Adropin levels in women with polycystic ovaries undergoing ovarian stimulation: correlation with lipoprotein lipid profiles

This study aimed to investigate serum and follicular fluid (FF) adropin levels in polycystic ovary syndrome (PCOS) and normal women undergoing controlled ovarian stimulation and correlate them with the lipid and lipoprotein levels. We included 60 women (30 lean and 30 overweight) with diagnosed PCOS, and 60 age and weight-matched non-PCOS controls (30 lean and 30 overweight), under in vitro fertilization (IVF) treatment. Serum lipid and lipoprotein levels were assessed by the Abbott Architect c8000 autoanalyzer while adropin levels were determined by enzyme immunoassay. Serum and FF adropin levels were significantly lower in PCOS women compared with controls and FF adropin levels were lower than serum levels. Significantly higher serum levels of total cholesterol, LDL-C, triglycerides, apolipoprotein B, lipoprotein(a) and homocysteine were encountered in PCOS subjects, while HDL-C and apolipoprotein A1 were significantly lower compared with controls. According to univariate and multivariate analysis, serum and FF adropin levels were positively correlated with BMI and HDL-C levels and negatively correlated with LDL-C levels. Women with polycystic ovaries exhibit lipid lipoprotein alterations increasing the risk of cardiovascular diseases later in life. Our findings suggest a probable involvement of adropin both in human metabolism and in the pathophysiology of PCOS.     

Symmetry in number of retrieved oocytes between two ovaries: a possible predictor of in vitro fertilization outcome

Objective.?To examine the relationship between the ratio of difference in number of retrieved oocytes from the two ovaries to total number of oocytes (difference ratio, |N_RO?N_LO|/N_TOTAL) and in vitro fertilization (IVF) outcome.

Methods.?Retrospective review of medical record for infertility patients with intact two ovaries who had undertaken controlled ovarian stimulation (COS) and IVF cycles in Seoul National University Hospital was conducted. Characteristics and IVF outcomes were compared according to the difference ratio (|N_RO?N_LO|/N_TOTAL) using student t-test and χ² test. To adjust for the effect of confounding factors, binary logistic regression test was performed.

Results.?When the study population was divided according to the difference ratio by cut-off value of 0.4, patients with difference ratio less than 0.4 showed significantly higher pregnancy rate (25.7% vs. 17.1%, p?=?0.021). A significant correlation was noted between the difference ratio and achievement of pregnancy after adjustment for patient's age and total number of top quality embryos transferred (adjusted OR?=?0.40, 95% CI 0.19–0.83, p?=?0.014).

Conclusions.?The difference ratio of retrieved oocytes in patients with intact two ovaries was observed to have prognostic value in IVF cycles.     

Serological markers of autoimmunity in pregnant women with polycystic ovary syndrome: a pilot study

Background.?Gestational diabetes mellitus (GDM) is highly prevalent in women with polycystic ovary syndrome (PCOS). Women with GDM have considerable risk for developing both type 1 and type 2 diabetes.

Aim.?To evaluate the prevalence of anti-GAD65 and anti-IA2 auto-antibodies in Chilean pregnant women with GDM, normal pregnancy (NP) and with PCOS (PPCOS) to establish whether in PCOS women GDM is partially induced by auto-antibodies.

Methods.?Women with singleton pregnancies matched by age and gestational age were included: 50 GDM, 59 NP and 50 PPCOS. During gestational weeks 22–28, a 2-h, 75?g oral glucose tolerance test was performed, with measurement of glucose, insulin, lipids and auto-antibodies.

Results.?A highly prevalence of anti-GAD65 antibodies (12%) was observed in women with GDM. PPCOS and NP women showed a similar distribution of anti-GAD65 antibodies (2.0% and 1.7%, respectively). Anti-IA2 antibodies were present in 4.0% of women with GDM, in 1.7% of NP women and 2.0% PPCOS women.

