Acanthosis nigricans: clinical predictor of abnormal glucose tolerance in Asian women with polycystic ovary syndrome.

The aim of this retrospective study was to assess whether acanthosis nigricans is a predictive factor for abnormal glucose tolerance (AGT) in Asian women with polycystic ovary syndrome (PCOS). Data from the record forms and electronic form of 121 PCOS women who consecutively attended the Reproductive Endocrinology and Infertility Unit were reviewed. In accordance with the unit's guidelines, all women received a physical examination, had anthropometric measurements taken and underwent as a 75-g oral glucose tolerance test after diagnosis. Their age, body mass index (BMI) and waist/hip ratio (WHR) was 29.1+/-6.1 years, 27.4+/-6.8 kg/m2 and 0.84+/-0.6 (mean+/-standard deviation), respectively. The prevalence of AGT was 42.9%, with 1.6% having impaired fasting glucose, 32.3% having impaired glucose tolerance and 9.1% having type 2 diabetes mellitus. The PCOS women with acanthosis nigricans had significantly higher BMI, WHR, fasting glucose, 2-h post-load glucose, fasting insulin, 2-h post-load insulin and prevalence of AGT compared with those without acanthosis nigricans. By logistic regression analysis, acanthosis nigricans and WHR were independent predictors for AGT, with an odds ratio (95% confidence interval) of 2.7 (1.1-7.1) and 10.1 (1.8-20.7), respectively. In conclusion, acanthosis nigricans was demonstrated as a predictive factor for AGT in Asian women with PCOS.     

Endometrial fluid collection in women with PCOS undergoing ovarian stimulation for IVF. A report of four cases

BACKGROUND: The presence of endometrial fluid collections' developing during ovarian-stimulation was previously reported to occur in women with hydrosalpinx. We report on the occurrence of endometrial fluid collections in four women with polycystic ovary syndrome (PCOS) undergoing ovarian stimulation for in vitro fertilization. CASES: Four women developed endometrial fluid collections during ovarian stimulation. These fluid collections were noted as early as day 5 of stimulation. The reproductive outcome when fluid collections were noted on the day of human chorionic gonadotropin (hCG) or of embryo transfer (ET) was poor. One of three women with fluid collection on the day of hCG conceived but had a missed abortion. One patient with fluid on the day of ET failed to conceive. Three of four patients who underwent repeat cycles conceived when no fluid collections were seen on day of hCG or ET. CONCLUSION: Abnormal endometrial milieu could be an underlying defect in some women with PCOS and chronic anovulation who fail to conceive with ovulation-induction agents. This is the first report of endometrial fluid collections in patients with PCOS in the absence of hydrosalpinx. Continuous monitoring of the endometrial lining during ovulation induction is mandatory to rule out any abnormality in endometrial development. Cryopreserving all embryos may be considering in cycles with fluid collections noted on the day hCG or ET.     

Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome.

BACKGROUND: The dichotomy between ovulation rates and pregnancy rates for women with polycystic ovary syndrome (PCOS) treated with clomiphene citrate (CC) prompted the present study to determine the effect of CC on endometrial maturity. METHODS: Retrospective case-control study of anovulatory women with PCOS (n = 119) on their third ovulatory cycle of CC and controls, 238 healthy regularly ovulating women whose partners had abnormal sperm, all of whom had an endometrial biopsy in the late luteal phase. RESULTS: Endometrial histology classified according to the classical Noyes criteria revealed out-of-phase endometrium in 19/119 (16%) of the CC group compared with 7/238 (3%) in controls (p < 0.0001). Duration of the luteal phase was not influenced by histological age of the endometrium. Endometrial biopsy performed during 138 conception cycles extracted from the database did not increase the miscarriage rate significantly (23.9%). CONCLUSIONS: CC treatment significantly increases the prevalence of out-of-phase endometrium and this could explain, in part, the large difference between ovulation and pregnancy rates. There was no correlation between the results of the endometrial biopsy and the duration of the luteal phase. Performing an endometrial biopsy during a conception cycle does not seem to have a significant negative effect on the outcome of pregnancy.     

