P-468 Personalized embryo transfer guided by transcriptomic endometrial receptivity analysis (ERA) in infertile patients: a systematic review and meta-analysis

Abstract Study question What is the effectiveness of a personalized embryo transfer (pET) guided by an endometrial receptivity test in assisted reproduction? Summary answer We have not found evidence supporting the routine use of a personalized embryo transfer guided by an endometrial receptivity test in any case yet. What is known already Currently, the outcomes of good quality embryo transfers are far from ideal. Clinical focus is shifting towards other actors that could play a key role in the good-quality embryos implantation failure, such as the endometrial preparation and the achievement of an embryo-endometrium synchrony, so that the embryo has a better chance to implant during the window of implantation (WOI). Today, there is a wide range of different endometrial receptivity tests that use different sets of genes to identify patients with displacements of their WOI in order to adjust the individual length of progesterone exposure in a personalized embryo transfer (pET). Study design, size, duration This is systematic review and meta-analysis were conducted following the Cochrane methods and the GRADE approach to rate the certainty of evidence (CoE). The protocol has been sent for registration to PROSPERO (CRD42022299827). We included studies that compared women that were tested with transcriptomic endometrial receptivity tests versus those that were not tested. We only included comparative studies, including randomized controlled trials (RCTs), and retrospective and prospective cohorts. Participants/materials, setting, methods Participants were women undergoing an infertility treatment (both with own or donor gametes), with or without repeated implantation failure (RIF), with or without preimplantation genetic testing for aneuploidies (PGT-A). Each of the above-mentioned populations was analyzed separately as different subgroups. Electronic searches in CENTRAL via the Cochrane Register of Studies Online (CRSO), PubMed, and Embase were performed from inception to October 2022. Screening, study inclusion and data extraction was performed by pairs of independent reviewers. Main results and the role of chance We included 35 studies. Two of them were RCTs and 25 were cohort studies that compared pET guided by an endometrial receptivity tests guided versus sET in women with non-tested endometrium. Besides, we included 16 studies that compared women with sET with a receptive endometrium versus pET in women with non-receptive endometrium. And we included three studies that compared pET guided by an endometrial receptivity test in a specific population of women (RIF or adenomyosis) versus a control population. The two RCTs included women with no history of RIF. In non-RIF women, no important differences (moderate-CoE) were found in live birth rate (LBR) and clinical pregnancy rate (CPR). In that population, cumulative CPR may be higher with pET (RR 1.15, 95%CI 1.00-1.34; low-CoE) but no differences were found in cumulative LBR. Seven cohort studies that adjusted by confounding were meta-analyzed. In RIF, pET may improve the CPR (OR 2.50, 95% CI 1.42-4.40; low-CoE) but, in agreement with the RCTs, no benefits were found in non-RIF. In summary, routine use of pET guided by endometrial receptivity tests is not supported by current published evidence in non-RIF women. However, low-CoE suggests that it may be useful in RIF. Limitations, reasons for caution Most data come from non-RCTs which increases the risk of bias. Besides, the large heterogeneity found in the population, interventions and comparisons led to large imprecision due to the few studies per analyzed strata. It is important to avoid the extrapolation of the results to any different setting. Wider implications of the findings Routine use of pET guided by endometrial receptivity tests is not supported by current published evidence in non-RIF women. However, low-CoE suggests that it may be useful in RIF. Better designed studies are needed to find out if any of these tests work in any specific population. Trial registration number not applicable