Effects of vaginal progesterone and placebo on preterm birth and antenatal outcomes in women with singleton pregnancies and short cervix on ultrasound: a meta-analysis.

Background: Vaginal progesterone in preterm birth and adverse outcomes caused by cervical insufficiency remains controversial. To address it, the effect of vaginal progesterone on preterm delivery and perinatal outcome of single pregnancy women with short cervix (less than 25 mm) was systematically evaluated by meta-analysis. Methods: "Vaginal progesterone," "placebo," "ultrasound," "cervix," "singleton pregnancy," "preterm birth," and "antenatal outcomes" were entered to screen clinical studies PubMed, Embase, and the Chinese Biomedical Literature Database (CBM). The study population consisted of women with singleton pregnancies and a short cervix on ultrasound, and were assigned into the progesterone group (n = 1,368) and the placebo group (n = 1,373). Treatment began after the patient was diagnosed with short cervix until delivery. Neonatal survival rate, Neonatal Intensive Care Unit (NICU) admission rate, respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), neonatal mortality, and birth weight <1,500 g were analyzed. Results: A total of 8 articles, totaling 2,741 study subjects, were enrolled. The progesterone group exhibited an obvious reduced rate of preterm birth at <34 weeks (OR = 0.67, 95% CI: 0.53∼0.84; Z = 3.53, P = 0.004), preterm birth at <32 weeks (OR = 0.46, 95% CI: 0.28∼0.77; Z = 2.99, P = 0.003), NICU admission rate (OR = 0.45, 95% CI: 0.30∼0.66; Z = 0.15, P < 0.0001), RDS rate (OR = 0.42, 95% CI: 0.28∼0.63; Z = 4.25, P < 0.0001), IVH incidence rate (OR = 0.40, 95% CI: 0.17∼0.95; Z = 2.08, P = 0.04), neonatal mortality (OR = 0.25, 95% CI: 0.13∼0.46; Z = 4.39, P < 0.0001), and proportion of neonates with birth weight < 1,500 g (OR = 0.45, 95% CI: 0.32∼0.64; Z = 4.50, P < 0.0001). Conclusion: Vaginal progesterone lowered the incidences of preterm birth and adverse pregnancy outcomes in women with singleton pregnancies and a short cervix.

The Role Played by Mitochondria in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) refers to an endocrine disorder syndrome that are correlated with multiple organs and systems. PCOS has an effect on women at all stages of their lives, and it has an incidence nearly ranging from 6% to 20% worldwide. Mitochondrial dysfunctions (e.g., oxidative stress, dynamic imbalance, and abnormal quality control system) have been identified in patients and animal models of PCOS, and the above processes may play a certain role in the development of PCOS and its associated complications. However, their specific pathogenic roles should be investigated in depth. In this review, recent studies on the mechanisms of action of mitochondrial dysfunction in PCOS and its associated clinical manifestations are summarized from the perspective of tissues and organs, and some studies on the treatment of the disease by improving mitochondrial function are reviewed to highlight key role of mitochondrial dysfunction in this syndrome.

How to minimize the dropout and crossover in an infertility trial?

Randomized controlled trials and intent-to-treat analyses are important for infertility clinical studies. Dropouts or crossovers during the study process will disrupt the randomization design and affect the intent-to-treat analysis. In this review, we have briefly introduced the occurrence of dropout and crossover from our previous Reproductive Medicine Network and other related studies and provided some experience obtained from these studies on how to minimize and reduce the occurrence of dropout and crossover for infertility randomized clinical studies.

Upregulation of TXNIP contributes to granulosa cell dysfunction in polycystic ovary syndrome via activation of the NLRP3 inflammasome.