The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a,and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is a common endocrinologic disorder in women of reproductive age characterized by polycystic ovaries, oligo/anovulation, and hyperandrogenism. Not only anovulation but also endometrial dysfunction can reduce fertility in PCOS patients. Wnt pathway is responsible for endometrial proliferation which be strongly regulated by estradiol. To determine the effects of clomiphene citrate (CC) and letrozole, we measured the expression of some main ligands of Wnt/β-catenin signaling including Wnt7a, Wnt3, and Wnt8b in the endometrial samples taken from PCOS women on day 12 of the menses who received 100?mg CC or 5?mg letrozole as well as from women without treatment. Significantly, the mean estrogen and progesterone concentration were lower and higher, respectively, in letrozole than CC. The mean endometrial thickness (ET) was significantly greater in letrozole compared to CC. Assessment of the mRNA and protein expression of Wnt7a, Wnt3, and Wnt8b showed significantly lower expression in CC than the letrozole and control groups. Collectively, letrozole provided a better molecular response in the endometrium of PCOS patients during the proliferative phase, similar to natural cycles, compared to CC. CC decreased the ligands expression of Wnt3, Wnt7a, and Wnt8b, resulting in endometrial dysfunction.     

Ultrasound and menstrual history in predicting endometrial hyperplasia in polycystic ovary syndrome

OBJECTIVE: To assess the role of endometrial thickness on vaginal ultrasound assessment and menstrual history in predicting endometrial hyperplasia in women with polycystic ovary syndrome (PCOS) who presented with infertility due to anovulation. METHODS: This was a prospective study in a university referral-based fertility and endocrine clinic. Fifty-six women with PCOS presenting with infertility due to anovulation underwent both vaginal ultrasound assessments and endometrial biopsies. The main outcome measures were the predictive value of sonographic endometrial thickness (primary objective) and the menstrual history with other clinical characteristics (secondary objective) for proliferative endometrium and endometrial hyperplasia in logistic regression analysis. Their predictive value was further examined by receiver operating characteristic curve analysis. RESULTS: Thirty-six PCOS patients (64.3%) had proliferative endometrium and 20 (35.7%) had endometrial hyperplasia. Five of the latter (25%) had cytologic atypia. Endometrial thickness less than 7 mm or intermenstrual interval less than 3 months (corresponding to more than four menstrual periods yearly) was associated with proliferative endometrium only. The endometrial thickness correlated positively with endometrial hyperplasia (P =.018) and, together with the average intermenstrual interval, were significant predictors of endometrial hyperplasia (P <.001). CONCLUSION: These findings point to the usefulness of obtaining a detailed menstrual history in women with PCOS by identifying those at increased risk of endometrial hyperplasia and who require an endometrial biopsy. The endometrial thickness corroborates this clinical impression and is particularly useful when the menstrual history is uncertain. Endometrial hyperplasia in this population is effectively excluded when the endometrial thickness is less than 7 mm.     

Can adiponectin predict abnormal glucose tolerance in Thai women with polycystic ovary syndrome?

