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Background Polycystic ovary syndrome (PCOS), which is often accompanied by insulin resistance, is closely related to increased apoptosis of ovarian granulosa cells. LNK is an important regulator of the insulin signaling pathway. When insulin binds to the receptor, the PI3K/AKT/FOXO signaling pathway is activated, and FOXO translocates from the nucleus to the cytoplasm, thereby inhibiting the expression of pro-apoptotic genes. Methods Granulosa cells were collected from PCOS patients to investigate the relationship between LNK, cell apoptosis and insulin resistance. KGN cells underwent LNK overexpression/silence and insulin stimulation. The AKT/FOXO3 pathway was studied by western blot and immunofluorescence. LNK knockout mice were used to investigate the effect of LNK on the pathogenesis of PCOS. Results The level of LNK was higher in PCOS group than control group. LNK was positively correlated with granulosa cell apoptosis and insulin resistance, and negatively correlated with oocyte maturation rate. LNK overexpression in KGN cells inhibited insulin-induced AKT/FOXO3 signaling pathway, causing nucleus translocation of FOXO3 and promoting granulosa cell apoptosis. LNK knockout partially restored estrous cycle and improved glucose metabolism in PCOS mice. Conclusions LNK was closely related to insulin resistance and apoptosis of granulosa cells via the AKT/FOXO3 pathway. LNK knockout partially restored estrous cycle and improved glucose metabolism in PCOS mice, suggesting LNK might become a potential biological target for the clinical treatment of PCOS.

Is the sole measurement of total testosterone sufficient to assess the presence of hyperandrogenism in women with polycystic ovary syndrome (PCOS)?Serum samples from 294 patients with PCOS who met the Rotterdam criteria were used for the analysis of total testosterone by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and chemiluminescent immunoassay (CLIA). The free androgen index (FAI) was calculated as total testosterone (TT)/sex hormone-binding globulin (SHBG) × 100%, and the presence/degree of hirsutism were assessed using the modified and simplified Ferriman-Gallwey (mFG and sFG, respectively) scoring systems.The hirsute subjects presented higher LC-MS/MS-based total testosterone and FAI values than the non-hirsute subjects (all P 0.001), including those defined based on mFG ≥5 or sFG ≥3. Total testosterone and FAI were both positively correlated with the mFG (rank correlation coefficient [RCC] 0.598 and 0.443, P 0.001) or sFG (RCC 0.747 and 0.568, P 0.001) score, and a receiver operating characteristic curve analysis indicated that both parameters could significantly predict the presence of hirsutism determined by the mFG (area under the curve [AUC] 0.797 and 0.725, P 0.001) or sFG (AUC 0.894 and 0.817, P 0.001) score. However, similar results were not obtained with the CLIA platform.In this East Asian population, total testosterone was found to be a strong predictor of the presence and degree of hyperandrogenism (i.e. assessed by the presence and degree of hirsutism), but this finding was obtained only if the total testosterone level was measured by LC-MS/MS and not by CLIA. These findings might have important implications for global epidemiologic, phenotypic and clinical studies of PCOS.

Infertility seriously endangers the reproductive health of women at childbearing age. It is defined as the failure to achieve successful pregnancy after 1 year or more of regular unprotected intercourse. Broadly defined, infertility includes two aspects – failure to conceive or have a live birth. This guideline only addressed content relevant to the former. It was proposed by the gynecological endocrine group of the Chinese Society of Obstetrics and Gynecology, Chinese Medical Association, based on relevant guidelines of the World Health Organization, the American Society for Reproductive Medicine, the National Institute for Health and Clinical Excellence, as well as the clinical practice in China. The guideline was reviewed by experts and doctors from medical institutions at all levels, which is applicable to the diagnosis of infertility by physicians in obstetrics, gynecology, and andrology at various medical institutions nationwide.

Background Our objective was to retrospectively analyze the influence of DE-T1, a type of amino-polysaccharide extracted from dandelions, on the rates of blastocysts obtained and live births in women undergoing IVF-ET treatment. Methods This was a retrospective cohort study, conducting a total of 1014 patients over the age of 30, who received IVF treatment at Hanabusa Women’s clinic from Aug. 1, 2012 to Feb. 29, 2020. The patients were divided into two groups, based on their own choice regarding DE-T1 supplementation, which is available as over the counter medicine at the Clinic. The two groups’ overall rates of blastocysts obtained were compared and the rates of blastocysts obtained in patients with different ages and Anti-Mullerian hormone (AMH) levels were also compared using an Intention-to-treat (ITT) analysis. Among the patients who completed embryo transfers (ET), the live birth rate was compared between the supplementation group and the non-supplementation group using a Chi-squared test. Results The blastocyst obtained rate in the supplementation group was 75.98%, which was significantly higher than that of 57.28% in the non-supplementation group (P=2.4×109). The blastocyst obtained rate across the range of ages in the supplementation group were significantly higher than those of the non-supplementation group (≥30 and 5). The blastocyst obtained rate for both AMH levels in the supplementation group were significantly higher than those of the non-supplementation group (AMH≤1.1: 56.47% vs 40.44%, P=0.002; AMH> 1.1: 88.48% vs 71.08%, P=2.52×107). The live birth rate of the supplementation group was significantly higher than that of the non-supplementation group (57.53% vs. 40.0%, P=0.045). Conclusion DE-T1 supplementation might be an influence on improving the blastocyst obtained rate and live birth rates in women receiving IVF-ET treatment. DE-T1 supplementation might be of benefit to women of different ages and AMH levels.

Background: To explore the role of insulin resistance (IR) in patients with recurrent pregnancy loss (RPL) and/or recurrent implantation failure (RIF) treated with assisted reproductive technology (ART).Methods: We conducted a case-control study in a tertiary hospital from 2012 to 2018, We included 212 cases of simple RPL (only involved in RPL), 123 cases of simple RIF (only involved in RIF), 67 cases involved in both conditions (complicated group). We screened 123 women as the control cohort, who underwent ART due to male infertile, with no adverse pregnant outcomes. We examined the plasm glucose and insulin level in both fasting and postprandial condition after the oral glucose tolerance test (OGTT) and calculated the area under the curve of glucose (AUGG) and insulin (AUCI) as well as the homeostasis model assessment for insulin resistance and β-cell function (HOMA-IR and HOMA-β).Results: Both the simple RPL group and the complicated group had significantly higher fasting insulin (FINS), HOMA-IR and HOMA-β than the control group. The simple RIF group had the lowest level of FINS, HOMA-IR and HOMA-β. The incidences of IR were significantly higher in both the simple RPL group and the complicated group than the other two groups. After adjusted for age and waist-hip ratio (WHR), the simple RIF group had the highest fasting plasma glucose (FPG) [adjusted-mean (95%CI), 5.20 (5.09-5.33) mmol/L] and lower FINS [adjusted-mean (95%CI), 10.77 (9.25-12.29) mU/L] and HOMA-β [adjusted-mean (95%CI), 127.76 (83.56-171.97)]; the simple RPL group had the highest FINS [adjusted-mean (95%CI), 12.09 (11.21-12.98) mU/L] and HOMA-β [adjusted-mean (95%CI), 189.74 (164.29-215.18)] and a lower FPG [adjusted-mean (95%CI), 5.03 (4.97-5.10) mmol/L]. The FINS tended to increase with times of implantation failure among those patients with implantation failure fewer than six times. However, patients with more than six times implantation failure had extremely low FINS when compared with those with a history of five or six times (PConclusion: In patients undergoing ART, insulin resistance may be a common etiopathogenesis of RPL and RIF and insulin secretion impairment may be related to RIF.

