Association of insulin resistance with lipid profile, metabolic syndrome, and hormonal aberrations in overweight or obese women with polycystic ovary syndrome.

This cross-sectional study was aimed to better clarify the associations of insulin resistance (IR) with endocrinometabolic parameters in polycystic ovary syndrome (PCOS). Anthropometric measurements, endocrine and metabolic profiles, and the presence of IR and metabolic syndrome (MetS) were assessed in 63 overweight or obese PCOS patients subdivided into insulin-resistant (IR) and insulin-sensitive (IS) groups. Fasting insulin concentration and HOMA-IR were higher (p<0.001), and quantitative insulin check index (QUICKI), glucose-to-insulin ratio (p<0.001), and high-density lipoprotein cholesterol (HDL-C) (p=0.012) were lower in IR group. MetS (p=0.034) and obesity (p=0.038) were more prevalent in IR group. For all PCOS patients, significant correlations of total cholesterol (TC) with dehydroepiandrosterone sulphate (DHEAS) (r=-0.27, p=0.031), HDL-C with QUICKI (r=0.26, p=0.036) were found. Partial correlations also showed significant associations between TG and BS2h (r=0.30, p=0.026) as well as TC and LH/FSH ratio (r=0.30, p=0.032). When the patients were divided into IR and IS groups, significant correlations of low-density lipoprotein cholesterol (LDL-C) with luteinizing hormone (LH) (r=0.50, p=0.017) as well as TC (r=0.42, p=0.043) and LDL-C (r=0.50, p=0.016) with LH/FSH ratio were observed in IR group. However, partial correlation suggested significant associations of HDL-C with testosterone (r=-0.35, p=0.049) as well as serum LDL-C (r=0.38, p=0.033), HDL-C (r=-0.32, p=0.047), and TC (r=0.34, p=0.056) with progesterone level only in the IS group. The findings of this study indicated that lipid abnormalities may occur in PCOS, irrespective of IR.

Correlation of Serum Lipoprotein Ratios with Insulin Resistance in Infertile Women with Polycystic Ovarian Syndrome: A Case Control Study.

BACKGROUND: Dyslipidemia and insulin resistance (IR), occurring in most infertile women with polycystic ovarian syndrome (PCOS), increase the risk of cardiovascular disease (CVD) and type 2 diabetes. This study aimed to assess the relationships between lipoprotein ratios and IR in PCOS women. MATERIALS AND METHODS: Thirty six infertile women with PCOS selected based on Androgen Excess Society (AES) criteria and 29 healthy women matched for age were recruited to this case-control study. After physical measurements, fasting serum glucose (Glu), insulin and lipid profile levels [triglycerides (TGs), total cholesterol (TC), low-density lipoproteincholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C)] were measured, while lipoprotein ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C) were calculated. IR was also calculated using homeostasis model assessment (HOMA)-IR. The optimal cutoffs of lipoprotein ratios in relation to HOMA-IR were calculated based on the Receiver Operating Characteristics (ROC) curve analysis using the area under curve (AUC). RESULTS: Waist circumference (WC), insulin levels, HOMA-IR, TG levels, and all lipoprotein ratios were significantly higher, while HDL-C was lower in PCOS group as compared to healthy controls. All lipoprotein ratios, TG levels, and WC are significantly correlated with insulin levels and HOMA-IR. Among lipoprotein ratios, the highest AUC of the ROC belonged to TG/HDL-C ratio with sensitivity of 63.6% and specificity of 84.4% (TG/HDL-C>3.19) as a marker of IR in infertile PCOS women. CONCLUSION: Lipoprotein ratios, particularly TG/HDL-C, are directly correlated with insulin levels and can be used as a marker of IR (HOMA-IR) in infertile PCOS patients.

Expression Levels of PPARγ and CYP-19 in Polycystic Ovarian Syndrome Primary Granulosa Cells: Influence of ω-3 Fatty Acid.

BACKGROUND: The omega-3 fatty acid (ω-3 fatty acid) such as eicosapentaenoic acid (EPA) is currently used in the clinic as a nutritional supplement in the treatment of poly- cystic ovarian syndrome (PCOS). The present study was designed to investigate the ef- fect of EPA on the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and cytochrome P450 aromatase (encoded by the CYP-19) in primary cultured granulosa cells (GC) from patients undergoing in vitro fertilization (IVF), and also to compare these effects with those in GC of PCOS patients. MATERIALS AND METHODS: In this experimental study, human GC were isolated, pri- mary cultured in vitro, exposed to a range of concentrations of the EPA and in- vestigated with respect to gene expression levels of PPARγ and CYP-19 using real time-polymerase chain reaction (PCR). The participants (n=30) were the patients admitted to the IVF Center in February-March 2013 at Alzahra Hospital, Tabriz, Iran, who were divided into two groups as PCOS (n=15) and non-PCOS (n=15) women (controls). RESULTS: All doses of the EPA significantly induced PPARγ mRNA gene expression level as compared to the control recombinant follicle stimulating hormone (rFSH) alone condi- tion. High doses of EPA in the presence of rFSH produced a stimulatory effect on expres- sion level of PPARγ (2.15-fold, P=0.001) and a suppressive effect (0.56-fold, P=0.01) on the expression level of CYP-19, only in the PCOS GC. CONCLUSION: EPA and FSH signaling pathway affect differentially on the gene ex- pression levels of PPARγ and CYP-19 in PCOS GC. Altered FSH-induced PPARγ activity in PCOS GC may modulate the CYP-19 gene expression in response to EPA, and possibly modulates the subsequent steroidogenesis of these cells.