Conclusion.?A highly prevalence of anti-GAD65 was observed in women with GDM which is in agreement with previous studies. Nevertheless, the frequency of these auto-antibodies was very low in NP and PPCOS women.     

Glucose action and adrenocortical biosynthesis in women with polycystic ovary syndrome

OBJECTIVE: To determine if insulin or glucose action plays a role in adrenocortical steroidogenesis in the polycystic ovary syndrome (PCOS). DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENT(S): Nine reproductive-aged patients with PCOS and nine age-, race-, and body mass index-matched controls. MAIN OUTCOME MEASURE(S): Insulin-modified frequently sampled intravenous glucose tolerance testing and an acute 60-minute ACTH-(1-24) stimulation test. From the glucose tolerance test, glucose and insulin were measured and the insulin sensitivity index, glucose effectiveness, and acute insulin response to glucose were determined. Dehydroepiandrosterone sulfate (DHEAS) basally and 17-hydroxypregnenolone, 17-hydroxyprogesterone, DHEA, androstenedione, and cortisol during ACTH testing at 0 and 60 minute (steroid(0) and steroid(60)) were determined. The net change in steroid during the ACTH test was calculated. RESULT(S): The insulin sensitivity index had limited correlation with adrenocortical variables in both groups. In patients with PCOS, glucose effectiveness was positively associated with DHEAS, cortisol(0), cortisol(60), change in cortisol, DHEA(0), DHEA(60), change in DHEA, 17-hydroxyprenenolone(60), change in 17-hydroxypregnenolone, DHEA(0), androstenedione(0), 17-hydroxyprenenolone(0), 17-hydroxyprogesterone(0), 17-hydroxyprenenolone(60), and 17-hydroxyprogesterone(60). CONCLUSION(S): Adrenocortical biosynthesis, basally and in response to ACTH, appears to be closely associated with glucose effectiveness in PCOS. A common factor determining both the effectiveness of glucose to control its own production or uptake and adrenocortical biosynthesis may be aberrant in PCOS.     

Serum and follicular fluid irisin levels in women with polycystic ovaries undergoing ovarian stimulation: correlation with insulin resistance and lipoprotein lipid profiles

Irisin, a novel exercise-induced myokine, has been implicated in different aspects of human metabolism and could be connected to polycystic ovary syndrome (PCOS). This study aimed to investigate serum and follicular fluid (FF) irisin levels in PCOS and normal women undergoing controlled ovarian stimulation and correlate them to the lipid and lipoprotein levels as well as with other metabolic parameters. Serum and FF irisin, together with serum lipid and lipoprotein levels were assessed in 70 women with diagnosed PCOS and 70 non-PCOS controls, under in vitro fertilization (IVF) treatment. Regardless of BMI, PCOS women had a significantly increased number of oocytes retrieved, fertilized oocytes and transferred embryos, although the number of women achieving pregnancies did not differ between groups. No correlation between FF irisin levels and pregnancy could be established. Serum and FF irisin levels were significantly higher in PCOS and overweight women and were positively associated with BMI and dyslipidemia. FF irisin levels correlated positively to and were lower than serum irisin levels. Further research would be helpful to analyze irisin’s role in female reproduction, if any, as well as in human metabolism and the pathophysiology of PCOS.     

盐酸吡咯列酮治疗多囊卵巢综合征临床疗效分析

目的探讨盐酸吡咯列酮对多囊卵巢综合征（PCOS）患者血清睾酮、血脂、空腹胰岛素、血糖的影响，为其临床应用提供依据。方法应用自身对照研究，对30例PCOS患者给予盐酸毗咯列酮每日30mg口服，3个月。进行服药前后的血清睾酮、血脂、空腹胰岛素、血糖及服糖后2h胰岛素和血糖的测定，同时于服药后记录月经周期、体重变化，服药后不适感及B超监测排卵。结果服药前后体重无明显变化（P〉0．05）。服药后空腹胰岛素、服糖后2h胰岛素和血糖、HOMA指数均有下降（P〈0.05）。服药后血清睾酮明显下降，特别是肥胖组下降明显（P〈0.05），而非肥胖组无变化（P〉0.05）。服药后高密度脂蛋白（HDL）升高，甘油三脂（TG）降低（P〈0.05）。23例无排卵患者服药后观察69个周期，21个周期有排卵，排卵率为30．43％。26例月经异常者中20例得到改善，改善率为76．92％。不良反应中，乳房胀痛1例，胃痛1例，疲劳感1例，其余患者无不适主诉，未发现肝、肾功能异常。结论吡咯列酮可以改善PCOS患者胰岛素抵抗，降低血清睾酮水平，调节脂代谢、诱发排卵，短期应用未出现严重的不良反应。     

