JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):2
Oral Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263516

O-02. Clinical Implications of Endometrial Functional Assessment in Patients with Recurrent Implantation Failure (RIF)

Julia Prestes dos Santos¹, Yangyun Zou¹, Yuanyuan Zhang¹, Sijia Lu¹

¹ Yikon Genomics Co. Ltd. - China

Objective: To (1) evaluate whether endometrial functional assessment-guided hour-level window of implantation (hlWOI) personalized embryo transfer improves clinical outcomes in patients with recurrent implantation failure (RIF), and (2) characterize the impact of endometrial immune microenvironment and tissue cell composition on reproductive success.
Methods: Endometrial functional assessment can provide hlWOI, status-level window of implantation (slWOI) and the endometrial immune and tissue cell composition. A retrospective cohort of 464 RIF patients with hlWOI personalized embryo transfer (Group htWOI-pET) or slWOI pET (Group slWOI-pET) and 288 RIF patients without WOI result received conventional embryo transfer (Group ET) were recruited. Leveraging RNA sequencing data, the proportions of immune and tissue cells were analyzed utilizing deconvolution algorithms to excavate their correlations with clinical outcomes. An independent validation cohort comprised RIF patients from two additional centers. The implantation rate (IR), intrauterine pregnancy rate (IPR), ongoing pregnancy rate (OPR), and miscarriage rate (MR) were compared between groups. Chi-square tests were used for categorical data analysis.
Results: The IR of Group slWOI-pET was significantly higher than that of Group ET (43.2% vs. 30.9%, p=0.032). Whereas, Group htWOI-pET achieved a significantly higher IR (48.4% vs. 30.9%, p<0.001), IPR (52.5% vs. 36.3%, p<0.001), OPR (48.0% vs. 29.1%, p<0.001) and a significantly lower MR (8.6% vs. 20.0%, p=0.024) compared to Group ET. The proportions of unciliated epithelial cells (P-UEC) from all RIF patients were stratified as seven different groups (P-UEC groups: <45%, 45%~50%, 50%~55%, 55%~60%, 60%~65%, 65%~70%, >70%), and IPR of each group was 27.3%, 30.0%, 37.5%, 35.3%, 44.7%, 56.1%, 58.8%, and displayed a tendency that higher IPR connected with higher proportion of unciliated epithelial cells (p=0.039). In the independent validation cohort, IPR also correlated positively with unciliated epithelial cell proportions (p=0.018). The proportions of uterine natural killer (uNK) cells were categorized as low, medium, and high-level, and patients with the medium- level uNK cells showed higher IPR (57.1% vs. 44% or 47%). Besides, patients with high-level proportions of plasma cells exhibited lower IPR than that of patients with low-level proportions of plasma cells (56.4% vs. 35.0%, p>0.05).
Conclusion: Endometrial functional assessment-guided hlWOI pET significantly improves pregnancy outcomes in RIF. The abundance of unciliated epithelial and plasma cell and balanced uNK cells emerge as critical determinants of endometrial competence.