Clomiphene citrate versus letrozole: molecular analysis of the endometrium in women with polycystic ovary syndrome

Objective: To compare the effect of clomiphene citrate (CC) and letrozole on endometrial receptivity in women with polycystic ovary syndrome (PCOS). Design: A randomized controlled trial. Setting: University teaching hospital. Patient(s): Ten anovulatory women with PCOS and 5 fertile ovulatory women. Intervention(s): Patients received 2.5 mg of letrozole on cycle days 3-7 (5 patients, 1 cycle) or 50 mg of CC on cycle days 5-9 (5 patients, 1 cycle). Main Outcome Measure(s): Serum estrogen (E) and progesterone (P) endometrial protein and messenger RNA (mRNA) expression of leukemia inhibitory factor (LIF), dickkhopf homolog 1 (DKK-1), fibroblast growth factor 22 (FGF-22), and endometrial mRNA expression of LIF/GP130 receptor (LIFR). Result(s): No statistically significant differences were observed between groups compared with fertile ovulatory women when serum E and P were examined, or between body mass index (BMI), and cycle day at time of biopsy. Letrozole increased mRNA expression of LIF, DKK1, LIFR, and FGF-22, whereas CC only increased endometrial mRNA expression of LIF. Letrozole mRNA expression directly translated into increased protein expression of like genes in the endometrium. The CC protein expression of DKK-1 was significantly decreased compared with controls. Conclusion(s): Letrozole positively influences a number of markers of endometrial receptivity compared with CC. (Fertil Steril (R) 2011; 96: 1051-6. (C) 2011 by American Society for Reproductive Medicine.)