Abstract

Abstract Study question Do patients with previous in vitro fertilization (IVF) implantation failures benefit more from endometrial receptivity analysis(ERA)-guided embryo transfer(ET) or sequential ET compared to traditional ET? Summary answer Our research suggests that both ERA-guided and sequential ET methods may lead to improved pregnancy outcomes compared to traditional ET in IVF-failure patients. What is known already In the field of IVF, achieving successful outcomes heavily relies on two crucial factors - embryo genetics and implantation in a receptive endometrium. The use of ERA-guided and sequential ET strategies has emerged in clinical practice as potential solutions to overcome embryo transfer failures. However, the controversy surrounding their advantages over traditional transplantation calls for a comprehensive comparative study. Study design, size, duration A retrospective cohort study was conducted in two private fertility clinics in Southwestern China (Dec 1, 2019 - Jun 30, 2024). Individuals experienced at least one IVF implantation failure were categorized into ERA-guided ET group (group A), sequential ET group(group B), or traditional ET group (group C) based on embryo transfer strategies. Analysis was restricted to patients who completed subsequent frozen-thawed embryo transplantation and were followed up at least 3 months to assess clinical outcomes Participants/materials, setting, methods A total of 6814 participants, with a mean age of 33.7 years were included. Among them, 15% (n = 1022) underwent ERA-guided ET (group A), which involved individualized ET guided by ERA testing. Another 10.3% (n = 703) utilized sequential transfer (group B), where two embryos were transferred at different timepoints. The remaining 74.7% (n = 5089) underwent traditional embryo transfer (group C) Main results and the role of chance The ongoing pregnancy rate was significantly higher in both group A (45.5%) and group B (44.8%) compared to group C (28.9%); however, there was no significant difference between group A and B (p = 0.79). Group A and B exhibited better clinical outcomes in terms of biochemical pregnancy (63.2%, 69.0%, 53.2%), clinical pregnancy (53.2%, 65.1%, 38.3%), implantation rate (46.6%, 38.5%, 34.6%), and spontaneous abortion rate (14.9%, 17.1%, 24.5%), compared to group C. The differences among three groups for multiple birth rate were significant (30.9%, 20.4%, 25.1%). In multivariate logistical regression, after adjusting for age, BMI, infertile type, IVF-failure times, and endometrium thickness, group A and B had odds ratios (OR) of achieving a successful ongoing pregnancy of 2.88 times [95% CI, 1.88-4.41] and 3.45 times [95% CI, 2.67-4.45], respectively. Among patients transferred at least two embryos, this beneficial effect was only significant in group A [OR, 1.90, 95% CI, 1.60-2.27]. Additionally, when comparing two blastocysts (D5+D5/D6, D6+D6) ET to two cleavage (D3+D3) ET, two blastocysts ET had a significantly higher chance [OR, 1.42, 95% CI, 1.22-1.65] of achieving an ongoing pregnancy. Similarly in one cleavage embryo plus one blastocyst (D3+D5/D6) ET [OR, 1.20, 95% CI, 1.58- 2.45] Limitations, reasons for caution The study has several limitations, including its retrospective observational nature, limited generalizability due to the study population being from two fertility centers in the same region, and potential biases from EHRs data source. Further studies are needed to validate these findings and explore the underlying mechanisms. Wider implications of the findings Overall, these findings suggest that both ERA-guided embryo transfer and sequential transfer methods may lead to better pregnancy outcomes compared to standard timing transfer in patients who have experienced IVF failures. Early adoption of these strategies and the transfer of two blastocysts are recommended. Trial registration number 2023(08)

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