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Concept: Polycystic ovary syndrome


While lifestyle management is recommended as first-line treatment of polycystic ovary syndrome (PCOS), the optimal dietary composition is unclear. The aim of this study was to compare the effect of different diet compositions on anthropometric, reproductive, metabolic, and psychological outcomes in PCOS. A literature search was conducted (Australasian Medical Index, CINAHL, EMBASE, Medline, PsycInfo, and EBM reviews; most recent search was performed January 19, 2012). Inclusion criteria were women with PCOS not taking anti-obesity medications and all weight-loss or maintenance diets comparing different dietary compositions. Studies were assessed for risk of bias. A total of 4,154 articles were retrieved and six articles from five studies met the a priori selection criteria, with 137 women included. A meta-analysis was not performed due to clinical heterogeneity for factors including participants, dietary intervention composition, duration, and outcomes. There were subtle differences between diets, with greater weight loss for a monounsaturated fat-enriched diet; improved menstrual regularity for a low-glycemic index diet; increased free androgen index for a high-carbohydrate diet; greater reductions in insulin resistance, fibrinogen, total, and high-density lipoprotein cholesterol for a low-carbohydrate or low-glycemic index diet; improved quality of life for a low-glycemic index diet; and improved depression and self-esteem for a high-protein diet. Weight loss improved the presentation of PCOS regardless of dietary composition in the majority of studies. Weight loss should be targeted in all overweight women with PCOS through reducing caloric intake in the setting of adequate nutritional intake and healthy food choices irrespective of diet composition.

Concepts: Nutrition, Obesity, Evidence-based medicine, Metformin, Menstrual cycle, Polycystic ovary syndrome, Diets, Free androgen index


Adenomyomatosis of gallbladder is an acquired hyperplastic lesion, characterized by focal or diffuse thickening of the gallbladder with intramural cysts or echogenic areas with comet tail on ultrasonography. But in some cases, especially in the localized fundal type of adenomyomatosis, the intramural anechoic cystic spaces are uncertainty which causes difficult to differential adenomyomatosis from GB cancer. The purpose of this study was to determine the accuracy of real-time contrast-enhanced ultrasonography(CEUS) in the diagnosis of the fundal localized type of gallbladder adenomyomatosis.

Concepts: Cyst, Polycystic ovary syndrome, Contrast-enhanced ultrasound, Differential diagnosis, Comet, Gallbladder polyp


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.

Concepts: Immune system, Signal transduction, Hormone, Endocrinology, Luteinizing hormone, Cellular differentiation, Receptor tyrosine kinase, Polycystic ovary syndrome


Although many studies indicate the interplay of genetic and environmental factors in the etiology of autism spectrum disorder (ASD), our limited understanding of the underlying mechanisms hampers the development of effective ways of detecting and preventing the disorder. Recent studies support the hypothesis that prenatal androgen exposure contributes to the development of ASD. This would suggest that maternal polycystic ovary syndrome (PCOS), a condition associated with excess androgens, would increase the risk of ASD in the offspring. We conducted a matched case-control study nested within the total population of Sweden (children aged 4-17 who were born in Sweden from 1984 to 2007). The sample consisted of 23 748 ASD cases and 208 796 controls, matched by birth month and year, sex and region of birth. PCOS and ASD were defined from ICD codes through linkage to health-care registers. Maternal PCOS increased the odds of ASD in the offspring by 59%, after adjustment for confounders (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.34-1.88). The odds of offspring ASD were further increased among mothers with both PCOS and obesity, a condition common to PCOS that is related to more severe hyperandrogenemia (OR 2.13, 95% CI 1.46-3.10). Risk estimates did not differ between sexes. In conclusion, children of women with PCOS appear to have a higher risk of developing ASD. This finding awaits confirmation, and exploration of potentially underlying mechanisms, including the role of sex steroids in the etiology of ASD.Molecular Psychiatry advance online publication, 8 December 2015; doi:10.1038/mp.2015.183.

