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Infertility is one of the important problems in the modern world. Male infertility is characterized by several clinical manifestations, including low sperm production (oligozoospermia), reduced sperm motility (asthenozoospermia), and abnormal sperm morphology (teratozoospermia). WDR4, known as Wuho, controls fertility in Drosophila. However, it is unclear whether WDR4 is associated with clinical manifestations of male fertility in human. Here, we attempted to determine the physiological functions of WDR4 gene. Two cohorts were applied to address this question. The first cohort was the general population from Taiwan Biobank. Genomic profiles from 68,948 individuals and 87 common physiological traits were applied for phenome-wide association studies (PheWAS). The second cohort comprised patients with male infertility from Wan Fang Hospital, Taipei Medical University. In total, 81 male participants were recruited for the genetic association study. Clinical records including gender, age, total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total sperm number, sperm motility, and sperm morphology were collected. In the first cohort, results from PheWAS exhibited no associations between WDR4 genetic variants and 87 common physiological traits. In the second cohort, a total of four tagging single-nucleotide polymorphisms (tSNPs) from WDR4 gene (rs2298666, rs465663, rs2248490, and rs3746939) were selected for genotyping. We found that SNP rs465663 solely associated with asthenozoospermia. Functional annotations through the GTEx portal revealed the correlation between TT or TC genotype and low expression of WDR4. Furthermore, we used mouse embryonic fibroblasts cells from mwdr4 heterozygous (+/‒) mice for functional validation by western blotting. Indeed, low expression of WDR4 contributed to ROS-induced DNA fragmentation. In conclusion, our results suggest a critical role of WDR4 gene variant as well as protein expression in asthenozoospermia.

Bisphenol A (BPA), an endocrine-disrupting chemical, is capable of producing reproductive toxicity. BPA results in mitochondrial DNA (mtDNA) deletion and mitochondrial dysfunction; however, the effect of BPA on the mitochondria of ovarian granulosa cells is not clear. Further, 1,25-dihydroxyvitamin D3 (1,25D3) may play a role in reproduction, because its receptor, VDR, contributes to the inhibition of oxidative stress and predominantly exists in the nuclei of granulosa cells. Hence, the role of 1,25D3 in BPA-mediated effects on mitochondrial function was examined in this study. Primary rat granulosa cells treated with BPA, 1,25D3, or both were subjected to molecular/biochemical assays to measure cell survival, mtDNA content, mtDNA deletion, superoxide dismutase activity, levels of proteins related to mitochondrial biogenesis, and mitochondrial function. We found that cell viability was dose-dependently reduced and reactive oxygen species (ROS) levels were increased by BPA treatment. BPA administration elevated Mn-superoxide dismutase (MnSOD) expression but negatively regulated total SOD activity. 1,25D3 treatment alone increased 17β-estradiol secretion, ATP production, and cellular oxygen consumption. In cells treated with both agents, 1,25D3 enhanced BPA-induced MnSOD protein upregulation and blocked the BPA-mediated decline in total SOD activity. Furthermore, 1,25D3 attenuated BPA-mediated mtDNA deletion but showed no effect on BPA-induced increases in mtDNA content. Although BPA had no influence on the levels of peroxisome proliferator-activated receptor-γ coactivator-1 α, nuclear respiratory factor-1, mitochondrial transcription factor A, or cytochrome c oxidase subunit IV, 1,25D3 plus BPA markedly increased mitochondrial biogenesis-related protein expression via the PI3K-Akt pathway. Moreover, BPA-mediated negative regulation of cytochrome c oxidase subunit I levels and 17β-estradiol secretion was attenuated by 1,25D3 pre-treatment. Our results suggest that 1,25D3 attenuates BPA-induced decreases in 17β-estradiol and that treatment with 1,25D3 plus BPA regulates granulosa cell mitochondria by elevating mitochondrial biogenesis-related protein levels.

Background: The oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types; however, the underlying mechanism of HPS/FGL1 in the KRAS mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear. Methods: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a KRAS-wild-type PDAC cell line (BxPC-3), and KRAS-mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. HEK293T cells were transiently transfected with corresponding KRAS-expressing plasmids to examine the level of HPS expression with KRAS activation. We knocked-down HPS/FGL1 using lentiviral vectors in SUIT-2 cells and measured the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenicity assays. Furthermore, a lipidomic analysis was performed to profile changes in lipid metabolism after HPS/FGL1 knockdown. Results: We found that the HPS/FGL1 level was significantly upregulated in KRAS-mutated PDAC cells and was involved in KRAS/phosphorylated (p)-signal transduction and activator of transcription 3 (STAT3) signaling, and the knockdown of HPS/FGL1 in SUIT-2 cells decreased cell proliferation through increasing G2/M cell cycle arrest and cyclin B1 expression. In addition, the knockdown of HPS/FGL1 in SUIT-2 cells significantly increased omega-3 polyunsaturated fatty acids (PUFAs) and EPA production but not docosahexaenoic acid (DHA). Moreover, EPA treatment in SUIT-2 cells reduced the expression of de novo lipogenic protein, acetyl coenzyme A carboxylase (ACC)-1, and decreased p-STAT3 and HPS/FGL1 expressions, resulting in the suppression of cell viability. Conclusions: Results of this study indicate that HPS is highly expressed by KRAS-mutated PDAC cells, and HPS/FGL1 plays a crucial role in altering lipid metabolism and increasing cell growth in pancreatic cancer. EPA supplements could potentially inhibit or reduce ACC-1-involved lipogenesis and HPS/FGL1-mediated cell survival in KRAS-mutated pancreatic cancer cells.

