Personalized embryo transfer guided by endometrial receptivity analysis: a systematic review with meta-analysis

Abstract

STUDY QUESTION Does a personalized embryo transfer (pET) guided by tests for endometrial receptivity (TER) increase the effectiveness of ART procedures? SUMMARY ANSWER The use of TER-guided pET is not supported by current published evidence in women without repeated implantation failure (RIF), while in women with RIF more research is needed to assess a potential benefit. WHAT IS KNOWN ALREADY Implantation rates are still far from ideal, especially in some patients that have RIF with good-quality embryos. As a potential solution, a wide range of diverse TER use different sets of genes to identify displacements of the window of implantation to adjust the individual length of progesterone exposure in a pET. STUDY DESIGN, SIZE, DURATION A systematic review with meta-analysis was performed. Search terms included endometrial receptivity analysis, ERA, personalized embryo transfer. CENTRAL, PubMed, Embase, reference lists, clinical trials registers, and conference proceedings (search date October 2022) were searched, with no language restrictions. PARTICIPANTS/MATERIALS, SETTING, METHODS Randomized controlled trials (RCTs) and cohort studies comparing a pET guided by TER vs standard embryo transfer (sET) in different subgroups that undergo ART were identified. We also investigated pET in non-receptive-TER vs sET in receptive-TER, and pET in a specific population vs sET in a general population. Risk of bias (RoB) was assessed with the Cochrane tool and ROBINS-I. Only those with low/moderate RoB underwent meta-analysis. The GRADE approach was used to evaluate the certainty of evidence (CoE). MAIN RESULTS AND THE ROLE OF CHANCE We screened 2136 studies and included 35 (85% used ERA and 15% used other TER). Two studies were RCTs comparing endometrial receptivity analysis (ERA)-guided pET vs sET in women with no history of RIF. In women without RIF, no important differences (moderate-CoE) were found in live birth rates and clinical pregnancy rates (CPR). We also performed a meta-analysis of four cohort studies that were adjusted for confounding. In agreement with the RCTs, no benefits were found in women without RIF. However, in women with RIF, low CoE suggests that pET might improve the CPR (OR 2.50, 95% CI 1.42–4.40). LIMITATIONS, REASONS FOR CAUTION We found few studies with low RoB. Only two RCTs in women without RIF were published, and none in women with RIF. Furthermore, the heterogeneity observed in populations, interventions, co-interventions, outcomes, comparisons, and procedures limited the pooling of many of the included studies. WIDER IMPLICATIONS OF THE FINDINGS In the population of women without RIF, in agreement with previously published reviews, pET did not prove to be more effective than sET and, therefore, it precludes the routine use of this strategy in this population until more evidence is available. However, more research is advisable in women with RIF as low-certainty evidence from observational studies adjusted for confounders suggests that the CPR might be higher with pET guided by TER in this population. Although this review presents the best available evidence, it is still insufficient to change current policies. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was obtained for this study. There are no conflicts of interest to declare. REGISTRATION NUMBER PROSPERO CRD42022299827.

Targeted gene expression profiling for accurate endometrial receptivity testing

“…Contrary to those reports, recent randomised controlled trials (RCT) and meta-analyses question the effectiveness of endometrial testing and find its impact insignificant 39 – 42 . Although other similar systematic meta-analyses and single cohort studies confirm these results of no benefit of WOI testing in good prognosis patients, they also report that in the RIF subgroup, there is a significant increase in pregnancy rates following pET 38 , 43 , 44 . Another study by Haouzi et al demonstrated that the implantation rate increased over three times, from 7 to 23%, after using the personalised WOI determination in IVF patients with RIF diagnosis 3 .…”

“…Another study by Haouzi et al demonstrated that the implantation rate increased over three times, from 7 to 23%, after using the personalised WOI determination in IVF patients with RIF diagnosis 3 . Despite generally supporting endometrial testing in RIF cases, these studies also stress low certainty of evidence, thus advocating continued research on this controversial topic 38 , 43 , 44 . One reason for the disparity between studies might be that the actual rate of recurrent implantation failure due to endometrial factors may be lower than previously thought.…”

Precise hourly personalized embryo transfer significantly improves clinical outcomes in patients with repeated implantation failure

“…All these results suggested that the routine clinical application of ERA was precluded in the general infertile population, due to ERA and pET not being more effective than standard ET ( 16 , 17 , 19 , 28 – 32 ). However, uncertainties remained regarding whether ERA can improve clinical outcomes in RIF patients ( 12 , 15 , 19 , 27 , 30 , 33 – 42 ). Therefore, we could conclude that ERA and pET present no or limited effectiveness in good prognosis patients, and whether ERA could benefit RIF patients still need more high-quality RCTs.…”