Concepts: Luteinizing hormone, Autism, Pervasive developmental disorder, Metformin, Asperger syndrome, Autism spectrum, PDD-NOS, Polycystic ovary syndrome



Human pre-ovulatory follicular fluid (FF) contains a higher concentration of melatonin than serum. The aim of this study was to evaluate the effect of melatonin supplementation of culture medium on the clinical outcomes of an in-vitro maturation (IVM) IVF-embryo transfer programme for patients with polycystic ovarian syndrome (PCOS). Melatonin concentrations in the culture media of granulosa cells (GC) or cumulus-oocyte-complexes (COC) were measured and the clinical outcomes after using IVM media with or without melatonin were analysed. In the culture media of GC or COC, melatonin concentrations gradually increased. When human chorionic gonadotrophin priming protocols were used, implantation rates in the melatonin-supplemented group were higher than those of the non-supplemented control group (P<0.05). Pregnancy rates were also higher, although not significantly. The findings suggest that the addition of melatonin to IVM media may improve the cytoplasmic maturation of human immature oocytes and subsequent clinical outcomes. It is speculated that follicular melatonin may be released from luteinizing GC during late folliculogenesis and that melatonin supplementation may be used to improve the clinical outcomes of IVM IVF-embryo transfer. Melatonin is primarily produced by the pineal gland and regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. Interestingly, human pre-ovulatory follicular fluid contains a higher concentration of melatonin than serum. However, in contrast to animal studies, the direct role of melatonin on oocyte maturation in the human system has not yet been investigated. So, the aim of the study was to evaluate the effect of melatonin supplementation of culture medium on the clinical outcome of an in-vitro maturation (IVM) IVF-embryo transfer programme for PCOS patients. The melatonin concentrations in culture medium of granulosa cells (GC) or cumulus-oocyte-complexes (COC) were measured and the clinical outcomes of IVM IVF-embryo transfer using IVM medium alone or supplemented with melatonin were analysed. In the culture media of GC or COC, the melatonin concentration gradually increased. With human chorionic gonadotrophin priming, the pregnancy and implantation rates in the melatonin-supplemented group were higher than those of the non-supplemented control (P<0.05). Our findings suggest that follicular melatonin is released from luteinizing GC during late folliculogenesis and plays a positive role in oocyte maturation. Therefore, addition of melatonin into IVM medium may improve cytoplasmic maturation of human immature oocytes and subsequent clinical outcomes.

Concepts: Luteinizing hormone, Pineal gland, Human chorionic gonadotropin, Circadian rhythm, Ovulation, Polycystic ovary syndrome, Folliculogenesis, Melatonin


BACKGROUND: The Bone Morphogenetic Proteins (BMPs) are growth factors involved in the folliculogenesis. Alteration in their expression may compromise the reproductive process in disease such as the polycystic ovary syndrome (PCOS). The present study investigated the expression and role of granulosa cell BMP from normal cycling and PCOS women. METHODS AND RESULTS: This prospective study was performed in granulosa cells obtained from 14 patients undergoing IVF : (i) 6 women with normal ovulatory cycles and tubal or male infertility and (ii) 8 women with PCOS. BMP-2, BMP-4, BMP-5, BMP-6, BMP-7 and BMP-8A, and their receptors BMPR-IA, BMPR-IB and BMPR-II were identified by RT-PCR in granulosa cells from normally cycling and PCOS women. BMP-4, 6 and 7 expression were confirmed by immunohistochemistry, Quantitative transcript analysis showed the predominant expression of BMP-6. In granulosa cells from PCOS women, an over-expression of BMP-6 (p<0.01) and BMPR-IA mRNA (p<0.05) were observed. Granulosa cell culture experiments demonstrated that basal estradiol (E2) production was 3-fold higher but FSH-induced E2 increment 2-fold lower in PCOS compared to controls. In PCOS, BMP-6 and 7 exerted a stimulatory effect on basal E2 production while BMP-4 and 6 inhibited FSH-induced E2 production. FSH receptor and aromatase expression were not different between both groups. CONCLUSION: The BMP system is expressed in human granulosa cells from normal cycling and PCOS women. The BMP may be involved in reproductive abnormalities found in PCOS.

Concepts: Protein, Signal transduction, Menstrual cycle, Polycystic ovary syndrome, Folliculogenesis, Anovulation, Granulosa cells, Bone morphogenetic protein


CONTEXT: Prevalence of Cushing’s syndrome (CS) in patients presenting with hirsutism is not well-known. OBJECTIVE: Screening of CS in patients with hirsutism. SETTING: Referral hospital PATIENTS AND OTHER PARTICIPANTS: This study was carried out on 105 patients who admitted to Endocrinology Department with the complaint of hirsutism. INTERVENTION: All the patients were evaluated with low dose dexamethasone suppression test (LDDST) for CS. MAIN OUTCOME MEASURE: Response to LDDST in patients presenting with hirsutism RESULTS: All the patients had suppressed cortisol levels following low dose dexamethasone administration excluding CS. The etiology of hirsutism were polycystic ovary syndrome in 79%, idiopathic hirsutism in 13%, idiopathic hyperandrogenemia in 6% and non-classical congenital hyperplasia in 2% of the patients. CONCLUSION: Routine screening for CS in patients with a referral diagnosis of hirsutism is not required. For the time being, diagnostic tests for CS in hirsute patients should be limited to patients who have accompanying clinical stigmata of hypercortisolism.

