Abstract:
BACKGROUND: Failure of the endometrium to achieve receptivity remains a key ratelimiting step in IVF success even 40 years after the birth of the first IVF baby. Based on a recent systemic review, an endometrial scratch may enhance endometrial receptivity leading to improved implantation rate. The injury may induce a healing response by triggering an upregulation of inflammatory genes, cytokines and growth factors, which may facilitate embryo implantation in the subsequent cycle. The aim of this experiment was to investigate any observable differences in the expression of selected genes prior and post injury in endometrium of infertile women who subsequently conceived and those who did not. METHODS: Prior to IVF cycle, two endometrial biopsies were taken approximately 7 days following ovulation during two consecutive menstrual cycles. Gene expression analysis of 25 selected genes was evaluated via real-time PCR using RNA isolated from biopsies. Steroid hormone regulation of the genes was also analysed in endometrial epithelial and stromal cells in vitro. RESULTS: 28.6% women got pregnant following IVF in this study. They displayed higher IL-6 expression in their first baseline biopsy and a lower expression of MIP-1[beta] in their second biopsy compared to women who did not conceive. Among the women who conceived, women with unexplained infertility displayed upregulation of endometrial IL-11, LIF, UPK1b, CHST2 and SDF1 expressions in second biopsies compared to women with male factor infertility. IL-11, CHST2, TGF[beta], TLR9 and SIRT1 levels differed significantly between nonpregnant groups with each infertility type. CONCLUSION: This is the first study to investigate the gene expression changes in response to endometrial injury and its effect on IVF outcome with stringent parameters; the use of the women as their own control to account for the substantial changes the endometrium undergoes during a menstrual cycle and the substantial inter-women variation in endometrial samples. Apart from IL-6 and MIP-1[beta], altered gene expression stemmed primarily from populations of women with different infertility diagnoses and was not associated with clinical outcomes or as a response to endometrial injury. Furthermore, administering endometrial scratch prior to IVF carried no benefit to women and did not improve pregnancy rates.