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Polycystic Ovarian Syndrome [keywords]
- Pregnancy complications in polycystic ovary syndrome patients. [JOURNAL ARTICLE]
- Gynecol Endocrinol 2014 Oct 30.:1-5.
Abstract Infertility is a widely disputed problem affecting patients suffering from polycystic ovary syndrome (PCOS). As a serious dysfunction, it frequently occurs in PCOS patients. It is, therefore, important to devote more attention to pregnancy in PCOS sufferers. According to various data, the risk of miscarriage in PCOS women is three times higher than the risk of miscarriage in healthy women. Unfortunately, the risk of most frequent pregnancy pathologies is also higher for PCOS patients, as gestational diabetes (GD), pregnancy-induced hypertension and pre-eclampsia, and small for gestational age (SGA) children. Impaired glucose tolerance and GD in pregnant PCOS patients occur more frequently than in healthy women. A quadruple increase in the risk of pregnancy-induced hypertension linked to arterial wall stiffness has also been observed in PCOS patients. The risk of pre-eclampsia, the most severe of all complications, is also four times higher in those suffering from PCOS. Pre-eclampsia is also more frequent in patients presenting additional risk factors accompanying PCOS, such as obesity or GD. At that point, it should be mentioned that PCOS patients are under 2.5 higher risk of giving birth to SGA children than healthy women. It appears that SGA can be linked to insulin resistance and insulin-dependent growth dysfunction. Therefore, PCOS pregnant women are patients of special obstetrical care.
- In vitro maturation as an alternative to standard in vitro fertilization for patients diagnosed with polycystic ovaries: a comparative analysis of fresh, frozen and cumulative cycle outcomes. [JOURNAL ARTICLE]
- Hum Reprod 2014 Oct 29.
Is in vitro maturation (IVM) as successful as standard in vitro fertilization (IVF) for the treatment of patients with polycystic ovaries (PCO) in terms of fresh, frozen and cumulative pregnancy outcomes?There was no difference in clinical pregnancy rates in fresh or frozen embryo transfer (FET) cycles between the two treatment groups however, the IVM group showed a lower clinical pregnancy rate cumulatively. There was significantly fewer live births resulting from IVM treatment for both fresh and cumulative cycle outcomes however, there was no difference in live birth rates resulting from FETs between IVM and IVF treatment.IVM is well recognized as the only treatment option to eliminate completely the incidence of ovarian hyperstimulation syndrome. However, historically IVM has been less successful than standard IVF in terms of clinical pregnancy, implantation and live birth rates.This paper represents a retrospective case-control study. The study involved 121 participants who underwent 178 treatment cycles. Cycles were completed between March 2007 and December 2012. All fresh cycles and subsequent FET cycles were included in the analysis to calculate cumulative outcomes.All participants were prospectively diagnosed with PCO morphology or polycystic ovarian syndrome (PCOS) and underwent either IVM or standard IVF treatment. Their treatment outcomes were analysed with regard to embryological data, and the rate of biochemical pregnancy, clinical pregnancy and live birth, in addition maternal and neonatal outcomes were assessed. Fifty-six patients underwent 80 cycles of IVM treatment and 65 patients underwent 98 cycles of standard IVF treatment.For fresh cycles, the differences in the biochemical pregnancy, clinical pregnancy or miscarriage rates between the two treatment groups were not statistically significant. The IVM group showed significantly lower live birth rates in fresh cycles in comparison to standard IVF treatment (18.8 versus 31.0%, P = 0.021). For frozen embryo transfer (FET) cycles the differences in biochemical pregnancy, clinical pregnancy, live birth or miscarriage rates between the two treatments groups were not statistically significant. The cumulative biochemical pregnancy (67.5 versus 83.7%, P = 0.018), clinical pregnancy (51.3 versus 65.3%, P = 0.021) and live birth rates (41.3 versus 55.1%, P = 0.005) were significantly lower in the IVM group in comparison to the standard IVF treatment group. There was no overall difference in the cumulative miscarriage rates between the two treatment groups. There was no difference between treatment methods with regard to the neonatal outcomes, and the IVM group had a significantly lower rate of ovarian hyperstimulation syndrome (0 versus 7.1%, P < 0.001).This was an observational study and further randomized clinical trials are required to clarify the difference in outcomes between standard IVF and IVM for patients with PCO/PCOS.This is the first study to compare IVM with standard IVF in PCO/PCOS patients using blastocyst development and single embryo transfer. Furthermore, it is the first study to show the results of fresh, frozen and cumulative treatment cycle outcomes between the two groups. Our results show similar success rates to those reported from other groups, particularly in relation to the incidence of miscarriage in fresh IVM cycles and improved success from FET cycles. Maternal and neonatal outcomes are consistent with the limited literature available.The study was supported by the Women's and Infant's Research Foundation of Western Australia. Professor Hart is Medical Director of Fertility Specialists of Western Australia (FSWA) and a shareholder Western IVF. He has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. T.H. is a consultant with FSWA and a shareholder in Western IVF. She has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. The other authors have no competing interests.
