Evaluation of serum anti-nuclear antibody among women with PCOS: a hospital based single center cross sectional study

Abstract

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8–12?h) fast with 75?g oral glucose load was done for 1?h, 2?h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67?±?5.53 vs. 22.84?±?3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p?<?.001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.     

Atherogenic metabolic profile in PCOS patients: role of obesity and hyperandrogenism

Objective. To investigate glyco-lipidic metabolism and androgenic profile in a cohort of women with polycystic ovary syndrome (PCOS) divided according to Rotterdam phenotypes and body mass index (BMI).

Design. A prospective case–control study.

Setting. Gynecology department in a teaching hospital.

Patients. A total of 223 PCOS women and 25 healthy control women were studied.

Methods. Patients and controls were subdivided into three groups according to their BMI: normal weight (18.5?≤?[BMI]?≤24.9?kg/m²), overweight (25.0?≤?BMI?≤29.9?kg/m²), or obese (BMI?≥30.0?kg/m²) and according to Rotterdam criteria of PCOS.

Main outcome measures. Pituitary-gonadal axis assessment including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, PRL, testosterone, androstenedione, DHEA-S, 17-hydroxyprogesterone and inhibin B. Metabolic parameters included cholesterol (Chol), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG) and apolipoproteins (APO) AII and B as well as serum fasting insulin, glucose and HOMA-IR.

Results. Serum fasting insulin, glucose, HOMA-IR, TG and HDL were significantly higher in women with PCOS compared to controls. Additionally, serum levels of Chol, LDL and TG were significantly higher and HDL levels were significantly lower in obese PCOS women compared with overweight/normal PCOS irrespective of Rotterdam phenotypes. Free testosterone index but not androstenedione or total testosterone significantly correlated with TG, HDL and APO B. No significant correlations were detected between gonadotropins, inhibin B or estradiol with metabolic parameters studied.

Conclusions. Obesity but not overweight in PCOS is associated with dyslipidemia. Hyperandrogenic women showed the most atherogenic lipid profiles.     

Diagnosis of Polycystic Ovary Syndrome: AMH in combination with clinical symptoms

Purpose

We assessed the utility of using anti-Müllerian hormone (AMH) and clinical features of polycystic ovary syndrome (PCOS), polycystic ovarian morphology (PCOM), oligo/amenorrhea (OA), and hyperandrogenism (HA) for diagnosing PCOS, and compared their diagnostic accuracy with those of classical diagnostic systems.

Methods

A total of 606 females were admitted to a university hospital with menstrual irregularities or symptoms of hyperandrogenism were enrolled in this cross-sectional study. Fasting blood samples were collected. Pelvic and/or abdominal ultrasonography and clinical examination were performed. Patients were evaluated for the presence of PCOS according to conventional diagnostic criteria. The diagnostic performance of using serum AMH levels alone and in various combinations with the clinical features of PCOM, OA, and HA were investigated.

Results

For the diagnosis of PCOS, the combination of OA and/or HA with AMH showed 83 % sensitivity and 100 % specificity according to the Rotterdam criteria; 83 % sensitivity and 89 % specificity according to the National Institutes of Health (NIH) criteria; and 82 % sensitivity and 93.5 % specificity according to the Androgen Excess Society (AES) criteria.

Conclusions

The serum AMH level is a useful diagnostic marker for PCOS and is correlated with conventional diagnostic criteria. The combination of AMH level with OA and/or HA markedly increased the clinical scope for PCOS diagnosis and can be introduced as a possible objective criterion for the diagnosis of this disease.     

Ovarian volume and PCOS: a controversial issue

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy. The Rotterdam criteria indicate four distinct phenotypes. In phenotypes with the typical ovarian morphology (ovarian volume ≥10?ml) the sensibility to clomiphene citrate (CC) ovulation therapy was demonstrated inversely proportional to the ovarian volume. In this retrospective study we evaluated the influence of ovarian volume on the success rate of CC ovulation induction in women with anovulatory phenotype 2 characterized only by the presence of hyperandrogenism and anovulation (ANOV?+?HA). Statistical analysis was conducted by stratifying patients both on the basis of CC dose (Group 1: n?=?37, 50?mg; Group 2: n?=?9, 100?mg; and Group 3: n?=?12, 150?mg) and on the basis of response to therapy. Eighty women were evaluated but overall only 58 women (72.5%) reached ovulation. In the phenotype studied, we didn’t find any correlations between ovarian volume and the chance of ovulation with the gradient increase in CC; furthermore, ovarian volume was comparable in CC responders and non-responders. Our study has shown that in the phenotype 2 examined, ovarian volume did not have any predictive value of the dosage required to induce ovulation. The significance of this result is discussed.     

