Group Of Polycystic Ovary Syndrome Patients Research Articles

Characteristics of Different Obesity Metabolic Indexes and their Correlation with Insulin Resistance in Patients with Polycystic Ovary Syndrome.

This study is aimed to investigate the characteristics of different obesity metabolic indexes [body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), cardiometabolic index (CMI), body roundness index (BRI), visceral adiposity index (VAI), and lipid aggregation products (LAP)] and their correlation with insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS). The study was conducted on 140 subjects with PCOS and 133 control subjects aged 18-44years. According to insulin resistance index (HOMA-IR) ≥ 2.69 and HOMA-IR < 2.69, PCOS group members were divided into insulin resistance group and non-insulin resistance group. Anthropometric and serological characteristics of the population with PCOS focused on calculating different obesity metabolic indexes and HOMA-IR. BMI, WC, WHR, WHtR, CMI, BRI, VAI, and LAP were significantly higher in PCOS patients than in the control group, and the differences were all statistically significant (P < 0.05); In the insulin resistance group of PCOS patients, BMI, WC, WHR, WHtR, CMI, BRI, VAI, and LAP were significantly higher than in the non-insulin resistance group (P < 0.05). In PCOS patients, BMI (r = 0.658, P < 0.001), WC (r = 0.0.662, P < 0.001), WHR (r = 0.377, P < 0.001), WHtR (r = 0.660, P < 0.001), CMI (r = 0.698, P < 0.001), BRI (r = 0.757, P < 0.001), VAI (r = 0.640, P < 0.001), and LAP (r = 0.767, P < 0.001) were positively correlated with IR. Obesity metabolic indexes associated with PCOS were elevated in the PCOS group compared to the control group, and in the PCOS insulin-resistant group compared to the non-insulin resistant group. Novel obesity metabolic indexes, especially CMI, BRI and LAP, might be more appropriate for evaluating the risk of concurrent IR in PCOS.

Changes in the serum metabolomics of polycystic ovary syndrome before and after compound oral contraceptive treatment.

Polycystic ovary syndrome (PCOS) is both a common endocrine syndrome and a metabolic disorder that results in harm to the reproductive system and whole-body metabolism. This study aimed to investigate differences in the serum metabolic profiles of patients with PCOS compared with healthy controls, in addition to investigating the effects of compound oral contraceptive (COC) treatment in patients with PCOS. 50 patients with PCOS and 50 sex-matched healthy controls were recruited. Patients with PCOS received three cycles of self-administered COC treatment. Clinical characteristics were recorded, and the laboratory biochemical data were detected. We utilized ultra-performance liquid chromatography-high-resolution mass spectrometry to study the serum metabolic changes between patients with PCOS, patients with PCOS following COC treatment, and healthy controls. Patients with PCOS who received COC treatment showed significant improvements in serum sex hormone levels, a reduction in luteinising hormone levels, and a significant reduction in the levels of biologically active free testosterone in the blood. Differential metabolite correlation analysis revealed differences between PCOS and healthy control groups in N-tetradecanamide, hexadecanamide, 10E,12Z-octadecadienoic acid, and 13-HOTrE(r); after 3 months of COC treatment, there were significant differences in benzoic acid, organic acid, and phenolamides. Using gas chromatography-mass spectrometry to analyse blood serum in each group, the characteristic changes in PCOS were metabolic disorders of amino acids, carbohydrates, and purines, with significant changes in the levels of total cholesterol, uric acid, phenylalanine, aspartic acid, and glutamate. Following COC treatment, improvements in sex hormone levels, endocrine factor levels, and metabolic levels were better than in the group of PCOS patients receiving no COC treatment, indicating that COC treatment for PCOS could effectively regulate the levels of sex hormones, endocrine factors, and serum metabolic profiles.

Divergent Associations Between Serum Androgens and Ovarian Reserve Markers Revealed in Patients With Polycystic Ovary Syndrome.

