20.500.12556/DiRROS-31263 Distinct endometrial protein profiles in spontaneous and stimulated cycles in women with poor ovarian response a prospective case-crossover clinical trial The window of implantation is a critical period for embryo implantation. Ovarian stimulation can disrupt endometrial receptivity, potentially through altered gene expression and downstream protein profiles. However, the impact on the endometrial proteome remains underexplored. Identifying biomarkers of endometrial receptivity may provide an opportunity to develop targeted interventions aimed at improving implantation outcomes. This prospective, case-crossover, open-label study was conducted at the Department of Human Reproduction, Division of Obstetrics and Gynecology, University Medical Centre Ljubljana, Slovenia, from September 2023 to June 2024. The study included 15 women aged <43 years with primary infertility and poor ovarian response. Endometrial samples were collected using a pipelle biopsy during the window of implantation in spontaneous and stimulated cycles and analyzed using protein microarrays targeting 1,466 proteins. Differential protein abundance was assessed using a multi-factorial linear model, including patient-specific effects as an additional factor to account for the paired case-crossover design. Effect sizes are reported as log2-fold changes with corresponding 95% confidence intervals. Differential abundance was defined a priori as |log2FC| > 0.5 with FDR-adjusted p-value < 0.05. Comparison of endometrial samples from spontaneous and stimulated cycles revealed 114 antibodies with differential abundance. Key proteins were associated with immune response (IL-8, proteins S100-A8 and S100-A9, CAMP) and extracellular matrix remodeling (MMP-9). Exploratory KEGG pathway mapping suggested involvement of immune and inflammatory pathways, including cytokine–cytokine receptor interaction and IL-17 signaling. Cluster analysis demonstrated distinct proteomic patterns, with all stimulated-cycle samples showing alterations and a subset of stimulated-cycle samples (40%) exhibiting more pronounced changes. The findings indicate that ovarian stimulation is associated with measurable alterations in the endometrial proteomic profile during the window of implantation. These changes may be relevant to biological pathways involved in endometrial receptivity and implantation. Further studies in larger cohorts are needed to validate the identified candidate markers and determine their clinical relevance for implantation outcomes. Trial registration: ClinicalTrials.gov NCT06804174. endometrium endometrial receptivity window of implantation ovarian stimulation proteomics endometrij receptivnost endometrija okno implantacije ovarijska stimulacija proteomika true false true Angleški jezik Slovenski jezik Neznano 2026-07-23 12:11:39 2026-07-23 12:11:40 2026-07-24 03:52:03 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Opis vira z dne 21. 5. 2026; str. 1-23 5, [article no.] e0338812 [Vol.] 21 19. maj 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 575.17:591.531.2 1932-6203 10.1371/journal.pone.0338812 278913283 RAZ_Abdulkhalikova_Dzhamilyat_2026.pdf RAZ_Abdulkhalikova_Dzhamilyat_2026.pdf 1 7A3A249A6AA95C65D8AE31AD59C4F5F4 ac21561928fa74a0ce942603b1263ad91ab946b73cd64703c7ea330cb17d5a24 02385a74-867f-11f1-812a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=48280 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338812 1 e6e51b10-867e-11f1-812a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=48279 Univerzitetni klinični center Ljubljana 0 0 0