生长分化因子-9和骨形成蛋白-15对多囊卵巢综合征患者卵丘细胞凋亡的影响

目的探讨控制性超促排卵(COH)周期多囊卵巢综合征(PCOS)患者生长分化因子-9(GDF-9)、骨形成蛋白-15(BMP-15)的表达对卵丘细胞凋亡的影响。方法收集本院行卵胞质内单精子注射(ICSI)治疗的PCOS组(n=30)和对照组(n=60)患者的卵丘细胞。TUNEL法及流式细胞术检测卵丘细胞凋亡;免疫组织化学方法检测卵丘细胞GDF-9、BMP-15蛋白表达,运用Motic Med 6.0数码医学图像分析系统对染色强度定量分析;Real-time PCR技术检测卵丘细胞GDF-9、BMP-15、B细胞淋巴瘤/白血病-2(BCL)-2、BCL-2相关X蛋白(BAX)mRNA表达。结果 PCOS组穿刺卵泡数、获卵数高于对照组(P0.01);PCOS组卵丘细胞凋亡率高于对照组(P0.05);GDF-9、BMP-15蛋白在PCOS组和对照组卵丘细胞胞质中均呈阳性表达;PCOS患者卵丘细胞GDF-9、BMP-15、BCL-2、BAX mRNA的表达低于对照组(P0.05),BAX/BCL-2比值高于对照组(P0.05)。Pearson相关分析结果显示PCOS患者GDF-9、BMP-15与BCL-2 mRNA表达呈正相关,与BAX mRNA的表达呈负相关。结论 PCOS患者卵丘细胞GDF-9、BMP-15异常表达可能是卵丘细胞凋亡增加的原因之一。     

控制性超促排卵周期多囊卵巢综合征患者生长分化因子-9和骨形成蛋白-15的初步研究

目的:探讨控制性超促排卵(COH)周期多囊卵巢综合征(PCOS)患者卵巢颗粒细胞生长分化因子-9(GDF-9)、骨形成蛋白-15(BMP-15)的表达及其与体外受精-胚胎移植(IVF-ET)治疗结局的关系。方法:选择接受IVF-ET治疗的PCOS患者45例,同期输卵管因素不孕患者103例作为对照组。应用免疫组织化学、Real-time PCR技术检测患者卵巢颗粒细胞GDF-9、BMP-15蛋白和mRNA的表达,并分析与IVF-ET的临床结局关系。结果:GDF-9、BMP-15蛋白在PCOS组和对照组患者卵巢颗粒细胞胞质均呈阳性表达,PCOS患者颗粒细胞GDF-9 mRNA、BMP-15 mRNA的表达水平低于对照组,差异有统计学意义(P0.01)。多元线性回归分析显示,颗粒细胞GDF-9 mRNA、BMP-15 mRNA表达水平与优质胚胎数呈正相关关系(P0.05)。临床妊娠组的颗粒细胞GDF-9mRNA、BMP-15 mRNA表达水平高于未妊娠组(P0.05)。结论:COH周期PCOS患者颗粒细胞GDF-9 mRNA、BMP-15 mRNA表达水平可能与胚胎发育潜能存在相关性。     

The effect of metformin treatment on ovarian stromal blood flow in women with polycystic ovary syndrome

Objective  To evaluate the effects of metformin on the ovarian stromal blood perfusion in the patients with polycystic ovary syndrome (PCOS). Methods  Twenty-five women with PCOS who underwent a Doppler examination of the ovarian stroma was evaluated; hormonal, anthropometric, and biochemical parameters of patients were determined. After the patients were treated with 850 mg metformin twice a day for 6 months, the same parameters were evaluated in the same patients. Results  After metformin treatment, although pulsatility index (PI) was increased from 1.80 ± 1.23, 1.84 ± 1.28 to 2.20 ± 1.10, 2.19 ± 0.83 in the right and left ovary, respectively, and resistance index was increased from 0.84 ± 0.25, 0.83 ± 0.23 to 1.16 ± 0.37, 1.10 ± 0.26 in the right and left ovary respectively (P < 0.05), peak systolic velocity (PSV) was decreased from 12.30 ± 1.72, 12.34 ± 1.55 to 10.25 ± 0.97, 10.53 ± 1.33 in the right and left ovary respectively (P < 0.05). PI and RI did not show any difference between the homeostatic model assessment insulin resistance index (HOMA-IR) ≥ 2.38 and HOMA-IR < 2.38 groups before and after metformin treatment (P > 0.05). However, PSV was decreased significantly from 13.05 ± 1.35, 12.82 ± 2.02 to 11.03 ± 0.71, 10.25 ± 0.42 in HOMA-IR ≥ 2.38 group in the right and left ovary, respectively, and PSV was decreased from 11.50 ± 2.67, 11.28 ± 0.26 to 9.10 ± 0.58, 9.28 ± 0.25 in HOMA-IR < 2.38 group in the right and left ovary, respectively, before and after metformin treatment (P < 0.05). PSV for both ovaries were positively correlated with HOMA scores before and after metformin treatment [(r = 0.713, P = 0.000; r = 0.617, P = 0.04 and r = 0.635, P= 0.03; r = 0.483, P = 0.031 respectively]. Conclusion  Metformin treatment affected ovarian stromal blood flow in PCOS patients.     