Polycystic ovary syndrome (PCOS) is a complex endocrine disease. Thioredoxin-interacting protein (TXNIP) promotes oxidative stress and triggers inflammation. Herein, we investigated the role and potential mechanism of TXNIP in PCOS. In a mouse model of dehydroepiandrosterone (DHEA)-induced PCOS, we found that TXNIP was upregulated in the ovaries, especially in granulosa cells (GCs). TXNIP was also upregulated in testosterone (T)-treated GCs in vitro. Knockdown of TXNIP by lentivirus-constructed shRNA attenuated T-induced GC injury and oxidative stress, as well as inflammation and the NLRP3 inflammasome. The mechanism by which TXNIP promotes inflammation may involve TXNIP dissociation from the TXNIP-TRX complex and binding to NLRP3 to form the inflammasome. Additionally, we verified that knockdown of TXNIP ameliorated ovarian injury and inflammation in mice with DHEA-induced PCOS in vivo. Collectively, we demonstrated that TXNIP is involved in GC inflammation by promoting NLRP3 inflammasome activation in PCOS.

Knowledge mapping of copper-induced cell death: A bibliometric study from 2012 to 2022.

BACKGROUND: The recent article Copper induces cell death by targeting lipoylated TCA cycle proteins has attracted much attention. Although copper-induced cell death has only recently been formally proposed, it has been studied much earlier. This study aims to undertake a bibliometric analysis of the literature on copper-induced cell death to understand the development of copper-induced cell death better and identify potential new research directions. METHODS: With the help of Cite Space software, visual analysis is carried out on the annual number of published papers, countries/regions and institutions, journals co-citation, literature co-citation and reference burst, keywords co-occurrence, clustering, and burst. RESULTS: A search of 770 articles published in English over the last ten years showed a fluctuating trend of increasing numbers of articles. China had the highest number of articles (190% or 24.68%), followed by the USA and India. Inflammation, biological evaluation, nanoparticle, and cu(ii) have been popular research themes in the last 4 years. The keyword clusters are summarized in 8 categories, including exposure, complexe, er stress, cleavage, paraptosis, cancer, glutamate, reactive oxygen species (ROS), expression. The hot topics are mainly focused on the exploration of mechanisms and related diseases, including induced apoptosis, aggregation, autophagy, endoplasmic reticulum stress, induced oxidative stress, and inflammation. Parkinson's disease and cancer are 2 diseases that are closely related to copper-induced cell death. CONCLUSION: This study provides a visual analysis of copper-induced cell death trends and provides some hidden potentially useful information for future research directions.

The role of serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome.

OBJECTIVE: To study the role of selected serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome (PCOS). METHODS: Selected serum inflammatory cytokines were analyzed in the particle cells, which were interfered by berberine, from 78 infertile women who were to be treated with In Vitro Fertilization (IVF) /Intracytoplasmic Sperm Injection-Embryo Transfer (icsi-et). Among them, 49 patients had PCOS infertility, and 29 were non-PCOS patients whose infertility resulted from fallopian tube and male factors. The elisa method was used to detect the changes in the expression levels of inflammatory factors in the cells. The correlations between the serum inflammatory cytokine expression levels and the corresponding clinical hormones were analyzed. The changes in the expression (mRNA and protein) levels of the serum inflammatory cytokines were studied by real-time quantitative PCR and protein printing. Fluorescence microscope and flow cytometry were used to detect the glucose uptake capacity of ovarian granulosa cells in PCOS patients under the action of insulin after berberine. RESULTS: In the PCOS group, IL-17a (P = 0.001), IL-1Ra (P<0.0001), and IL-6 (P = 0.035) were significantly higher than those in the non-PCOS group. In the non-PCOS group, AMH level was negatively correlated with inflammatory cytokines IL-17a (r = -0.819;P = 0.004), IL-1a (r = -0.716;P = 0.0.02), IL-1b (r = -0.678;P = 0.031), IL-2 (r = -0.765;P = 0.01), and IL-8 (r = -0.705;P = 0.023). However, in the PCOS group, AMH levels were not significantly correlated with the levels of the examined inflammatory cytokines. Berberine significantly reduced the expression level of mTOR mRNA (P = 0.001), and increased the expression level of IRS-1 mRNA (P = 0.009) in the PCOS granule cells. CONCLUSION: In this study, we find that the elevated levels of serum inflammatory factors IL-17a, IL-1Ra, and IL-6 cause women to be in a subclinical inflammatory state for a long time. Abnormal changes in inflammatory factors alter their original negative correlations with AMH levels, thereby weakening the metabolism of glycolipids, promoting insulin resistance, destroying the normal ovulation and fertilization system of women, leading to polycystic ovary syndrome characterized by menstrual thinning and abnormal ovulation. Berberine can improve the sensitivity of insulin by regulating the signal pathway of insulin receptor substrate-1 (IRS-1) and mammalian target of rapamycin (mTOR) in PCOS patients and achieve a therapeutic effect of treating PCOS.