Incidence of polycystic ovaries and polycystic ovary syndrome amongst women in Melbourne, Australia

BACKGROUND: The incidence of polycystic ovaries (PCO) in the Australian population is unknown. AIMS: To determine the incidence of PCO in a random population of Melbourne women. METHODS: A retrospective survey of the transvaginal ultrasound of female partners of sterile males was undertaken. RESULTS: Twenty-three percent of subjects had polycystic ovaries on ultrasound criteria, 17% bilateral and 6% unilateral. CONCLUSIONS: The incidence of PCO in Australian women is similar to that of other Caucasian populations.     

中心型肥胖对多囊卵巢综合征不孕患者体外受精结局的影响

目的：探讨中心型肥胖对多囊卵巢综合征(PCOS)不孕患者体外受精(IVF)结局的影响。方法：回顾性分析2009-2010年中山大学孙逸仙纪念医院 PCOS不孕患者行IVF治疗的188个新鲜周期,按照是否为中心型肥胖分为腰围≥80 cm组(70个周期)和腰围<80 cm组(118个周期),比较两组基础内分泌代谢和IVF的临床及实验室参数。结果：腰围≥80 cm与腰围<80 cm组相比,体重指数(BMI)、腰臀比增加,血游离雄激素指数(FAI)高,性激素结合球蛋白(SHBG)低,空腹葡萄糖、空腹胰岛素、稳态胰岛素评价指数(HOMA-IR)、2 h口服葡萄糖耐量试验(OGTT2h)葡萄糖及胰岛素高,胰岛素抵抗、空腹血糖受损(IFG)、糖耐量异常(IGT)的发生率高,三酰甘油(TG)高、高密度脂蛋白(HDL)低,差异均有统计学意义(P<0.05)。校正BMI后,腰围与空腹胰岛素、HOMA-IR及FAI呈正相关(P<0.01);促性腺激素(Gn)用量[(2014.8±825.8)U vs.(1491.2±558.9)U ]及天数[(12.5±4.0)d vs.(10.7±3.0)d]增加(P<0.01),峰值雌二醇水平低[(8492.7±4771.2)pmol/L vs.(11918.1±5329.0)pmol/L,P<0.001],诱发卵子成熟的人绒毛膜促性腺激素(HCG)用量多(P=0.011)而成熟卵泡及获卵数少[(11.6±5.7)个vs.(13.8±7.3)个,P<0.05];胚胎种植率降低(24.3% vs.36.3%,P=0.019),早期流产率增加(38.5% vs.7.5%,P=0.002),临床妊娠率差异无统计学意义(40.6% vs.55.2%, P=0.07)。校正年龄及病因,Logistic回归分析显示HOMA-IR是PCOS患者IVF妊娠后早期流产的风险因素(OR=0.143,95%CI=0.026~0.768,P=0.023)。结论：中心型肥胖PCOS患者胰岛素抵抗和高雄激素血症更显著,糖脂代谢紊乱发生率高,负面影响PCOS患者IVF促排卵的反应,且胚胎种植率下降、早期流产率增加。     

Correlation of visfatin levels and lipoprotein lipid profiles in women with polycystic ovary syndrome undergoing ovarian stimulation

