Ultrasound-guided transvaginal ovarian needle drilling for clomiphene-resistant polycystic ovarian syndrome in subfertile women.

BACKGROUND: Ovulatory disturbance is a key diagnostic feature of polycystic ovarian syndrome (PCOS), leading to infertility and correspondingly heavy disease burden. Many therapeutic strategies have been used to induce ovulation for women with PCOS who are infertile. Ultrasound-guided transvaginal ovarian needle drilling (UTND) is a novel surgical method used to induce ovulation for women with clomiphene-resistant PCOS at the outpatient clinic.  OBJECTIVES: To evaluate the efficacy and safety of UTND for subfertile women with clomiphene-resistant PCOS. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, and other databases to December 2020. We checked conference abstracts, reference lists, and clinical trials registries. We also contacted experts and specialists in the field for any additional trials . SELECTION CRITERIA: We planned to include randomised controlled trials comparing UTND to laparoscopic ovarian drilling, and UTND combined with gonadotropins to gonadotropins, in women of reproductive age with clomiphene-resistant PCOS and infertility. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the trials identified by the search for inclusion, assessed methodological quality and risk of bias, and extracted data. The primary outcomes were live birth rate and incidence of surgical complications (bleeding and infection). Secondary outcomes included pregnancy rate, ovulation rate, and ovarian hyperstimulation syndrome. We planned to calculate odds ratios with 95% confidence intervals for dichotomous data. We would assess overall quality of the evidence by applying the GRADE criteria. MAIN RESULTS: We did not identify any trials for inclusion in the review. We were unable to assess the benefit or harm of applying UTND for women with clomiphene-resistant PCOS, as no studies could be included in the current review. We moved the previously included trials to studies awaiting classification due to concerns regarding methodology. AUTHORS' CONCLUSIONS: Since we did not identify any studies for inclusion, we were unable to assess the benefit or harm of applying UTND for women with clomiphene-resistant PCOS.

TRAF4 knockdown triggers synergistic lethality with simultaneous PARP1 inhibition in endometrial cancer.

Endometrial cancer (EC) is one of the most common cancers among females worldwide. Advanced stage patients of EC have poor prognosis. Inevitable side effects and treatment tolerance of chemotherapy for EC remain to be addressed. Our results in this study showed that EC cells with higher tumor necrosis factor receptor-associated factor 4 (TRAF4) expression have lower sensitivity to poly ADP-ribose polymerase 1 (PARP1) inhibitors. Upon TRAF4 knockdown, the colony numbers of EC cells were markedly down-regulated, and the markers of DNA double-strand breakage were significantly up-regulated after the treatment of olaparib, a PARP1 inhibitor. TRAF4 knockdown reduced the phosphorylation of protein kinase B (Akt), promoted DNA double-strand breakage, and decreased levels of DNA repair related proteins, including phosphorylated-DNA-dependent protein kinase (p-DNA-PK) and RAD51 recombinase (RAD51). In addition, TRAF4's effect on the sensitivity of EC cells to olaparib was further found to be mainly mediated by Akt phosphorylation. Moreover, in vivo results showed that TRAF4 knockdown enhanced the sensitivity of EC to PARP1 inhibitors using a mouse xenograft model. Collectively, our data suggest that combined application of TRAF4 knockdown and PARP1 inhibition can be used as a promising strategy for synthetic lethality in EC treatment.

Ultrasound-guided transvaginal ovarian needle drilling for clomiphene-resistant polycystic ovarian syndrome in subfertile women.