Berberine increases glucose uptake and intracellular ROS levels by promoting Sirtuin 3 ubiquitination.

OBJECTIVE: Berberine improves insulin sensitivity and ovulation function in PCOS patients. However, the mechanism by which berberine initiates glucose metabolism-related signaling pathways in ovarian cells remains unknown. This study unveiled a new mechanism by which berberine promotes ovarian cell glucose uptake, and demonstrated that SIRT3 ubiquitination is involved in the insulin sensitizing effect of berberine. METHODS: Berberine was used at different concentrations to treat cultured KGN cells. Then, cell viability, cell apoptosis, intracellular ROS levels, mitochondrial depolarization and activation of related signaling pathways were evaluated. RESULTS: Berberine administration led to mitochondrial depolarization and AMP accumulation by promoting SIRT3 ubiquitination. We confirmed that AMP accumulation activated AMPK signaling and further promoted glucose uptake. Meanwhile, berberine reduced the activity of mitochondrial complex I in a dose-depended manner, but not that of mitochondrial complex II. Furthermore, intracellular ROS levels and the expression of mitochondrial apoptosis pathway related factors increased with berberine concentration. Berberine caused significant SIRT3 ubiquitination and degradation by activating the AMPK pathway and increasing intracellular ROS levels. Interestingly, berberine induced ubiquitination paralleled the increased FOXO3a phosphorylation and FOXO3a/Parkin pathway activation. CONCLUSIONS: Berberine promotes glucose uptake and inhibits mitochondrial function by promoting SIRT3 ubiquitination, and is likely to regulate autophagy related function in ovarian cells by activating the AMPK pathway. These findings may provide novel insights into the development of drugs for the treatment of abnormal reproductive functions of the ovary.

Lower prevalence of non-cavity-distorting uterine fibroids in patients with polycystic ovary syndrome than in those with unexplained infertility.

OBJECTIVE: To study whether there is a difference in the prevalence of non-cavity-distorting uterine fibroids between infertile patients with polycystic ovary syndrome (PCOS) and those with unexplained infertility (UI). DESIGN: A secondary analysis of data from three randomized clinical trials. SETTING: Academic health centers. PATIENT(S): A total of 2,249 patients with normal uterine cavities. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): The presence or absence of non-cavity-distorting fibroids. RESULT(S): Compared with women with UI, those with PCOS were younger, had a higher body mass index, and were more likely to be Hispanic or African American, with a lower percentage of previous conception and live birth, a higher percentage of current smokers, a lower percentage of current alcohol users, and higher total testosterone, fasting insulin, and homeostasis-model-assessment insulin resistance. The prevalence of women with non-cavity-distorting uterine fibroids was lower in women with PCOS than in those with UI (6.7% vs. 12.4%); this result held after patients were divided into Black and non-Black or into three different body mass index groups. After adjustment for all the other variables in the final model, patients with PCOS had a significantly lower prevalence of fibroids than those with UI (odds ratio 0.54). No differences in the prevalence of non-cavity-distorting fibroids with any dimensions ≥4 cm or the volume of the largest fibroid was found between the two groups. CONCLUSION(S): A lower prevalence of non-cavity-distorting uterine fibroids was found in infertile women with PCOS than in those with UI.

Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.

Chinese Obstetrics & Gynecology journal club: a randomised controlled trial.