- Overlap of proteomics biomarkers between women with pre-eclampsia and PCOS: a systematic review and biomarker database integration. [JOURNAL ARTICLE]
- Hum Reprod 2014 Oct 28.
Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS).Five previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls.Various studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known.A systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013.In all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192.Five proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies.The techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues.This data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. If validated, these biomarkers could provide a useful framework for the knowledge infrastructure in this area. To accomplish this goal, a well co-ordinated multidisciplinary collaboration of clinicians, basic scientists and mathematicians is vital.No financial support was obtained for this project. There are no conflicts of interest.
- The Effect of Atorvastatin and Atorvastatin-Ezetimibe Combination Therapy on Androgen Production in Hyperandrogenic Women with Elevated Cholesterol Levels. [JOURNAL ARTICLE]
- Exp Clin Endocrinol Diabetes 2014 Oct 28.
Statins decreased serum androgen levels in hyperandrogenemic women with polycystic ovary syndrome. No previous study has investigated whether this effect is dose-dependent and observed in patients simultaneously treated with other hypolipidemic agents. The study included 23 premenopausal women with elevated total testosterone levels coexisting with hypercholesterolemia, unsuccessfully treated for at least 6 months with atorvastatin (20 mg daily). These patients were then treated with either an increased dose of atorvastatin (40 mg daily, n=11) or atorvastatin (20 mg daily) plus ezetimibe (10 mg daily) (n=12). Plasma lipids, glucose homeostasis markers and serum levels of androgens, sex hormone-binding globulin and gonadotropins were assessed at baseline and after 3 months of treatment. Although both treatments decreased plasma levels of total and LDL-cholesterol levels, only high-dose atorvastatin reduced serum levels of total testosterone, free testosterone and androstendione. The effect of high-dose atorvastatin on serum androgen levels did not differ between insulin-resistant and insulin-sensitive subjects. The obtained results suggest that atorvastatin reduces serum androgen levels in a dose-dependent manner and that its administration in a higher dose is associated with a more pronounced effect on serum androgens than combination therapy with low-dose atorvastatin and ezetimibe.
- Exploring the potential association between brominated diphenyl ethers, polychlorinated biphenyls, organochlorine pesticides, perfluorinated compounds, phthalates, and bisphenol a in polycystic ovary syndrome: a case-control study. [JOURNAL ARTICLE]
- BMC Endocr Disord 2014 Oct 28; 14(1):86.
Polycystic Ovary Syndrome (PCOS) is an endocrine-metabolic disorder that affects approximately 6-10% of women of child-bearing age. Although preliminary studies suggest that certain pollutants may act as endocrine disruptors in animals, little is known about their potential association with PCOS. The objective of this case-control pilot study is to determine whether women with PCOS have higher concentrations of specific environmental contaminants compared to women who have not developed PCOS.Fifty-two PCOS case-patients (diagnosed using the National Institutes of Health 1990 definition) and 50 controls were recruited in 2007-2008, from an urban academic medical center in Los Angeles, CA. Brominated diphenyl ethers, polychlorinated biphenyls (PCBs), organochlorine pesticides, and perfluorinated compounds (PFCs) were measured in serum, and phthalates metabolites and bisphenol A (BPA) in urine.PCOS case-patients had significantly higher geometric mean (GM) serum concentrations of two PFCs: perfluorooctanoate (PFOA) (GMcases = 4.1 mug/L, GMcontrols = 2.3 mug/L; p = 0.001) and perfluorooctane sulfonate (PFOS) (GMcases = 8.2 mug/L, GMcontrols = 4.9 mug/L; p = 0.01), and lower urinary concentrations of monobenzyl phthalate (mBzP) (GMcases = 7.5 mug/g creatinine, GMcontrols = 11.7 mug/g creatinine; p = 0.02). Logistic regression, controlling for body mass index, age and race, identified an increased likelihood of PCOS in subjects with higher serum concentrations of PFOA and PFOS (adjusted-ORs = 5.8-6.9, p < 0.05), and with lower urine concentrations of mBzP and mono-n-butyl phthalate (mBP) (aORs = 0.14-0.25, p < 0.05).Our data suggest that PCOS case-patients may differ from controls in their environmental contaminant profile. PCOS subjects had higher serum concentrations of two PFCs, PFOA and PFOS, and lower urine concentrations of mBP and mBzP. Future studies are needed to confirm these preliminary findings and determine if these chemicals or their precursors may have a role in the pathogenesis of PCOS.