Background: The oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types, however, the underlying mechanism of HPS/FGL1 in the KRAS mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear. Methods: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a KRAS-wild-type PDAC cell line (BxPC-3), and KRAS-mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. HEK293T cells were transiently transfected with corresponding KRAS-expressing plasmids to examine the level of HPS expression with KRAS activation. We knocked-down HPS/FGL1 using lentiviral vectors in SUIT-2 cells and measured the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenicity assays. Furthermore, a lipidomic analysis was performed to profile changes in lipid metabolism after HPS/FGL1 knockdown. Results: We found that the HPS/FGL1 level was significantly upregulated in KRAS-mutated PDAC cells and was involved in KRAS/phosphorylated (p)-signal transduction and activator of transcription 3 (STAT3) signaling, and the knockdown of HPS/FGL1 in SUIT-2 cells decreased cell proliferation through increasing G2/M cell cycle arrest and cyclin B1 expression. In addition, the knockdown of HPS/FGL1 in SUIT-2 cells significantly increased omega-3 polyunsaturated fatty acids (PUFAs) and EPA production but not docosahexaenoic acid (DHA). Moreover, EPA treatment in SUIT-2 cells reduced the expression of de novo lipogenic protein, acetyl coenzyme A carboxylase (ACC)-1, and decreased p-STAT3 and HPS/FGL1 expressions, resulting in the suppression of cell viability. Conclusions: Results of this study indicate that HPS is highly expressed by KRAS-mutated PDAC cells, and HPS/FGL1 plays a crucial role in altering lipid metabolism and increasing cell growth in pancreatic cancer. EPA supplements could potentially inhibit or reduce ACC-1-involved lipogenesis and HPS/FGL1-mediated cell survival in KRAS-mutated pancreatic cancer cells.

The aim of this study was to investigate the biomarkers of insulin resistance in non-obese women.This was a retrospective study.A total 229 non-obese women (Body mass index: BMI 25) were evaluated.Serum levels of various androgens, cardiovascular risk and metabolic components.There were no significant differences in the prevalence of polycystic ovary syndrome (PCOS), hyperprolactinemia, or premature ovarian failure (POF) between the non-obese women with and without insulin resistance. Non-obese women with insulin had significantly higher serum thyroid stimulation hormone (TSH) levels and resistin and lower serum adiponectin levels than non-obese women without insulin resistance; however, the inflammatory biomarkers and serum androgen levels did not differ between the two groups. Furthermore, using step-wise multivariate regression analysis applied by the risk factors listed above, TSH was the only predictive factor for insulin resistance in non-obese reproductive-aged women.Thyroid function should play an important role in developing insulin resistance for non-obese women. Serum androgens and inflammation might not contribute to insulin resistance in these women.

Bisphenol A (BPA), an endocrine-disrupting chemical, is capable of producing reproductive toxicity. BPA results in mitochondrial DNA (mtDNA) deletion and mitochondrial dysfunction; however, the effect of BPA on the mitochondria of ovarian granulosa cells is not clear. Further, 1,25-dihydroxyvitamin D

Chemotherapy damages the reproductive system by enhancing apoptosis, and evidence suggests that targeted anti-apoptotic therapy may preserve fertility in patients receiving chemotherapy. To investigate the protective effect of sphingosine-1-phosphate (S1P) on chemotherapeutic agent-induced ovarian gonadotoxicity, busulfan-treated female mice were pre-treated with low (0.5 mM) and high (2.0 mM) doses of S1P or vehicle 1 h before busulfan injection. In the S1P groups, each mouse was injected with low-dose S1P in one ovary and high-dose S1P in the contralateral ovary. Four weeks later, the ovaries were removed for histological and biochemical examinations. Caspase 3 immunoreactivity was greater in mice treated with busulfan compared with mice pre-treated with S1P, in which more primordial follicles were observed (P < 0.05). The mRNA level of anti-Mullerian hormone was higher in mice pre-treated with S1P than those that received busulfan only, indicating a better ovarian function in mice pre-treated with S1P. No difference was observed in the levels of growth differentiation factor-9 among all groups. In conclusion, S1P protects primordial follicles from chemotherapy-induced gonadotoxicity, and may partially preserve ovarian function.

Anti-Müllerian hormone (AMH) level has been found to be a useful marker of ovarian reserve, and a predictor of poor and hyper-responses in patients undergoing controlled ovarian stimulation (COS). The study aimed to determine the association of serum AMH level with achieving pregnancy in patients undergoing COS with intrauterine insemination. The cross-sectional study investigated 204 patients who underwent COS with intrauterine insemination at the Obstetrics and Gynecology Department of Taipei Medical University Hospital, from January 2011 to March 2012. The medical records of these patients were reviewed, and serum AMH levels were evaluated for association with successful clinical pregnancy. The AMH level in the patients who achieved clinical pregnancy was significantly higher than in patients who did not (median 2.7 vs 2.0 ng/ml, p = 0.005). Controlling for factors affecting infertility, AMH level had a significant independent influence on outcome; a higher AMH level was associated with a decreased risk of a non-pregnant outcome (odds ratio, OR = 0.895, p = 0.026). In patients undergoing COS and intrauterine insemination, a low AMH level is associated with a decreased chance of a clinical pregnancy, and this association remains irrespective of the presence or absence of endometriosis.

Objective Menstrual irregularity is one of the major complaints in women of reproductive age. The aim of this study was to evaluate the complications in women with different menstrual disturbances. Materials and methods This is a retrospective study. A total of 576 women were screened first, and 470 women were included later [257 women with oligo/amenorrhea (149 hyperandrogenic and 108 nonhyperandrogenic women) and 213 normocyclic controls]. Endocrine and metabolic parameters and insulin resistance were compared among different menstrual patterns. Results The average duration of menstrual cycle length was positively correlated with age, levels of androgens and prolactin, lipid profiles, and the parameters of insulin resistance. Hyperandrogenic women with amenorrhea had higher levels of androgens and more lipid profiles disorders than hyperandrogenic women with oligomenorrhea. However, nonhyperandrogenic women with amenorrhea had a degree of insulin resistance and metabolic disturbance similar to that of nonhyperandrogenic women with oligomenorrhea. Interestingly, for women with normal prolactin levels, serum prolactin levels were significantly lower in amenorrhea than oligomenorrhea in both hyperandrogenic and nonhyperandrogenic groups. Conclusion The degree of menstrual disturbances does not correlate with the severity of insulin resistance and metabolic disturbances in women without excess levels of androgen. For women with normal prolactin levels, amenorrheic patients had significantly lower serum prolactin levels than oligomenorrheic patients.