BackgroundThe role of excess androgen in ovarian reserve remains unclear in patients with polycystic ovary syndrome (PCOS). Our study highlights the associations of serum androgen levels and ovarian reserve markers in PCOS and non-PCOS women.MethodsTotally 584 menstrual abnormalities women of 20-45 years were retrospectively evaluated at the Beijing Obstetrics and Gynecology Hospital between January 2021 to October 2021. The enrolled patients were classified into two groups: the PCOS group (n=288) and the non-PCOS group (n=296) based on the Rotterdam consensus for PCOS diagnosis. The serum androgens, including testosterone (T), free testosterone (FT, calculated), bioavailable testosterone (Bio-T, calculated), androstenedione (A2), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) were assessed with an in-house developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The associations between the serum androgens and the hormone markers commonly used for evaluating ovarian reserve function, such as anti-mullerian hormone (AMH) and the ratio of luteinizing hormone (LH)/follicle stimulating hormone (FSH) were explored.ResultsThe serum T, FT, Bio-T, A2, DHT, DHEA, DHEAS, AMH and LH/FSH of the PCOS group were 51.7 ± 23.2 ng/dL/mL, 8.5 ± 5.0 pg/mL, 210.1 ± 127.7 pg/mL, 1.9 ± 0.8 ng/mL, 0.2 ± 0.1 ng/mL, 6.4 ± 4.2 ng/mL, 2431.0 ± 1030.7 ng/mL, 6.7 ± 3.8 ng/mL, and 1.8 ± 1.4 respectively, which were significantly higher than those in the non-PCOS group (p<0.05). In the group of PCOS patients, T and A2 levels were positively associated with AMH in both multivariate linear regression analysis and Pearson’s correlation analysis. Similar but weaker associations were observed in the non-PCOS patients. In the PCOS patients with hyperandrogenemia (HA), the AMH level was significantly higher in the subjects with T increased than in the subjects with non-T androgen(s) increased (A2, DHT, DHEA or DHEAS).ConclusionsThe serum androgen levels are positively associated with ovarian reserve markers in both of the PCOS and the non-PCOS patients in our study. In the PCOS group, the highest AMH level was observed in the subjects with the T elevation subgroup, suggesting that T is more closely related with the increase of AMH when compared with other androgens investigated.

Role of Oxidative Stress in Obese and Nonobese PCOS Patients.

Objective The aim of this study was to evaluate the relationship between the oxidant-antioxidant status, endothelial dysfunction, lipid metabolism, and metabolic syndrome risk in women with polycystic ovary syndrome (PCOS). Materials and Methods Forty-five obese (BMI >30 kg/m2) woman diagnosed with PCOS in the study, forty-five nonobese (BMI <30 kg/m2) PCOS diagnosis working groups, and forty-nine healthy control groups were created with patients. Serum malondialdehyde (MDA) levels with antioxidant activities, such as SOD, GSH, GPx, and CAT activities, were measured by spectrophotometry. Results There was a statistically significant difference in the mean serum MDA level in the obese PCOS group compared to the nonobese group and the control group (p < 0.001). When the antioxidant parameters, such as SOD, GPx, GSH, and CAT, were compared with the healthy control group, nonobese, and obese PCOS groups, the difference between the groups was statistically significant (p < 0.001). A positive correlation was observed between MDA and BMI, triglyceride, LDL, SBP, DBP, and HOMA-IR in the PCOS patient group. Conclusion Oxidative stress and decreased antioxidant parameters in PCOS patients were correlated with hyperinsulinemia, hypertension, and dyslipidemia findings, and we think that this oxidative stress condition may contribute to metabolic syndrome and cardiovascular diseases in PCOS patients.

Metabolic syndrome and its components in different phenotypes of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-age women. Important factors in its pathogenesis are hyperinsulinaemia and insulin resistance, which lead to higher risk of metabolic syndrome (MetS) and its complications. With the implementation of the Rotterdam diagnostic criteria in 2003, the group of PCOS patients became highly heterogeneous, with varying metabolic risk reported for different phenotypes of the syndrome. The aim of the present review is to assess the prevalence and severity of MetS and its components in patients with the four phenotypes of PCOS. A comprehensive search of Pubmed database was performed to identify studies comparing metabolic characteristics between PCOS patients with different phenotypes of the syndrome. The results of 60 studies published between 2004 and 2020 were retrieved and analysed. More adverse metabolic profile was observed in PCOS patients with hyperandrogenic phenotypes in comparison to normoandrogenic patients, as well as in classic phenotypes, defined by National Institutes of Health criteria, in comparison to newer phenotypes introduced by the Rotterdam criteria. In the majority of observations, normoandrogenic PCOS patients did not differ significantly from controls in terms of metabolic characteristics, although some East Asian studies reported more adverse metabolic profile in normoandrogenic phenotype in comparison to healthy women. In conclusion, metabolic abnormalities in PCOS seem to be associated with joint effects of hyperandrogenism, insulin resistance and visceral obesity. The differences observed between the four phenotypes of PCOS underline the need for individualised diagnostic and therapeutic approach.