BACKGROUND: Ovulatory disturbance is a key diagnostic feature of polycystic ovarian syndrome (PCOS), leading to infertility and correspondingly heavy disease burden. Many therapeutic strategies have been used to induce ovulation for women with PCOS who are infertile. Ultrasound-guided transvaginal ovarian needle drilling (UTND) is a novel surgical method used to induce ovulation for women with clomiphene-resistant PCOS at the outpatients clinic. Nevertheless, the quality in most of the studies seemed low, and the safety and efficacy of UTND is still uncertain. OBJECTIVES: To evaluate the efficacy and safety of UTND for subfertile women with clomiphene-resistant PCOS. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, and six other databases to November 2018. We checked conference abstracts from the 2018 ESHRE, reference lists, and clinical trials registries. We contacted experts and specialists in the field. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing UTND to laparoscopic ovarian drilling (LOD), and UTND combined with gonadotropins to gonadotropins alone for women of reproductive age with clomiphene-resistant PCOS and infertility. DATA COLLECTION AND ANALYSIS: Two review authors independently screened appropriate trials for inclusion, assessed methodological quality and risk of bias, and extracted data. The primary outcomes were live birth rate and incidence of surgical complications (bleeding and infection). We included ovarian hyperstimulation syndrome (OHSS) as a secondary outcome. Meta-analyses could only be conducted for the secondary outcomes pregnancy rate and ovulation rate in the comparison of UTND versus LOD using a random-effect model. We calculated odds ratios (OR) with 95% confidence intervals (CI) for dichotomous data. We assessed the overall quality of the evidence by applying GRADE criteria. MAIN RESULTS: We included five trials involving 639 clomiphene-resistant women with PCOS. Three studies compared UTND with LOD, and two compared UTND combined with gonadotropins with gonadotropins alone. The evidence was of low to very low quality. The main limitations were serious risk of bias due to poor reporting of methods, inconsistency resulting from heterogeneity, imprecision induced by limited sample size, and lack of reporting of clinically relevant outcomes such as live birth and surgical complications.UTND versus LODNo studies reported on the main outcome live birth. One study reported on surgical complications; however, the evidence for this outcome was of very low quality because it was based on one study with small sample size and there were no events in either arm. Thus, we are uncertain whether there is any difference in surgical complications between UTND and LOD.We are also uncertain whether there is any difference in pregnancy rate when comparing UTND with LOD (OR 0.54, 95% CI 0.28 to 1.03; I2 = 56%; 3 RCTs, n = 473; very-low quality evidence). UTND may lead to a slight decrease in ovulation rate when compared to LOD (OR 0.66, 95% CI 0.45 to 0.97; I2 = 0%; 3 RCTs, n = 473; low-quality evidence). This suggests that among clomiphene-resistant women with PCOS using LOD with an expected ovulation rate of 69.5%, the ovulation rate among women using UTND may be between 50.6% and 68.8%No studies reported on the outcomes OHSS and multiple pregnancy. There was also insufficient evidence to reach a conclusion regarding miscarriage as there was only one study of very low quality.UTND combined with gonadotropins versus gonadotropins aloneNo studies reported on the main outcomes live birth and incidence of surgical complications. The evidence for the outcomes OHSS, pregnancy, ovulation, miscarriage, and multiple pregnancy in this comparison was of very low quality. Thus, we are uncertain whether there is any difference in these outcomes for women with clomiphene-resistant PCOS using UTND combined with gonadotropins as compared with gonadotropins. AUTHORS' CONCLUSIONS: Based on very low-quality evidence, It is uncertain whether there is any difference in pregnancy rate, incidence of surgical complications, and miscarriage rate between UTND and LOD in women with clomiphene-resistant PCOS. UTND may lead to a slight decrease in ovulation rate when compared to LOD. No studies reported on the outcomes live birth rate, incidence of OHSS, and multiple pregnancy rate. No studies reported on the main outcomes live birth and surgical complications for the comparison UTND combined with gonadotrophins versus gonadotrophins alone. The evidence for the outcomes OHSS, pregnancy, ovulation, miscarriage, and multiple pregnancy in this comparison was of very low quality. Thus, it is unclear if there is a difference in any of the outcomes between UTND combined with gonadotrophins versus gonadotrophins alone.

MicroRNA-377-3p inhibits growth and invasion through sponging JAG1 in ovarian cancer.

BACKGROUND: Ovarian cancer is the one of the most deadly gynecologic malignancy among cancer related death in women. However, the treatment for ovarian cancer is still limited. In this study, we aimed to explore the inhibition potential of miR-377-3p in ovarian cancer and explore the mechanism of this effect. METHODS: Quantitative real-time PCR was used to detect the mRNA or microRNA (miRNA) levels. CCK-8, wound-healing, transwell assay were used to detect cell proliferation, migration and invasion. The protein levels were examined by western blot. The dual luciferase reporter assay was conducted to examine the luciferase activity. Tumor volume was measured and Ki67 was detected via immunohistochemistry. RESULTS: qRT-PCR results showed that miR-377-3p was downregulated in ovarian cancer patients. MiR-377-3p mimics suppressed cell proliferation, migration, invasion and decreased the JAG1 level. However, miR-377-3p inhibitor promoted these appearances. Interestingly, we found JAG1 was a target gene of miR-377-3p. JAG1 overexpression reversed the miR-377-3p-induced inhibition of proliferation and invasion. In addition, miR-377-3p inhibited ovarian cancer tumorigenesis in vivo, indicating by decreased tumor volume and staining of Ki67. CONCLUSION: The results showed that miR-377-3p inhibited growth and invasion of ovarian cancer cells by targeting JAG1.