Objective Hyperhomocysteinaemia is a well-established risk factor for cardiovascular disease. This study investigated the relationship between hyperhomocysteinaemia and factors related to polycystic ovary syndrome (PCOS). Study design Case–control study. Three hundred and thirty-nine women were included; of these, 84 had hyperhomocysteinaemia (homocysteine >12.4 μmol/l) and 255 had normal homocysteine levels. Homocysteine, high-sensitivity C-reactive protein, insulin resistance, metabolic disturbance and PCOS-related disturbance were evaluated. The clinical and biochemical characteristics of women with hyperhomocysteinaemia and normal homocysteine levels, including insulin resistance, metabolic disturbance and PCOS-related disturbance, were compared. Results Correlation was found between serum homocysteine level and serum total testosterone level and diastolic blood pressure. No correlation was found between serum homocysteine level and age, body mass index, insulin resistance and lipid profile. Women with hyperhomocysteinaemia had a significantly higher risk for biochemical hyperandrogenaemia and higher serum total testosterone levels than women with normal homocysteine levels. The prevalence rates of PCOS, oligo-amenorrhoea, polycystic ovary morphology and metabolic disturbance did not differ between the two groups. The parameters of insulin resistance and lipid profiles were similar between the two groups, and signs of clinical hyperandrogenism (hirsutism and the modified Ferriman–Gallwey score) did not differ between the two groups. Logistic regression analysis found a significant association between hyperandrogenaemia and hyperhomocysteinaemia (odds ratio 2.24, 95% confidence interval 1.26–4.01). Conclusions For women with PCOS, an elevated serum total testosterone level is the main factor associated with hyperhomocysteinaemia. The association between biochemical hyperandrogenism and hyperhomocysteinaemia may contribute to cardiovascular risk for women with PCOS.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women. The diagnosis of PCOS is mainly based on the following three components: (1) hyperandrogenism, (2) oligo-amenorrhea, and (3) the observation of polycystic ovaries on a sonogram. The comorbidities may include insulin resistance, type II diabetes mellitus, hypertension and cardiovascular disease. Importantly, the diagnostic criteria and complications related to PCOS are age-dependent. Androgen production in women may decrease because of ovarian aging or decreased production by the adrenal glands over time. The prevalence of hirsutism and acne decreases with age. Ovarian volume and follicle number also decrease with age, with the age-related decrease in follicle number seemingly greater than that of ovarian volume. Aging may also be associated with increased risk of insulin resistance and metabolic disturbances. Therefore, these age-related changes may affect the observed incidence and complications of PCOS. In adolescent patients, the criteria described above pose particular diagnostic problems because the characteristics of normal puberty often overlap with the signs and symptoms of PCOS. Hyperandrogenism and chronic anovulation are the primary disturbances in younger women with PCOS; whereas, obesity, insulin resistance, and metabolic disturbances are predominant in older women with PCOS. The deterioration of insulin resistance during the reproductive life of women with PCOS appears to be mainly attributable to the increase in obesity. Therefore, if body weight could be controlled properly, younger hyperandrogenic PCOS women might reduce their risk of insulin resistance and metabolic disturbances later in life.

This study is designed to evaluate the relationship between endometrial thickness and clinical/biochemical parameters in women with chronic anovulation. One hundred and twenty women with ovulatory dysfunction were prospective included, endometrial thickness and endocrine and metabolic parameters were measured. The interval between the examination day and the day of the most recent menstrual bleeding (the anovulatory interval) for the studied subject was an average of 145 ± 186 days. The endometrial thickness averaged 7.1 ± 3.2 mm. Correlation analyses revealed that the endometrial thickness was positively correlated with body mass index but was not correlated with age, serum androgens, or estradiol (E2) levels. We further classified the subjects into two groups based on endometrial thickness: Group A, endometrial thickness

Androgen is a steroid hormone associated with high blood pressure (BP). The effect of androgen on BP in females is unknown.Androgen, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 were evaluated in females with menstruation disorders (n = 135, 28 ± 5 years old) and normal BP, pre-hypertension, stage 1 hypertension, and stage 2 hypertension.Normal-BP (n = 57), pre-hypertension (n = 44), stage-1-hypertension (n = 21), and stage-2-hypertension (n = 13) females had similar androgen (3.3 ± 1.5, 2.7 ± 1.2, 3.1 ± 1.4, and 3.5 ± 1.3 ng/ml, p0.05) and IL-6 levels (1.7 ± 2.2, 1.9 ± 2.6, 1.3 ± 1.2 and 2.4 ± 3.3 pg/ml, p0.05). However, normal BP females had lower MMP-9 (609 ± 307 versus 891 ± 385 ng/ml, p0.05) than stage-1-hypertension females. In addition, normal BP females had lower VEGF (166 ± 103 versus 255 ± 139, 272 ± 128 and 301 ± 216 pg/ml, p0.05) than the other three groups. In normal-androgen females, VEGF levels were similar among the four groups. However, in high-androgen females, normal BP groups had lower VEGF levels than pre-hypertension, stage-1, and stage-2 hypertension groups (166 ± 94 versus 294 ± 153, 281 ± 160 and 357 ± 253 p0.05).Androgen can modulate growth factors and extracellular matrix proteins, which may contribute to the pathophysiology of hypertension in young females.