OBJECTIVES: To assess whether a journal club model could improve comprehension and written and spoken medical English in a population of Chinese medical professionals. SETTING AND PARTICIPANTS: The study population consisted of 52 medical professionals who were residents or postgraduate master or PhD students in the Department of Obstetrics and Gynecology, Heilongjiang University of Chinese Medicine, China. INTERVENTION: After a three-part baseline examination to assess medical English comprehension, participants were randomised to either (1) an intensive journal club treatment arm or (2) a self-study group. At the conclusion of the 8-week intervention participants (n=52) were re-tested with new questions. OUTCOME MEASURES: The primary outcome was the change in score on a multiple choice examination. Secondary outcomes included change in scores on written and oral examinations which were modelled on the Test of English as a Foreign Language (TOEFL). RESULTS: Both groups had improved scores on the multiple choice examination without a statistically significant difference between them (90% power). However, there was a statistically significant difference between the groups in mean improvement in scores for both written (95% CI 1.1 to 5.0; p=0.003) and spoken English (95% CI 0.06 to 3.7; p=0.04) favouring the journal club intervention. CONCLUSIONS: Interacting with colleagues and an English-speaking facilitator in a journal club improved both written and spoken medical English in Chinese medical professionals. Journal clubs may be suitable for use as a self-sustainable teaching model to improve fluency in medical English in foreign medical professionals. TRIAL REGISTRATION NUMBER: NCT01844609.

Predictors of participant retention in infertility treatment trials.

OBJECTIVE: To identify variables associated with retention (or dropout) in infertility clinical trials. Retention of subjects in randomized controlled clinical trials (RCTs) has received considerable attention, but there have been few consistent findings. DESIGN: Secondary analysis of data from RCTs. SETTING: Academic medical centers. PATIENT(S): Women with polycystic ovary syndrome (PCOS) or couples with unexplained infertility, aged 18-40 years. INTERVENTION(S): This study is not an intervention study, but the patients in the original RCTs were treated with any or combination of metformin, clomiphene citrate (CC), letrozole, and gonadotropins. MAIN OUTCOME MEASURE(S): Successful retention versus dropout during the RCTs. RESULT(S): Race, ethnicity, body mass index (BMI), insurance coverage, history of smoking, and history of alcohol use were significantly associated with retention whether they were considered in bivariate analyses or a multivariable logistic model. Specifically, white race, higher income, having graduate degrees, normal weight, better insurance coverage, nonsmokers, and those who reported current use of alcohol at the start of the trial, had higher retention rates. CONCLUSION(S): We identified several additive and persistent predictors of retention that can be used to guide the conduct of RCTs and improve the retention rate. Given the limitation of our association analysis, methodologically sound and theoretically grounded research are warranted so that high quality data can be collected to improve our understanding on the causes of dropout. CLINICAL TRIAL REGISTRATION NUMBER: NCT00068861 (PPCOS-I), NCT00719186 (PPCOS-II), and NCT01044862 (AMIGOS).

Identification and replication of prediction models for ovulation, pregnancy and live birth in infertile women with polycystic ovary syndrome.