High Intake of Energy and Fat in Southwest Chinese Women with PCOS: A Population-Based Case-Control Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrinological disease with heterogeneous phenotype. Obesity contributes to the increased prevalence and severity of PCOS. Whether the intakes of major nutrients are higher in Chinese PCOS patients is still unknown. OBJECTIVES: To study the intakes of total energy, protein, fat and carbohydrate in Southwest Chinese PCOS patients. METHODS: 1854 women were included in the cross-sectional study. A population-based case-control study was conducted. The dietary habits and nutrients intake status of 169 PCOS patients and 338 age-matched controls were investigated by the method of semi-quantitative food frequency questionnaire. RESULTS: The actual intake of total energy (P = 0.01) and fat (P = 0.01) were higher, but carbohydrate was lower (P = 0.01) in PCOS patients as compared with the controls. The energy percentage supplied by protein (12.33% ± 2.27% vs. 19.26% ± 5.91%, P<0.001) and carbohydrate (48.72% ± 6.41% vs. 68.31% ± 8.37%, P<0.001) were lower in Southwest Chinese PCOS patients than those of control, however, the energy percentage supplied by fat was higher (38.95% ± 5.71% vs. 12.42% ± 5.13%, P<0.001) in PCOS. CONCLUSIONS: Limit the intake of total energy and fat shall be recommended to the Southwest Chinese PCOS patients. Women with PCOS in Southwest China shall consult with the nutritionist for improving the dietary structure.

Plasma visfatin levels and mRNA expression of visfatin in peripheral blood mononuclear cells and peripheral blood monocyte-derived macrophages from normal weight females with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrinology disease, however, an explicit etiology is not known. Insulin resistance (IR) appears to be central to the pathogenesis of PCOS and inflammation may be significant in the pathogenesis of IR in PCOS. The aims of the present study were to investigate the plasma visfatin level and the gene expression of visfatin in peripheral blood mononuclear cells (PBMCs) and peripheral blood monocyte-derived macrophages (PBMMs) from PCOS patients, in addition to investigating the association between PCOS and IR. A total of 21 PCOS patients and 21 control subjects were enrolled in the study; the homeostasis model assessment of insulin resistance (HOMA-IR) was considered to be a stratified method for establishing the subgroups. Fasting blood samples were collected and the levels of sex hormones, insulin, glucose, blood lipids and visfatin were measured. In addition, visfatin gene expression levels in PBMCs and PBMMs were assessed using quantitative polymerase chain reaction. The plasma visfatin and gene expression levels of visfatin in PBMCs and PBMMs were not observed to increase in the normal weight PCOS and normal weight IR patients. Furthermore, plasma visfatin levels did not correlate with the normal weight PCOS patients or the normal weight IR patients per se. Further investigation into the role of visfatin in the pathogenesis of PCOS or IR should examine macrophages in the tissues, rather than macrophages in the peripheral blood.

Prevalence of the polycystic ovary syndrome in female residents of Chengdu, China.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. The data on this syndrome in a Chinese community are limited. METHODS: A community-based cross-sectional survey was undertaken. Cluster-randomized sampling was used. Female residents of Chengdu aged between 12 and 44 were included according to the constituent ratio of the female population of Sichuan province. We used three diagnostic criteria to determine the prevalence: the National Institutes of Health diagnostic criteria of PCOS (NIH-1990), the revised Rotterdam diagnostic criteria of PCOS (Rott-2003), and the recommended diagnostic criteria of PCOS by the Androgen Excess Society (AES-2006). RESULTS: 1,645 participants were included. The prevalence of PCOS in women aged between 12 and 44 was 7.1, 11.2 and 7.4%, respectively, according to the three different criteria. After the onset of puberty, the prevalence of PCOS increased rapidly from 12 to 14 years of age, peaked between 15 and 24 and decreased gradually thereafter and reached its lowest point before menopause. CONCLUSIONS: The prevalence of PCOS in this study was in the PCOS prevalence range from existing studies. According to the trend of prevalence, PCOS might be a temporary condition.

The plasma level and gene expression of resistin in polycystic ovary syndrome.