Objective To evaluate the contribution to glucose intolerance and metabolic syndrome of obesity combined with the diagnostic criteria of polycystic ovary syndrome (PCOS). Design Prospective study. Setting University teaching hospital from 31 August 2010 to 31 August 2011. Population Two hundred and twenty women with PCOS and seventy normal control women. Methods The clinical and biochemical characteristics of women with PCOS and control women were evaluated. Main outcome measures. The impact of obesity, hyperandrogenism, oligo-anovulation and polycystic ovary morphology on impaired glucose tolerance and metabolic disturbances. Results Obese women with PCOS had significantly higher insulin resistance than obese normal control women. Logistic regression analysis showed that obesity was the only factor that predicted impaired glucose tolerance and metabolic syndrome. Use of the area under the receiver operating characteristic curve (AUROC) for the body mass index to predict impaired glucose tolerance and metabolic syndrome was more accurate than AUROCs for serum total testosterone level and the average menstrual interval. Conclusions Body weight status was the major factor determining the risk of impaired glucose tolerance and metabolic syndrome in women with PCOS. Obesity should be treated as the major factor determining long-term health consequences associated with PCOS.

Objective To determine the feasibility of bioluminescence imaging (BLI) to evaluate the efficiency of germ cell transplantation in vitro and in vivo in fertility preservation for infertile male mice. Design Transgenic mouse model. Setting University-based teaching hospital. Animal(s) Transgenic mice. Intervention(s) Busulfan was used to induce testicular failure in 3-week-old immature FVB/NJNarl wild-type recipient mice. At 8 weeks of age they received hemizygotic germinal cells from 3-week-old immature male FVB/N-Tg (PolII-luc) Ltc strain transgenic donor mice, transplanted into the seminiferous tubules. Main Outcome Measure(s) Isolated germinal cells were suspended in multiwell plates with the bioluminescent substrate d-luciferin in excess to quantify viable germ cells in vitro. Quantitatively in vivo BLI was applied to demonstrate the efficiency and success of transplantation and BLI of live pups born from wild-type in vivo. Result(s) Live birth pup of FVB/N-Tg (PolII-luc) Ltc transgenic mouse were born and imaged by bioluminescence after mating FVB/NJNarl female wild-type and male wild-type infertile recipient 4–6 months after transplantation of germinal cells of FVB/N-Tg (PolII-luc) . Conclusion(s) The BLI could be applied successfully to this transgenic small animal model. It proved a useful tool for quantifying germ cells in vitro and for assessing the efficacy of germ cell transplantation in vivo.

Objective Sonographic gray-scale histogram is used to assess the endometrial changes in the different phases of the menstrual cycle. The objective was to examine the usefulness of a gray-scale histogram and computer-assisted image analysis software in assessing normal physiologic states of the endometrium with sonography. Materials and Methods Thirty-eight patients, who visited the Taipei Medical University-Wan Fang Hospital and matched the eligibility criteria, were categorized into one of three groups: (1) menstrual phase; (2) follicular phase; and (3) luteal phase of the menstrual cycle. Ultrasonography of the uterus was performed on each patient and the endometrium was analyzed with ImageJ image analysis software. Results A statistically significant difference in signal intensity scores of the gray-level histogram, represented as mj, was found among the three groups. Conclusion Sonographic images analyzed by using computer-assisted image analysis software and gray-level histogram are proven to be useful in assessing the physiological state of the endometrium.

Polycystic ovary syndrome (PCOS) is an extremely common disorder in women of reproductive age. Diagnosis of PCOS is principally based on clinical and physical findings. Diagnostic criteria and PCOS definitions used by clinicians and researchers are almost as heterogeneous as the syndrome. Of those diagnosed with PCOS using the 2003 Rotterdam criteria, 61% fulfilled the 1990 National Institutes of Health criteria for unexplained hyperandrogenic chronic anovulation. Patient populations with the new phenotypes have less severe ovulatory dysfunction and less androgen excess than patients diagnosed using the 1990 National Institutes of Health criteria. These findings might be common across all female populations with PCOS, in Asian or Western countries. Data for clinical hyperandrogenism indicates that the prevalence of hirsutism in Taiwanese PCOS women is lower than that for Caucasian/Western women. The extent of metabolic abnormalities in women with PCOS may vary with phenotype, age and ethnicity. Obesity represents a major risk factor for metabolic syndrome and insulin resistance. Approximately 40–50% of all women with PCOS are overweight or obese. Obese subjects with PCOS have a higher risk of developing oligomenorrhea, amenorrhea and biochemical hyperandrogenemia than non-obese women with PCOS. Moreover, obese women with PCOS have significantly more severe insulin resistance, lower serum luteinizing hormone levels, and lower luteinizing hormone to follicle-stimulating hormone ratios than those of non-obese women with PCOS. PCOS women in Taiwan have a higher luteinizing hormone to follicle-stimulating hormone ratio and lower insulin resistance than those in PCOS women in Western countries. However, the average body mass index is significantly lower in Taiwanese PCOS women than in Western women, which might partially explain the difference between these two populations in terms of clinical and biochemical presentations. To further document the ethnic variation between women with PCOS in Taiwan and Western countries, future studies should pay attention to the effect of obesity on the diagnosis and clinical presentations of PCOS-related syndromes.

Aim: To examine the usefulness of a gray scale histogram and computer assisted image analysis software in assessing physiologic states of the endometrium with ultrasonography. Methods: Seventy patients at the Taipei Medical University-Wan Fang Hospital who matched eligibility criteria were categorized into one of three groups: (i) normal menstrual cycle, (ii) postmenopausal, and (iii) post incomplete abortion. Ultrasonography of the uterus was performed on each patient and the endometrium was analyzed with ImageJ image analysis software. Results: A statistically significant difference in signal intensity scores of the gray level histogram, represented as mj, was found between the groups. Conclusion: Ultrasonographic images analyzed using computer assisted image analysis software and gray level histogram are useful in assessing the physiological state of the endometrium.