Purpose To determine the utility of short gamete coincubation in in vitro fertilization (IVF‐S) combined with early rescue intracytoplasmic sperm injection (R‐ICSI) and split IVF‐ICSI in preventing low fertilization based on a retrospective cohort study. Methods Couples with a high risk of low IVF fertilization during the first ART cycle underwent IVF‐S with R‐ICSI or split IVF‐ICSI. Fertilization rate, embryo quality, and clinical outcomes were measured. Results After propensity score matching, we included 188 couples in the IVF‐S with R‐ICSI group as Group 1 and 720 in the split IVF‐ICSI group as Group 2. Normal fertilization rates were similar; however, Group 1 had a higher multiple pronuclei rate (10.42% vs. 4.50%, p

Background: Low levels of sex hormone-binding globulin (SHBG) is a potential predictor of type 2 diabetes mellitus (T2DM), and when combined with insulin resistance (IR), lead to impaired glucose m...

Context Obesity management prior to infertility treatment remains a challenge. To date, results from randomized clinical trials involving weight loss by lifestyle interventions have shown no evidence of improved live birth rate. Objective This work aimed to determine whether pharmacologic weight-loss intervention before in vitro fertilization and embryo transfer (IVF-ET) can improve live birth rate among overweight or obese women. Methods We conducted a randomized, double-blinded, placebo-controlled trial across 19 reproductive medical centers in China, from July 2017 to January 2019. A total of 877 infertile women scheduled for IVF who had a body mass index of 25 or greater were randomly assigned to receive orlistat (n = 439) or placebo (n = 438) treatment for 4 to 12 weeks. The main outcome measurement was the live birth rate after fresh ET. Results The live birth rate was not significantly different between the 2 groups (112 of 439 [25.5%] with orlistat and 112 of 438 [25.6%] with placebo; P = .984). No significant differences existed between the groups as to the rates of conception, clinical pregnancy, or pregnancy loss. A statistically significant increase in singleton birth weight was observed after orlistat treatment (3487.50 g vs 3285.17 g in the placebo group; P = .039). The mean change in body weight during the intervention was −2.49 kg in the orlistat group, as compared to −1.22 kg in the placebo group, with a significant difference (P = .005). Conclusion Orlistat treatment, prior to IVF-ET, did not improve the live birth rate among overweight or obese women, although it was beneficial for weight reduction.

MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression post-transcriptionally. We explored whether connexin 43 (Cx43) was differently expressed in luteinized granulosa cells from women with polycystic ovary syndrome (PCOS) compared with luteinized granulosa cells from women with a normal menstrual cycle, and whether certain miRNAs regulate the Cx43 level and gap junctional intercellular communication (GJIC). The miRNA profile was investigated in ovarian cortex tissues from five women with PCOS and five women without PCOS using a miRNA microarray. The levels of miR-130b and Cx43 mRNA were measured using real-time PCR in human luteinized granulosa cells from 20 women with PCOS and 25 women without PCOS. Protein and mRNA expression analysis and luciferase assays were conducted to confirm the substrate of miR-130b. PCOS ovarian cortex showed differential expression of miRNAs compared with non-PCOS ovarian cortex. Furthermore, miR-130b levels were increased in PCOS ovarian cortex and in luteinized granulosa cells compared with those in women with normal menstrual cycles, whereas the level of Cx43 mRNA, the identified target of miR-130b, was decreased in granulosa cells from patients with PCOS. Overexpression of miR-130b in a granulosa cell line resulted in reduced Cx43 protein levels and inhibited GJIC using scrape loading and dye transfer assay. Meanwhile, inhibition of miR-130b increased the Cx43 level. In conclusion, miR-130b was increased in PCOS granulosa cells, where it targets Cx43 to affect GJIC. The results of the present study suggested that miR-130b, via post-transcriptional regulation of Cx43, is involved in the pathophysiology of PCOS, which provides new insight into the pathological mechanism of PCOS.

STUDY QUESTION Does an artificially induced FSH surge at the time of hCG trigger improve IVF/ICSI outcomes? SUMMARY ANSWER An additional FSH bolus administered at the time of hCG trigger has no effect on clinical pregnancy rate, embryo quality, fertilization rate, implantation rate and live birth rate in women undergoing the long GnRH agonist (GnRHa) protocol for IVF/ICSI. WHAT IS KNOWN ALREADY Normal ovulation is preceded by a surge in both LH and FSH. Few randomized clinical trials have specifically investigated the role of the FSH surge. Some studies indicated that FSH given at hCG ovulation trigger boosts fertilization rate and even prevents ovarian hyperstimulation syndrome (OHSS). STUDY DESIGN, SIZE, DURATION This was a randomized, double-blinded, placebo-controlled trial conducted at a single IVF center, from June 2012 to November 2013. A sample size calculation indicated that 347 women per group would be adequate. A total of 732 women undergoing IVF/ICSI were randomized, using electronically randomized tables, to the intervention or placebo groups. Participants and clinical doctors were blinded to the treatment allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients aged ≤42 years who were treated with IVF/ICSI owing to tubal factor, male factor, unexplained, endometriosis and multiple factors were enrolled in this trial. Subjects all received a standard long GnRHa protocol for IVF/ICSI and hCG 6000–10 000 IU to trigger oocyte maturation. A total of 364 and 368 patients were randomized to receive a urinary FSH (uFSH) bolus (6 ampules, 450 IU) and placebo, respectively, at the time of the hCG trigger. The primary outcome measure was clinical pregnancy rate. The secondary outcome measures were FSH level on the day of oocyte retrieval, number of oocytes retrieved, good-quality embryo rate, live birth rate and rate of OHSS. MAIN RESULTS AND THE ROLE OF CHANCE There were no significant differences in the baseline demographic characteristics between the two study groups. There were also no significant differences between groups in cycle characteristics, such as the mean number of stimulation days, total gonadotrophin dose and peak estradiol. The clinical pregnancy rate was 51.6% in the placebo group and 52.7% in the FSH co-trigger group, with an absolute rate difference of 1.1% (95% CI −6.1% to 8.3%). The number of oocytes retrieved was 10.47 ± 4.52 and 10.74 ± 5.01 (P = 0.44), the rate of good-quality embryos was 37% and 33.9% (P = 0.093) and the implantation rate was 35% and 36% (P = 0.7) in the placebo group and the FSH co-trigger group, respectively. LIMITATIONS, REASONS FOR CAUTION This was a single-center study, which may limit its effectiveness. The use of uFSH is a limitation, as this is not the same as the natural FSH. We did not collect follicular fluid for further study of molecular changes after the use of uFSH as a co-trigger. WIDER IMPLICATIONS OF THE FINDINGS Based on previous data and our results, an additional FSH bolus administered at the time of hCG trigger has no benefit on clinical pregnancy rates in women undergoing the long GnRHa protocol in IVF/ICSI: a single hCG trigger is sufficient. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Key Research and Development Program of China (2016YFC1000205); Sun Yat-Sen University Clinical Research 5010 Program (2016004); the Science and Technology Project of Guangdong Province (2016A020216011 and 2017A020213028); and Science Technology Research Project of Guangdong Province (S2011010004662). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-12002246). TRIAL REGISTRATION DATE 20 May 2012. DATE OF FIRST PATIENT’S ENROLMENT 10 June 2012.

Central obesity (CO) is a defining characteristic of polycystic ovary syndrome (PCOS) and PCOS-induced disorders are likely to be exacerbated in the presence of CO. This study aims to evaluate the impact of CO on infertile women with PCOS undergoing in vitro fertilization (IVF).It is a retrospective and case–control study. One hundred eighty-eight infertile PCOS women undergoing IVF were divided into CO group (n = 70, waist circumference [WC] ≥80 cm) and noncentral obesity (NCO) group (n = 118, WC

Recent studies show that vitamin D (VitD) deficiency is associated with metabolic syndrome (MetS). Current evidence suggests that estrogen and VitD have similar physiological functions and potentially interact with bone health. We investigated the association between estradiol (E2) and 25-hydroxyvitamin-D [25(OH)D] with MetS and its components in Chinese postmenopausal women.In this cross-sectional study, we examined 616 postmenopausal women (aged 49-86 y) from southern China who were not taking estrogen and VitD/calcium supplements. At the end of data collection, serum E2 and 25(OH)D were measured for each participant. MetS was defined according to the 2006 International Diabetes Federation standard.There was a positive correlation between 25(OH)D and E2. Higher 25(OH)D was associated with a favorable lipid profile, blood pressure, and glucose level. E2 was negatively associated with cholesterol, triglycerides, and blood pressure. The odds ratio for MetS was 2.19 (95% CI, 1.19-4.01, P value for trend=0.009) for deficient compared with sufficient women after multivariable adjustment. This association remained unchanged after further adjusting for E2 levels. After stratified analysis by VitD status, low E2 increased MetS risk in women with VitD deficiency (odds ratio = 3.49, 95% CI, 1.45-8.05 for the lowest vs the highest tertile).These results suggest a synergistic role of VitD and E2 deficiency in MetS in Chinese postmenopausal women.

