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.

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.

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.