AIM: To evaluate whether adiponectin levels could predict abnormal glucose tolerance (AGT) in Thai women with polycystic ovary syndrome (PCOS). METHODS: A 75-g oral glucose tolerance test (OGTT) with fasting adiponectin and insulin (FI) blood sampling in 170 women with PCOS were performed consecutively. RESULTS: The prevalence of AGT was 45.9%. The body mass index (BMI), waist-to-hip ratio (WHR), fasting glucose and 2-h postload glucose were greater in the PCOS women with AGT than those without AGT (P<0.001). In addition, the PCOS women with AGT had more severe insulin resistance (IR) and lower adiponectin levels than those without AGT. However, the area under the ROC curve of adiponectin and insulin in predicting AGT was smaller than that of homeostatic model of IR (HOMA-IR) (P<0.01). The arbitrary cut-off values at 12 ug/mL of adiponectin, 10 microiu/mL of FI and 2 of HOMA-IR showed the sensitivity and specificity of 80.8% and 33.7%; 87.2% and 34.8%; and 89.7% and 31.5%, respectively. With these cut-off points, 46 (27.1%), 42 (24.7%) and 37 (21.8%) women, respectively, could be eliminated from performing OGTT. However, 15 (19.2%), 10 (12.8%) and 8 (10.3%), respectively, missed the diagnosis. In addition, with WHR and acanthosis nigricans adjustment, HOMA-IR, but not adiponectin, was a significant predictor of AGT. CONCLUSION: Our study demonstrated that almost half of the women with PCOS had AGT. Adiponectin levels were significantly lower in the PCOS women with AGT than those without AGT. However, adiponectin was not shown to be as strong a predictive factor and might not be such an excellent screening test as FI and HOMA-IR.     

Body fat patterning in polycystic ovary syndrome women as a predictor of the response to clomiphene

BACKGROUND: To investigate the difference in the response to clomiphene citrate (CC) based on body fat distribution in women with polycystic ovary syndrome (PCOS). METHODS: Ninety anovulatory PCOS women were divided into two subgroups based on treatment response: women who ovulated with CC (CC responders, n = 49) and those who did not ovulate with CC (CC nonresponders, n = 41). Baseline characteristics included age, age at menarche, height, weight and body mass index [BMI; weight/(height)2]. Percentage of body fat, body fat mass and the ratio of trunk fat to leg fat mass amount (trunk-leg fat ratio) were measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: Age, age at menarche and height did not differ between the two groups. However, trunk-leg fat ratio in CC responders (0.9 +/- 0.4) was significantly lower than that in CC nonresponders (1.3 +/- 0.4) (p < 0.001). Percentage of body fat, body fat mass and BMI were also lower in CC responders (p < 0.01). On multiple regression analysis, however, trunk-leg fat ratio proved to be a superior predictor of CC responder to percentage of body fat, BMI or body fat mass (standardized regression coefficient > or = 0.510; t-values > or = 3.432; p < 0.001). CONCLUSIONS: Response to CC in anovulatory PCOS women differs with body fat distribution.     

Using gonadotropin-releasing hormone agonist before frozen embryo transfer may improve ongoing pregnancy rates in hyperandrogenic polycystic ovary syndrome women

Polycystic ovary syndrome (PCOS), affecting more than 5–10% of woman at reproductive childbearing age, is characterized by anovulation and hyperandrogenism. Frozen-thawed embryo transfer (ET) has been widely used for PCOS women to minimize the risk of ovarian hyperstimulation syndrome. However, the hyperandrogenic status of PCOS women deteriorates endometrial function, which has subsequently increased miscarriage rates in PCOS women. Therefore, we conducted this retrospective study to compare the pregnancy outcomes of hyperandrogenic PCOS women with (n?=?29) and without (n?=?31, controls) pretreatment of gonadotropin-releasing hormone (GnRH) agonist before frozen-thawed ET. We found that pretreatment with GnRH agonist before frozen-thawed ETs could not significantly improve the clinical pregnancy rate in these hyperandrogenic PCOS women. However, the ongoing pregnancy rate was significantly increased in women with GnRH agonist pretreatment (odds ratio: 3.98, 95% confidence interval: 1.12–14.20, p?=?0.033). We concluded that androgen deprivation status due to pretreatment with GnRH agonist might improve the ongoing pregnancy rate in hyperandrogenic PCOS women. Additional large, well-designed prospective studies are worthwhile and necessary.     

Prevalence of the metabolic syndrome in Asian women with polycystic ovary syndrome: using the International Diabetes Federation criteria.