Proteomic analysis of human follicular fluid from polycystic ovary syndrome patients.

Comparative proteomic profiling of human follicular fluid (HFF) from polycystic ovary syndrome (PCOS) and non-PCOS patients who displayed low levels of fertility was carried out via two-dimensional gel electrophoresis (2-DE) combined with mass spectrometry. HFF, an important reproductive fluid, was used for the proteomic analysis of PCOS patients to determine the effect of PCOS on folliculogenesis. HFF was obtained from 10 women (average age, 35 years) undergoing in vitro fertilization at two hospitals. The proteins of HFF were separated using 2-DE analysis and validated by Western blot assay. Approximately 250 protein spots were separated on the 2-DE gel. Among them, the expression levels of seven proteins were found to change at least 1.5-fold in the PCOS patient group. Three protein spots, albumin, uncharacterized protein 1, and uncharacterized protein 2, were downregulated in PCOS patients. However, four protein spots, gelsolin, vitamin D binding protein, serum albumin, and complement factor B, were upregulated in PCOS patient group. These proteins may serve as a panel of potential pathological biomarkers during fertilization and oocyte development.

Body Composition, Serum Concentrations of Androgens and Insulin Resistance in Different Polycystic Ovary Syndrome Phenotypes.

Insulin resistance and hyperandrogenemia observed in polycystic ovary syndrome (PCOS) are associated with metabolic disturbances and could be connected with body composition pattern. To date, several studies defining the parameters of body composition using dual energy X-ray absorptiometry (DXA) method in the group of PCOS patients have been published, however, without the analysis in different phenotypes. The aim of the present study was to investigate the relationships between serum androgens concentration, insulin resistance and distribution of fat mass using DXA method in various PCOS phenotypes according to the Rotterdam criteria. We examined 146 women: 34 (38%) had PCOS phenotype A, 20 (23%) phenotype B, 20 (23%) phenotype C and 15 (16%) phenotype D (with mean age of each phenotype 25 years), and 57 control subjects (mean age of 25.5 years). Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Serum concentrations of testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEA-S) were assessed and free androgen index (FAI) was calculated. In phenotypes A, B and C, we observed higher FAI in comparison to the control group (all p < 0.01). Serum concentrations of androstenedione and DHEA-S were higher in phenotypes A and C in comparison to the control group (all p < 0.01). However, only in phenotype A we found higher visceral adipose tissue (VAT) mass and android/gynoid ratio (A/G ratio) in comparison to the control group (all p < 0.01). In phenotype A, we observed connection of VAT with FAI (r = 0.58, p < 0.01). Accordingly, A/G ratio was related with FAI in all phenotypes (all p < 0.05). Additionally, in phenotype C, A/G ratio was related to serum concentrations of DHEA-S and androstenedione (r = 0.46, p = 0.03; r = 0.53, p = 0.01, respectively). We also found connections of HOMA-IR with VAT and A/G ratio in all phenotypes (all p < 0.05). Women with phenotype A had higher amount of VAT and A/G ratio in comparison to the control group. Serum concentration of androgens and insulin resistance are connected with VAT and A/G ratio in normoandrogenic and hyperandrogenic PCOS phenotypes.

Plasmatic free light chains in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS), as systemic disease, is accompanied by different indexes of inflammation. Free light chains of immunoglobulins (FLCs), produced by plasmacells, are released in slight excess for the immune requests, with still poorly defined physiological role but surely they represent a marker of inflammation. In order to evaluate their levels and correlate them with hyperandrogenism, we have studied a group of PCOS patients, age range 18–37 yrs, mean ± SEM body mass index (BMI) 24.1 ± 0.9 kg/m2), compared with age- and BMI-matched controls, with assay of k and λ FLCs, by turbidimetric method, and their ratio in blood plasma. PCOs exhibited higher levels vs. controls: (mean ± SEM λ: 10.0 ± 0.85 mg/L vs. 8.41 ± 0.45 mg/L; k: 12.45 ± 0.72 mg/L vs. 6.41 ± 0.34 mg/L; k/λ: 1.31 ± 0.07 vs. 0.78 ± 0.04). A significant direct correlation was observed between λ-FLCs and testosterone levels, no correlation was indeed found with HOMA-IR index. These data confirm high levels of FLCs in PCOS, suggesting systemic inflammatory state and a possible role in the pathophysiology of such complex syndrome.

