Endometrial transcriptomic and ciliation analysis after scratch shows no signature linked to live birth following IVF

Abstract

ObjectiveTo determine whether endometrial scratch induces differences in transcriptomic profiles or epithelial cell ciliation in the endometrium at the window of implantation that associate with live birth following IVF. DesignSecondary analysis of 50 matched endometrial biopsies collected within a randomised controlled trial evaluating the clinical effectiveness of endometrial scratch before first-time IVF. SettingEndometrial biopsy samples were obtained from women attending the Jessop Wing of Sheffield Teaching Hospitals. Population or SampleWomen undergoing first-time IVF who received an endometrial scratch in the preceding cycle at the window of implantation (6-10 days after LH surge). MethodsEndometrial biopsies were molecularly dated using transcriptomic menstrual-cycle staging algorithms. Bulk RNA sequencing was analysed using DESeq2 with FDR correction, and principal component analysis (PCA) assessed clustering patterns. Epithelial cell ciliation was quantified using immunohistochemistry and an automated Python-based image analysis pipeline. Main Outcome MeasuresDifferential endometrial gene expression between women with and without live birth after IVF; percentage coverage of ciliated epithelial cells in luminal and glandular regions. ResultsTranscriptomic dating confirmed no differences in menstrual-cycle timing between live-birth and no-live-birth groups. No significant differential gene expression was detected (log2FC >2, FDR <0.05), and PCA showed no clustering by pregnancy outcome. Ciliation coverage did not differ between outcome groups or between glandular and luminal surfaces. ConclusionsWhen implantation timing is precisely defined, endometrial scratch does not produce detectable transcriptomic changes or alterations in epithelial ciliation that distinguish women who achieve live birth after IVF. FundingWellbeing of Women RG2147; Wessex Medical Research; Rosetrees Trust (PGS23/100171).