OBJECTIVES: To investigate the relationship between plasma resistin, polycystic ovary syndrome (PCOS), and insulin resistance (IR). To compare the mRNA level of resistin in mononuclear cells and monocyte-derived macrophages in women with PCOS and controls. MATERIALS AND METHODS: Patients with PCOS and controls were enrolled and IR was considered as the stratified factor for subgroups. Fasting blood was collected to determine the levels of sex hormones, insulin, glucose, blood lipid, and resistin. Resistin gene expression was evaluated by quantitative real-time RT-PCR in mononuclear cells and monocyte-derived macrophages cultured with or without rosiglitazone for 96 h. RESULTS: No significant difference of plasma resistin levels was found among PCOS-IR, PCOS-non-IR, control-IR, and control-non-IR groups. There were no significant differences in resistin mRNA expression between participants with and without PCOS and with and without IR. Resistin mRNA expression in monocyte-derived macrophages was higher than that in mononuclear cells (p = 0.04), and could be reduced by rosiglitazone (p < 0.001). CONCLUSIONS: Plasma resistin does not correlate with normal weight PCOS or IR. Resistin gene expression in mononuclear cells and monocyte-derived macrophages in PCOS and IR is the same as controls. Further researches on the role of resistin in the pathogenesis of PCOS or IR should concentrate on the tissue level.

Chinese herbal medicine for subfertile women with polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common reproductive endocrinology abnormalities, affecting 5% to 10% of women of reproductive age. Western medicines, such as oral contraceptives and insulin sensitizers, have been widely used to improve the symptoms and signs for PCOS. Recently, many studies have been published considering Chinese herbal medicine (CHM) as an alternative treatment for women with PCOS. OBJECTIVES: To evaluate the efficacy and safety of Chinese medicinal herbs for subfertile women with PCOS. SEARCH STRATEGY: We searched the following databases (from inception to March 2010): Menstrual Disorders and Subfertility Group Specialised Register (MDSG), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Allied and Complementary Medicine (AMED), PsycINFO, Chinese National Knowledge Infrastructure (CNKI), VIP, Wanfang. In addition, all reference lists of included trials were searched and experts in the field were contacted to locate trials. SELECTION CRITERIA: Randomized controlled trials (RCT) considering the use of CHM for the treatment of subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: Two review authors independently screened appropriate trials for inclusion, assessed methodological quality, and extracted data. We contacted primary authors for additional information. Meta-analysis was conducted. Odds ratio (OR) was used for reporting dichotomous data with 95% confidence intervals (CI). MAIN RESULTS: Four RCTs involving 344 participants were included. The methodological risk of bias of included studies was poor. Different interventions were used in these four RCTs.There was evidence of statistically significant difference seen improving pregnancy rate (per woman) between CHM plus clomiphene and clomiphene (OR 2.97, 95%CI 1.71 to 5.17). However, there was no statistically significant difference seen in the other comparison groups for improving pregnancy rate (per woman).There was no evidence of statistically significant difference in improving ovulation rate (per woman) between CHM and clomiphene (OR 1.42, 95%CI 0.19 to 10.49), between CHM plus laparoscopic ovarian drilling (LOD) and LOD (OR 2.43, 95%CI 0.39 to 15.08).There were not statistically significant difference between CHM plus follicle aspiration, ovulation induction and follicle aspiration plus ovulation induction for adverse events including LUFS, OHSS and multiple pregnancy.Live birth rate was not reported by any studies. AUTHORS' CONCLUSIONS: There is limited evidence that the addition of CHM to clomiphene is associated with improved clinical pregnancy outcomes and no other evidence of any other effect. The methodology of RCTs was not adequately reported by primary studies.

[Effects of Kuntai Capsule and hormone replacement therapy on cognitive function and mental symptoms of early postmenopausal women: a randomized controlled trial].

BACKGROUND: Conjugated equine estrogen (CEE) treatment, a hormone replacement therapy, is restricted for use in perimenopausal and postmenopausal women because of security issues. Consequently, traditional Chinese herbal medicine has become an alternative choice for the patients with contraindications to hormone replacement therapy. OBJECTIVE: To evaluate the efficacy and safety of Kuntai Capsule and CEE in treating cognitive function disorder and mental symptoms of early postmenopausal women. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 57 cases of early postmenopausal women from Outpatient Department of West China Women and Children's Hospital were included. The subjects were randomly divided into two groups: Kuntai group with 28 cases and CEE group with 29 cases. The patients in Kuntai group received 6 g Kuntai capsules three times a day. The patients in CEE group received CEE 0.3 mg and 0.6 mg alternately once a day (average dose of 0.45 mg/d). The patients with intact uterus in CEE group were treated with 2 mg medroxyprogesterone acetate daily. MAIN OUTCOME MEASURES: In one-year treatment course, the recognition function and mental symptoms of each patient were investigated by questionnaires of Mini-Mental State Examination (MMSE), Kupperman, and quality of life (QOL) every three months. Both intention-to-treat (ITT) and per-protocol set (PPS) analyses were done. RESULTS: The MMSE, Kupperman index and QOL scores at each time point were improved as compared with those before treatment (P<0.05), however there were no statistical differences between the two groups (P>0.05). The MMSE scores showed a tendency to escalate while mental symptoms investigated by Kupperman index and QOL scale showed a downtrend. No severe adverse effects occurred in the study phase and no statistical difference in incidence of side effects between the two groups was found except for vaginal bleeding. The incidence rates of vaginal bleeding in CEE and Kuntai groups were 39.3% and 11.1% respectively (P=0.029). CONCLUSION: Both Kuntai Capsule and CEE may contribute to maintain the cognitive function and ameliorate mental symptoms of early postmenopausal women.