The effect of metformin treatment to ovarian response in cases with PCOS

Objective. To examine the effect of metformin therapy on ovarian response in clomiphene-resistant PCOS patients. Design. Randomized prospective study. Setting. Zeynep Kamil Hospital IVF Center. Patients. Thirty-two female PCOS patients with clomiphene citrate resistance. Interventions. Test group A received 2×850 mg/day metformin therapy for 8 weeks, followed by gonadotropin induction. Only gonadotropin induction was applied to Control group B. Main outcome measures. Total gonadotropin dosage, duration of gonadotropin therapy, estradiol level on HCG-day, number of follicles with ≥16 mm diameter, number of cases with hyperstimulation development, number of cancelled cycles, endometrial thickness on HCG-day, pregnancy outcome, multiple pregnancy rate. Results. The total gonadotropin doses given to metformin-study group was significantly lower than the control group. In addition, duration of therapy, HCG level, plasma estradiol level on HCG-day in the study group was significantly lower than in the control group. Conclusions. Metformin therapy has led to a higher pregnancy outcome, as well as to a decrease in hyperstimulation risk, cycle cancellations, and multiple pregnancy rates with a lower gonadotropin dosage.     

瘦素和性激素与多囊卵巢综合征的相关性

目的探讨瘦素(Leptin)和激素水平与多囊卵巢综合征(PCOS)的相关性。方法采用病例对照的方法,对深圳市第二人民医院妇科于2009年1月至8月确诊的31例PCOS患者(研究组)及同期30例健康女性(对照组)进行血清Leptin、卵泡刺激素(FSH)、黄体生成素(LH)及睾酮(TESTO)测定,并对它们之间的的相关性进行分析。结果研究组Leptin[(10.03±8.64)μg/L]、LH[(18.35±14.50)U/L]、TESTO[(0.68±0.26)μg/L]和LH/FSH比值(2.71±1.79)都明显高于对照组[分别为(5.79±1.86)μg/L,(6.15±4.25)U/L,(0.48±0.15)μg/L,0.82±0.50],经过统计学t检验,差异有统计学意义(P<0.05)。结论Leptin升高与性激素分泌紊乱与P-COS的发病有一定的相关性。     

Clomiphene citrate versus tamoxifen for ovulation induction in women with PCOS: a prospective randomized trial

Objective

To reevaluate the efficacy of induction of ovulation with CC versus TMX in a group of anovulatory subfertile women with PCOS in a randomized controlled trial.

Study design

A prospective randomized controlled study in which 371 PCOS patients were randomly allocated into two treatment groups: group A (187 patients) where women received CC and group B (184 patients) where they received Tamoxifen for one treatment cycle. The outcome measures were number of growing and mature follicles, serum E₂ (pg/ml), serum progesterone (ng/ml) and endometrial thickness, the occurrence of pregnancy and miscarriage.

Results

The number of stimulated follicles reaching ≥16 mm diameter was significantly more in the CC group compared to Tamoxifen stimulated group (2.1 SD ± 0.1 vs. 1.1 SD ± 0.7, p < 0.0001). The endometrium at the time of hCG administration was significantly thicker in the TMX group (10.1 ± 0.1 mm vs. 9.3 ± 0.4 mm, p < 0.0001). Ovulation occurred in 120/187 cycles (64%) in the CC group and 95/184 cycles (51.6%) in the TMX group with a significant difference between two groups in favors of clomiphene (p = 0.01). Serum E₂, on the day of hCG administration, was significantly higher in the clomiphene group (p < 0.0001). Pregnancy occurred in 35/187 cycles in group A (18.7%) and 20/184 cycles (10.8%) in group B and the difference was statistically significant (p = 0.04).

Conclusions

Clomiphene citrate is more successful than tamoxifen as a first line therapy for ovulation induction in women with PCOS.     