Clomiphene citrate plus tamoxifen versus laparoscopic ovarian drilling in women with clomiphene-resistant polycystic ovary syndrome

Objective

To compare the efficacy of clomiphene citrate (CC) plus tamoxifen with that of laparoscopic ovarian drilling in clomiphene-resistant women with polycystic ovary syndrome (PCOS).

Method

We randomly allocated 150 women with CC-resistant PCOS to a combined medication group (group 1) or a laparoscopic surgery group (group 2). The primary outcome was the live birth rate in each group; secondary outcomes were the rates of ovulation, clinical pregnancy and miscarriage.

Results

There were no significant differences between the groups regarding rates of ovulation (81.3% vs 85.3%), pregnancy (53.3% vs 50.7%), or live births (49.3% vs 44.0%), but the mean endometrium thickness was significantly greater on the day of human chorionic gonadotropin administration in group 1 (P < 0.001).

Conclusion

Clomiphene citrate plus tamoxifen was as effective as laparoscopic ovarian drilling in promoting ovulation and pregnancy.     

GDF-9及其受体在PCOS大鼠卵巢中的表达

目的:探讨生长分化因子-9(GDF-9)蛋白及其受体BMPR-ⅡmRNA在PCOS大鼠卵巢的表达。方法:皮下注射DHEA建立PCOS模型,用免疫组化法检测卵巢GDF-9表达;用RT-PCR法检测BMPR-ⅡmRNA的表达。结果:GDF-9主要于PCOS发育正常的初级、窦前、窦状卵泡卵母细胞胞浆中表达,表达强度与对照组的差异无统计学意义(P>0.05)。BMPR-ⅡmRNA相对含量则显著高于对照组(P<0.05)。结论:GDF-9是促进P- COS卵泡发育的主要原因;受体表达上调是诱导雄激素增高的原因之一。     

Treatment strategies for women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women, and it is the main cause of infertility in women of reproductive age due to anovulation. PCOS also increases the risk of diseases such as cardiovascular disease and type 2 diabetes in women with this disorder. The mechanism of pathogenesis is not clear, as it may be related to heredity, the environment and internal embryonic factors; thus, the treatment strategies remain unclear. This review summarizes current treatments for PCOS worldwide. Lifestyle modification (LSM) is considered the first-line treatment, regardless of fertility status, without the addition of metformin. Oral contraceptive (OC) pills should be used as a first-line treatment for long-term management for patients with no reproductive requirements. For patients with fertility requirements, ovulation therapy is an effective treatment. For refractory ovulation disorders, patients can choose from among the latest treatments, including ovarian hippocampal signal path block theory, the theory of leptin, inositol treatment, bilateral ovarian drilling to stimulate ovulation and assisted reproductive technology. Because current treatments cannot cure PCOS, lifelong administration is still the mainstream method of management; however, the optimal treatment plan needs further research and exploration.     

Metformin therapy in women with polycystic ovary syndrome.

OBJECTIVE: To determine the clinical, biochemical, hormonal, and ultrasonographic effects of 6 months of metformin therapy in women with polycystic ovary syndrome (PCOS) and compare with pretherapy parameters. METHOD: 50 Indian women with PCOS, 25 unmarried and 25 married, infertile women, were enrolled in this prospective clinical study. After a baseline workup, including body mass index (BMI), waist hip ratio (WHR), Ferriman Gallwey hirsutism scoring, menstrual pattern, levels of fasting insulin, lipids, oral glucose tolerance test (OGTT), serum gonadotropins, estradiol (E2), testosterone, androstenedione, sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulphate (DHEAS), patients were given 1000 gm of metformin for 6 months and then reevaluated. RESULT: In 41 of 50 women who completed treatment, significant improvement in BMI, WHR, menstrual cyclicity (80.5%), ovulation rate (66%), and pregnancy rate (28%) was noted. Statistically significant decrease in lutenising hormone (LH) and LH/FSH ratio with an increase in follicle stimulating hormone (FSH) levels were seen. Levels of high-density lipoprotein (HDL) cholesterol (Chol) increased along with a decrease in total cholesterol. Improvement was noted in ovarian volume, stromal thickness, and number of follicles. There was no change in hirsutism, acne, levels of other sex steroid hormones, and lipids. CONCLUSION: A 6-month course of metformin therapy may improve menstrual cyclicity and fertility in women with PCOS.     