- The local effects of ovarian diathermy in an ovine model of polycystic ovary syndrome. [Journal Article]
- PLoS One 2014; 9(10):e111280.
In order to develop a medical alternative to surgical ovarian diathermy (OD) in polycystic ovary syndrome (PCOS) more mechanistic information is required about OD. We therefore studied the cellular, molecular and vascular effects of diathermy on the ovary using an established ovine model of PCOS. Pregnant sheep were treated twice weekly with testosterone propionate (100 mg) from day 30-100 gestation. Their female offspring (n = 12) were studied during their second breeding season when the PCOS-like phenotype, with anovulation, is fully manifest. In one group (n = 4) one ovary underwent diathermy and it was collected and compared to the contralateral ovary after 24 hours. In another group a treatment PCOS cohort underwent diathermy (n = 4) and the ovaries were collected and compared to the control PCOS cohort (n = 4) after 5 weeks. Ovarian vascular indices were measured using contrast-enhanced ultrasound and colour Doppler before, immediately after, 24 hours and five weeks after diathermy. Antral follicles were assessed by immunohistochemistry and ovarian stromal gene expression by quantitative RT-PCR 24 hours and 5 weeks after diathermy. Diathermy increased follicular atresia (P<0.05) and reduced antral follicle numbers after 5 weeks (P<0.05). There was an increase in stromal CCL2 expression 24 hours after diathermy (P<0.01) but no alteration in inflammatory indices at 5 weeks. Immediately after diathermy there was increased microbubble transit time in the ovarian microvasculature (P = 0.05) but this was not seen at 24 hours. However 24 hours after diathermy there was a reduction in the stromal Doppler blood flow signal (P<0.05) and an increased ovarian resistance index (P<0.05) both of which persisted at 5 weeks (P<0.01; P<0.05). In the ovine model of PCOS, OD causes a sustained reduction in ovarian stromal blood flow with an increased ovarian artery resistance index associated with atresia of antral follicles.
- Effects of exercise training in women with polycystic ovary syndrome on adipose expression of perilipin 3. [JOURNAL ARTICLE]
- Eur J Endocrinol 2014 Oct 23.
Objective: Polycystic Ovary Syndrome (PCOS) is associated with reduced adipose tissue lipolysis that can be rescued by aerobic exercise. We aimed to identify differences in gene expression of perilipins and associated targets in adipose tissue in women with PCOS before and after exercise. Design and Methods: We conducted a cross-sectional study in 8 women with PCOS and 8 women matched for BMI and age with normal cycles. Women with PCOS also completed a 16-week prospective aerobic exercise-training study. Abdominal subcutaneous adipose tissue biopsies were collected, and primary adipose-derived stromal/stem cell cultures were established from women with PCOS before 16 weeks of aerobic exercise training (n=5) and controls (n=5). Gene expression was measured using real time PCR, in vitro lipolysis was measured using radiolabeled oleate, and PLIN3 protein content was measured by western blotting. Results: The expression of PLIN1, PLIN3, and PLIN5, along with coatomers ARF1, ARFRP1, and βCOP were ~80% lower in women with PCOS (all p<0.05). Following exercise training, PLIN3 was the only perilipin to increase significantly (p<0.05), along with coatomers ARF1, ARFRP1, βCOP, and Sec23a (all p<0.05). Furthermore, PLIN3 protein expression was undetectable in the cell cultures from women with PCOS vs. controls. Following exercise training, in vitro adipose oleate oxidation, glycerol secretion, and PLIN3 protein expression were increased, along with reductions in triglyceride content and absence of large lipid droplet morphology. Conclusions: These findings suggest that PLIN3 and coatomer GTPases are important regulators of lipolysis and triglyceride storage in the adipose tissue of women with PCOS.
