The expression of bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9 (GDF-9) in oocytes of women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization

Abstract

OBJECTIVE: To evaluate the expression of BMP15 and GDF9 in oocytes of patients with PCOS and controls undergoing controlled ovarian hyperstimulation (COH) for IVF treatment and analyze the expression of these genes with the levels of steroids present in the follicular fluid (FF). DESIGN: Case-control study. MATERIALS AND METHODS: Eighteen oocytes from 18 patients with PCOS and 48 oocytes from control patients were obtained individually. The FF of a small follicle (10-14 mm) and a large follicle (<18 mm) from each patient was used for steroid determination. Real time PCR was used to determine the expression of BMP15 and GDF9 in oocytes. Steroids were determined by chemiluminescence and radioimmunoassay. RESULTS: The expression of BMP15 in oocytes was significantly higher in patients with PCOS compared to control group (median 5.95 and 0.59, respectively) P=0.0006, as also was the expression of the GDF9 (median=2.70 and 0.63, respectively) P=0.0009. Progesterone levels in the follicles of the PCOS group (8.095 ± 4151 ng/mL) were lower than control (9.824 ± 3128 ng/mL) P=0.03 (Mann Whitney test). Testosterone levels differed between small control follicle (326.6 ± 124.4ng/dL) and large control follicle (205.8 ± 98.91 ng/dL) P<0.001, and between large control follicle (205.8 ± 98.91 ng/dL) and large PCOS follicle (351.10 ± 122.1ng/dL) P<0.001 (Kruskal Wallis Dunn's). Pregnancy rates were not different between PCOS (50%; 9/18) and controls (37.14%; 13/35) P=0.3941 (Exact Fisher test). Among the patients with positive pregnancy, BMP15 and GDF9 were higher in PCOS patients (median 11.5 and 7.3, respectively) compared to the control group (median 0.58 and 0.75, respectively) (P=0,0042 and P=0.039, respectively) (Mann Whitney test). CONCLUSION: The lack of difference of pregnancy rates between PCOS and control groups submitted to COH with recombinant FSH for IVF treatment may be explained by increased expression of BMP15 and GDF9 in patients with PCOS despite high levels of testosterone in FF.