STUDY QUESTION: Can we build and validate predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: We were able to develop and validate a predictive model for pregnancy outcomes in women with PCOS using simple clinical and biochemical criteria particularly duration of attempting conception, which was the most consistent predictor among all considered factors for pregnancy outcomes. WHAT IS KNOWN ALREADY: Predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome have been reported, but such models require validation. STUDY DESIGN, SIZE, AND DURATION: This is a secondary analysis of the data from the Pregnancy in Polycystic Ovary Syndrome I and II (PPCOS-I and -II) trials. Both trials were double-blind, randomized clinical trials that included 626 and 750 infertile women with PCOS, respectively. PPCOS-I participants were randomized to either clomiphene citrate (CC), metformin, or their combination, and PPCOS-II participants to either letrozole or CC for up to five treatment cycles. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: Linear logistic regression models were fitted using treatment, BMI, and other published variables as predictors of ovulation, conception, clinical pregnancy, and live birth as the outcome one at a time. We first evaluated previously reported significant predictors, and then constructed new prediction models. Receiver operating characteristic (ROC) curves were constructed and the area under the curves (AUCs) was calculated to compare performance using different models and data. Chi-square tests were used to examine the goodness-of-fit and prediction power of logistic regression model. MAIN RESULTS AND THE ROLE OF CHANCE: Predictive factors were similar between PPCOS-I and II, but the two participant samples differed statistically significantly but the differences were clinically minor on key baseline characteristics and hormone levels. Women in PPCOS-II had an overall more severe PCOS phenotype than women in PPCOS-I. The clinically minor but statistically significant differences may be due to the large sample sizes. Younger age, lower baseline free androgen index and insulin, shorter duration of attempting conception, and higher baseline sex hormone-binding globulin significantly predicted at least one pregnancy outcome. The ROC curves (with AUCs of 0.66-0.76) and calibration plots and chi-square tests indicated stable predictive power of the identified variables (P-values ≥0.07 for all goodness-of-fit and validation tests). LIMITATIONS, REASONS FOR CAUTION: This is a secondary analysis. Although our primary objective was to confirm previously reported results and identify new predictors of ovulation and pregnancy outcomes among PPCOS-II participants, our approach is exploratory and warrants further replication. WIDER IMPLICATIONS OF THE FINDINGS: We have largely confirmed the predictors that were identified in the PPCOS-I trial. However, we have also revealed new predictors, particularly the role of smoking. While a history of ever smoking was not a significant predictor for live birth, a closer look at current, quit, and never smoking revealed that current smoking was a significant risk factor. STUDY FUNDING/COMPETING INTERESTS: The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD27049, U10 HD38992, U10HD055925, U10 HD39005, U10 HD33172, U10 HD38998, U10 HD055936, U10 HD055942, and U10 HD055944; and U54-HD29834. Heilongjiang University of Chinese Medicine Grants 051277 and B201005. R.S.L. reports receiving consulting fees from Euroscreen, AstraZeneca, Clarus Therapeutics, and Takeda, and grant support from Ferring, Astra Zeneca, and Toba. K.R.H. reports receiving grant support from Roche Diagnostics and Ferring Pharmascience. G.C. reports receiving Honorarium and grant support from Abbvie Pharmaceuticals and Bayer Pharmaceuticals. M.P.D. holds equity from Advanced Reproductive Care Inc. and DS Biotech, receives fees from Advanced Reproductive Care Inc., Actamax, Auxogyn, ZSX Medical, Halt Medical, and Neomed, and receives grant support from Boehringer-Ingelheim, Abbott, and BioSante, Ferring Pharmaceuticals, and EMD Serono. H.Z. receives research support from the Chinese 1000-scholar plan. Others report no disclosures other than NIH grant support. TRIAL REGISTRATION NUMBER: PPCOS-I and -II were respectively registered at Clinicaltrials.gov: NCT00719186 and NCT00719186.

The effect of complementary and alternative medicine on subfertile women with in vitro fertilization.

About 10-15% of couples have difficulty conceiving at some point in their reproductive lives and thus have to seek specialist fertility care. One of the most commonly used treatment options is in vitro fertilization (IVF) and its related expansions. Despite many recent technological advances, the average IVF live birth rate per single initiated cycle is still only 30%. Consequently, there is a need to find new therapies to promote the efficiency of the procedure. Many patients have turned to complementary and alternative medical (CAM) treatments as an adjuvant therapy to improve their chances of success when they undergo IVF treatment. At present, several CAM methods have been used in infertile couples with IVF, which has achieved obvious effects. However, biologically plausible mechanisms of the action of CAM for IVF have not been systematically reviewed. This review briefly summarizes the current progress of the impact of CAM on the outcomes of IVF and introduces the mechanisms.

Letrozole, berberine, or their combination for anovulatory infertility in women with polycystic ovary syndrome: study design of a double-blind randomised controlled trial.