Downregulation of Extracellular Matrix and Cell Adhesion Molecules in Cumulus Cells of Infertile Polycystic Ovary Syndrome Women with and without Insulin Resistance.

Objective The extracellular matrix (ECM) of the cumulus oocyte complex (COC) is composed of several molecules that have different roles during follicle development. This study aims to explore gene expression profiles for ECM and cell adhesion molecules in the cumulus cells of polycystic ovary syndrome (PCOS) patients based on their insulin sensitivity following controlled ovarian stimulation (COS). Materials and Methods In this prospective case-control study enrolled 23 women less than 36 years of age who participated in an intracytoplasmic sperm injection (ICSI) program. Patients were subdivided into 3 groups: control (n=8, fertile women with male infertility history), insulin resistant (IR) PCOS (n=7), and insulin sensitive (IS) PCOS (n=8). We compared 84 ECM component and adhesion molecule gene expressions by quantitative real-time polymerase chain reaction array (qPCR-array) among the groups. Results We noted that 21 of the 84 studied genes differentially expressed among the groups, from which 18 of these genes downregulated. Overall, comparison of PCOS cases with controls showed downregulation of extracellular matrix protein 1 (ECM1); catenin (cadherin-associated protein), alpha 1 (CTNNA1); integrin, alpha 5 (ITGA5); laminin, alpha 3 (LAMA3); laminin, beta 1 (LAMB1); fibronectin 1 (FN1); and integrin, alpha 7 (ITGA7). In the IS group, there was upregulation of ADAM metallopeptidase with thrombospondin type 1 motif, 8 (ADAMTS8) and neural cell adhesion molecule 1 (NCAM1) compared with the controls (P<0.05). ConclusionDownregulation of ECM and cell adhesion molecules seem to be related to PCOS. Gene expression profile alterations in cumulus cells from both the IS and IR groups of PCOS patients seems to be involved in the composition and regulation of ECM during the ovulation process. This study highlights the association of ECM gene alteration as a viewpoint for additional understanding of the etiology of PCOS.

Ameliorative effect of myo-inositol on red blood cell alterations in polycystic ovary syndrome: in vitro study

Polycystic ovary syndrome (PCOS)is a gynecological endocrine disorder which is associated with systemic inflammatory status inducing red blood cells (RBC) membrane alterations related to insulin resistance and testosterone levels which could be greatly improved by myo-inositol (MYO) uptake. In this study we aim to evaluate the effect of MYO in reducing oxidative-related alterations through in vitro study on PCOS RBC. Blood samples from two groups of volunteers, control group (CG, n = 12) and PCOS patient group (PG, n = 12), were analyzed for band 3 tyrosine phosphorylation (Tyr-P), high molecular weight aggregate (HMWA), IgG in RBC membranes, and glutathione (GSH) in cytosol, following O/N incubation in the presence or absence of MYO. PCOS RBC underwent oxidative stress as indicated by higher band 3 Tyr-P and HMWA and increased membrane bound autologous IgG. Twenty four hours (but not shorter time) MYO incubation, significantly improved both Tyr-P level and HMWA formation and concomitant membrane IgG binding. However, no relevant modification of GSH content was detected. PCOS RBC membranes are characterized by increased oxidized level and enhanced sensitivity to oxidative injuries leading to potential premature RBC removal. MYO treatment is effective in reducing oxidative related abnormalities in PCOS patients probably restoring the inositol phospholipid pools of the membranes.

Association between copy-number variation on metabolic phenotypes and HDL-C levels in patients with polycystic ovary syndrome.

Polygenic diseases with a broad phenotypic spectrum, such as polycystic ovary syndrome (PCOS), present a particular challenge in terms of identifying the underlying genetic mechanisms, nevertheless genetic variants have impact on the individual phenotype. We aimed to determine if next to genetic variations like SNPs further mechanisms might play a role in the pathogenesis of PCOS. We examined the effect of copy-number variations (CNVs) on metabolic phenotypes in PCOS. The intragenic rs1244979, rs2815752 in NEGR1 gene, and rs780094 in GCKR gene were genotyped and CNVs were determined by droplet digital polymerase chain reaction (ddPCR) in PCOS patients (n = 153) and controls without metabolic syndrome (n = 142). The study indicated that SNPs are not associated with the pathogenesis of PCOS but affect metabolic phenotypes. The CNVs investigated show a lower variability in PCOS than in CON. Furthermore, we provided direct evidence that the copy number, but not the genotype of the CNV in the genomic regions of rs780094(GCKR) is associated with low level of high-density lipoprotein cholesterol in PCOS. This study supports the hypothesis that not only genetic variants, but also CNVs in metabolically relevant genes, have an effect on metabolic phenotypes in our group of PCOS patients.