Objective: Nonalcoholic fatty liver disease is the commonest diffuse liver disease, of which women with polycystic ovary syndrome are at an increased risk. The aim of the present study was to assess the diagnostic value of the semiquantitative strain parameters of real-time ultrasound elastography for nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. Subjects and methods: Thirty-five polycystic ovary syndrome patients with nonalcoholic fatty liver disease, 70 polycystic ovary syndrome patients without nonalcoholic fatty liver disease, and 70 healthy female controls of reproductive age were included. All participants underwent ultrasonic examination and semiquantitative analysis of real-time ultrasound elastography of the liver. Results: Main semi quantitative strain parameters, such as average strain value, differed significantly among groups polycystic ovary syndrome with nonalcoholic fatty liver disease, polycystic ovary syndrome without nonalcoholic fatty liver disease, and control (87.02 ± 10.16 vs. 96.31 ± 11.44 vs. 104.49 ± 7.28, p < 0.001). Clinical and laboratory parameters differed significantly between the two subgroups with low or high average strain value. For diagnostic value of average strain value for elevated aminotransferase, the area under the curve was 0.808 (range 0.721-0.895). In multiple linear regression analysis, polycystic ovary syndrome, waist circumference, and metabolic syndrome were stand-alone independent factors associated with average strain value among subjects without nonalcoholic fatty liver disease. Conclusion: Semiquantitative real-time ultrasound elastography analysis could distinguish liver parenchyma alterations in patients with polycystic ovary syndrome more sensitively. The diagnostic value of the proposed method for nonalcoholic fatty liver disease need further research.

This study explored the correlation between serum anti-Mullerian hormone (AMH) concentration and the number of retrieved oocytes after ovarian stimulation in Chinese infertile women undergoing assisted reproductive technology treatment and AMH cut-off values predicting low and high ovarian response. This was a prospective, multi-centre, observational study. A total of 615 subjects were included in nine assisted reproductive centres in China for outcome analysis. Subjects received assisted reproductive technology treatment and used recombinant human FSH (r-HFSH) or r-HFSH plus recombinant LH (rLH) for ovarian stimulation according to conventional treatment regimens. The main outcome variables were correlations between AMH and the number of retrieved oocytes and the cut-off values of AMH predicting low and high ovarian response. Serum AMH concentration was positively correlated with the number of oocytes retrieved in Chinese infertile women treated with IVF/intracytoplasmic sperm injection (ICSI) (Pearson correlation coefficient = 0.4754, P < 0.0001). The optimal AMH cut-off value was 2.6 ng/ml (sensitivity: 81.28%, specificity: 59.51%) in predicting high and normal response, and 1.1 ng/ml (sensitivity: 52.27%, specificity: 87.23%) in predicting low and normal response. In conclusion, serum AMH concentration can be used as a biomarker to predict ovarian response in Chinese infertile women treated with assisted reproductive technology.

The transfer of fresh embryos is generally preferred over the transfer of frozen embryos for in vitro fertilization (IVF), but some evidence suggests that frozen-embryo transfer may improve the live-birth rate and lower the rates of the ovarian hyperstimulation syndrome and pregnancy complications in women with the polycystic ovary syndrome.In this multicenter trial, we randomly assigned 1508 infertile women with the polycystic ovary syndrome who were undergoing their first IVF cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. After 3 days of embryo development, women underwent the transfer of up to two fresh or frozen embryos. The primary outcome was a live birth after the first embryo transfer.Frozen-embryo transfer resulted in a higher frequency of live birth after the first transfer than did fresh-embryo transfer (49.3% vs. 42.0%), for a rate ratio of 1.17 (95% confidence interval [CI], 1.05 to 1.31; P=0.004). Women who underwent frozen-embryo transfer also had a lower frequency of pregnancy loss (22.0% vs. 32.7%), for a rate ratio of 0.67 (95% CI, 0.54 to 0.83; P0.001), and of the ovarian hyperstimulation syndrome (1.3% vs. 7.1%), for a rate ratio of 0.19 (95% CI, 0.10 to 0.37; P0.001), but a higher frequency of preeclampsia (4.4% vs. 1.4%), for a rate ratio of 3.12 (95% CI, 1.26 to 7.73; P=0.009). There were no significant between-group differences in rates of other pregnancy and neonatal complications. There were five neonatal deaths in the frozen-embryo group and none in the fresh-embryo group (P=0.06).Among infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth, a lower risk of the ovarian hyperstimulation syndrome, and a higher risk of preeclampsia after the first transfer than was fresh-embryo transfer. (Funded by the National Basic Research Program of China and others; ClinicalTrials.gov number, NCT01841528.).

Polycystic ovary syndrome (PCOS) progression involves abnormal insulin signaling. SH2 domain-containing adaptor protein (Lnk) may be an important regulator of the insulin signaling pathway. We investigated whether Lnk was involved in insulin resistance (IR). Thirty-seven women due to receive laparoscopic surgery from June 2011 to February 2012 were included from the gynecologic department of the Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Samples of polycystic and normal ovary tissues were examined by immunohistochemistry. Ovarian cell lines underwent insulin stimulation and Lnk overexpression. Expressed Lnk underwent coimmunoprecipitation tests with green fluorescent protein-labeled insulin receptor and His-tagged insulin receptor substrate 1 (IRS1), and their colocalization in HEK293T cells was examined. Ovarian tissues from PCOS patients with IR exhibited higher expression of Lnk than ovaries from normal control subjects and PCOS patients without IR; mainly in follicular granulosa cells, the follicular fluid and plasma of oocytes in secondary follicles, and atretic follicles. Lnk was coimmunoprecipitated with insulin receptor and IRS1. Lnk and insulin receptor/IRS1 locations overlapped around the nucleus. IR, protein kinase B (Akt), and ERK1/2 activities were inhibited by Lnk overexpression and inhibited further after insulin stimulation, whereas IRS1 serine activity was increased. Insulin receptor (Tyr1150/1151), Akt (Thr308), and ERK1/2 (Thr202/Tyr204) phosphorylation was decreased, whereas IRS1 (Ser307) phosphorylation was increased with Lnk overexpression. In conclusion, Lnk inhibits the phosphatidylinositol 3 kinase-AKT and MAPK-ERK signaling response to insulin. Higher expression of Lnk in PCOS suggests that Lnk probably plays a role in the development of IR.

In this review, we summarize existing research on a variety of environmental factors potentially involved in the etiology, prevalence, and modulation of polycystic ovary syndrome (PCOS), and we suggest avenues for future research. The main environmental factors we consider include environmental toxins, diet and nutrition, socioeconomic status, and geography. There is some evidence that environmental toxins play a role in disrupting reproductive health, but there is limited research as to how these toxins may affect the development of PCOS. Although research has also shown that PCOS symptoms are reduced with certain dietary supplements and with weight loss among obese women, additional research is needed to compare various approaches to weight loss, as well as nutritional factors that may play a role in preventing or mitigating the development of PCOS. Limited studies indicate some association of low socioeconomic status with certain PCOS phenotypes, and future research should consider socioeconomic conditions during childhood or adolescence that may be more relevant to the developmental onset of PCOS. Finally, the limited scope of comparable international studies on PCOS needs to be addressed, because global patterns of PCOS are potentially valuable indicators of cultural, environmental, and genetic factors that may contribute to excess risk in certain regions of the world.