BACKGROUND: Since insulin resistance and compensatory hyperinsulinemia are the major causes of the metabolic syndrome (MS) and are also the main pathophysiology of polycystic ovary syndrome (PCOS), PCOS women are at risk of MS. The aim of the present cross-sectional study was to determine the prevalence of MS in Asian women with PCOS using the International Diabetes Federation (IDF) criteria and to define the risk factors. METHODS: One hundred and seventy women with PCOS were enrolled in the study from September 3, 2002 to June 14, 2005. A 75-g oral glucose tolerance test with plasma glucose and serum insulin levels was performed. Also, blood samples were examined for fasting triglycerides, high-density lipoprotein cholesterol and adiponectin levels. RESULTS: The mean (+/-standard deviation) age, body mass index (BMI) and waist-to-hip ratio were 28.8+/-5.9 years, 27.1 +/- 7.0 kg/m(2) and 0.85+/-0.06, respectively. The prevalence of MS was 35.3%. Age, BMI, waist circumference and all metabolic parameters were higher in PCOS women with MS than in those without MS. MS prevalence increased with age, BMI and insulin resistance as determined by homeostasis model assessment (HOMA-IR), but not with adiponectin after BMI adjustment. CONCLUSIONS: According to the IDF criteria, one-third of the PCOS women had MS. This study also showed that age, BMI and HOMA-IR are important risk factors for MS.     

Serum levels of prostate-specific antigen and androgens after nasal administration of a gonadotropin releasing hormone-agonist in hirsute women.

We aimed to determine whether ovarian suppression affects the production rate of prostate-specific antigen (PSA) in hirsute women. A total of 34 hirsute women who had a modified Ferriman-Gallwey (FG) score of > or = 7 and 14, non-hirsute women as the control group were recruited for this prospective controlled study. Serum samples for evaluation of basal hormones and PSA concentration were collected and were analyzed by commercial kits and chemiluminescent enzyme immunoassay. The hirsute women were given 400 microg/day nafarelin acetate for 3 months. Basal hormones, PSA levels and FG scores were then assessed. ANOVA and Tukey test were used to compare differences in means between the hirsute and the non-hirsute group at the beginning of the study. Student's t test, Tukey test and repeated measures variance analysis were used to evaluate differences in the study group and between the women with polycystic ovary syndrome (PCOS) and idiopathic hirsutism after gonadotropin releasing hormone (GnRH)-agonist administration. Statistical significance was assumed with a value of p < 0.05. PCOS and idiopathic hirsutism were diagnosed in 58.8% and 41.2% of 34 hirsute women, respectively. Age and body mass index (BMI) were similar in the hirsute and the control group (p > 0.05). FG scores in the PCOS group (20.3 +/- 1.7) were statistically similar to those of the group with idiopathic hirsutism (17.6 +/- 1.7) (p > 0.05). The non-hirsute women had significantly lower serum PSA concentrations than the hirsute group (p < 0.001).The basal mean level of PSA was 0.095 +/- 0.001 in the PCOS, 0.0061 +/- 0.009 in the idiopathic hirsute and 0.0040 +/- 0.004 ng/ml in the control group. No significant difference in the mean PSA levels was noted between the PCOS and the idiopathic hirsute subgroups before and after GnRH agonist treatment (0.0096 +/- 0.01 and 0.0051 +/- 0.032 ng/ml, respectively) (p > 0.05). FG scores, testosterone, 17alpha-hydroxyprogesterone and dehydroepiandrosterone sulfate levels were significantly decreased in the hirsute group following treatment (p < 0.001). PSA levels in hirsute women were higher than in non-hirsute women and independent of BMI, age and androgen deprivation. PSA concentration may be mediated through extragonadal sites and possibly through a long-standing hyperandrogenemic environment such as in PCOS and idiopathic hirsutism. Further investigation as to the significance of PSA in women with hirsutism and whether antiandrogens directly act to inhibit biosynthesis of PSA is warranted.     

Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome

Background.?The dichotomy between ovulation rates and pregnancy rates for women with polycystic ovary syndrome (PCOS) treated with clomiphene citrate (CC) prompted the present study to determine the effect of CC on endometrial maturity.