The relationship between epicardial fat tissue thickness and visceral adipose tissue in lean patients with polycystic ovary syndrome.

BackgroundPolycystic ovary syndrome (PCOS) is related to metabolic syndrome, insulin resistance, and cardiovascular metabolic syndromes. This is particularly true for individuals with central and abdominal obesity because visceral abdominal adipose tissue (VAAT) and epicardial adipose tissue (EAT) produce a large number of proinflammatory and proatherogenic cytokines. The present study aimed to determine whether there are changes in VAAT and EAT levels which were considered as indirect predictors for subclinical atherosclerosis in lean patients with PCOS.MethodsThe clinical and demographic characteristics of 35 patients with PCOS and 38 healthy control subjects were recorded for the present study. Additionally, the serum levels of various biochemical parameters were measured and EAT levels were assessed using 2D-transthoracic echocardiography.ResultsThere were no significant differences in mean age (p = 0.056) or mean body mass index (BMI) (p = 0.446) between the patient and control groups. However, the body fat percentage, waist-to-hip ratio, amount of abdominal subcutaneous adipose tissue, and VAAT thickness were higher in the PCOS patient group than in the control group. The amounts of EAT in the patient and control groups were similar (p = 0.384). EAT was correlated with BMI, fat mass, waist circumference, and hip circumference but not with any biochemical metabolic parameters including the homeostasis model assessment of insulin resistance index or the levels of triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein (HDL) cholesterol. However, there was a small positive correlation between the amounts of VAAT and EAT. VAAT was directly correlated with body fat parameters such as BMI, fat mass, and abdominal subcutaneous adipose thickness and inversely correlated with the HDL cholesterol level.ConclusionsThe present study found that increased abdominal adipose tissue in patients with PCOS was associated with atherosclerosis. Additionally, EAT may aid in the determination of the risk of atherosclerosis in patients with PCOS because it is easily measured.

The importance of speckle tracking echocardiography in the early detection of left ventricular dysfunction in patients with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is characterized by hormonal and metabolic abnormalities and is thought to increase a risk for cardiovascular diseases. In this study we use speckle tracking echocardiography (STE) to evaluate left ventricular (LV) dysfunction in the early period of the disease. We enrolled 31 patients with PCOS and 32 healthy volunteers as a control group. The participants' ages ranged between 18 and 40 years. PCOS was diagnosed according to the Rotterdam criteria. LV strain (LS) and strain rate (SR) were evaluated using apical two-chamber (2C), three-chamber (3C), and four-chamber (4C) imaging. Global LS and SR were calculated as average of three apical views. The waist-to-hip ratio, homeostasis model assessment-insulin resistance (HOMA-IR), and fasting insulin and triglyceride levels were higher in the PCOS group than in the controls (p=0.001, p=0.001, p=0.001, and p=0.005, respectively). In the PCOS group, the mitral A wave, deceleration time (DT), and isovolumetric relaxation time (IVRT) were significantly higher than in the controls (all p<0.05). The LV global longitudinal strain (GLS) and global longitudinal SR systolic (GLSRS) were significantly lower in the PCOS patient group (both p= 0.001). There were strong negative correlations between GLS and both fasting insulin (r=-0.64) and DT (r=-0.62) (both p<0.05). The study demonstrated that PCOS patients had decreased LV function using STE. Therefore, STE imaging appears to be useful for the early detection of subclinical LV dysfunction in patients with PCOS.

Genetic variants of the HSD11B1 gene promoter may be protective against polycystic ovary syndrome.

