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.