The aim of this study was to determine serum and follicular fluid (FF) visfatin levels in age and weight-matched women with polycystic ovary syndrome (PCOS) and normally ovulating subjects undergoing controlled ovarian stimulation and correlate them with their lipid and lipoprotein levels. We included 80 PCOS women (40 lean and 40 overweight) and 80 age- and weight-matched controls, enrolled in the IVF program. In PCOS women, we determined significantly increased serum and FF visfatin as well as serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B, lipoprotein(a) and homocysteine, while high-density lipoprotein cholesterol and apolipoprotein A1 were significantly lower compared to controls. Serum visfatin levels positively correlated with total cholesterol, LDL cholesterol, triglycerides, lipoprotein(a) and homocysteine levels and negatively with apolipoprotein A1. FF visfatin levels positively correlated with triglycerides and homocysteine and negatively with apolipoprotein A1. Dyslipidemia is common in reproductive age women with PCOS exposing them to risk for cardiovascular diseases. However, the detailed role of visfatin on lipoprotein lipid profile awaits further clarification through future investigation.     

Relationship between insulin resistance and gonadotropin dissociation in obese and nonobese women with polycystic ovary syndrome

OBJECTIVE: To test the interdependence between insulin resistance (IR) and gonadotropin dissociation (GD) in polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional prospective study. SETTING: Clinical research center. PATIENT(S): Thirty-two PCOS patients aged 19-34 years; 16 obese (BMI > or = 27) and 16 nonobese (BMI < 27). INTERVENTION(S): A 75-g oral glucose tolerance test (OGTT) and a 100-microg i.v. GnRH test were performed on different days. Blood was taken at 0, 30, 60, 90, 120, and 180 minutes in each test. Serum glucose, insulin, LH, and FSH were measured. MAIN OUTCOME MEASURE(S): Area under the curve was calculated for glucose, insulin, and glucose-to-insulin ratio (GIR), and for LH, FSH, and LH-FSH ratio. RESULT(S): Glucose, insulin, and GIR were not modified significantly during the GnRH test, nor LH, FSH and LH-FSH ratio throughout the OGTT. There were no significant differences in GIR response of patients with and without GD, nor in LH-FSH ratio of patients with and without IR, after OGTT and GnRH test. However, obese patients with IR had a significantly larger (P<.04) area under the curve for LH-FSH ratio than those without IR after GnRH test, but not after OGTT test. CONCLUSION(S): Insulin resistance and GD do not appear to be related events in PCOS, suggesting that each one might be determined by different genetic disorders. However, IR can affect GD after chronic stimulation in obese patients.     

Higher circulating irisin levels in patients with polycystic ovary syndrome:a meta-analysis

Insulin resistance (IR) has been reported to be highly associated with the pathogenesis of polycystic ovary syndrome (PCOS). Although irisin, a newly identified myokine that may be closely associated with IR, has been implicated in the development of PCOS, the results are still ambiguous. We performed this meta-analysis to compare the circulating irisin levels between PCOS and healthy women and assess the association of irisin with IR. Published works were retrieved from PubMed and Embase databases using combinations of ‘irisin’ and (‘polycystic ovary syndrome’ or ‘PCOS’). Eight studies involving 1918 PCOS patients and 528 controls were included in the meta-analysis. Publication bias was observed using a funnel plot and Egger's regression asymmetry test. The pooled data indicated that the levels of irisin were at least 45.78?ng/ml [95% confidence interval (CI)] (12.45, 79.12, p?=?.007) higher in patients with PCOS than that in the healthy controls. Additionally, we did not observe a significant correlation between circulating irisin levels and IR in study populations, although the results may not be reliable for small sample sizes. The current meta-analysis suggested that irisin might contribute to the development of PCOS independent of IR.     