The HSD11B1 gene encodes the type 1 isoform of the 11-β-hydroxysteroid dehydrogenase that is responsible for the regeneration of glucocorticoids from hormonally-inactive metabolites into active forms in a tissue-specific manner. Altered activity of the enzyme, and certain genetic variants of the HSD11B1 gene, has been associated with various metabolic morbidities. In this study, our aim was to systematically test the potential role of the HSD11B1's single nucleotide polymorphisms (SNPs) in polycystic ovary syndrome (PCOS). Nine HSD11B1 SNPs were selected and genotyped using Taqman SNP assays on real-time PCR in a group of PCOS patients (n = 58) and in age-matched healthy controls (n = 64). Genotype-phenotype correlations were determined and haplotype analysis was performed. An in silico prediction for potential transcription factor binding sites was also performed. Of the 5 promoter SNPs, 3 (rs760951; rs4844880; rs3753519) were less frequent in the PCOS group compared to healthy controls. SNPs rs4844880 and rs3753519 were in a complete linkage and the mutant haplotype (AA) was less frequent in the PCOS group. No association between HSD11B1 variants and clinical, pathological findings was observed in patients, but in healthy women the rs4844880 and the AA haplotype were associated with higher levels of homeostasis model assessment of beta cell function. The polymorphic form of the rs4844880 was predicted to bind Pbx-1. Promoter SNPs of the HSD11B1 gene might exert a potential genetic protective role against the development of PCOS, possibly via their beneficial effect on carbohydrate homeostasis due to facilitation of insulin efflux from pancreatic beta-cells.

Leptin levels in relation to marital status and neuroendocrine function in Iraqi females with polycystic ovary syndrome

The present study was designed to evaluate the relationship between serum leptin levels and the hormones related to fertility in Iraqi females with polycystic ovary syndrome (PCOS) and marital status. This study was conducted during the period from July to December 2007. Twenty-four women (12 married and 12 unmarried) with PCOS and not maintained on any type of therapy were included in the study. Twelve healthy and normal ovulatory women with an age range matched with that of PCOS women were included. After an overnight fasting, blood samples were drawn from all women at random days. While in those with regular menstrual cycles, blood samples were obtained during the follicular phase of the cycle, except for samples utilized for the assay of progesterone that performed in the day 21 of the cycle (luteal phase). After preparation of serum, the levels of leptin, luteinizing hormone (LH), follicle-stimulation hormone (FSH), progesterone, testosterone and prolactin were analyzed. Both groups of PCOS patients showed significantly lower levels of serum leptin, while prolactin, LH and FSH and testosterone were significantly elevated compared to controls. No significant differences were reported among PCOS patients with different marital status. In conclusion, impaired plasma leptin levels in PCOS women were associated with impaired endocrinological parameters related to fertility.

Metformin administration is more effective when non-obese patients with polycystic ovary syndrome show both hyperandrogenism and hyperinsulinemia

Background. Polycystic ovary syndrome (PCOS) is a common endocrine disease that is frequently observed to be related to increased insulin resistance independent of body weight. The use of insulin-sensitizer compounds, such as metformin, permits great improvement of such metabolic abnormality, restoring ovarian function and gonadal steroid synthesis and reducing insulin resistance.Aim. On this basis we aimed to evaluate a group of non-obese amenorrheic PCOS patients before and after 6 months of metformin administration (500 mg orally twice daily) to better understand upon which basis of clinical and endocrine parameters metformin administration might be chosen as a putative therapeutic tool.Method. A group of non-obese PCOS patients (n = 42) was enrolled after informed consent. They underwent an oral glucose tolerance test for insulin, glucose and C-peptide levels and provided blood samples for determination of plasma levels of luteinizing hormone (LH), follicle-stimulating hormone, prolactin, estradiol, androstenedione, 17-hydroxyprogesterone, insulin, cortisol and testosterone levels on two occasions: before and on day 7 of the first menstrual cycle occurring after the 5th month of treatment.Results. Plasma LH, estradiol, insulin and C-peptide were decreased significantly by metformin treatment in the entire group of PCOS patients. When subdividing PCOS patients according to insulin sensitivity (i.e. hyper- and normoinsulinemic subjects), a greater rate of positive endocrine changes was observed in hyperinsulinemic patients and the highest rate was observed in hyperinsulinemic hyperandrogenic subjects. Menstrual cyclicity was recovered in all patients under treatment.Conclusions. Our data show that metformin modulates ovarian function and greatly affects LH secretion through reduction of the hyperandrogenic condition. The highest rate of endocrine changes was observed in the hyperinsulinemic hyperandrogenic non-obese PCOS patients. Our study demonstrates that metformin administration is more appropriate in hyperinsulinemic hyperandrogenic non-obese PCOS patients.