INTRODUCTION: Letrozole is being used as an alternative to clomiphene citrate in women with polycystic ovary syndrome (PCOS) requiring ovulation induction. Berberine, a major active component of Chinese herbal medicine rhizoma coptidis, has been used to improve insulin resistance to facilitate ovulation induction in women with PCOS but there is no study reporting the live birth or its potential as a complementary treatment to letrozole. We aim to determine the efficacy of letrozole with or without berberine in achieving live births among 660 infertile women with PCOS in Mainland China. METHODS AND ANALYSIS: This study is a multicentre randomised, double-blind trial. The randomisation scheme is coordinated through the central mechanism and stratified by the participating site. Participants are randomised into one of the three treatment arms: (1) letrozole and berberine, (2) letrozole and berberine placebo, or (3) letrozole placebo and berberine. Berberine is administered three times a day (1.5 g/day) for up to 24 weeks, starting on day 1 after a spontaneous period or a withdrawal bleeding. Either letrozole or letrozole placebo 2.5 mg is given daily from day 3 to day 7 of the first three cycles and the dose is increased to 5 mg/day in the last three cycles, if not pregnant. The primary hypothesis is that the combination of berberine and letrozole results in a significantly higher live birth rate than letrozole or berberine alone. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine. Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01116167.

Acupuncture and clomiphene citrate for live birth in polycystic ovary syndrome: study design of a randomized controlled trial.

Acupuncture is an alternative therapy to induce ovulation in women with polycystic ovary syndrome (PCOS), but there is no study reporting the live birth rate following ovulation induction by acupuncture or its potential as an adjuvant treatment to clomiphene citrate (CC). We assess the efficacy of acupuncture with or without CC in achieving live births among 1000 PCOS women in Mainland China. This paper reports the methodology of an ongoing multicenter randomized controlled trial. The randomization scheme is coordinated through the central mechanism and stratified by the participating sites. Participants will be randomized into one of the four treatment arms: (A) true acupuncture and CC, (B) control acupuncture and CC, (C) true acupuncture and placebo CC, and (D) control acupuncture and placebo CC. To ensure the quality and integrity of the trial we have developed a unique multinational team of investigators and Data and Safety Monitoring Board. Up to the end of April 2013, 326 subjects were recruited. In conclusion, the success of this trial will allow us to evaluate the additional benefit of acupuncture beyond the first line medicine for fertility treatment in PCOS women in an unbiased manner.

Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial.

BACKGROUND: Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, ovulatory dysfunction, and presence of polycystic ovaries on pelvic scanning. Insulin resistance is significantly associated with the long-term risks of metabolic syndrome and cardiovascular disease. Berberine has effects on insulin resistance but its use in women with PCOS has not been fully investigated. In this paper, we present a research design evaluating the effects of berberine on insulin resistance in women with PCOS. METHODS/DESIGN: This is a multicenter, randomized, placebo-controlled and double-blind trial. A total of 120 patients will be enrolled in this study and will be randomized into two groups. Berberine or placebo will be taken orally for 12 weeks. The primary outcome is the whole body insulin action assessed with the hyperinsulinemic-euglycemic clamp. DISCUSSION: We postulate that women with PCOS will have improved insulin resistance following berberine administration. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov, NCT01138930.

[Of berberine and puerarin on dexamethasone-induced insulin resistance in porcine ovarian thecal cells].