This study aimed to detect serum microRNAs (miRNAs) differentially expressed between polycystic ovary syndrome (PCOS) patients with impaired glucose metabolism (IGM), PCOS patients with normal glucose tolerance (NGT), and healthy controls. A TaqMan miRNA array explored serum miRNA profiles as a pilot study, then selected miRNAs were analyzed in a validation cohort consisting of 65 PCOS women with IGM, 65 PCOS women with NGT, and 45 healthy women The relative expression of miR-122, miR-193b, and miR-194 was up-regulated in PCOS patients compared with controls, whereas that of miR-199b-5p was down-regulated. Furthermore, miR-122, miR-193b, and miR-194 were increased in the PCOS-IGM group compared with the PCOS-NGT group. Multiple linear regression analyses revealed that miR-193b and body mass index contributed independently to explain 43.7 % (P

Objective To study the distribution and progression of terminal hair growth in pregnant women and to determine the feasibility of a simplified scoring system for assessing hirsutism. Design Prospective follow-up observational study. Setting Academic hospital. Patient(s) A total of 115 pregnant women (discovery cohort) and 1,159 women with polycystic ovary syndrome (PCOS) (validation cohort). Intervention(s) Facial and body terminal hair growth assessed by modified Ferriman and Gallwey score system (mFG score), and total testosterone (TT) level detected by liquid chromatography with tandem mass spectrometry. Main Outcome Measure(s) Degree of facial and body terminal hair growth. Result(s) The serum TT level and mFG score increased as pregnancy progressed. Both the prospective study and receiver operating characteristics curve indicated that the body areas with the greatest contribution to hirsutism (defined as an mFG score ≥5) with new terminal hair growth were the upper lip, lower back, lower abdomen, and thigh. A simplified mFG scoring system (sFG) was developed, and a cutoff value of ≥3 was defined as hirsutism. Pregnant hirsute women were distinguished from nonhirsute women with an accuracy of 95.2%, sensitivity of 96.8%, and specificity of 94.3% for detecting hirsutism. This was further validated in the PCOS population with a sensitivity, specificity, and positive predictive value of 97.6%, 96.4%, and 96.4%, respectively. Conclusion(s) This study suggests that the upper lip, lower back, lower abdomen, and thigh may be an effective simplified combination of the mFG system for the evaluation of excess hair growth in Chinese women. Clinical Trial Registration Number ChiCTR-OCH-14005012.

PURPOSE: The objective of this study was to determine whether ammonium accumulates in IVF media during fertility process and whether the brief co-incubation of gametes (bIVF) benefited the outcomes of newborns. METHODS: Ammonium levels in IVF media during gamete co-incubation were measured and the effects of bIVF on neonatal outcomes were evaluated retrospectively in this study. RESULTS: A total of 609 live newborns cycles were included in this study. The results showed that ammonium levels in the conventional IVF (cIVF) media was significantly increased than that in bIVF and control media (27.32 ± 5.60 vs 20.71 ± 3.89, P = 0.03; 27.32 ± 5.60 vs 19.46 ± 1.31, P = 0.01, respectively). In the cIVF group, the mean gestational age was significantly lower (37.36 ± 2.29 vs. 37.74 ± 1.94 weeks, P = 0.031) and the incidence of preterm birth (

This retrospective study is to compare the follicular mild stimulation and luteal simulation protocols for poor responders undergoing in vitro fertilization (IVF). A total of 131 women were diagnosed as poor responders. Thirty-three women started ovarian stimulation in early-luteal phase and 98 women started in early follicular phase with 100 mg/d clomiphene citrate and 75-150 IU/d HMG. There were more oocytes retrieved (2.8 ± 2.0 versus 2.0 ± 1.2, p 0.05), more available embryos (1.8 ± 1.4 versus 1.3 ± 1.1, p 0.05) and top-quality embryos (0.9 ± 0.9 versus 0.4 ± 0.6, p 0.05), and reduced cycle cancellation rate (12.1% versus 30.6%, p 0.05) in luteal group than in follicular group. The clinical pregnancy (17.7%, 20.0% and 41.2%) and live-birth rates (10.78%, 20.0% and 29.4%) after transferring embryos obtained from luteal, follicular and mixed stages were comparable (p 0.05). For poor responders, luteal phase stimulation could be an option because of increasing the chance to obtain competent embryos and reducing the cycle cancellation rate.

Background: Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age. The patients often develop insulin resistance (IR) or hyperinsulinemia despite manifesting anovulation and signs of hyperandrogenism. The cause and effect relationship of hyperinsulinemia and hyperandrogenemia (HA) is still debated. Micro-ribonucleic acids (miRNAs) have recently been shown to play a role in regulation of ovarian function. Our current study focused on the altered expression of miRNAs with PCOS. Methods: Ovarian theca interna tissues were obtained from 10 PCOS patients and 8 controls that were non-PCOS and had normal insulin sensitivity undergoing laparoscopy and/or ovarian wedge resection. Total RNA of all samples was extracted. We studied the repertoire of miRNAs in both PCOS and non-PCOS women by microarray hybridization. Bioinformatic analysis was performed for predicting targets of the differentially expressed miRNAs. Furthermore, selected miRNAs were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results: A total of 27 miRNAs were differentially expressed in PCOS patients with respect to the controls in our discovery evaluationand two (miR-92a and miR-92b) of them were significantly downregulated in PCOS women in followed validation (P < 0.05). Targets prediction revealed that miR-92a targeted both GATA family of zinc finger transcription factor GATA-binding factor 6 (GATA6) and insulin receptor substrate proteins 2 (IRS-2). Conclusions: MiRNAs are differentially expressed between PCOS patients and controls. We identified and validated two miRNAs-miR-92a and miR-92b. They are significantly downregulated and may be involved in the pathogenesis of PCOS.

Introduction: There is considerable individual and racial variation in the degree and pattern of body hair among PCOS patients. The purposes of this study were to define: 1) a suitable standard of hirsutism for Chinese women with PCOS and the general Chinese population; 2) the characteristics of hair distribution and degree in Chinese women with PCOS and the general population; and 3) the correlation of PCOS and FG score in Chinese women. Material and methods: This retrospective study in Chinese women with PCOS in the reproductive centre of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, comprised 850 patients with PCOS and 2,988 members of the general population. It was conducted crosssectionally by interview, physical examination, ultrasound scan, and modified Ferriman-Gallwey score. Eight hundred and fifty Chinese women with PCOS (aged 20–41) underwent an interview, blood drawing, physical and ultrasound examination. Body hair at nine sites (lip, chin, arm, thigh, chest, upper belly, lower belly, upper back and lower back) were evaluated using the scoring system described by Ferriman and Gallwey; 2,988 healthy women (aged 20–45) underwent an interview, physical examination, ultrasound scan and FG score evaluation by trained gynaecologists. Terminal body hair growth was assessed using the mFG scoring system in Chinese women with PCOS and the control group; nine body areas were scored from 0–4 for terminal hair growth distribution. Results: Our findings showed that of the 850 patients, 367 had a FG score equal to or greater than 5 points [43.2% (367/850)], 282 patients had a FG score equal to or greater than 6 points [33.18% (282/850)], and 21% had a score of at least 8 points. Nobody’s FG score was equal to or greater than 24 points. Hirsutism was significantly higher in PCOS patients (score≥ 5 = 43.2%) than in the general population (score ≥ 5 = 10%). The lip is the most common place (score 0–3) where terminal hair grows in 850 PCOS patients and the general population. Next came the upper back and chest, and the number of 4 points was only recorded for the region of the lip (16), thigh (3), lower belly (3), arm (1), chest (1), and lower back (1). None of the PCOS patients displayed a score of more than 4 points for the chin, upper belly and upper back. Conclusions: Our data indicates that: 1) an mFG score of 5 or above is out of the norm for the general unselected population and forms almost half of the possibility of diagnosing PCOS in Chinese women; 2) lips and upper back are the most common places that hair grows (score 1–2), but in terms of the serious situation (score 3–4), lips and thighs are the most common places that hair grows; 3) there is a good predictive value to diagnose PCOS by FG score for Chinese people; and 4) hirsutism is more common in PCOS than in the general population in China. (Endokrynol Pol 2014; 65 (5): 365–370)