Prevalence of polycystic ovary syndrome in unselected women from southern China

OBJECTIVE: The objective was to determine the prevalence and metabolic parameters of polycystic ovary syndrome (PCOS) in southern China. STUDY DESIGN: The study was observational with a parallel study. Participants were studied in a medical examination center. A population of 915 women of reproductive age was investigated at the time of their annual physical examination to determine the prevalence of PCOS in unselected women from southern China. RESULTS: Our results demonstrated a 2.2% (20/915) prevalence of PCOS. Women with PCOS had higher levels of luteinizing hormone and higher luteinizing hormone/follicle-stimulating hormone ratios than those in the other groups. Women with PCOS had higher fasting insulin levels and lower fasting glucose/fasting insulin ratios than women in any of the other groups. CONCLUSIONS: Some clinical and biochemical characteristics were apparent in PCOS patients in our population, and ethnic differences may be considered when studying the clinical and metabolic features of PCOS in China.     

B超测量卵巢体积和卵泡数目在青春期多囊卵巢综合征诊断中的价值

目的探讨B超测量卵巢体积和卵泡数目用于诊断青春期多囊卵巢综合征（PCOS）的价值。方法对66例青春期PCOS患者（病例组）和27例对照组少女,进行经直肠双侧卵巢B超检查,并计算卵巢体积和卵泡数目,比较两组测量值的均数,采用受试者工作曲线（ROC）分析比较卵巢各指标的诊断价值并确定诊断界值。结果病例组与对照组的平均卵巢体积（MOV）、较大卵巢体积（MaxOV）和平均卵泡数目（MFN）分别为（9．2±3．2）cm^3、（11．4±4．7）cm^3、（12．0±3．9）个和（4．9±1．7）cm^3、（6．1±2．5）cm^3、（6．6±2．4）个,分别比较,差异有统计学意义（P〈0．01）。MOV、MaxOV和MFN诊断青春期PCOS的ROC曲线下面积（AUC）分别是0．914、0．884和0．838,3者比较,差异均无统计学意义（P〉0．05）。MOV≥6．4cm^3（敏感度84．8％,特异度87．5％）、MaxOV≥8．6cm^3（敏感度75．8％,特异度95．2％）或MFN≥8个（敏感度86．7％,特异度78．3％）分别是B超诊断青春期PCOS的较好界值。结论B超检测卵巢体积和卵泡数目对于青春期PCOS具有较好的诊断价值。以MaxOV≥8．6cm^3、MOV≥6．4cm^3或MFN≥8个作为界定青春期PCOS的B超标准,可获得较好的敏感度和特异度的平衡。     

Doppler analysis of uterine perfusion and ovarian stromal blood flow in polycystic ovary syndrome

Objective

To investigate blood flow velocity in the ovarian stromal artery and uterine artery in women with polycystic ovary syndrome (PCOS) and to correlate these velocities with clinical and biochemical parameters.

Methods

A prospective study was carried out in 55 patients with PCOS and 42 age-matched women who did not have PCOS. Clinical, biochemical, and hormonal characteristics, and utero-ovarian Doppler ultrasound blood flow parameters were determined, and correlations between the parameters were evaluated.

Results

Ovarian stromal blood flow was higher (P < 0.01) and uterine perfusion was lower (P < 0.01) in women with PCOS compared with women who did not have PCOS. Ovarian stromal artery pulsatility index (PI) was inversely correlated with levels of dehydroepiandrosterone sulfate (DHEAS) and insulin-like growth factor-1, and with the luteinizing hormone/follicle-stimulating hormone ratio. There was a positive correlation between uterine artery PI and DHEAS level.

Conclusion

Doppler analysis of the uterine and intraovarian arteries may provide additional information about the etiopathogenesis of PCOS and partly explain the clinical implications of the condition.     

Gremlin-1 and gremlin-2 levels in polycystic ovary syndrome and their clinical correlations

Objective: Gremlin 1 and 2 regulate oocyte primordial follicle transition in animal models. The main objective of this study is to measure the blood levels of Gremlin 1 and 2 in the women with Polycystic Ovary Syndrome (PCOS). We also aimed to evaluate the association of these markers with hormonal and biochemical parameters of PCOS as interrupted folliculogenesis in those women is related to metabolic dysfunction.