Polycystic ovary syndrome (PCOS) and hyperprolactinaemia are both common causes of secondary amenorrhoea in reproductive women. The relationship between PCOS and hyperprolactinaemia has been reported with controversial results. To evaluate the clinical and laboratory features of women with mild hyperprolactinaemia and PCOS, we studied 474 Taiwan Chinese women: 101 had mild hyperprolactinaemia, 266 had PCOS and 107 were the control group. In this study, we found that 64% of the women with mild hyperprolactinaemia fulfilled the PCOS diagnostic criteria, regardless of their prolactin levels. Obese women with PCOS had significantly lower luteinising hormone (LH) and LH-to-FSH ratios than non-obese women with PCOS. Obese hyperprolactinaemic women had significantly lower follicle-stimulating hormone (FSH), but higher LH-to-FSH ratios than the non-obese hyperprolactinaemic women. For women with PCOS, the BMIs were significantly negative with LH (γ = -0.253, p 0.001), but not with FSH (γ = -0.061, p = 0.319). For the hyperprolactinaemic women, the BMIs were significantly negative with FSH (γ = -0.353, p 0.001), but not with LH (γ = -0.021, p = 0.837). Although PCOS-related syndrome was very prevalent in women with hyperprolactinaemia, the patterns of disturbance in gonadotropin secretion were different between the PCOS and the hyperprolactinaemia patients.

Objective: To evaluate the prevalence of daytime urinary frequency among Taiwanese women aged 60 years and older. Materials and Methods: There were an estimated 1.25 million female residents aged 60 years and over in Taiwan in 2000. A sample of 2,410 women was selected using a multistage random sampling method. Face- to-face visits with 1,523 women were completed by trained professional interviewers within 3 months of the subjects' selection. Questions about urinary frequency and other lower urinary tract symptoms, sociodemo-graphics, reproduction, and medical and surgical histories were recorded. The factors were assessed by frequency and Pearson's χ2 test using a significance level of < 0.05. Results: The prevalence of urinary frequency in Taiwanese women aged 60 years and over was 18.8% (286/1,521). The response rate was 85.0% (1,521/1,789). For those who complained of frequency, 45.8% voided 8–15 times a day, 37.8% voided 16–23 times a day, 1.7% voided 24–31 times and a day, and 14.7% voided more than 31 times a day. The prevalence of urinary frequency was significantly associated with age (p < 0.001). Conclusion: Urinary frequency is a common symptom in menopausal women and is significantly related to age. More than half of the women interviewed experienced intervals of < 1 hour between visits to the restroom during the day.

Objective To evaluate inappropriate gonadotropin secretion in women with polycystic ovary syndrome (PCOS). Design Retrospective study. Setting Academic tertiary center. Patient(s) A total of 373 women were classified into three groups: [1] healthy control women (n = 48); [2] women who were positive for PCOS risk factor; and [3] women with PCOS (n = 251). Intervention(s) None. Main Outcome Measure(s) Gonadotropin levels, LH-FSH ratio, body mass index, and clinical and/or biochemical presentations of PCOS. Result(s) The area under the receiver operating characteristic curve, used to predict PCOS for the LH-FSH ratio, showed similar diagnostic performance to total T and average ovarian volume. The LH-FSH ratio exhibits greater observed accuracy than total T and average ovarian volume for evaluation of women with oligomenorrhea or anovulation. An LH-FSH ratio of >1 presented the best combination of sensitivity and specificity. Body mass index was positively correlated with total T in non-PCOS and PCOS groups; however, body mass index was negatively correlated with LH in PCOS but showed no correlation in non-PCOS subjects. Conclusion(s) The LH-FSH ratio is a valuable diagnostic tool in evaluating women with PCOS and oligomenorrhea or anovulation, and an LH-FSH ratio of >1 may be used as a decision threshold. The link between body mass index and LH may provide clues for further understanding the pathological milieu of PCOS.

We have successfully fabricated pentacene-based organic thin film transistor at a low temperature process with silicon oxide as a gate dielectric deposited by atmospheric-pressure plasma technology (APPT). The major merit of scanning atmospheric-pressure plasma technology was low deposition temperature at one standard atmosphere which was suitable for the application of flexible electrons. The organic thin film transistor demonstrated in this study could operate at the voltage less than -5V and the leakage current of silicon oxide dielectric with MIM structure is about 9×10A/cm at 0.5 MV/cm. The low operation voltage and low leakage current properties are required in portable applications. Leakage current of not define pentacene region is higher than define pentacene region. And leakage current of have HMDS is higher than not have HMDS.

Polycystic ovary syndrome (PCOS) is one of the most common hormonal endocrine disorders in women of reproductive age. It consists of a heterogeneous collection of signs and symptoms that together form a disorder spectrum. The diagnosis of PCOS is principally based on clinical and physical findings. The extent of metabolic abnormalities in women with PCOS varies with phenotype, body weight, age, and ethnicity. For general population, the prevalence of hyperandrogenism and oligomenorrhea decreases with age, while complications such as insulin resistance and other metabolic disturbances increase with age. Obese women with PCOS have a higher risk of developing oligomenorrhea, amenorrhea, hyperandrogenemia, insulin resistance, and lower luteinizing hormone (LH) to follicle stimulation hormone (FSH) ratios than non-obese women with PCOS. The LH to FSH ratio is a valuable diagnostic tool in evaluating Taiwanese women with PCOS, especially in the diagnosis of oligomenorrhea. Overweight/obesity is the major determinant of cardiovascular and metabolic disturbances in women of reproductive age.