OBJECTIVE: To explore the direct contribution of dexamethasone (Dex) for insulin resistance inducing in thecal cells and effects of berberine (Ber) and puerarin (Pue). METHODS: Ovarian thecal cells from porcine follicles were isolated and cultured in vitro. Insulin resistance of thecal cells was induced by Dex treatment for 48 h. Then the glucose utilization ratio of thecal cells was detected. Meanwhile, the effects of Ber and Pue on insulin signal transmission and steroid hormones synthesis were determined by RT-PCR and Western blotting. RESULTS: (1) After being treated by Dex for 48 h, the [3-3H] -glucose uptake in cells was lowered by about half, and the glucose content in supernate increased for about 1/3. (2) The RT-PCR and Western blotting showed that levels of insulin receptor substrate-1 (IRS-1), mRNA and protein expression of glucose transporter 4 (GLUT4) lowered, peroxisome proliferator-activated receptor -gamma(PPARgamma) and cytochrome P450 17 hydroxylase (CYP17) mRNA or protein expression increased in the model cells. However, the changes of above insulin signal molecules and CYP17 expression were inversed significantly after treated with Ber and Pue for 48 h. (3) As compared with the control, in the model cells, levels of testosterone (T, microg/mL) was higher (0.82 +/- 0.20 vs 0.38 +/- 0.01, P < 0.05), while after Ber and Pue treatment it was 0.44 +/- 0.24 and 0.45 +/- 0.21 respectively, all lower than that in the model cells (P < 0.05). No significant change of serum progesterone was found in all groups (P > 0.05). CONCLUSIONS: After insulin resistance has been induced, the androgen synthetic capacity of thecal cells enhanced significantly. Ber and Pue could lower the degree of insulin resistance and the androgen synthesis in the model cells, displaying the favorable prospect of the two insulin sensitizing agents for the treatment of polycystic syndrome.

[Effects of ginseng total saponins on nerve growth factor expression in rat with estradiol valerate-induced polycystic ovaries].

OBJECTIVE: To investigate the effect of ginseng total saponins (GTS) on expression of nerve growth factor in rat with polycystic ovaries. METHODS: A total of thirty rats were randomly divided into normal control group, untreated group and GTS group. Polycystic ovaries were induced by a single intramuscular injection of 4 mg estradiol valerate (EV) in rats of the untreated group and GTS group. The rats in the GTS group were administered 50 mg/kg GTS every other day by intraperitoneal injection for 30 days after the EV injection. The expressions of NGF in the ovaries, pituitary and hippocampus were observed by method of immunohistochemistry. RESULTS: Comparison with the normal control group revealed that the expressions of NGF in ovaries, pituitary and hippocampus of rats in the untreated group were increased (P<0.05). The ovarian morphology of the GTS group was almost as normal as that of the normal control group. As compared with the untreated group, the expression of NGF in ovaries of the rats in GTS group was obviously decreased (P<0.05), while the expression of NGF in pituitary and hippocampus showed on difference. CONCLUSION: GTS can decrease the expression of NGF in ovary tissue in rats with polycystic ovaries induced by EV, which may be its mechanism in lessening the polycystic ovary.

[Comparison of clinical efficacies for treatment of 93 patients with chronic pelvic inflammation by Chinese composite yanting decoction medicated via two different paths].

OBJECTIVE: To compare the clinical efficacies of Chinese composite Yanting Decoction medicated via two different paths (via oral and via retention enema) in treating chronic pelvic inflammation. METHODS: Adopting the randomized multicentered parallel contrast principle, 93 patients were assigned to the retention enema (RE) group (47 cases) and the oral medicated (OM) group (46 cases) at random, Yanting Decoction was administered via respective paths for 10 days as one course. The changes of syndromes (qi-stagnance and blood stasis) and local signs were observed before and after treatment. RESULTS: In the 47 patients of the RE group, 3 were cured, the treatment was markedly effective in 20, effective in 22 and ineffective in 2, the total effective rate being 95.7%; while in the 46 patients of the OM group, the corresponding number were 1, 8, 30, 7 and 84.8%, respectively, the difference of the total effective rate between groups was statistically significant (P <0.05). The total effective rate for TCM syndromes in the RE and the OM group was 95.7% (45/47) and 82.6% (38/46) respectively, and that for local signs, 97.9% (46/47) and 84.8% (39/46) respectively, the improvements in the RE group were better than those in the OM group (P <0.05). CONCLUSION: Chinese preparation Yanting Decoction shows good clinical efficacy in treating chronic pelvic inflammation of qi-stagnant blood-stasis type, the effect could be enhanced by medicating via retention enema than that via oral.