Effects of low-dose metformin in Japanese women with clomiphene-resistant polycystic ovary syndrome

Background and Aims  The aim of the present prospective observational study was to evaluate the effects of low-dose, short-term metformin, in combination with domiphene (CC), in CC-resistant infertile Japanese women with polycystic ovary syndrome (PCOS). Methods  Metformin therapy was administered orally (one 250 mg tablet, twice daily) to 15 CC-resistant infertile patients with PCOS, beginning on the third day of progestin-induced withdrawal bleeding, and was continued for 14 days in the first cycle. In the event of anovulation, 100 mg/day of CC was given during subsequent cycles on days 5–9, in addition to the aforementioned dose of metformin. Hormonal and metabolic parameters were measured on the second or third days of the first cycle and also the fourth cycle, following an overnight fast. Results  None of the 15 women successfully ovulated during the first cycle with metformin treatment alone. After two subsequent cycles with the combination of CC and metformin, ovulation was confirmed in 17 of 29 cycles (61%) and in 13 of 15 patients (87%). Two women became pregnant within 2 months of therapy (13%). There were no cases of ovarian hyperstimulation syndrome. Following three cycles of metformin therapy, a slight reduction in serum levels of luteinizing hormone (LH), free testosterone, androstenedione, dehydroepiandrosterone sulfate, hemoglobin Alc and total cholesterol was seen, while serum LH/follide-stimulating hormone ratio and serum level of low-density lipoprotein cholesterol were significantly decreased. Although there were no significant differences between the responder (n = 11) and non-responder (n = 2) groups at baseline, the levels of plasma fasting insulin was significantly higher and fasting glucose/insulin ratio was significantly lower in the non-responder group compared with the responder group after three cycles. Conclusion  Low-dose, short-term metformin, combined with CC, can improve ovulation rates in CC-resistant infertile Japanese women with PCOS.     

Insulin response to oral glucose in healthy,lean young women and patients with polycystic ovary syndrome

Background and aim. Insulin resistance and consequent hyperinsulinemia are common among patients with polycystic ovary syndrome (PCOS). Ethnicity and dietary habits affect insulin levels. There is little published information from India on insulin levels in PCOS patients. Thus the present study aimed to determine the insulin response to oral glucose in women with PCOS and healthy women.

Methods. In a case–control study design, women with PCOS and lean healthy women without a family history of diabetes mellitus underwent oral glucose tolerance testing. Samples were collected at 0, 1 and 2 h after glucose ingestion.

Results. Two hundred and eighty-five women with PCOS and 27 lean healthy young women were enrolled into the study. The mean age of controls was 22.8 ± 4.5 years (range 15–32 years) and their mean body mass index (BMI) was 19.7 ± 2.6 kg/m². Mean blood glucose at 0, 1 and 2 h was 88.2 ± 7.2, 115.5 ± 25.5 and 91.8 ± 20.5 mg/dl, respectively. Corresponding plasma insulin levels were 5.8 ± 1.1, 32.7 ± 26.5 and 14.6 ± 9.6 mIU/l. Peak insulin levels were seen at 1 h and these came down to less than 40% of the peak value by 2 h. Glucose/insulin ratio at 0, 1 and 2 h was 15.6 ± 3.1, 7.0 ± 3.1 and 11.4 ± 7.0. Homeostasis model assessment of insulin resistance (HOMA-IR) was 1.2 ± 0.2.

The age of the PCOS women ranged from 15 to 40 years (mean 23.4 ± 6.2 years) and their BMI ranged from 16.4 to 50.4 kg/m² (mean 27.7 ± 6.3 kg/m²). One hundred and seventy-six (62%) PCOS patients had normal glucose tolerance (NGT), 39 (14%) had impaired fasting glucose (IFG), 49 (17%) had impaired glucose tolerance (IGT) and 21 (7%) had type 2 diabetes mellitus (T2DM). Insulin response was higher in women with PCOS. Peak insulin was observed at 1 h. The difference between 1-h and 2-h post-glucose insulin decreased with worsening glucose tolerance. Both plasma insulin and BMI showed a rising trend from NGT to IFG to IGT. There was no further increase in either insulin or BMI from IGT to T2DM. Glucose/insulin ratio at 0, 1 and 2 h was lower (8.3 ± 4.2, 2.0 ± 1.6 and 3.2 ± 3.5) than that of healthy controls. HOMA-IR was 3.1 ± 3.0.