- Visceral adiposity index (VAI) and dehydroepiandrosterone-sulphate (DHEA-S) are useful markers of diabetes risk in women with Polycystic Ovary Syndrome (PCOS). [JOURNAL ARTICLE]
- Eur J Endocrinol 2014 Oct 23.
On the basis of the known diabetes risk in Polycystic Ovary Syndrome (PCOS) recent guidelines of the Endocrine Society recommend the use of an Oral Glucose Tolerance Test (OGTT) to screen for Impaired Glucose Tolerance (IGT) and Type 2 Diabetes (T2DM) in all women with PCOS. However, given the high prevalence of PCOS, OGTT would have a high cost-benefit ratio. In this study we identified, through a Receiver Operating Characteristic (ROC) analysis, simple predictive markers of the composite endpoint [Impaired Fasting Glucose (IFG) or IGT or IFG + IGT or T2DM] in women with PCOS according to the Rotterdam criteria.We conducted a cross-sectional study of 241 women with PCOS in a university hospital setting.Clinical, anthropometric, and metabolic (including OGTT) parameters were evaluated. The homeostasis model assessment of insulin resistance (HOMA2-IR), the Matsuda index of insulin sensitivity (ISI) and the Oral Dispositional Index (DIo) and VAI were determined.28/241 (11.6%) women had an IFG, 13/241 (5.4%) had IGT, 4/241 (1.7%) had IFG + IGT, and 4/241 (1.7%) had T2DM. Among the anthropometric variables examined the VAI had a significantly higher C-statistic compared to BMI [0.760 (95%CI: 0.70-0.81) vs 0.613 (95%CI: 0.54-0.67); p=0.014] and waist circumference (WC) [0.760 (95%CI: 0.70-0.81) vs 0.619 (95%CI: 0.55-0.68); p=0.028]. Among all the hormonal and metabolic serum variables examined DHEA-S showed the highest C-statistic (0.720 (95%CI: 0.65-0.77), p<0.001).In addition to fasting glucose, the VAI and DHEA-S may be considered useful tools for prescreening in all women with PCOS without the classical risk factors for diabetes.
- Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. [REVIEW]
- World J Gastroenterol 2014 Oct 21; 20(39):14172-14184.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance (IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease (NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases.
- Intrinsic factors rather than vitamin D deficiency are related to insulin resistance in lean women with polycystic ovary syndrome. [Journal Article]
- Eur Rev Med Pharmacol Sci 2014 Oct; 18(19):2851-6.
To investigate the correlation between insulin resistance (IR) and serum 25-OH-Vit D concentrations and hormonal parameters in lean women with polycystic ovary syndrome (PCOS).50 lean women with PCOS and 40 body mass index (BMI) matched controls were compared in terms of fasting insulin and glucose, homeostatic model assessment insulin resistance (HOMA-IR), 25-OH-Vit D, high sensitivity C-reactive protein (hs-CRP), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, dehydroepiandrosterone sulfate (DHEA-S), total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides and Ferriman-Gallway (FG) scores. Correlation analyses were performed between HOMA-IR and metabolic and endocrine parameters.30% of patients with PCOS demonstrated IR. Levels of 25-OH-Vit D, hsCRP, cholesterol, HDL, LDL, triglyceride and fasting glucose did not differ between the study and control groups. Fasting insulin, HOMA-IR, LH, total testosterone, and DHEA-S levels were higher in PCOS group. HOMA-IR was found to correlate with hs-CRP and total testosterone but not with 25-OH-Vit D levels in lean patients with PCOS.An association between 25-OH-Vit D levels and IR is not evident in lean women with PCOS. hs-CRP levels do not indicate to an increased risk of cardiovascular disease in this population of patients. Because a strong association between hyperinsulinemia and hyperandrogenism exists in lean women with PCOS, it is advisable for this population of patients to be screened for metabolic disturbances, especially in whom chronic anovulation and hyperandrogenism are observed together.