To evaluate whether delayed initiation of gonadotropin in luteal long protocol affected the outcome of in vitro fertilization (IVF).Prospective randomized study at the reproductive centre of a university-based hospital. Eighty-five subfertile women undergoing IVF embryo transfer after a standardized gonadotropin-releasing hormone agonists (GnRHa) long protocol. The patients were randomized into group A (stimulated 3 weeks after GnRHa administration) and group B (stimulated 2 weeks after GnRHa administration), according to the time of gonadotropin initiation after GnRHa-mediated pituitary suppression. The main outcome measures were clinical pregnancy and live birth rates.There were no significant differences in baseline characteristics such as age, body mass index and basal follicle-stimulating hormone (bFSH) between the two groups. In group B, the days of gonadotropin stimulation were significantly greater than that in group A (p 0.05), while the total dose of gonadotropin in group A was comparable to that in group B. Serum luteinizing hormone was lower and follicle-stimulating hormone higher in group A than in group B (p 0.05) on initiation day. There were no significant differences in hormone profile measurements between the two groups. Moreover, the clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate and moderate ovarian hyperstimulation syndrome rate were not significantly different between the groups.Delay of gonadotropin stimulation in a standard long protocol may increase clinical efficiency, without significantly changing clinical outcome.

Acanthosis nigricans (AN) usually correlates to insulin resistance (IR) or obesity in obese populations, but adequate studies on the significance of AN in people with normal body mass index (BMI) have not been performed and discussed. Three hundred and thirty-nine polycystic ovary syndrome (PCOS) patients with normal BMI (

Background Resistant ovary syndrome (ROS) is a rare endocrine disorder characterized with hypergonadotrophic hypogonadism. Infertility is a common complaint of woman presenting with ROS, and little progress has been made in term of reproduction with the patient’s own gamete. So far only one case report of live birth has been reported after in vitro maturation (IVM) of oocytes in a patient suffering from ROS in 2013. Case presentation A secondary infertile woman of 33 years-old was manifested with oligomenorrhea and markedly increased gonadotropin levels around postmenopausal range, but had normal antral follicle count, normal serum inhibin B and anti-Müllerian hormone levels. She had normal karyotype of 46,XX and normal thyroid function. There were no abnormal findings in some autoantibody assays and FSH receptor sequencing. After oral contraceptive pills combined with triptorelin depot were administered, her gonadotropin levels reduced but it showed no response to high doses of exogenous gonadotropins (hp-HMG 300IU/d for 15 days). Then endometrium was prepared with estradiol valerate and IVM from small antral follicles were performed. Five immature oocytes were retrieved. Twenty-four hours after IVM culture, 3 oocytes matured to metaphase II stage and were inseminated by intracytoplasmic sperm injection using her husband’s sperm. Two top-quality embryos were transferred and one embryo was cryopreserved. The patient got pregnant and delivered a healthy boy at term. Conclusion IVM using their own oocytes could be an available treatment for infertile women with ROS.

Objective(s) To determine the normative cut-off value for the free androgen index (FAI) among reproductive-age women in China. Design Cross-sectional, population-based study. Setting A multistage systematic cluster random sampling among 16 communities from two rural and two city regions. Patient(s) A total of 1526 women were randomly selected from a representative sample of 3009 women aged 20–45 years from the general population of southern China. Among these women, 444 subjects without known factors affecting androgen levels were selected as the reference group. Intervention(s) Subjects underwent physical examination, blood tests of hormone and metabolic profiles, and ultrasound evaluations. Measurement of the main outcomes The FAI was calculated according to the following equation: FAI = 100 × total testosterone (nmol/l)/sex hormone-binding globulin (nmol/l). The normative cut-off value of the FAI was computed based on the 5th–95th percentiles and K-means cluster analysis (K = 2). Results A reference range of 0·7–6·4 of the FAI was indicated by the 5th and 95th percentiles. K-means cluster analysis identified 6·1 as the cut-off value for the FAI in the total population, which was close to the upper limit determined by the 95th percentile. Hyperandrogenic women present with elevated risk factors for metabolic disorders. The mean FAI values decreased with age among the total population, as evaluated by either K-means clustering or a percentile analysis. The FAI value was negatively correlated with age (r = −0·185, P

Aim: The apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio is well known to be related to metabolic syndrome (MS) and its components in adults of different races. There is low prevalence of MS but high occurrence of various metabolic disorders in Chinese adolescent women with polycystic ovary syndrome (PCOS). We sought to assess if the ApoB/ApoA1 ratio can be used as a predictive marker of MS and pre-MS in Chinese adolescent women with PCOS. Material and Methods: This cross-sectional study included 160 Chinese adolescent women. Based on International Diabetes Federation criteria for MS, patients who had no less than two components of MS but did not meet the criteria for the diagnosis of MS were considered as having pre-MS. Results: The ApoB/ApoA1 ratio was higher in obese subjects with high free androgen index (FAI). The ApoB/ApoA1 ratio increased significantly as the number of MS components increased and provided 87.5% of sensitivity and 78.9% of specificity with a threshold value of 0.63 for MS, 86.2% of sensitivity and 79.4% of specificity with a threshold value of 0.58 for pre-MS in Chinese adolescent women with PCOS. Conclusion: The ApoB/ApoA1 ratio was a good predictive marker of MS and pre-MS in Chinese adolescent women with PCOS. FAI could be involved in obesity-related metabolic abnormalities.

BACKGROUND Women with polycystic ovary syndrome (PCOS) have increased risks of developing metabolic abnormalities compared with the women without PCOS. Hyperandrogenemia is one of the most important characteristics of PCOS. However, the correlations between hyperandrogenemia and metabolic disorders are uncertain. AIM To elucidate the relationship between androgen indices and metabolic abnormalities in Chinese women with PCOS. SUBJECTS AND METHODS A retrospective analysis of the anthropometric and biochemical records of 408 women with PCOS. RESULTS The prevalence of metabolic syndrome (MetS) was 15.7% in women with PCOS. No association existed between total testosterone (TT) and metabolic profile. Free testosterone (FT) correlated with most of the metabolic variables by unadjusted correlation analyses. The women with elevated FT levels exhibited more unfavorable metabolic profiles compared with the women with normal FT levels. After adjusting for the confounding factors by multivariate logistic regression analysis, the women with elevated FT levels had higher prevalence of central obesity than the women with normal FT levels (odds ratio [OR] 2.346, p=0.042). Women with reduced sex hormone-binding globulin levels were more likely to have central obesity, overweight, raised fasting glucose, insulin resistance, and raised diastolic blood pressure. Raised dehydroepiandrosterone sulfate (DHEAS) level was associated with a lower probability of having central obesity (OR 0.293, p=0.001) and overweight (OR 0.47, p=0.023). CONCLUSIONS FT has closer association with metabolic parameters than TT. FT can involve in the development of metabolic disorders dependent on central obesity. Raised DHEAS level can reduce the risks of central obesity and overweight.