Conclusion. Women with PCOS had an exaggerated insulin response to glucose. Thirty-eight percent of PCOS women had some form of abnormal glucose tolerance. Greater insulin response was seen with impairment of glucose tolerance. Obesity had no effect on fasting insulin or insulin response to oral glucose in PCOS women with NGT.     

PCOS患者未成熟卵体外成熟培养后妊娠结局分析

目的:探讨PCOS患者未成熟卵母细胞体外成熟(in vitro maturation,IVM)治疗的有效性和安全性。方法:分析比较PCOS合并不孕症自愿要求行IVM或IVF治疗的患者临床结局。结果:IVF组的平均优质胚胎数明显高于IVM组(P<0.05),两者的临床妊娠率(39.22%vs 40.32%)和着床率(24.37%vs 23.89%)无差异(P>0.05)。IVM组的妊娠丢失率为38.0%,高于IVF患者(21.1%,P<0.05),出生婴儿(单胎)的平均体质量组间无统计学差异(P>0.05)。结论:对于PCOS患者进行IVM治疗可以获得与IVF周期相类似的临床妊娠率和着床率;但是IVM治疗后流产率明显增加。     

多囊卵巢综合征年轻不孕患者体外受精-胚胎移植结局研究

目的 探讨对<35岁多囊卵巢综合征（PCOS）不孕患者行体外受精-胚胎移植 (in vitro fertilization and embryo transfer, IVF-ET)受孕后的结局。方法 选取2007年10月至2010年8月间在中山大学附属第一医院生殖中心第一次行IVF的<35岁PCOS患者共68例,对照组为<35岁的第一次行IVF的输卵管性不孕患者共1164例。对两组患者的基本资料、IVF-ET周期的卵子和胚胎情况以及妊娠结局进行回顾性比较。结果　<35岁PCOS患者IVF周期中的临床妊娠率（30.9% vs. 44.1%）、流产率（14.3% vs.12.9%）、多胎率（42.9% vs. 38.4%）、早产率（22.2 %vs.14.7%）、小于胎龄儿（9.5% vs.11.1%）以及大于胎龄儿（9.5% vs. 3.1%）,与对照组患者比较,差异无统计学意义（P>0.05）,但其妊娠期糖尿病（14.3% vs.4.1%）以及妊娠期高血压疾病（4.0% vs. 1.0%）的发生率高于对照组,差异有统计学意义（P<0.05）。结论 <35岁PCOS不孕患者行IVF-ET治疗后的妊娠期糖尿病、妊娠期高血压疾病的发生率增加。     

Infertile polycystic ovary syndrome patients undergoing in vitro fertilization with the gonadotropin-releasing hormone-antagonist protocol: role of hyperandrogenism

This retrospective cohort study is to assess the effects of hyperandrogenism (HA) in polycystic ovary syndrome (PCOS) patients with gonadotropin-releasing hormone (GnRH)-antagonist protocol during in vitro fertilization (IVF). Total 892 infertile Patients between 20 and 35 years of age with normal body mass index (BMI, 18.50 ?24.99 kg/m²), including those with tubal factor infertility (control, n?=?318), PCOS infertility with HA (HA PCOS, n?=?244), and PCOS infertility without HA (non-HA PCOS, n?=?330), were included. Number of retrieved oocytes was significantly higher and total Gonadotropin consumption was significant lower in the HA PCOS group, whereas abortion rate was significantly higher and live birth rate was significantly lower in the HA PCOS group, compared with the control and non-HA PCOS groups. In the HA PCOS group, the number of available embryos tended to be higher with no significance. The GnRH-antagonist protocol is more suitable for HA PCOS patients, with lower cost and more number of embryos available for transfer. Due to the high abortion rate and low live birth rate, a freeze-all approach might be a preferable option for HA PCOS patients so as to create a buffer for reducing androgen levels before transferring freeze-thawed embryos.