Evidence-based reproductive medicine in clinical practice: the case of clomiphene-resistant PCOS

Evidence-based medicine (EBM) tries to integrate best research evidence with clinical expertise and patient values. Clinicians can use this method to provide their counseled patients with the best available evidence. The aim of the present article is to demonstrate the application of EBM in everyday practice. We present a case of a woman with subfertility due to polycystic ovary syndrome (PCOS) who was not responding to treatment with clomiphene citrate. Herein a search of the literature is discussed, and a randomised clinical trial assessing the effectiveness of a strategy starting with laparoscopic electrocoagulation (LEO) and gonadotrophins is scrutinised with regard to internal validity. Studies on treatment should be appraised regarding method randomisation, concealment of allocation, blinding or masking, comparability of the groups, completeness of follow-up, analysis according to the intention-to-treat principle, equality of treatment of both groups, and adequate sample size. The study reports both treatments to be equally effective with respect to ongoing pregnancy, which is the primary outcome. A strategy starting with LEO seems to be more cost-effective and reduces the number of multiple pregnancies, which are arguments in favour of it. These arguments should be weighed against individual characteristics such as the risk of laparoscopic surgery and individual patient preferences.     

Relationship between serum anti-Mullerian hormone and intrafollicular AMH levels in PCOS women

Polycystic ovary syndrome is a complex disease characterized by various endocrine disorders that are the potential cause of anovulation and hyperandrogenism. Anti-Müllerian hormone expression is suspected to be overexpressed in PCOS granulosa cells. AMH acts as a regulator of folliculogenesis: it is produced by the granulosa cells of follicles from the stage of the primary follicle to the initial formation of the antrum. Serum and intrafollicular AMH levels are elevated in patients with PCOS due to increased number of small follicles and an increased secretion within each of these small follicles. This excess of AMH is strongly suspected to play a role in the characteristic follicular arrest of PCOS, through a negative action on aromatase expression and on FSH action. Value above 5?ng/ml or 35?pmol/l might be considered as a diagnostic criterion for PCOS. The aim of our study is to demonstrate the presence of higher AMH serum levels and higher AMH intrafollicular fluid level of PCOS patients, undergone to IVF cycles, compared to normovulatory patients. The results clearly indicate that blood and intrafollicular AMH levels are significantly higher in PCOS women comparing to the normovulatory population. Serum AMH level appears to be a good predictive marker for the risk ovarian hyperstimulation syndrome: thus, its evaluation should be recommended before starting a controlled ovarian stimulation for IVF.     

联合LC-MS和化学发光免疫法分析不同类型PCOS的雄激素水平

目的:利用液相色谱-质谱联用(LC-MS)方法和化学发光免疫分析法测定不同临床类型PCOS患者的血清雄激素水平,分析中国PCOS女性的高雄激素血症的生化特点。方法:纳入有排卵障碍和多囊卵巢的PCOS患者149例,根据血清睾酮(T)和硫酸脱氢表雄酮(DHEAS)值及F-G多毛评分情况分为两组:高雄组55例,非高雄组94例。同期选取输卵管性不孕患者82例作为对照组。化学发光法测定性激素结合球蛋白(SHBG)水平,计算游离雄激素指数(FTI)。LC-MS法测定各组血清睾酮、雄烯二酮(AD)和脱氢表雄酮(DHEA)。结果:高雄组的血清T水平及FTI值显著高于非高雄组及对照组(P0.05),非高雄组高于对照组(P0.05);高雄组、非高雄组的DHEAS及AD水平均高于对照组(P0.05);3组的DHEA水平比较,差异均无统计学意义。结论:血清T、AD、DHEAS及FTI均为诊断PCOS高雄激素血症的敏感指标;T及FTI是PCOS分型(高雄及非高雄)的主要依据;LC-MS和化学发光免疫分析法对PCOS高雄激素血症的诊断具有一致性。     

Coadministration of metformin or spironolactone enhances efficacy of rosiglitazone in management of PCOS