Objective To evaluate the impact of the number of retrieved oocytes on pregnancy outcome. Materials and Methods We retrospectively examined the cycles of 2491 women undergoing in vitro fertilization therapy at Taipei Medical University (Taipei, Taiwan) from August 1995 to March 2009. We divided them into three groups based on their response rate (where H = high, M = middle, and L = low). We conducted this study to evaluate and compare pregnancy outcome in these three groups. Results The total number of retrieved oocytes had a significantly positive correlation with peak E2 levels, and the number of fertilized oocytes, good quality embryos, and available frozen embryos. The number of retrieved oocytes had a positive correlation with pregnancy rates and a negative correlation with fertilization rates. The implantation and abortion rates among the three groups were essentially the same. Compared to the middle and higher responders, the pregnancy rates for lower responders were significantly lower. The pregnancy rates for middle responders and higher responders were not significantly different. Conclusion The benefits of more retrieved oocytes between the lower and the middle responders were obvious. However, the benefits and risks for retrieving more oocytes for the middle and the higher responders remained controversial.

Objective To evaluate the roles of obesity and inflammatory biomarkers associated with medical complications in women with PCOS. Study design Retrospective, BMI-matched study. A total of 330 patients, including 165 women with PCOS and 165 women without PCOS, were evaluated. The insulin resistance (homeostasis model assessment insulin resistance index – HOMA) and lipid profiles were assessed. The adiponectin, leptin, ghrelin, resistin, anti-mullerian hormone (AMH), sex hormone-binding globulin (SHBG), high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) levels were also measured. Results Women with PCOS had significantly higher AMH, fasting insulin, total cholesterol, and low-density lipoprotein levels and lower SHBG levels compared with the controls. There was no difference in the serum obesity and inflammatory biomarkers between the PCOS cases and the controls. After adjusting for BMI and age, IL-6 was positively correlated with HOMA, and SHBG was negatively correlated with HOMA, triglyceride, and LDL. Conclusions The serum adipokines levels are not good markers for PCOS. PCOS patients were characterized by their high AMH and low SHBG levels. A low level of SHBG should play an important role in the pathogenesis of the medical complications observed in women with PCOS. Clinical trial registration number NCT01989039 .

Objective The aim of this study is to evaluate serum ferritin levels and polycystic ovary syndrome (PCOS)-related complications in obese and nonobese women. Materials and methods This retrospective study included 539 (286 with PCOS and 253 without PCOS). Results Serum ferritin correlated with menstrual cycle length, sex hormone-binding globulin, total testosterone, androstenedione, triglyceride, and total cholesterol in both obese and nonobese women. Obese women with high ferritin levels exhibited higher insulin resistance, impaired glucose tolerance, and liver enzymes (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase) than obese women with low ferritin levels. However, among nonobese women, insulin resistance and risk of diabetes were not significantly different between the high and low ferritin groups. Independent of obesity, hypertriglyceridemia was the major metabolic disturbance observed in women with elevated serum ferritin levels. Conclusion Elevated serum ferritin levels are associated with increased insulin resistance and risk of diabetes in obese women but not in nonobese women. However, higher serum ferritin levels were correlated with a greater risk of hyperglyceridemia in both obese and nonobese women. Therefore, hypertriglyceridemia in women with PCOS might be associated with iron metabolism.

Significant follicle loss from frozen ovarian grafts is unavoidable. The authors evaluated the protective effects of the antiapoptotic agent sphingosine-1-phosphate (S1P) on vitrified ovarian grafts. Three-week-old sexually immature female FVB mice were divided into 4 groups, fresh, control without S1P, 0.5 mmol/L S1P, and 2 mmol/L S1P. The ovaries were pretreated with S1P for 1 hour and then cryopreserved by modified vitrification. The frozen–thawed ovaries were autotransplanted under the back muscles of mice for 10 days. Expression of apoptosis-related genes encoding caspase 3 and c-Myc was analyzed in the vitrified ovaries and 10 days after transplantation using real-time quantitative polymerase chain reaction. To quantify the ovarian reserve, anti-Mullerian hormone (AMH) levels and follicles were measured in the 10-day vitrified ovarian grafts. Caspase 3 and c-Myc messenger RNA did not differ significantly in the 4 groups after vitrification but was significantly upregulated in the control group after transplantation. The AMH levels and primordial follicle pool were significantly higher in the S1P-treated groups than in the control group but lower than that in the fresh group. The S1P protects vitrified ovarian grafts from ischemic reperfusion injury rather than from vitrification-associated process.

Purpose: Our purpose was to examine the timing ofimplantation and early embryo development following uterinetransfer of oocytes/embryos previously subjected to zonapellucida micromanipulation. Methods: A total of 68 singleton pregnancies resulting fromIVF and embryo transfer with/without micromanipulation.Patients were divided into four groups according to the typeof micromanipulation technique: assisted hatching, embryobiopsy, intracytoplasmic sperm injection, and nomicromanipulation (control group). Serial serum β-hCG levels weremeasured between 10 and 25 days after fertilization andlog-transformed. Linear regression analyses were performedand extrapolated to hCG = 10 mIU/ml (hCG10) to estimatedetectable implantation. The slopes of the regression lineswere used to estimate the rising speed of hCG, an indirectsign of embryo development. Results: There were no significant differences among groupswith respect to hCG10, the slopes or intercepts of theregression lines. Conclusions: Various oocyte/embryo microsurgicalprocedures used in ART involving zona pellucida manipulationdo not appear to affect the timing of implantation or earlyembryo development.