Sulfonylureas are ATP-sensitive potassium (KATP) channel blockers commonly used in the treatment of type 2 diabetes mellitus (T2DM). Activation of KATP channels plays a neuroprotective role in ischemia; thus, whether sulfonylureas affect the outcomes of stroke in patients with T2DM needs to be further studied. In our study, streptozotocin (STZ)-induced diabetic mice subjected to transient middle cerebral artery occlusion (MCAO) showed larger areas of brain damage and poorer behavioral outcomes. Blocking the KATP channel by tolbutamide increased neuronal injury induced by oxygen-glucose deprivation (OGD) in vitro and permanent MCAO (pMCAO) in vivo. Activating the KATP channel by diazoxide reduced the effects of both the OGD and pMCAO. Western blot analysis in STZ mouse brains indicated an early increase in protein levels of N-methyl-d-aspartate receptor 2B and postsynaptic density protein-95, followed by a decrease in phosphorylation of glycogen synthase kinase 3β. Our systematic meta-analysis indicated that patients with T2DM treated with sulfonylureas had a higher odds ratio for stroke morbidity than those who received comparator drugs. Taken together, these results suggest that sulfonylurea treatment in patients with T2DM may inhibit the neuroprotective effects of KATP channels and increase the risk of stroke.

To determine the normative cut-off levels of free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS) and total testosterone (TT) among reproductive age women in China.A total of 450 reference subjects without known factors affecting androgen levels were selected from a total study population of 904 presumably healthy women undergoing annual check-ups. The upper limits of normal levels of biochemical androgens were computed by k-means cluster analysis, with the results categorized by age and expressed as both concentrations and percentiles.The upper limits (cut-off levels) of normal FT, DHEAS and TT levels as determined by k-means cluster analysis are 26 pmol/L, 4.92 μmol/L and 2.39 nmol/L, respectively, in the selected reference subjects. The corresponding percentiles of the cut-off levels of FT (91.8th vs. 87.9th), DHEAS (69.8th vs. 67.6th) and TT (90.0 th vs. 83.8th) were all higher in the reference subjects than in the total study population, suggesting that there were fewer abnormal subjects with elevated androgens in the healthier reference population than in the total study population. The level of DHEAS significantly declined by age (P0.05), whereas there was no significant difference in the mean FT or TT levels between age groups among these women of reproductive age.The normal hyperandrogenism cut-off values for FT, DHEAS and TT are 26.00 pmol/L, 4.92 μmol/L and 2.39 nmol/L, respectively, among women of reproductive age in China who are without factors that might affect androgen levels. The cut-off levels in percentiles are 91.8th for FT, 69.8th for DHEAS and 90.0 th for TT.

PURPOSES: To explore the serum anti-mullerian hormone (AMH) level in adolescent and young adult Chinese patients with polycystic ovary syndrome (PCOS), and to evaluate its diagnostic value for PCOS. STUDY DESIGN: Serum AMH was measured in a cohort of 47 adolescent and young adult Chinese patients with PCOS and 40 age-matched controls. Its diagnostic potential was evaluated by Receiver Operating Characteristic (ROC) curves. RESULTS: The serum AMH level was higher in PCOS patients than in controls (9.85 ± 4.93 ng/mL vs. 7.13 ± 3.02 ng/mL, P = 0.002), and positively related to the mean ovarian volume in PCOS patients (r = 0.319, P = 0.029). The area under the ROC curve for AMH reached a value of 0.664 (0.551–0.778, 95% confidence interval). The best compromise between specificity (70%) and sensitivity (61.7%) was obtained with a cut-off value of 8 ng/mL. CONCLUSIONS: Serum AMH levels are elevated in adolescent and young adult Chinese patients of PCOS. Serum AMH measurement offers a relatively poor diagnostic potency with a sensitivity of 61.7% and a specificity of 70% at 8 ng/mL.

The aim of the current study was to examine the effects of gonadotropin-releasing hormone agonist (GnRH-a) and antagonist (GnRH-ant) on the expression of GnRH receptor-I (GnRHR-I) in pituitary and ovaries in cyclophosphamide (CTX) chemotherapeutic rats and to investigate the possible mechanism of interventions of GnRH-a and GnRH-ant in CTX-induced ovarian damage. In total, 36 female rats were distributed into 6 groups at random: normal saline (NS) group, CTX group, GnRH-a + NS group, GnRH-a + CTX group, GnRH-ant + NS group, and GnRH-ant + CTX group. After the rats were killed, the expression of GnRHR-I messenger RNAs (mRNAs) and proteins in pituitary and ovaries were examined by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively. The distribution of GnRHR-I in various compartments of the ovaries was observed by immunohistochemistry. Significant downregulation of GnRHR-I mRNA and protein expression in the pituitary were observed after treatment with GnRH-a or GnRH-ant. Moreover, GnRH-ant was more potent for this direct and fast inhibition. In ovary, GnRHR-I expression was significantly downregulated by GnRH-a. Although GnRH-ant slightly decreased the ovarian expression of GnRHR-I mRNA, the protein level was only weakly changed. In the ovarian compartment, GnRHR-ant groups had markedly GnRHR-I expression in early and late growing follicles compared to GnRHR-a groups that exhibited decreased expression of GnRHR-I, especially in late growing follicles. In summary, this study presents evidence for the different regulating effects of GnRH-a and GnRH-ant on the expression of GnRHR-I in pituitary and ovaries, which may provide insight into the mechanism of GnRH-a and GnRH-ant interventions on chemotoxic ovarian damage.

Objective To evaluate the effect of hyperandrogenism on metabolic disorders among patients with polycystic ovary syndrome (PCOS) diagnosed using the Rotterdam criteria. Methods A retrospective analysis of the clinical records of 883 women with PCOS and 717 premenopausal controls identified from the general population. Results A total of 686 (77.7%) patients were classified with PCOS based on National Institutes of Health (NIH) criteria, and 164 out of 197 (83.2%) additional patients had no hyperandrogenism. Women with normal androgen levels exhibited lower frequencies of obesity, type 2 diabetes, acanthosis nigricans, genetic history of diabetes, and elevated Matsuda index compared with hyperandrogenic patients. Hyperandrogenemia, but not hirsutism, was independently associated with the risk for type 2 diabetes (odds ratio [OR] 5.7; P = 0.028) and obesity (OR 1.7; P = 0.005) among Chinese patients with PCOS. Conclusions Hyperandrogenemia is associated with type 2 diabetes and obesity in Chinese women with PCOS and should be considered at first-line management of hyperandrogenism and infertility due to PCOS.

ObjectiveVariations in the prevalence of metabolic syndrome (MetS) among women with polycystic ovary syndrome (PCOS) in different races were reported. We sought to report this prevalence and its components in Chinese women with PCOS and compared these characteristics with healthy controls.DesignAnthropometric measurements and biochemical parameters were evaluated in 578 PCOS patients diagnosed by the Rotterdam criteria and 281 age- and body mass index (BMI)-matched controls. International Diabetes Federation criteria for MetS were used.ResultsThe prevalence of MetS was 16.8% in this study, and 60.7% of patients displayed at least one component of MetS. Among the patients, the rates of dyslipidemia, impaired fasting glucose, and elevated blood pressure were 41.6, 19.8, and 16.1% respectively; the rates of these corresponding components in age- and BMI-matched controls were 14.6, 5.3, and 5.7% respectively. In PCOS patients, the prevalence of MetS was 0.0, 3.9, 20.2, and 51.1% for four different BMI groups respectively; the prevalence of MetS was 7.3, 14.9, 24.2, and 42.4% in the four age groups respectively. Nearly 90% of patients diagnosed with MetS belonged to overweight and obese groups. BMI and age rather than free testosterone, free androgen index, fasting insulin, or sex hormone-binding globulin were included in formulation for predicting MetS according to multivariable logistic regression.ConclusionsLow prevalence of MetS but high occurrence of various metabolic disorders was found in women with PCOS compared with age- and BMI-matched controls in this study. BMI and age appeared to contribute more to developing MetS than other parameters associated with insulin resistance or hyperandrogenism.

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.