Concepts: Obesity, Glucocorticoid, Cortisol, Spironolactone, Polycystic ovary syndrome, Cushing's syndrome, Hirsutism, Dexamethasone suppression test


OBJECTIVE: Although extensive evidence indicates the hyperinsulinemia directly contributes to reproductive dysfunction in polycystic ovarian syndrome (PCOS), influence of insulin resistance (IR) on assisted reproductive technology outcomes is poorly understood. In this study we aimed to evaluate the effects of IR on in vitro maturation - in vitro fertilization-embryo transfer (IVM-IVF-ET) in patients with PCOS. DESIGN: Prospective observational study. PATIENTS: Women with PCOS (n = 115) commencing IVM. MEASURMENTS: IR (n = 51) and non-IR (n = 64) women with PCOS ready to commence an IVM cycle were recruited. IR was diagnosed using the glucose tolerance test (GTT) and homeostasis model assessment (HOMA) index. Patients with an abnormal GTT and/or HOMA index > 2.4 were considered IR. Patients underwent 115 cycles of unstimulated hCG-primed IVM. RESULTS: Maturation, fertilization, cleavage rates, the number of good-quality embryo, and blastocyst formation rates were not significantly different between groups. However, implantation (11.6% vs 28.7%, P = 0.001, respectively), clinical pregnancy (23.5% vs 53.1%, P = 0.002, respectively), and ongoing pregnancy rates (21.6% vs 46.9%. P = 0.006, respectively) were significantly decreased in the IR group. The negative effect of IR on pregnancy outcomes remained after controlling for age, body mass index (BMI) and lipid profiles (OR 4.928, 95% CI 1.735-13.991, P = 0.003). CONCLUSIONS: Pregnancy rate after IVM is impaired in IR patients with PCOS. Oocyte development and embryo quality are not affected, suggesting that the effects of hyperinsulinemia on endometrial function and implantation process underlie the decreased pregnancy rate. © 2012 Blackwell Publishing Ltd.

Concepts: Pregnancy, Embryo, Glucose tolerance test, In vitro fertilisation, Menstrual cycle, Implantation, Polycystic ovary syndrome, Blastocyst


STUDY OBJECTIVE: To evaluate the differences in adipokines, namely adiponectin, leptin, and ghrelin, in obese adolescent girls with or without polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: University hospital. PARTICIPANTS: 38 adolescent girls (age 15-20 years). Group I: 17 Obese adolescent girls with PCOS (BMI ≥ 30 kg/m(2)); Group II: Control group of 21 obese adolescent girls (BMI ≥ 30 kg/m(2)). MAIN OUTCOME MEASURES: Adiponectin, leptin, and ghrelin measurements. RESULTS: LH, LH/FSH, and cortisol levels were significantly higher in the obese PCOS girls compared to the obese controls (6.94 ± 3.28 vs 4.44 ± 1.79; 1.50 ± 0.72 vs 0.90 ± 0.36; 16.02 ± 4.28 vs 12.46 ± 5.29; P < .05, respectively). Adiponectin, leptin, and ghrelin levels were similar between the obese PCOS girls and the obese controls (11.13 ± 6.00 vs 15.26 ± 12.66; 23.66 ± 11.54 vs 23.11 ± 11.17; 665.69 ± 402.12 vs 650.22 ± 467.73, respectively). Adiponectin negatively correlated with BMI (r = -0.32; P = .04) and positively correlated with fasting glucose (r = 0.40; P = .01). Leptin positively correlated with BMI (r = 0.534; P = .001), estradiol (r = 0.354; P = .02), and TSH (r = 0.374; P = .02). No significant correlation was found between ghrelin and the test parameters. CONCLUSION: Among obese adolescents with PCOS, adiponectin, and leptin levels do not seem to be determined by the existence of PCOS, while ghrelin presents no significant correlation.

Concepts: Obesity, Luteinizing hormone, Adipose tissue, Metformin, Menstrual cycle, Polycystic ovary syndrome