N-acetylcysteine compared to metformin, improves the expression profile of growth differentiation factor-9 and receptor tyrosine kinase c-kit in the oocytes of patients with polycystic ovarian syndrome

Background: Paracrine disruption of growth factors in women with polycystic ovarian syndrome [PCOS] results in production of low quality oocyte, especially following ovulation induction. The aim of this study was to investigate the effects of metformin [MET], N-acetylcysteine [NAC] and their combination on the hormonal levels and expression profile of GDF-9, BMP-15 and c-kit, as hallmarks of oocyte quality, in PCOS patients

Materials and Methods: This prospective randomized, double-blind, placebo controlled trial aims to study the effects of MET, NAC and their combination [MET+NAC] on expression of GDF-9, BMP-15 and c-kit mRNA in oocytes [10 at the germinal vesicle [GV] stage, 10 at the MI stage, and 10 at the MII stage from per group] derived following ovulation induction in PCOS. Treatment was carried out for six weeks, starting on the third day of previous cycle until oocyte aspiration. The expression of GDF9, BMP15 and c-kit were determined by quantitative real time polymerase chain reaction [RT-qPCR] and western blot analysis. Data were analyzed with one-way ANOVA

Results: The follicular fluid [FF] level of c-kit protein significantly decreased in the NAC group compared to the other groups. Significant correlations were observed between the FF soluble c-kit protein with FF volume, and rostenedione and estradiol. The GDF-9 expression in unfertilized mature oocytes were significantly higher in the NAC group com- pared to the other groups [P<0.001]. Similar difference was not observed between the MET, NAC+MET and control groups. The c-kit expression in unfertilized mature oocytes were significantly lower in the NAC group compared to the other groups [P<0.001]. Similar difference was not observed between the MET, NAC+MET and control groups [Registration number: IRCT201204159476N1]

Conclusion: We concluded that NAC can improve the quality of oocytes in PCOS

Ovary stereological features and serum biochemical factors following induction of polycystic ovary syndrome with testosterone enanthate in mice: an experimental study

Background: Polycystic ovary syndrome [PCOS] is an endocrine disorder featured by insulin resistance and hyperandrogenism. Testosterone enanthate can induce PCOS in mice models

Objective: We investigated the ovary stereological features along with the oxidative stress and inflammatory factors in mice following PCOS induction using testosterone enanthate

Materials and Methods: Twelve female NMRI mice [3 wk old] were divided into 2 groups [n=6/each]: Control and PCOS. PCOS was induced through daily injections of testosterone enanthate [1 mg/100g subcutaneous s.c for 5 wk]. Finally, ovaries were studied stereologically. The serum levels of the follicle-stimulating hormone, luteinizing hormone, testosterone, interleukin-6, and tumor necrosis factor-alpha were measured using ELISA kit. Serum levels of Malondialdehyde and the antioxidant capacity were measured relatively using thiobarbituric acid and ferric reducing antioxidant power assay

Results: The mean total volume of ovary and the mean volume of cortex [p<0.001], volume of oocyte in the preantral [p=0.011] and antral follicle [p=0.015], thickness of zona pellucida [p=0.016], the number of antral follicles [p=0.012], the serum levels of follicle-stimulating hormone [p<0.001] and the antioxidant capacity [p=0.020] reduced significantly in the PCOS group compared to the control. The number of primary [p=0.017] and preantral [p=0.006] follicles and the serum levels of testosterone [p<0.001], Luteinizing hormone [p=0.002], Malondialdehyde, Interleukin 6 and Tumor necrosis factor-? [p<0.001] showed a significant increase in the PCOS group compared to the control

Conclusion: Testosterone enanthate induced PCOS causes stereological features in the ovary, increases the oxidative stress and inflammatory markers in mice

Co-administration of metformin and N-acetyl cysteine fails to improve clinical manifestations in PCOS individual undergoing ICSI

Background: Studies have demonstrated the efficacy of metformin [MTF] in reducing insulin resistance and N-acetyl cysteine [NAC] in inhibiting oxidative stress which are involved in the pathogenesis of polycystic ovarian syndrome [PCOS]. We aimed to compare the effects of MTF and NAC combination on serum metabolite and hormonal levels during the course of ovulation induction in PCOS individual candidates of intracytoplasmic sperm injection [ICSI]

Materials and Methods: In this prospective randomized clinical trial, placebo con- trolled pilot study, 80 patients of polycystic ovarian syndrome at the age of 25-35 years were divided into 4 groups [n=20]: i. NAC=treated with N-acetyl cysteine [600 mg three times daily], ii. MTF=treated with metformin [500 mg three times daily], iii. MTF+NAC=treated with N-acetyl cysteine plus metformin [the offered doses] and iv. placebo [PLA]. A total number of 20 patients [6 from MTF group, 4 from NAC group, 6 from MTF+NAC group and 4 from PLA group] were dropped of the study. The drugs were administrated from day 3 of menses of previous cycle until ovum pick-up

Results: Serum levels of luteinizing hormone [LH], total testosterone, cholesterol and triglyceride, insulin and leptin significantly reduced in the MTF and NAC groups compared to the placebo [p<0.01]. But levels of LH, total testosterone, cholesterol and triglyceride had no significant reduction in the MTF+NAC groups compared to the placebo. The serum levels of malonyldialdehyde [MDA], insulin and leptin reduced significantly after treatment in the MTF+NAC group compared to the placebo [p<0.05]

Conclusion: Considering the adverse effect of combination therapy, we proposed the conadministration might have no beneficial effect for PCOS patient during course of ovulation induction of ICSI [Registration Number: IRCT201204159476N1]