To explore the prevalence of menopausal symptoms in Chinese women aged 40-65 years living in Guangdong province in southern China, and to investigate their care-seeking behavior.A cross-sectional population-based study performed in Guangdong province, PR China.A total of 9939 women were selected by multistage cluster sampling. From November 2003 to July 2004, women were interviewed in person with a prepared questionnaire about symptoms experienced in the 2 months preceding the survey. The main outcome measurements were self-reported menopausal symptoms and related factors.The mean age of natural menopause was 48.9 years. The prevalence and severity of menopausal symptoms were low. The three most prevalent symptoms were insomnia, joint and muscle pain, and dizziness (in 37.2%, 35.7%, and 31.5% of the sample, respectively). Hot flushes were experienced by 17.5% of women. The factors associated with the frequency of menopausal symptoms included profession, education, type of menopause and the presence of physical or emotional problems. Ever and current hormone replacement therapy usage was reported in 0.8% and 1.3% of women, respectively. Of the total study population, 28.9% had sought health care because of menopausal symptoms.The prevalence of menopausal symptoms in southern Chinese women is low, and this is accompanied by low usage of hormone replacement therapy.

It remains unclear whether neo-oogenesis occurs in postnatal ovaries of mammals, based on studies in mice. We thought to test whether adult human ovaries contain germline stem cells (GSCs) and undergo neo-oogenesis. Rather than using genetic manipulation which is unethical in humans, we took the approach of analyzing the expression of meiotic marker genes and genes for germ cell proliferation, which are required for neo-oogenesis, in adult human ovaries covering an age range from 28 to 53 years old, compared to testis and fetal ovaries served as positive controls. We show that active meiosis, neo-oogenesis and GSCs are unlikely to exist in normal, adult, human ovaries. No early meiotic-specific or oogenesis-associated mRNAs for SPO11, PRDM9, SCP1, TERT and NOBOX were detectable in adult human ovaries using RT–PCR, compared to fetal ovary and adult testis controls. These findings are further corroborated by the absence of early meiocytes and proliferating germ cells in adult human ovarian cortex probed with markers for meiosis (SCP3), oogonium (OCT3/4, c-KIT), and cell cycle progression (Ki-67, PCNA), in contrast to fetal ovary controls. If postnatal oogenesis is confirmed in mice, then this species would represent an exception to the rule that neo-oogenesis does not occur in adults.

A retrospective study conducted in an academic reproductive medicine centre evaluated the feasibility and safety of early fetal reduction in dichorionic triplets to dichorionic twin or singleton pregnancies. Thirty-three dichorionic triplets that underwent early transvaginal fetal reduction mechanically between 2002 and 2013 were included, of which 21 patients underwent fetal reduction to dichorionic twins (Group A) and 12 patients underwent fetal reduction to a singleton pregnancy (Group B). A further 84 patients with trichorionic triplets reduced to twins were included as the control group (Group C). The main outcome measures were live birth and preterm labour rates. Both early and late spontaneous abortion rates, were similar in group A compared with groups B and C. Gestational age at delivery was significantly lower in group C versus group A (P = 0.02). The preterm labour rate in group A, which was comparable with that in group C, was greater than in group B, but not significantly. Neonatal birth weight, low birth weight rate and neonatal body height were similar among groups. Small for gestational age rates were comparable. Live birth rates were similar among the groups. Early transvaginal fetal reduction for dichorionic triplets to dichorionic twins may be feasible and safe.

The objective of this retrospective study was to determine whether patients undergoing in vitro fertilization (IVF) benefit from reducing the gamete co-incubation time. Patients (n = 570) were enrolled, including 281 patients in the reduced incubation time group (2-h incubation) and 289 patients in the standard IVF group (18-h incubation). The observed outcomes, including the clinical pregnancy rate (CPR), implantation rate (IR), live birth rate (LBR), and miscarriage rate (MR), were similar between the two groups. When the data were divided into two subgroups based on the maternal age (≤30 and >30 years), the rates of top-quality embryos (30.83 vs. 25.89 %; p = 0.028), CPR (66.67 vs. 42.11 %; p = 0.013), and IR (41.90 vs. 31.25 %, p = 0.019) of the 2-h incubation group were significantly higher in the younger subgroup. However, for older patients, only a lower MR (7.59 vs. 20.83 %; p = 0.019) was achieved. Reducing the time of incubation still improved the CPR (OR = 1.993, 95 % CI 1.141–3.480) and MR (OR = 3.173, 95 % CI 1.013–9.936) in the younger and older subgroups, respectively, after it was adjusted for potential confounders. Reducing incubation time improves the clinical results of IVF, although the LBR is not statistically different between the 2- and 18-h incubation time groups. And the specific clinical outcomes of reducing incubation time varied between the >30-year-old and the ≤30-year-old.

MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression post-transcriptionally. Whether differently expressed miRNAs contribute to promoting granulosa cell proliferation in polycystic ovarian syndrome disease (PCOS) remains unknown.We explored whether certain miRNAs are involved in the ovarian dysfunction of PCOS and the mechanism of increased granulosa cells proliferation. Patients and Cells: miRNA expression was analyzed in excised ovarian cortexes from 16 women with PCOS and 8 non-PCOS. An immortalized human granulosa (KGN) cell was used for the mechanism study.Expressions of miRNAs in ovarian cortexes were measured using qRT-PCR and KGN granulosa cells were cultured for proliferation assays after overexpression or inhibition of miR-93 or after insulin treatment. Bioinformatics were used to identify the potential miRNA targets. Protein expression analysis, luciferase assays, and rescue assays were used to confirm the substrate of miR-93.MiR-93 expression was higher in PCOS ovarian cortex and its identified target, CDKN1A, was downregulated. MiR-93 overexpression promoted cell proliferation and G1 to S transition. Knocking down CDKN1A promoted cell growth and cell cycle progression in granulosa cells, and CDKN1A re-introduction reversed the promotional role of miR-93. High concentrations of insulin induced upregulation of miR-93, stimulated KGN cells proliferation and reduced CDKN1A expression.miR-93 was increased in PCOS granulosa cells and targeted CDKN1A to promote proliferation and cell cycle progression. Insulin could upregulate the expression of miR-93 and stimulate cell proliferation. This might provide a new insight into the dysfunction of granulosa cells in PCOS.

Objective To evaluate the effects of berberine on the menstrual pattern, ovulation rate, hormonal and metabolic profiles in anovulatory Chinese women with polycystic ovary syndrome. Methods Berberine 0.4 g three times per day was given for four months to 102 anovulatory Chinese women with polycystic ovary syndrome. The menstrual pattern, ovulation rate, hormonal and metabolic profiles were compared before and after the berberine treatment. Ovulation was confirmed by serum progesterone level ≥10ng/ml. Results A total of 98 of 102 subjects (96.1%) completed the four month treatment, including 69 (70.4%, 69/98) normal weight and 29 (29.6%, 29/98) overweight/obese. Fourteen women (14.3%, 14/98) had regained regular menses after berberine treatment and there was no significant difference between normal weight and overweight/obese groups. The ovulation rate was 25.0% over four months in the whole group, 22.5% in the normal weight group and 31.0% in the overweight/obese group. Sex hormone binding globulin, insulin resistance, total cholesterol, total triglyceride and low-density lipoprotein cholesterol decreased after berberine treatment in the normal weight group only. Conclusions Our study found that administration of berberine alone may improve the menstrual pattern and ovulation rate in anovulatory Chinese women with polycystic ovary syndrome. Berberine can also decrease sex hormone binding globulin, insulin resistance, total cholesterol, triglycerides and low-density lipoprotein cholesterol in normal weight polycystic ovary syndrome women. Trial Registration Chictr.org ChiCTR-OO-13003943

Background.Single-nucleotide polymorphisms (SNPs) in the follicle stimulating hormone receptor (FSHR) gene are associated with PCOS. However, their relationship to the polycystic ovary (PCO) morphology remains unknown. This study aimed to investigate whether PCOS related SNPs in the FSHR gene are associated with PCO in women with PCOS.Methods. Patients were grouped into PCO (n=384) and non-PCO (n=63) groups. Genomic genotypes were profiled using Affymetrix human genome SNP chip 6. Two polymorphisms (rs2268361 and rs2349415) of FSHR were analyzed using a statistical approach.Results. Significant differences were found in the allele distributions of the GG genotype of rs2268361 between the PCO and non-PCO groups (27.6% GG, 53.4% GA, and 19.0% AA versus 33.3% GG, 36.5% GA, and 30.2% AA), while no significant differences were found in the allele distributions of the GG genotype of rs2349415. When rs2268361 was considered, there were statistically significant differences of serum follicle stimulating hormone, estradiol, and sex hormone binding globulin between genotypes in the PCO group. In case of the rs2349415 SNP, only serum sex hormone binding globulin was statistically different between genotypes in the PCO group.Conclusions. Functional variants in FSHR gene may contribute to PCO susceptibility in women with PCOS.