Influence of ω-3 fatty acid eicosapentaenoic acid on IGF-1 and COX-2 gene expression in granulosa cells of PCOS women.

BACKGROUND: The omega-3 (ω-3) fatty acid eicosapentaenoic acid (EPA) is currently used in the clinic as a nutritional supplement to improve infertility, particularly in women with polycystic ovarian syndrome (PCOS). OBJECTIVE: The present study was designed to investigate the effect of EPA on insulin-like growth factor 1 (IGF-1) and cyclooxygenase 2 (COX-2) gene expression in primary cultured granulosa cells from patients undergoing in vitro fertilization (IVF), and also to compare this effect with those in granulosa cells of PCOS patients. MATERIALS AND METHODS: In this experimental study, human granulosa cells were isolated from follicular fluid of normal and PCOS women undergoing IVF by hyaluronidase digestions, followed by Percoll gradient centrifugation. Cells were cultured in vitro, exposed to a range of concentrations of the EPA (25-100 µM) for 24 hr, and investigated with respect to COX-2 and IGF-1 gene expression by real time-PCR. RESULTS: In both groups, all doses of the EPA significantly induced IGF-1 mRNA gene expression compared to the untreated control. High doses of EPA in the presence of recombinant (r) FSH produced a stimulatory effect on IGF-1 and a suppressive effect (p=0.01) on the COX-2 gene expression, which were more pronounced in granulosa cells from PCOS patients. CONCLUSION: EPA affect diversely the gene expression of IGF-1 and COX-2 in granulosa cells, which were more pronounced in PCOS compared to control. These findings represent the possible underlying molecular mechanisms for the positive impact of the ω-3 fatty acids on reproduction, especially in patients with PCOS.

Metabolic Syndrome and Its Characteristics among Reproductive-Aged Women with Polycystic Ovary Syndrome: A Cross-sectional Study in Northwest Iran.

BACKGROUND: Metabolic syndrome (MetS) is a clustering of factors known to increase the risk for cardiovascular disease (CVD) and diabetes mellitus. Polycystic ovary syndrome (PCOS), the most common endocrine disorder among reproductive-aged women, is also closely linked to MetS. Limited information is available pertaining to the prevalence of MetS in Iranian PCOS women; therefore this study assesses the frequency of MetS and its components among PCOS women from Tabriz, Iran. MATERIALS AND METHODS: In this cross-sectional study, we evaluated a total of 200 women with PCOS who referred to the only specialty and subspecialty gynecological center in Northwestern Iran. PCOS was diagnosed according to Rotterdam criteria. This study defined clinical and biochemical parameters for MetS by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Statistical analyses were performed with descriptive-analytical methods using SPSS software version 16. RESULTS: MetS was identified in 39.5% of PCOS women. The frequencies of individual components of MetS among studied subjects were: high-density lipoprotein cholesterol level (HDL-C)<50 mg/ dL (99.5%), waist circumference(WC) ≥88cm (65%), triglycerides (TG) ≥150 mg/dL(98%), and blood pressure≥130/85 mmHg(34%).There were no fasting glucose concentrations≥110 mg/dL. The frequency of MetS increased with body mass index (BMI)as follows: normal (5.4%), overweight (41.5%) and obese (85.7%) women (p<0.0001). CONCLUSION: The PCOS women in this study had a high frequency of MetS and its individual components, particularly decreased HDL-C and increased triglyceride levels. These data can useful for lifestyle modification programs.

Methylenetetrahydrofolate Reductase C677T and A1298C Mutations in Women with Recurrent Spontaneous Abortions in the Northwest of Iran.

Introduction. Recurrent spontaneous abortion (RSA) is a significant obstetrical complication that may occur during pregnancy. Various studies in recent years have indicated that two common mutations (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene are risk factor for RSA. This study was carried out to determine the influence of (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene mutations with RSA. Materials and Methods. A total of 139 women were included in this study: 89 women with two or more consecutive miscarriages and 50 healthy controls. Total genomic DNA was isolated from blood leukocytes. To determine the frequency of the two common C677T and A1298C MTHFR gene mutations in the patients and controls, we used two methods, amplification refractory mutation system-PCR and PCR-restriction fragment length polymorphism. Results. There is no significant difference in the prevalence of 677T/T genotype among women with RSA and healthy controls (P = 0.285). Also no statistically significant difference in the frequency of A1298C MTHFR gene mutation was detected between the two groups (P = 0.175 ). Conclusion. In conclusion, the results indicate that the Amplification Refractory Mutation System-PCR method was in complete concordance with the results obtained by standard PCR-restriction fragment length polymorphism method. The results also show no significant difference in MTHFR C677T/A1298C genotype distribution among the two groups; therefore, further studies on larger population and other genetic variants to better understand the pathobiology of RSA are needed.