Methods.?Retrospective case–control study of anovulatory women with PCOS (n = 119) on their third ovulatory cycle of CC and controls, 238 healthy regularly ovulating women whose partners had abnormal sperm, all of whom had an endometrial biopsy in the late luteal phase.

Results.?Endometrial histology classified according to the classical Noyes criteria revealed out-of-phase endometrium in 19/119 (16%) of the CC group compared with 7/238 (3%) in controls (p < 0.0001). Duration of the luteal phase was not influenced by histological age of the endometrium. Endometrial biopsy performed during 138 conception cycles extracted from the database did not increase the miscarriage rate significantly (23.9%).

Conclusions.?CC treatment significantly increases the prevalence of out-of-phase endometrium and this could explain, in part, the large difference between ovulation and pregnancy rates. There was no correlation between the results of the endometrial biopsy and the duration of the luteal phase. Performing an endometrial biopsy during a conception cycle does not seem to have a significant negative effect on the outcome of pregnancy.     

多囊卵巢综合征患者糖耐量异常及相关因素分析

目的:探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者糖耐量受损(IGT)和2型糖尿病(NIDDM)的发生率及其高危因素。方法:回顾分析101例PCOS患者口服葡萄糖耐量(OGTT)实验后的临床资料,多因素logistic回归分析探讨PCOS患者糖耐量异常的危险因素。结果:(1)根据葡萄糖耐量实验结果分成糖耐量正常组(NGT)77例与糖耐量异常组(AGT)24例(IGT22例、NIDDM2例),IGT发生率21.8%,NIDDM发生率1.98%;(2)AGT组的年龄、腰臀比(WHR)、体重指数(BMI)、睾酮(T)、空腹血糖(FPG)、2h血糖增高,与NGT组的差异有统计学意义(P<0.05),空腹胰岛素(FINS)、2h胰岛素、稳态模式胰岛素抵抗指数(HOMA-IR)升高,差异有统计学意义(P<0.01)。初潮年龄、黄体生成素/卵泡刺激素(LH/FSH)两组差异无统计学意义(P>0.05);(3)AGT组糖尿病家族史发生率高于NGT组,差异有统计学意义(P<0.01);(4)多因素logistic回归分析显示,年龄、BMI、2型糖尿病家族史、空腹胰岛素升高为PCOS糖耐量异常的高危因素。结论:多囊卵巢综合征发生糖耐量受损、糖尿病的危险性增加,葡萄糖耐量2h血糖水平是监测PCOS糖耐量异常的较好指标。年龄、BMI、2型糖尿病家族史、空腹胰岛素升高是PCOS糖耐量异常发生的危险因素。     

Does ovarian blood flow distinguish between ovulatory and anovulatory patients with polycystic ovary syndrome?

OBJECTIVE: The purpose of this study was to determine whether parameters of ovarian blood flow distinguish between women with polycystic ovary syndrome (PCOS) who ovulate and those who are anovulatory. STUDY DESIGN: This was a prospectively enrolled trial, carried out as a cross-sectional comparison of 12 ovulatory patients with PCOS and 20 matched subjects with classic PCOS and 10 healthy control subjects. Hormonal parameters and ovarian blood flow by color flow Doppler imaging were obtained in the early follicular phase. RESULTS: Characteristic elevations in luteinizing hormone (LH) and androgens were found in both groups with PCOS compared with control groups. Women with anovulatory PCOS had high insulin levels and lower Quantitative Insulin-Sensitivity Check Index (QUICKI) values compared with women with ovulatory PCOS, although both groups had values that were different from healthy control subjects (P<.01). Ovarian volume was similar in the two groups with PCOS, but pulsatility and resistance indices were lower in anovulatory PCOS (P<.01) compared with ovulatory PCOS and control subjects, who had similar findings. Insulin correlated negatively with the resistance index and QUICKI correlated positively (r=0.653, P<.01). There was a negative correlation between the resistance index and unbound testosterone (r=-0.5, P<.05). CONCLUSION: These data suggest that differences in ovarian blood flow in anovulatory versus ovulatory women with PCOS and that hormonal factors, including insulin resistance, may influence this relationship. The alterations in blood flow in anovulatory PCOS may contribute toward or result from anovulation.     