Objective: To assess the relationships among perifollicular blood flow; follicular fluid pO 2 , pCO 2 , and pH; oocyte developmental capacity; preimplantation embryo quality. Design: Prospective study. Setting: Academic, tertiary care institution. Patient(s): Unselected, gonadotropin-stimulated IVF cycles. Intervention(s): Color, pulsed Doppler analysis of perifollicular blood flow, and follicular pO 2 , pCO 2 , and pH determinations of randomly designated, mapped ovarian follicles. Main Outcome Measure(s): Fertilization and day 3 embryo cleavage and morphology. Result(s): Perifollicular vascularity indices were significantly and negatively correlated with day 3 embryo cleavage. Pulsatility index and S-D ratio also were significantly and negatively correlated with follicular pO 2 . The same correlation was found between resistance index and the fertilization rate of preovulatory oocytes. No relationship existed between follicular metabolic analysis and fertilization or embryo quality. The resistance index had a sensitivity of 0.57 and a specificity of 0.71 for the prediction of advanced embryo cleavage status. Conclusion(s): Results confirm and extend previous reports demonstrating that color, pulsed Doppler ultrasound analysis of individual preovulatory follicles during IVF therapy may provide an indirect index of the developmental competence of the corresponding oocyte. Although these methods may provide means to select embryos for transfer with the highest implantation potential, the moderate predictive power showed so far may limit their clinical applicability.

Many peripheral reproductive tissues have been found to contain gonadotrophin-releasing hormone (GnRH) and express the GnRH gene at low levels, presumably because the hormone functions in a paracrine/autocrine fashion. This study was designed to investigate and characterize GnRH gene expression in human endometrial tissue at different stages of the endometrial cycle. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis together with Southern blot assay demonstrated that human endometrial tissue expresses the proGnRH gene. RNA samples from endometrial tissue were analysed with two pairs of oligonucleotide primers. Both gave a doublet 870 bases apart at the expected sizes, indicating that both the upstream and downstream transcriptional start sites of the GnRH gene are used in endometrial tissue and that transcripts with and without intron 1 were produced. Our data also demonstrated that utilization of the two promoters varies with the stage of the endometrial cycle. The largest difference came from the mRNA transcribed from the downstream promoter and without intron 1. This mRNA was expressed at a very low level during the proliferative phase and dramatically increased almost 10-fold (P , 0.01) during the early secretory phase, and subsequently decreased 5-fold during the late secretory stage. The presence of GnRH mRNA in the endometrium, as well as the differential expression of the GnRH gene during the early secretory phase provides physiological evidence that human GnRH may play a paracrine/autocrine function in the human uterus.

Purpose: Our purpose was to examine implantation of singleton pregnancies achieved following various assisted reproductive technologies (ARTs) through the appearance and rising titers of serum human chorionic gonadotropin (hCG) levels. Methods: A total of 114 singleton pregnancies resulting from in vitro fertilization and intrauterine insemination was analyzed. Patients were divided into five groups according to the type of ovarian stimulation protocol {gonadotropin stimulation with/without the use of gonadotropin-releasing hormone agonist (GnRHa), long protocol, or flare-up technique] and to the day of embryo transfer (day 2 or day 3 after oocyte retrieval). Serial serum hCG levels were measured between 10 and 25 days after fertilization and log-transformed. Linear regression analyses were performed and extrapolated to hCG = 10 mlUlml

Background Hypertension induces cardiac dysfunction, calcium (Ca 2+ ) dysregulation, and arrhythmogenesis. Dipeptidyl peptidase (DPP)-4 inhibitors, an antidiabetic agent with anti-inflammation and anti-hypertension potential, may regulate peroxisome proliferator-activated receptors (PPARs)-α, -γ, and -δ and Ca 2+ homeostasis. Objective The purpose of this study was to investigate whether DPP-4 inhibitor, sitagliptin, can modulate PPARs and Ca 2+ handling proteins in hypertensive hearts. Methods A Western blot analysis was used to evaluate protein expressions of myocardial PPAR isoforms, tumor necrosis factor (TNF)-α, interleukin (IL)-6, sarcoplasmic reticulum ATPase (SERCA2a), Na + –Ca 2+ exchanger (NCX), ryanodine receptor (RyR), voltage-dependent Ca 2+ (CaV1.2), slow-voltage potassium currents (Kvs), angiotensin II type 1 receptor (AT1R), and receptor of advanced glycated end-products (RAGE) from Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and SHR treated with sitagliptin (10mg/kg for 4weeks). Conventional microelectrodes were used to record action potentials (APs) in the ventricular myocytes from each group. Results Compared to the control group, SHR had lower cardiac PPAR-α and PPAR-δ protein expressions, but had greater cardiac PPAR-γ levels, and TNF-α, IL-6, RAGE, and AT1R protein expressions, which were ameliorated in the sitagliptin-treated SHR. SHR had prolonged QT interval and AP duration with less SERCA2a and RyR, and greater CaV1.2 expressions, which were also attenuated in sitagliptin-treated SHR. Conclusions Sitagliptin significantly changed the cardiac electrophysiological characteristics and Ca 2+ regulation, which may have been caused by its effects on cardiac PPARs, proinflammatory cytokines, and AT1R.

Polycystic ovary syndrome (PCOS) is a common and complex female endocrinopathy that is associated with multiple vascular risk factors. Our objective was to investigate the relationship between carotid intima-media thickness (CIMT) and endogenous androgens in young Taiwanese-Chinese women with PCOS. We measured CIMT with B-mode ultrasound in 42 young PCOS patients and 43 controls. Atherosclerosis-associated profiles and endocrinological parameters were also measured. The results showed that although Taiwanese-Chinese PCOS patients tend to possess more risk factors for atherosclerosis than controls, there was no evidence to support that they have a greater CIMT at this age. Furthermore, androstenedione appears to be inversely associated with CIMT.

