Steroid receptor expression in the human endometrium during the follicular phase of stimulated cycles

Abstract

To assess steroid receptor expression in human endometrium at different days during the follicular phase in stimulated cycles. Prospective randomized study. Thirty women <39 years of age with basal levels of estradiol <80 pg/ml and progesterone <1.6 ng/ml, have been so far included in this study. All women received 100 IU/day of recombinant follicle stimulating hormone, starting on day 2 of the cycle. Addition of gonadotropin releasing hormone antagonists was performed as soon as a follicle of 12 mm was present, while human chorionic gonadotropin (HCG) was administrated as soon as a follicle of 18 mm was present. Ultrasound-guided aspirational biopsy of the endometrium was performed on the first day after the end of menstruation (day 0) in all women. According to random allocation, a second biopsy was performed two (Group 0 + 2, n = 10) or four (Group 0 + 4, n = 10) days after the first biopsy or on the day of HCG administration (Group 0 + HCG, n = 10). The immunohistochemical signal of estrogen receptor (ER)-alpha and both progesterone receptor (PR) isoforms in epithelial cells from the endometrial glands and in stromal cells was recorded and graded as either absent, weak, moderate or strong (0 to 3 scale). 1000 stromal and 1000 glandular cells were examined in each sample and a mean score was produced (range: 0–3). Difference in receptor expression between the two biopsies performed in each group is expressed as median difference (MD) in intensity of staining. ER expression did not significantly change in the 0 + 2 group (stroma: MD = −0.08, P=0.46; glands: MD = 0.04, P=0.92), the 0 + 4 group (stroma: MD = 0.13, P=0.6; glands: MD = 0.01, P=0.92) and the 0 + HCG group (stroma: MD = 0.08, P=0.89; glands: MD = −0.01, P=0.89). On the contrary, PR expression was significantly increased in the 0 + 2 group in both glands (MD = 0.16, P=0.04) and stroma cells (MD = 0.19, P=0.03). In addition, a significant increase in PR expression was present in group 0 + 4 in the stroma (MD = 0.16, P=0.03) but not in glandular cells (MD = 0.25, P=0.09). Finally, PR expression was significantly increased in the 0 + HCG group (stroma: MD = 0.39, P=0.04; glands: MD = 0.53, P=0.03). Estradiol receptor expression appears to remain stable throughout the duration of the follicular phase in stimulated cycles. However, progesterone receptor expression is significantly increased already two days after the end of menstruation in both stromal and glandular cells and remains significantly increased on the day of HCG administration.