Impaired uterine perfusion associated with metabolic disorders in women with polycystic ovary syndrome

BACKGROUND: Risk factors for cardiovascular disease, including chronic anovulation, obesity, hyperandrogenism, hyperinsulinemia, and dyslipidemia, are commonly observed in women with polycystic ovary syndrome (PCOS). We evaluated uterine perfusion and its correlation with clinical and biochemical parameters in women with PCOS. METHODS: We performed a pulsed Doppler study on uterine arterial blood flow in 25 women with PCOS and 45 control women with regular menstrual cycles. PCOS was diagnosed based on oligomenorrhea, polycystic ovaries determined by means of ultrasonography, and elevated luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio. RESULTS: Women with PCOS had a significantly higher body mass index (BMI) and serum testosterone, and showed insulin resistance and dyslipidemia, including increased total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), and decreased high-density lipoprotein-cholesterol (HDL-C). The uterine arterial pulsatility index (PI) in women with PCOS was significantly higher than that in the control women during the follicular phase. The PI was correlated with BMI, LH/FSH ratio, or LDL-C/HDL-C ratio, whereas it was inversely correlated with the HDL-C level. Women with PCOS had reduced endometrial thickness and elevated uterine arterial PI in the luteal phase, in which implantation occurs. CONCLUSIONS: Elevation of uterine arterial blood flow resistance is associated with risk factors for cardiovascular events. Furthermore, the impaired uterine perfusion in the luteal phase may cause endometrial dysfunction in women with PCOS.     

Endometrial abnormality in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Although the clinical and biochemical features are heterogeneous with individuals, the most widely accepted clinical characteristics of PCOS are oligo- or anovulation combined with hyperandrogenism. With the higher rate of implantation failure after induction of ovulation or higher risk of spontaneous miscarriage after pregnancy, the reduced fertility is apparently attributed not only to anovulation but also to endometrial dysfunction in patients with PCOS. Here we review the features of the endometrial abnormalities in women with PCOS. The ability to improve the endometrial functions is of potential therapeutic targets to increase reproductive outcome of women with PCOS.     

Management of anovulatory infertility associated with polycystic ovary syndrome: tamoxifen citrate an effective alternative compound to clomiphene citrate.

Clomiphene citrate (CC) is widely used as first-line treatment for ovulation induction in anovulatory women with polycystic ovary syndrome (PCOS). Tamoxifen citrate (TMX), another non-steroidal selective estrogen receptor modulator, may also be effective on the resumption of ovulation in these women. The aim of this controlled observational study was to compare the efficacy and safety of ovulation induction with TMX versus CC in anovulatory infertile women with PCOS. A total of 102 consecutive women (mean age+/-SD: 31+/-3.6 years; range: 26-38) with PCOS were studied. Following a spontaneous or progesterone-induced withdrawal bleed, women received either 50 mg daily of CC (days 2-6) or 20 mg daily of TMX (days 2-5). In case ovulation failed to occur, the dose was sequentially increased to 100 mg daily of CC and 40 mg daily of TMX, respectively. Serum progesterone levels were measured on cycle day 21 to monitor the ovulation pattern. The overall ovulation rate was significantly higher in women who received TMX compared with those who received CC (61/98, 62.2% vs. 60/127, 47.2%, p=0.03). Although not statistically significant, the pregnancy rate per ovulatory cycle was higher in the TMX group compared to the CC group (14/61, 22.9% vs. 11/60, 18.3%, respectively). All pregnancies were single and there were no side-effects in either group of treatment. Collectively, these data demonstrate that TMX is a safe and effective agent, and a suitable alternative to CC for anovulatory infertility in women with PCOS.     

