Local production of 17β-oestradiol in the endometrium during the implantation window: a pilot study

Sex steroids are converted to bioactive metabolites and vice versa by endometrial steroid-metabolising enzymes. Studies indicate that alterations in this metabolism might affect endometrial receptivity. This pilot study determined whether the endometrial formation and inactivation of 17β-oestradiol differed between the supposedly embryo-receptive endometrium and non-receptive endometrium of women undergoing IVF/intracytoplasmic sperm injection (ICSI). Endometrial biopsies were obtained from IVF/ICSI patients 5–8 days after ovulation in a natural cycle, prior to their second IVF/ICSI cycle with fresh embryo transfer (ET). Endometrial biopsies from patients who achieved clinical pregnancy after fresh ET (n = 15) were compared with endometrial biopsies from patients that did not conceive after fresh ET (n = 15). Formation of 17β-oestradiol (oxidative 17β-hydroxysteroid dehydrogenases (HSDs)), oestrone (reductive HSD17Bs) and inhibition of HSD17B1 activity were determined by high-performance liquid chromatography. The endometrial transcriptome was profiled using RNA sequencing followed by principal component analysis and differentially expressed gene analysis. The false discovery rate-adjusted P 0.5 were selected as the screening threshold. Formation and inactivation of 17β-oestradiol resulted similar between groups. Inhibition of HSD17B1 activity was significantly higher in the non-pregnant group when only primary infertile women (n = 12) were considered (27.1%, n = 5 vs 16.2%, n = 7, P = 0.04). Gene expression analysis confirmed the presence of HSD17B1 (encoding HSD17B1), HSD17B2 (encoding HSD17B2) and 33 of 46 analysed steroid metabolising enzymes in the endometrium. In the primary infertile subgroup (n = 10) 12 DEGs were found including LINC02349 which has been linked to implantation. However, the exact relationship between steroid-metabolising enzyme activity, expression and implantation outcome requires further investigation in larger, well-defined patient groups

Local production of 17B-estradiol in the endometrium during the implantation window:a pilot study

Sex steroids are converted to bioactive metabolites and vice versa by endometrial steroid-metabolising enzymes. Studies indicate that alterations in this metabolism might affect endometrial receptivity. This pilot study determined whether the endometrial formation and inactivation of 17B-estradiol differed between the supposedly embryo-receptive endometrium and non-receptive endometrium of women undergoing IVF/ICSI. Endometrial biopsies were obtained from IVF/ICSI patients 5-8 days after ovulation in a natural cycle, prior to their second IVF/ICSI cycle with fresh embryo transfer (ET). Endometrial biopsies from patients who achieved clinical pregnancy after fresh ET (n=15) were compared with endometrial biopsies from patients that did not conceive after fresh ET (n=15). Formation of 17B-estradiol (oxidative 17B hydroxysteroid dehydrogenases [HSDs]), estrone (reductive HSD17Bs) and inhibition of HSD17B1 activity was determined by high-performance liquid chromatography (HPLC). The endometrial transcriptome was profiled using RNA-sequencing followed by principal component analysis and differentially expressed gene (DEG) analysis. The False Discovery Rate-adjusted p<0.05 and log FoldChange>0.5 were selected as screening threshold. Formation and inactivation of 17B-estradiol resulted similar between groups. Inhibition of HSD17B1 activity was significantly higher in the non-pregnant group when only primary infertile women (n=12) were considered (27.1%,n=5 versus 16.2%,n=7,p=0.04). Gene-expression analysis confirmed the presence of HSD17B1 (encoding HSD17B1), HSD17B2 (encoding HSD17B2) and 33 of 46 analysed steroid metabolizing enzymes in the endometrium. In the primary infertile subgroup (n=10) 12 DEGs were found including LINC02349 which has been linked to implantation. However, the exact relationship between steroid metabolizing enzyme activity, expression and implantation outcome requires further investigation in larger, well-defined patient groups