Investigating Cycle-to-Cycle Variation and the Impact of Endometrial Injury through Differential Gene Expression Analysis

This prospective study investigated whether endometrial gene expression changes across two consecutive menstrual cycles and whether prior endometrial injury alters molecular profiles during the mid-luteal phase. Twenty women underwent paired endometrial biopsies, and differential gene expression was analysed using a paired design, adjusting for cycle timing. While samples from the same individual showed slightly greater similarity than those from different individuals, no significant gene expression changes were observed after endometrial injury (p > 0.05), including in subgroup analyses of fertile and infertile participants. Principal component analysis showed no clear clustering by individual, further highlighting cycle-to-cycle variability. These findings suggest that intra-individual molecular variability is largely due to biological fluctuations rather than any lasting effect of endometrial injury. This may help explain inconsistent outcomes in implantation and limited utility of interventions like endometrial injury and molecular receptivity testing in IVF.