Polycystic Ovary Syndrome: Fertility Management

Polycystic ovary syndrome (PCOS) is characterized by a series of symptoms, including oligomenorrhea or amenorrhea anovulation or infertility; it is associated with insulin resistance and compensatory hyperinsulinemia. Several treatment options are available for women with anovulatory infertility related to PCOS. Clomiphene citrate (CC) is the first-choice for induction of ovulation in PCOS patients. Laparoscopic ovarian drilling (LOD) or gonadotropin ovarian stimulation can be offered after failure of CC to achieve pregnancy. Hyperinsulinemia related to PCOS can be corrected by weight loss or insulin-sensitizing agents, such as metformin, which alone or in combination with other agents are capable of restoring ovulation. Only very limited clinical data are available on the use of letrozole at present, so letrozole cannot be recommended for routine use in ovulation induction. When all treatments fail, in vitro fertilization and embryo transfer (IVF/ET) can be tried and can have excellent results. Many treatment options available today ensure that the majority of women who are subfertile due to PCOS can be treated successfully.     

Review of nonsurgical and surgical treatment and the role of insulin-sensitizing agents in the management of infertile women with polycystic ovary syndrome

OBJECTIVES: To review the nonsurgical and surgical treatment and the role of insulin-sensitizing agents in the management of anovulatory infertile women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: The search term of subfertile women with anovulation and PCOS was used for identification of randomized controlled trials. Nonrandomized controlled studies were identified through computer MEDLINE and EMBASE searches for the years 1980-2002. RESULTS: For obese PCOS women weight loss of > 5% of pretreatment weight restores menstrual regularity in 89%, of whom 30% achieved spontaneous pregnancy. It was estimated that 75-80% of anovulatory PCOS women will respond to clomiphene citrate (CC) and 35-50% will achieve pregnancy. For CC-resistant PCOS women (20-25%), CC + metformin (1.5 g/day) for 3-6 months has a 70% chance of restoration of regular menses and ovulation, and a 23% chance of pregnancy. Laparoscopic ovarian drilling (LOD) can be offered to CC-resistant PCOS women. There was no statistically significant difference in the ovulation rate following LOD with electrocoagulation and laser [83% vs. 77.5%; odds ratio (OR) 1.4; 95% CI 0.9-2.1], while there was a significantly higher cumulative pregnancy rate at 12 months after surgery (65% vs. 54.5%; OR 1.5; 95% CI 1.1-2.1). CONCLUSION: Diet and exercise followed by CC should be used for nonsurgical ovulation induction. For CC-resistant PCOS women, metformin may be included in a stepwise approach before a surgical approach. LOD with electrocautery is superior to laser drilling and gonadotropin therapy.     

The pathogenesis of infertility and early pregnancy loss in polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) frequently present with reproductive dysfunction. Ovarian function might be disturbed, with resultant abnormal folliculogenesis and steroidogenesis and, although it is difficult to define the exact pathogenesis of anovulation, many possible mechanisms have been postulated. Folliculogenesis in anovulatory women with PCOS is characterized by failure of dominance and the ovary has multiple small follicles, which are arrested but capable of steroidogenesis. Abnormalities in gonadotrophin and insulin secretion and disordered paracrine function have been identified. Women with PCOS have an increased prevalence of miscarriage, both after spontaneous and induced ovulation. Hypersecretion of LH, hyperandrogenaemia and hyperinsulinaemia have all been investigated as possible causes of PCOS. It is likely that these factors are interlinked and together might result in disordered ovarian and endometrial function. Multiple other possible abnormalities have been postulated as contributory factors in the reproductive failure. These include decreased plasminogen activator inhibitor activity, endothelial dysfunction and obesity. Ideally, therapy should target the underlying disorders but at present data are inadequate and further investigations are essential before therapeutic recommendations are truly based on an understanding of the pathophysiology.     