Objective To determine the inflammatory response in the peritoneal cavity by the presence of endometrial cells and the role of the mesothelium. Design In vivo study using mice. Setting University research laboratory. Animal(s) Female Swiss Webster mice, 8 to 10 weeks old. Intervention(s) Homogenous mouse endometrial epithelial and stromal cells were injected intraperitoneally. Peritoneal lavage and mesothelium were collected 4 to 72 hours after the administration. Main outcome measure(s) We determined the number of peritoneal macrophages, and the production and gene expression of monocyte chemotactic protein-1 (MCP-1/JE), interleukin 1α (IL-1α), and interleukin 6 (IL-6). Result(s) The intraperitoneal administration of endometrial cells increased the number of peritoneal macrophages, production of MCP-l, IL-1α, and IL-6, and expression of mesothelial MCP-1/JE, IL-1α, and IL-6 genes in recipient mice. Conclusion(s) These results suggest that retrograde menstruation could account for the increased presence of inflammatory mediators in the peritoneal cavity of women with endometriosis. The mesothelium could play an active role in endometriosis in addition to providing an attachment stratum for the endometrial cells.

Postoperative pancreatic fistula (PF) is the leading morbidity after pancreaticoduodenectomy (PD). The pancreatoenteric anastomosis method after PD is associated with the occurrence of PF. Evidence shows that pancreaticogastrostomy (PG) is possibly superior to pancreaticojejunostomy (PJ) in reducing the incidence of PF after PD; however, this remains to be definitively confirmed.Randomized clinical trials (RCTs) comparing the outcomes of PG versus PJ after PD were retrieved for meta-analysis.After a thorough search of the English literature published until March 23rd, 2014, we identified seven RCTs involving 1095 patients (PG group, 548; PJ group, 547) for final analysis. Meta-analysis revealed that the incidence of PF was significantly lower in the PG group (15.7%) than in the PJ group (23.0%, 126/547; OR = 0.61, 95% CI: 0.45-0.83, P = 0.002). Furthermore, the incidence of intra-abdominal fluid collection was also lower in the PG group than in the PJ group (OR = 0.43, 95% CI: 0.28-0.65, P0.0001). No significant differences were found between the PG and PJ groups in terms of delayed gastric emptying, hemorrhage, overall morbidity and mortality.PG seemed to be superior to PJ in reducing the incidence of PF and intra-abdominal fluid collection after PD.

The objective of this study was to further investigate the association of low androgen levels and poor ovarian response or negative pregnancy outcome in in vitro fertilisation treatment using a retrospective cohort study. Chinese women (n = 1950) of relatively young age, with normal range of basal FSH and antral follicle count undergoing an in vitro fertilisation cycle were selected and testosterone and dehydroepiandrosterone sulfate levels were measured on Day 3 of the menstrual cycle before subsequent in vitro fertilisation treatment. The main outcome measures of the study were ovarian stimulation parameters and clinical pregnancy. Basal testosterone levels of poor responders and non-pregnant women were significantly lower than normal responders and pregnant women, respectively. Patients with low basal testosterone levels had significantly lower number of mature oocytes, cleavage-stage embryos, frozen embryos, lower fertilisation and pregnancy rates and required higher doses of gonadotrophins. Androgen levels had no correlation with early spontaneous abortion rates. Multivariable logistic analysis revealed that low basal testosterone (

Objects: Metabolic syndrome (MS) is an independent risk factor for chronic metabolic disorders (CMD). This study investigated the prevalence of MS and overweight/obesity among women of childbearing age in southern China. Methods: A nationally representative sample of 3200 southern Chinese women aged 20-45 years were randomly selected from 16 sampling units of two rural areas (Zhongshan and Xinhui) and two city regions (Guangzhou and Shenzhen) in Guangdong Province in China between June 2008 and July 2009. The prevalence of MS according to modified ATP III criteria and overweight/obesity (≥ 23.0 kg/m2) were analyzed. Results: Approximately 1.28 million women in Guangdong, China, were estimated to have MS, with an ageadjusted prevalence of 6.6% (95% CI 5.3%-7.5%), and 4.22 million [21.7% (95% CI 20.2%-23.2%)] were estimated to have overweight/obesity. In total, 39.5% women had one component of MS, 19.4% two components, 5.6% three components, and 0.9% at least four components. Compared to the 4.7% MS prevalence in women aged 20-25 years, the prevalence increased in women aged 31-35 years (1.3-fold) and increased more sharply in women aged 36-45 years (2.3-fold). The age-specific prevalence of overweight/obesity increased steadily by 1.3-1.8-fold beginning at 26-30 years of age (9.0%), and it reached a peak at 36-45 years of age (36.0%). The prevalence of MS and overweight/obesity increased in rural residents who preferred unhealthy diets and exercised less compared to urban residents. Conclusion: Some women of reproductive age in southern China had MS, and a significant, and perhaps growing, proportion of women were overweight. Less exercise contributes to the higher prevalence of MS and overweight/obesity among rural residents than urban residents.

Objective To review published randomized controlled trials (RCTs) evaluating the outcomes of in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) utilization of gonadotropin-releasing hormone (GnRH) antagonists for ovarian stimulation in polycystic ovarian syndrome (PCOS) patients compared with classic luteal long agonist protocols. Design A meta-analysis of prospective randomized trials published in English between 2002 and 2013. Patient(s) and Interventions Nine RCTs examining PCOS patients undergoing IVF/ICSI including 588 women who underwent long agonist protocols and 554 women who underwent GnRH antagonist protocols. Main Outcome Measure(s) Clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and ovarian hyperstimulation syndrome (OHSS) rate. Result(s) Nine RCTs were included in this analysis. The CPR-per-embryo transferred was similar in the two groups (relative risk (RR): 0.97, 95% confidence interval (CI): 0.85–1.10). Non-significant estimates comparing the two protocols were found for age, BMI, total dose of gonadotropin administered, number of days of stimulation and number of oocytes retrieved. After meta-analysis of 4 of the RCTs, it was concluded that a GnRH antagonist protocol is better than an agonist long protocol to reduce the rate of severe OHSS (odds ratio (OR): 1.56, 95% CI: 0.29–8.51). Conclusion(s) With respect to CPR, a GnRH antagonist protocol is similar to a GnRH agonist long protocol. However, for severe OHSS, a GnRH antagonist protocol is significantly better in PCOS patients.

We aimed to evaluate the effectiveness of granulocyte colony-stimulating factor (G-CSF) administration for infertile women with thin endometrium in frozen embryo transfer program. Among 59 infertile patients with thin endometrium (≤7 mm), 34 patients received uterine infusion of recombinant human G-CSF (100 μg/0.6 mL) on the day of ovulation or administration of progesterone or human chorionic gonadotropin, with 40 cycles defined as G-CSF group and 49 previous cycles as self-controlled group, and 25 patients refused, with 80 cycles defined as the control group. Higher proportion of induced cycles and lower proportion of natural cycles were observed in the G-CSF group, when compared to the self-controlled group or control group (P.05). The cycle cancellation rate was, in descending order, 69.39% in self-controlled group, 48.75% in control group, and 17.50% in G-CSF group, with significant difference (P.05). The implantation rate and clinical pregnancy rate per embryo transfer were similar in all the groups (P.05). Our study fails to demonstrate that G-CSF has the potential to improve embryo implantation and clinical pregnancy rate of the infertile women with thin endometrium.