[Sexual hormone and traditional Chinese patent medicine for early postmenopausal women: effect on quality of life and cost-utility analysis].

OBJECTIVE: To evaluate the effect of Premarin and Kuntai capsule (a traditional Chinese patent medicine) on the quality of life (QOL) and their cost-utility in early postmenopausal women. METHODS: Fifty-seven women with menopausal syndrome in the early postmenopausal stage were randomly allocated into Premarin group (0.3 mg/day and 0.6 mg/day alternately, n=29) and Kuntai group (4 g/day, n=28). The therapies lasted for one year and the patients were followed up every 3 months. The QOL of the patients was evaluated and the utility scores were obtained from rating scale to conduct a cost-utility analysis (CUA). RESULTS: At each follow-up examination, no significant difference was found in the QOL between the two groups (P>0.05). The QOL obviously increased after the 1-year-long therapy in both the groups, and Kuntai required longer treatment time than Premarin to take effect. The cost-utility ratio of Premarin and Kuntai were 13581.45 yuan/QALY (quality adjusted life year) and 25105.12 yuan/QALY, respectively. Both incremental cost analysis and sensitivity analysis showed that Kuntai was more costly than Premarin. The result of per-protocol analysis was consistent with that of intention-to-treat analysis. CONCLUSION: At early stage of menopause, the QOL of women with menopausal syndrome can be significantly improved by low-dose Premarin and Kuntai capsule, but the latter is more costly.

Preventive effects of glycyrrhizin on estrogen-related endometrial carcinogenesis in mice.

We have previously reported on the inhibitory effect of Glycyrrhizae radix (Gl radix) on mouse endometrial carcinogenesis. The present study was performed to clarify the effects of Gl radix and glycyrrhizin (GL), the main part of Gl radix, on estradiol (E2)-related endometrial carcinogenesis. Both Gl radix and GL exerted a significant decrease in the COX-2, IL-1alpha and TNF-alpha mRNA expressions. GL generated a significant decrease in the incidence of endometrial adenocarcinoma. Accordingly, the preventive effects of Gl radix may be attributable to GL, thus being related with the suppression of COX-2, IL-1alpha and TNF-alpha. Gl radix and GL could therefore be a promising formula for the chemoprevention of human endometrial cancer.

Inhibitory effects of Hochu-ekki-to on endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17beta-estradiol in mice.

An evaluation of the effects of a traditional Chinese herbal medicine, Hochu-ekki-to (Bu-zong-yi-qi-tang) on endometrial carcinogenesis was performed in experiments with female mice. In the short-term experiment, dietary exposure of Hochu-ekki-to (0.2% for 2 weeks) decreased the estradiol-17beta (E2)-stimulated expression levels of c-jun (P<0.001), tumor necrosis factor (TNF)-alpha (P<0.005), estrogen receptors (ER)-alpha (P<0.001) and ER-beta (P<0.005), as determined by reverse transcription-polymerase chain reaction and a Southern blot analysis in the uteri of the ovarectomized mice. In the long-term experiment, the mice were given N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body weight) and normal saline (as controls) into their left and right uterine corpora, respectively, and then were divided into four groups. Group 1 (25 mice) was given a diet with Hochu-ekki-to and 5 ppm E2. Group 2 (25 mice) was given a diet with E2 alone. Group 3 (25 mice) was given a diet with Hochu-ekki-to alone. Group 4 (25 mice) was kept on the basal diet alone and treated as a control. The incidence of uterine endometrial cancer in the group with Hochu-ekki-to treatment was substantially lower than of the control group. The inhibitory effect of Hochu-ekki-to on endometrial carcinogenesis is thus suggested to decrease the expressions of c-jun, TNF-alpha, ER-alpha and -beta.