Material and methods: Fifty women with PCOS were diagnosed according to Rotterdam criteria, and thirty age-matched female controls were included in this prospective study. Gremlin 1 and 2 levels along with hormonal and metabolic parameters were compared between PCOS and control groups.

Results: Serum Gremlin 1 levels were significantly higher in the PCOS group than in the control group (p?=?.001). Gremlin 2 levels were similar between the groups. Besides, there was a significant positive correlation between Gremlin 1 and insulin levels, Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) and waist to hip ratio (WHR) (r?=?0.305; r?=?0.297; r?=?0.303, respectively).

Conclusion: Our data suggest that Gremlin 1 may be the key regulator in the pathogenesis of PCOS. In future, Gremlin 1 may be a novel therapeutic target for the treatment of PCOS.     

多囊卵巢综合征患者卵泡发育不良与干细胞因子表达水平的相关性研究

目的:研究辅助生殖治疗的多囊卵巢综合征(PCOS)患者卵泡中干细胞因子(SCF)、生长分化因子-9(GDF-9)和骨形态发生蛋白-15(BMP-15)的表达水平与卵泡发育异常的关系。方法:收集30例PCOS患者和40例正常对照者的卵泡液和颗粒细胞。采用酶联免疫吸附实验(ELISA)检测卵泡液中SCF、GDF-9和BMP-15的表达水平,采用免疫荧光染色法测定颗粒细胞中SCF的表达水平。结果:PCOS患者(n=30)卵泡液中GDF-9、BMP-15和SCF的浓度均明显低于正常对照组(n=40),差异有统计学意义(P0.05)。与对照组相比,PCOS患者颗粒细胞中SCF的表达水平显著下降(P0.05)。结论:PCOS患者卵泡液中GDF-9、BMP-15和SCF的表达均明显降低,并且PCOS患者颗粒细胞中SCF的表达也显著下降,这可能与其卵泡发育不良有关。     

Assessment of pulmonary functions and anthropometric measurements in women with polycystic ovary syndrome

Objectives.?The aims of this study were to compare pulmonary function tests of patients with polycystic ovary syndrome (PCOS) versus healthy women, and to investigate correlations between pulmonary function tests and anthropometric measurements of them.

Materials and Methods.?A total of 31 women with PCOS and 29 controls matched for age and body mass index (BMI) were enrolled into the study. Pulmonary function tests were performed with spirometer. Body fat percentage was calculated from the skinfold thicknesses using the formula. Biacromial, chest antero-posterior and lateral diameter measurements were carried out with anthropometric set.

Results.?There were no significant differences between patients with PCOS and healthy controls in the pulmonary function tests, body fat %, chest and abdomen region anthropometric measurements. There were moderate negative correlations only between forced expiratory volume per 1?s and BMI, abdomen circumference, body fat percentage in patients with PCOS. In the control group, however, there were moderate or strong negative correlations between anthropometric measurements (BMI, body fat percentage, abdominal circumference, chest lateral diameter) and at least three different pulmonary function tests.

Conclusion.?These results suggest that the upper body anthropometry and respiratory function relations might have impaired in patients with PCOS. We think that this situation might support the increased tendency for poor health status in patients with PCOS.     

Metformin versus laparoscopic ovarian drilling in clomiphene- and insulin-resistant women with polycystic ovary syndrome

Objective

To compare the hormonal-metabolic profiles and reproductive outcomes in clomiphene-resistant patients with polycystic ovary syndrome and insulin resistance between women receiving metformin and those undergoing laparoscopic ovarian drilling.

Methods

A total of 110 eligible participants were randomly allocated to diagnostic laparoscopy plus metformin therapy (group 1, n = 55) or laparoscopic ovarian drilling (group 2, n = 55). The t test was used for mean comparisons of hormonal-metabolic parameters and OGTT values before and after treatment. The χ² test was used for comparisons of ovulation, pregnancy, and abortion rates.

Results

Groups 1 and 2 showed a significant decline in testosterone, insulin-like growth factor-1 (P < 0.001 vs P < 0.001), and luteinizing hormone (P < 0.05 vs P < 0.001), while the glucose to insulin ratio was significantly increased (P < 0.001 vs P < 0.05) compared with baseline. Group 2 patients had more regular cycles and higher rates of ovulation and pregnancy compared with group 1: 76.4% [42/55] vs 58.2% [32/55], P < 0.04; 50.8% [131/258] vs 33.5% [94/281], P < 0.001; and 38.2% [21/55] vs 20.0% [11/55], P < 0.03, respectively. The difference in the early abortion rate between the groups was not statistically significant.

Conclusion

Although metformin results in a better attenuation of insulin resistance, laparoscopic ovarian drilling is associated with higher rates of ovulation and pregnancy.