Abstract

The aim of this study was to compare the efficacy and safety of adding metformin or spironolactone to rosiglitazone in women with polycystic ovary syndrome (PCOS). This is a prospective non-randomized study in a tertiary care with at in a tertiary care endocrine clinic. Women (n?=?138) diagnosed with PCOS on the basis of Rotterdam criteria 2003 were categorized into three groups on the basis of drug intake as – rosiglitazone (R), rosiglitazone with spironolactone (R?+?S), and rosiglitazone with metformin (R?+?M). Clinical, biochemical, hormonal, and insulin sensitivity parameters were assessed at baseline and after six months of follow up. There was a significant improvement in number of menstrual cycles per year and Ferriman Gallwey (FG) score in all three groups after 6 months. Plasma insulin (0, 2?h), HOMA-IR and serum total testosterone levels decreased after six months in all the three groups. The inter group comparison showed higher efficacy of R?+?S in improving hyperandrogenism whereas R?+?M was most effective in decreasing body weight and plasma insulin levels compared to R and R?+?S (p<.05). Treatment of women with PCOS using rosiglitazone alone and in combination with spironolactone or metformin is safe and efficacious with limited adverse events however randomized trials with longer duration of follow up are warranted.     

Divalent cations in women with PCOS: implications for cardiovascular disease

Polycystic ovary syndrome (PCOS) patients are known to have a high incidence of insulin resistance and glucose intolerance and tend to be at eventual high risk of hypertension ,diabetes mellitus and cardiovascular disease. It has been repeatedly shown that a low serum ionized magnesium (Mg²⁺) and a high ionized calcium to magnesium (Ca²⁺/Mg²⁺) ratio is often associated with insulin resistance ,cardiovascular problems ,diabetes mellitus and hypertension. We were therefore interested in assessing the serum divalent cation profile of PCOS patients compared with that of normal women of similar age. We found significantly lower serum Mg²⁺ and total magnesium and a significantly higher serum Ca²⁺/Mg²⁺ ratio in the PCOS patients compared with the controls. No correlation was found ,however ,between the serum concentrations of steroid hormones (estrogen ,progesterone and testosterone) ,or any of the cations in the PCOS patients or the controls.     

多囊卵巢综合征患者hCG注射日血清睾酮水平对IVF-ET结局的影响

目的:探讨多囊卵巢综合征患者hCG注射日血清睾酮(T)水平对IVF-ET结局的影响。方法:因顽固性排卵障碍而行IVF助孕的187例PCOS患者,于促排卵前均口服短效避孕药预治疗3￣6个月,T降至正常水平后,采用GnRHa长方案,观察比较妊娠组和非妊娠组hCG注射日血清T水平、获卵数、受精率、优质胚胎率。结果:非妊娠组T水平明显高于妊娠组,受精率及优质胚胎率均低于妊娠组,差异有统计学意义。结论:PCOS患者促排卵过程中T明显升高,可能对卵子质量及妊娠结局产生不良影响。     

Polymorphism of MDM2 promoter 309 (rs 2279744) and the risk of PCOS

This study aimed at evaluating possible association between MDM2 SNP309 polymorphism (rs 2279744) and polycystic ovary syndrome (PCOS). One hundred and twenty-five women with PCOS and two hundred and fifty women without PCOS were collected from the department of reproductive medicine of college hospital in this case–control study. Peripheral blood samples were collected from all participants and DNA was extracted, MDM2 SNP309 polymorphism (rs 2279744) was determined from the 125 cases and 250 controls. Women were grouped into PCOS (n?=?125) group and control group (n?=?250). Odds ratios (OR) and 95% confidence intervals (CI) were used to evaluate the association between MDM2 SNP309 polymorphism (rs 2279744) and PCOS. The distribution of T allele was significant higher in PCOS cases than controls. MDM2 SNP 309?T allele is associated with PCOS.     

Fertility management in the PCOS population: results of a web-based survey at IVF-worldwide.com

Purpose

To identify the leading treatment strategies for infertile women with PCOS on an international scale.

Methods

A retrospective evaluation using the results of a web-based survey, (IVF-Worldwide (www.IVF-worldwide.com), posted from 1 to 30 September 2010 was performed. Binomial confidence intervals for proportions were calculated by the modified Wald method with significance defined as P < 0.05 using a DataStar software package (DataStar, Waltham, MA, USA). Incomplete surveys were excluded from the analysis.

Results

The results from 262 centers in 68 nations were obtained. Clomiphene citrate was the clear first choice, 68 %, for PCOS treatment in the respondent group. Eighty-eight percent of respondents utilized ultrasound follicular monitoring when conducting ovulation induction with oral medications. A significant (p < 0.05) proportion of respondents (66 %) did use some BMI cutoff beyond which IVF treatment was not offered. The preferred IVF protocols for PCOS patients were gonadotropin releasing hormone (GnRH) antagonist, 46 %, and GnRH agonist, 51 %. There was heterogeneity of responses observed regarding the management of a patient at very high risk of OHSS.

