Background: Despite advances in embryology, success rates for IVF remain at ~30% per cycle. Endometrial receptivity has been largely ignored.A number of potential biomarkers for determining endometrial receptivity during the receptive mid-secretory phase have been reported. However in an IVF cycle, sampling of endometrial tissue or secretions is not possible during the receptive window due to possible interference to a transferring embryo and required assay times. We have investigated which markers may be utilised in the pre-receptive phase of either a natural or stimulated cycle.
Methods & Results: Multiplex assays determined concentrations of 8 potential receptivity biomarkers in uterine fluid, collected with informed consent from natural cycling fertile and infertile women. Cycle stage was determined by Noyes’ criteria of an endometrial biopsy. Biomarker performance across fertile and infertile, early secretory and mid-secretory sample cohorts (n≥16/group) was determined using ROC plot and t-test analysis. Five biomarkers discriminated fertile from infertile in the mid-secretory phase. Only one, CSF3, significantly discriminated fertile and infertile during the early secretory phase (AUC = 0.760 p=0.001, t-test p = 0.006). CSF3 and its receptor are expressed by endometrial epithelial and stromal cells; however among infertile women there was low epithelial receptor expression. In a second cohort of women undergoing IVF, from whom uterine lavage was collected at the time of egg collection, CSF3 was elevated and CSF3R diminished for those whose outcome was unsuccessful compared to those for whom a successful pregnancy was attained.
Conclusion: CSF3 discriminates between fertile and infertile women during the pre-receptive phase. CSF3 was applicable in determining IVF outcome when sampling at the time of egg collection. CSF3 may be applicable in IVF cycles to determine if embryo attachment will be successful, or whether a frozen transfer in a subsequent cycle may be optimal for success.