[1] Li FL, Xu JY, Xia X-H. Beta-90Sr irradiation treatment of the silicon wafer coated with extracellular matrix protein to mimic the beta-32P radiation application in intravascular brachytherapy. Int J cardiol 2012;158(3):473–4. [2] Wu YP, Stella PR, Chen SF, Wang YT, Wang JY, Moerland MA, et al. Beta-radiation reduces the reactivity of extra cellular matrix proteins in intravascular brachytherapy (IVBT), resulting in decreased platelet adhesion. Int J Cardiol 2012;156: 283–8. [3] Raizner AE, Kaluza GL, Ali NM. Clinical experience with a spiral balloon centering catheter for the delivery of intracoronary radiation therapy. Cardiovasc Radiat Med 1999;1:214–9. [4] GALILEOTM Intravascular Radiotherapy System—P000052 U.S. Food and Drug Administration Home Address. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/ cfTopic/pma/pma.cfm?num=p000052.

Response: We thank Dr. Cheong for his careful reading of and suggestions for our articles.1 The clinical diagnosis of pelvic inflammatory disease (PID) is notoriously difficult.2 Subclinical PID, acute PID, chronic PID, and tubo-ovarian abscess (TOA) were indicated as upper genital infection in female reproductive system. In clinical experience, PID is usually accompanied by lower genital tract infection. In pathological experience, PID is a polymicrobial infection heralded by the acquisition of a sexually transmitted pathogen and results in increasing spread of aerobic and anaerobic vaginal bacteria.3 The original idea of this study was to evaluate the impact of female genital tract infection on the prevalence of stroke. Furthermore, bacterial vaginosis, a common lower-genital infection, is not associated with PID, but specific subgroups of patients with bacterial vaginosis that may be difficult to identify clinically are at increased risk for PID.4 All ICD-9-CM codes 614 to …

background: The clinical features and metabolic complications of polycystic ovary syndrome (PCOS) may change with age. This study was designed to investigate the clinical and biochemical characteristics of PCOS patients between the ages of 20 and 40. methods: The study included 781 Taiwanese women, of whom 453 were diagnosed with PCOS and 328 were non-PCOS controls. Anthroponmetric components, androgens, endocrine, insulin resistance, and metabolic components were measured and correlated with age. Above parameters were compared between younger and elder women with PCOS. results: Age had significant negative correlations with androgens (total testosterone and dehydroepiandrosterone sulfate), the modified Ferriman–Gallwey score and the prevalence of acne and hirsutism. Age had significant positive correlations with fasting glucose, cholesterol, triglycerides and low-density lipoprotein. The 453 women who fulfilled diagnostic criteria for PCOS were classified by age into two groups: Group A (20– 29 years old, n ¼ 294) and Group B (30 –40 years old, n ¼ 159). Group A had significantly higher total testosterone levels than Group B. Group B had higher fasting insulin and glucose levels, triglycerides, body mass index and waist measurements and a higher incidence of obesity than Group A. The average ovarian volume was not significantly different among the two groups. conclusions: Increased age is accompanied by a decrease in the prevalence of both clinical and biochemical hyperandrogenism in women. Hyperandrogenism is the important factor for young women with PCOS; however, abdominal obesity and certain metabolic disturbances became major concerns for older women with PCOS.

Background There is evidence that chronic inflammation may promote atherosclerotic disease. The purpose of this study was to test the hypothesis that pelvic inflammatory disease (PID) is a risk marker for myocardial infarction (MI). Method Using the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005), this cohort study comprised patients with a recorded diagnosis of PID ( N =68,668) between January 1, 2004 and December 31, 2005, with age-matched controls (1:2) ( N =136,906). Each patient was followed-up using entry data until the end of 2006. Cox proportional hazard regressions were used to evaluate the up to 3-year MI-free survival rates, after adjusting for known confounding factors. Results We found that patients with PID were more likely to have MI than the control population after adjusting for potential confounders [adjusted hazard ratio (HR), 1.86, 95% confidence interval (CI), 1.23–2.81]. When stratified by patient's age, the adjusted HR for MI was 2.09 (95% CI, 1.24–3.52) for patients with PID aged over 55years. However, the adjusted HR for MI occurring was not significant for patients with PID aged≤55years. Conclusions PID is a risk marker for MI that is independent of traditional MI risk factors. Further research in this important area of public health is warranted.

Background. Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality of reproductive-aged women and increases the risk of cardiovascular disease. However, the effects of PCOS on electrocardiograms (ECGs) are not fully elucidated. The aim of this study was to evaluate the characteristics of ECGs in patients with PCOS.Methods. This study included 24 patients with PCOS and 12 patients without PCOS. The heart rate, PR interval, QRS duration, Sokolow-Lyon voltage (SV1 + RV5/6), Cornell voltage (RaVL + SV3), QT interval and QTc interval were measured in 12-lead ECGs.Results. The QRS duration was wider in patients with PCOS than those without PCOS (91 ± 8 vs. 81 ± 10 ms, p

To examine the diagnostic feasibility of sonographic gray scale histograms to assess changes in the endometrium following abortion induced by mifepristone and misoprostol.Retrospective study.Taipei Medical University-Wan Fang academic medical center.A total of 109 patients who matched eligibility criteria were divided into three groups: (a) complete abortion, (b) normal menstrual cycles, and (c) incomplete abortion.Ultrasonographic examination of the uterus with fixed settings on each patient and sonographic gray scale histograms with image analysis software, using multivariate analysis by the partial least square model.Thickness, brightness, area and distribution of pixels of the endometrium and its contents.The groups could be discriminated (p0.01, Kruskal-Wallis test) using the analyzed gray scale histograms. The classification between complete and incomplete abortion reached 97% sensitivity and 100% specificity.Partial least square analysis of gray scale histograms of the endometrium in ultrasonographic images is useful in assessing endometrial changes.