at an overall high risk of bias when assessed on the following areas: sequence generation, allocation concealment, blinding of participants, personnel, and outcome assessors, incomplete outcome data, selective outcome reporting, and other sources of bias. Limitations, reasons for caution Only 36 studies included were RCTs. Twelve of the RCTs had post randomisation drop outs. There was a lack of detail on the instillation medium for several of the included studies. There was no placebo used in many of the control groups. All meta-analyses had high levels of heterogeneity. Wider implications of the findings: Our findings are in keeping with the literature suggesting a possible improvement in live birth rate following flushing the endometrium with oil soluble contrast medium when compared with a control group. Mechanistic studies are now required to understand how oil-based medium improves fertility. Trial registration number NA

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