The in vitro maturation (IVM) of human oocytes for in vitro fertilization (IVF): is it time yet to switch to IVM-IVF?

The recent study by Li et al. observed that human oocytes from patients with polycystic ovary syndrome (PCOS) matured in vitro exhibited a higher proportion of abnormal spindle structures and disturbed chromosomal configurations compared with in vivo-matured oocytes from a control group of PCOS patients. This article discusses the obstacles that must be overcome and factors that must be monitored when attempting to optimize conditions for the in vitro maturation of human oocytes, with particular attention to the strengths and weaknesses of the study by Li et al.

Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease.

The polycystic ovary syndrome (PCOS), one of the most common reproductive abnormalities, shares some components of the metabolic cardiovascular syndrome. Therefore, PCOS patients may represent the largest group of women at high risk for the development of early-onset cardiovascular disease (CVD) and/or diabetes. C-reactive protein (CRP) is a strong independent predictor of future CVD and/or stroke. Only one small published study has looked for such an association (17 PCOS patients vs. 15 controls). The objective of this study was to compare the levels of CRP and other risk factors of CVD in a large group of PCOS patients and controls. CRP measurements were undertaken in 116 PCOS patients and 94 body mass index-matched controls with regular menstrual cycles. Whereas 36.8% of the PCOS patients had CRP levels above 5 mg/liter, only 9.6% of the controls exhibited high CRP levels (P < 0.001). The mean +/- SD was 5.46 +/- 7.0 in the PCOS group vs. 2.04 +/- 1.9 mg/liter in the control (P < 0.001). The body mass index, white blood cell count, TSH, glucose, cholesterol, and homocysteine levels were not significantly different between the two groups. CRP levels are elevated in patients with PCOS and may be a marker of early cardiovascular risk in these patients. High CRP levels may explain why some PCOS women may possibly be at an increased risk for the development of early-onset CVD. Consequently, whether treatment regimens directed toward lowering CVD risk factors should be more aggressive for those PCOS women with increased CRP levels, awaits further clinical experience.

Pregnancy outcome in women with PCOS and in controls matched by age and weight.

The aim of this study was to compare the pregnancy outcome, especially the prevalence of gestational diabetes mellitus (GDM), in a group of patients with polycystic ovary syndrome (PCOS), with a group of healthy weight-matched women. Retrospectively, we evaluated the pregnancies of 66 women with PCOS, who had been treated for infertility and who delivered at our department. These were compared with a group of 66 age- and weight-matched controls. We did not find any significant differences in the prevalence of pregnancy complications such as gestational diabetes mellitus, pregnancy-induced hypertension (PIH) and premature deliveries between the group of PCOS patients and the controls. When differences in age and weight between PCOS patients and controls are negligible, PCOS is not associated with a higher risk of pregnancy complications.

Endocrino-metabolic features in women with polycystic ovary syndrome during pregnancy.

To elucidate the mechanism of metabolic adaptation of women with polycystic ovary syndrome (PCOS) during pregnancy, the endocrino-metabolic features of a group of PCOS patients with or without gestational diabetes were studied longitudinally during the three trimesters of gestation. Oral glucose tolerance test (OGTT, 100 g) and hyperinsulinaemic-euglycaemic clamp were performed throughout the study. Plasma concentrations of insulin and glucose were determined by radioimmunoassay and glucose oxidase technique, respectively. Five of 13 PCOS patients developed gestational diabetes (GD) at the third trimester (PCOS-GD), while the other eight patients did not develop any alteration of glucose metabolism (PCOS-nGD). Both fasting glucose and insulin plasma concentrations did not change significantly during pregnancy and no difference was seen between the two groups. On the contrary PCOS-GD group early exhibited higher values of area under the curve (AUC) for glucose and insulin response to OGTT with respect to those found in PCOS-nGD group. This difference was already significant in the first gestational trimester. Moreover insulin sensitivity value (M) was significantly lower in the first trimester of gestation in PCOS-GD as compared with that found in PCOS-nGD group. However, as gestation proceeded, M value decreased in PCOS-nDG group and the difference from PCOS patients developing gestational diabetes was not sustained into the second and third trimesters. Both groups had similar body mass index values and AUC insulin increase from first to third trimester of gestation. It is concluded that early alteration of insulin sensitivity and secretion constitute specific risk factors in PCOS patients for the development of abnormalities of glucose tolerance.