多囊卵巢综合征的分型探讨

目的探讨不同分型方法用于多囊卵巢综合征(PCOS)分型时,其临床、内分泌、糖和脂代谢紊乱的特征,以指导临床治疗。方法将192例PCOS患者按鹿特丹修订的分型标准分为A组110例[长期无排卵;具有雄激素水平升高的临床和(或)生化依据;卵巢增大,单侧卵巢体积大于10ml或超声下至少有直径2~9mm的小卵泡≥12个;并排除其他疾病所致的雄激素增多症];B组46例[长期无排卵;具有雄激素水平升高的临床和(或)生化依据,并排除其他疾病所致的雄激素增多症];C组36例(长期无排卵;卵巢增大,单侧卵巢体积>10ml或超声下至少有直径2~9mm的小卵泡≥12个;并排除其他疾病所致的雄激素增多症)。又按肥胖与否将192例患者分为肥胖型PCOS70例(OB-PCOS组)和非肥胖型PCOS122例(NOB-PCOS组)。以同期就诊、年龄及体重匹配、基础体温(BBT)双相的输卵管因素不孕症患者104例为对照组。采用多毛评分及痤疮评分法对192例患者进行评分并测定其血清生殖激素、胰岛素、血脂及血糖的水平。采用空腹胰岛素(FINS)及胰岛素曲线下面积(IAUC)评估高胰岛素血症;采用稳态模型的胰岛素抵抗指数(HOMA-IR)评估胰岛素抵抗;糖耐量试验(OGTT)及葡萄糖曲线下面积(GAUC)评估糖代谢状态。采用游离雄激素指数(FAI)评估雄激素增多症及雄激素生物学活性。结果(1)评分:多毛评分A组为(7·1±1·8)分,B组为(6·9±1·9)分,均明显高于C组的(3·9±1·5)分,差异有统计学意义(P<0·01);痤疮评分A组为(0·9±1·1)分,B组为(0·7±1·1)分,均高于C组的(0·2±0·4)分,差异也有统计学意义(P<0·01);OB-PCOS组与NOB-PCOS组多毛评分及痤疮评分比较,差异均无统计学意义(P>0·05)。(2)黑棘皮症:A组的发生率为21·8%(20/110),B组的发生率为19·6%(9/46),C组的发生率为0(0/36),A、B组黑棘皮症的发生率均明显高于C组,差异有统计学意义(P<0·01);OB-PCOS组黑棘皮症的发生率为35·0%(25/70),NOB-PCOS组为6·0%(8/122),两组比较,差异有统计学意义(P<0·01)。(3)生殖激素:①FAI:A组为2·6±1·8,B组为2·2±1·4,均明显高于C组的1·2±0·6,差异有统计学意义(P<0·01);OB-PCOS组FAI为3·4±1·8,NOB-PCOS组为1·8±1·2,两组比较,差异也有统计学意义(P<0·01)。②黄体生成素(LH)与卵泡刺激素(FSH)的比值:NOB-PCOS组LH/FSH为2·4±1·1,明显高于OB-PCOS组的1·5±0·8,差异有统计学意义(P<0·01),A、B、C3组比较,差异无统计学意义(P>0·05)。(4)生化指标:OB-PCOS组FINS、HOMA-IR、IAUC、GAUC、甘油三酯(TG)分别为(17±11)mIU/L、1·0±0·6、(249±128)mIU·h·L-1、(19·6±7·8)mmol·h·L-1和(1·9±1·0)mmol/L,均明显高于NOB-PCOS组的(8±10)mIU/L、0·1±0·8、(132±81)mIU·h·L-1、(16·7±3·4)mmol·h·L-1和(1·1±0·7)mmol/L,分别比较,差异均有统计学意义(P均<0·01);A、B、C3组间上述生化指标比较,差异均无统计学意义(P>0·05)。结论鹿特丹修订的PCOS分型方法可反映疾病的基本特征;而肥胖分型不仅能反映病情的基本特征和严重程度,而且对代谢并发症的风险评估具有重要意义。