Prednisolone treatment reduces endometrial spiral artery development in women with recurrent miscarriage

Background Uterine natural killer (uNK) cells and endometrial blood vessel maturation are increased in the luteal phase of the menstrual cycle in a subset of women with recurrent miscarriage (RM). uNK cell numbers are reduced after treatment with prednisolone (20 mg/day for 3 weeks). Hypotheses Prednisolone treatment reduces endometrial vascular maturation and angiogenic growth factor expression in women with RM with increased uNK cells. Methods Endometrial biopsies (n = 18 paired samples) from women with RM at LH + 7 before and during prednisolone treatment (20 mg/day for 3 weeks) were snap frozen. Total RNA and cDNA was prepared and used in a human angiogenesis RT-PCR superarray (84 genes, n = 6 pairs) with results validated using RT-PCR (n = 15 pairs). Immunohistochemistry (n = 15 pairs) was performed for Factor VIII, alpha-smooth muscle actin (alpha-SMA) and myosin heavy chain (MyHC) and the total number of vessels and the percentage of vessels completely surrounded by vascular smooth muscle cells (VSMCs) were determined. Results During prednisolone treatment there was no change in the total number of endometrial blood vessels but the percentage of vessels completely surrounded by VSMCs was decreased (alpha-SMA P < 0.0001; MyHC P < 0.0001). Endometrial EGF and STAB 1 expression was decreased during prednisolone treatment in samples from woman who went on to have a live birth. Conclusions The effect of prednisolone therapy for some women with RM may be due to altered endometrial angiogenic growth factor expression and reduced blood vessel maturation.