Conclusions

While some advances, such as the use of GnRH antagonist regimen in IVF cycles, were relatively underutilized, the survey gives an unfiltered snapshot at the practice patterns of a large number of clinics. Results from this survey may be used by researchers and professional organizations to improve the clinical care of PCOS women suffering with infertility.     

再生基因Reg IV在多囊卵巢综合征(PCOS)模型大鼠卵巢中的表达

目的:探讨再生基因Reg IV在多囊卵巢综合征(PCOS)模型大鼠卵巢组织中的表达情况。方法:采用Poretsky法用胰岛素联合hCG诱导SD大鼠建立PCOS模型,观察大鼠体质量变化及卵巢相对质量;测定血清T、LH、FSH、E2、Ins水平;HE染色观察卵巢形态改变;免疫组织化学方法检测Reg IV蛋白在卵巢组织的定位表达;定量RT-PCR和Western blotting分别检测Reg IV在mRNA水平和蛋白水平的表达。结果:Reg IV分别表达于大鼠颗粒细胞、卵泡膜细胞以及黄体等部位;模型组卵巢中Reg IV mRNA及蛋白表达均低于正常对照组(P<0.05)。结论:Reg IV的表达下调可能与PCOS的发病有关。     

Association of AQP8 in women with PCOS

Aquaporin 8 (AQP8) has been identified as a novel gene participating in female reproductive physiology. The present study was designed to determine whether an association exists between AQP8 and polycystic ovary syndrome (PCOS). This study recruited 192 women with PCOS and 191 controls. High-resolution melting and sequencing were employed to investigate the genotypes of six single-nucleotide polymorphisms within AQP8 (rs7198838, rs1076973, rs1076974, rs2287797, rs2287798 and rs2287796). A significant difference was found in rs2287798 between PCOS cases and controls (P = 0.0007). Possible associations between AQP8 genotypes and three different phenotypes of this syndrome were investigated. The results support the earlier evidence for a possible role of AQP8 in the pathogenesis of PCOS. Further studies are still needed to elucidate its functional role.Aquaporin 8 (AQP8) has been identified as a novel gene participating in female reproductive physiology. The present study was designed to determine whether there is an association between AQP8 and polycystic ovary syndrome (PCOS). This study recruited 192 women with PCOS and 191 controls. High-resolution melting and sequencing were employed to investigate the genotypes of six single-nucleotide polymorphisms within AQP8 (rs7198838, rs1076973, rs1076974, rs2287797, rs2287798 and rs2287796). We observed a significant difference in allele frequency of rs2287798 between PCOS cases and controls (P = 0.0007). The possible association between AQP8 genotypes and three different phenotypes of this syndrome in this locus were investigated. Our results support the earlier evidence for a possible role of AQP8 in the pathogenesis of PCOS. Further studies are still needed to elucidate its functional role.     

多囊卵巢综合征患者IVF-ET前达英-35预处理不同时间临床效果分析

目的:探讨不同的达英-35预处理时间对多囊卵巢综合征患者IVF-ET助孕结局的影响。方法:回顾性分析在我院接受IVF助孕的119个PCOS助孕周期。所有患者均接受达英-35预处理,根据达英-35预处理周期数分为A组(达英-35预处理时间≤3个月),B组(达英-35预处理时间>3个月),检测比较治疗前、后血清LH水平、睾酮水平、游离雄激素指数(FAI)、获卵数、空卵泡率、临床妊娠率、着床率、OHSS发生率等。结果:A、B组达英-35预处理前血清LH值分别为:5.96±3.03 IU/L、6.91±4.40 IU/L;FAI分别为:1.42±1.10、1.76±1.67,治疗后均明显下降,与治疗前比有显著统计学差异(LH:3.50±2.19 IU/L,3.78±0.21 IU/L,FAI:0.54±0.38,0.54±0.48,P<0.05);B组空卵泡率、OHSS发生率分别为17.4%、6.8%,均低于A组(30.2%,20.0%),受精率为83.5%,较A组(74.8%)高,差异均有统计学意义(P<0.05)。结论:IVF前达英-35预处理可以显著降低PCOS患者高LH、高雄激素水平;随着达英-35预处理时间延长,空卵泡率和OHSS发生率进一步下降,受精率得到改善。