The effect of clomiphene citrate, herbal mixture, and herbal mixture along with clomiphene citrate on clinical and para-clinical parameters in infertile women with polycystic ovary syndrome: a randomized controlled clinical trial.

INTRODUCTION: To evaluate the effect of a herbal mixture (i.e., Mentha spicata, Zingiber officinale, Cinnamomum zeylanicum, and Citrus sinensis) alone and in combination with clomiphene citrate (CC) compared to CC on the treatment of polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: This single-blind randomized clinical trial was conducted on 60 infertile participants with PCOS who were randomly divided into three groups. After spontaneous or progestin-induced withdrawal bleeding, group 1 (n = 20) received routine treatment with CC (50-150 mg) for three menstrual cycles from the 3rd to 5th day of menstruation for 5 days while group 2 (n = 20) and group 3 (n = 20) received herbal mixture capsules 700 mg/day and the herbal mixture along with CC for 3 months, respectively. Finally, several related parameters were measured, including the level of sex steroids, homeostatic model assessment for insulin resistance (HOMA-IR), lipid profile (primary outcomes), thyroid hormones, and clinical features. The analysis was based on intention-to-treat analysis. RESULTS: No statistically significant differences were observed between the groups in terms of socio-demographic characteristics. However, after adjustment for baseline, luteinizing hormone (aMD = 4.9; 95% CI: 3.7-6.2), luteinizing hormone/follicle-stimulating hormone (aMD = 0.9; 95% CI: 0.7-1.2), total testosterone (aMD = -0.12; 95% CI: -0.2 to -0.01) in group 2 and free testosterone (aMD = -6.0; 95% CI: -9.7 to -2.3) in group 3 revealed a significant difference compared to group 1. In addition, HOMA-IR in group 2 (aMD = -1.3; 95% CI: -2.4 to -0.2) decreased significantly compared to group 1. Further, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol decreased significantly in group 2 (aMD = -21.8; 95% CI: -31.5 to -12.1; aMD = -29.9; 95% CI: -47.9 to -12.0; aMD = -21.2; 95% CI: -31.3 to -11.1; aMD = -5.1; 95% CI: -7.5 to -2.7) and group 3 (aMD = -18.3; 95% CI: -27.4 to -9.2; aMD = -26.9; 95% CI: -43.8 to -9.9; aMD = -21.4; 95% CI: -31.1 to -11.7; aMD = -5.9; 95% CI: -8.3 to -3.6) compared to group 1, respectively. However, high-density lipoproteins cholesterol in group 2 (aMD = 6.8; 95% CI: 2.9-10.7) and group 3 (aMD = 10.7; 95% CI: 7.2-14.7) increased remarkably compared to group 1. Overall, clinical outcomes improved significantly in all groups (p < 0.05). CONCLUSIONS: In general, the herbal mixture along with CC was found to improve free testosterone, HOMA-IR, lipid profile, and clinical features of PCOS women.

An Association and Meta-Analysis of Esophageal Squamous Cell Carcinoma Risk Associated with PLCE1 rs2274223, C20orf54 rs13042395 and RUNX1 rs2014300 Polymorphisms.

One of the highest risk of esophageal squamous cell carcinoma (ESCC) in the world has been reported in Iran, which is located in the Asian esophageal cancer belt. ESCC constitutes 90% of the esophageal cancer cases in Iran. Genome wide association studies (GWASs) in Chinese have identified a number of candidate variants, of which PLCE1rs2274223, C20orf54rs13042395 and RUNX1rs2014300 are studied in high risk populations including Chinese, Caucasians and Africans. However, results are inconsistent and it is unknown whether similar associations exist in Iranian population. We evaluated association of three GWAS identified variants with risk of ESCC in an Iranian cohort consisted of 200 ESCC patients and 300 healthy controls and conducted meta-analysis of ESCC risk associated with rs2274223 (involving 9810 cases and 13,128 controls) and rs13042395 (involving 2363 cases and 5329 controls). Logistic regression analysis showed that rs2274223 was associated with ESCC under codominant [GG/AA, 2.47(1.17-5.23), P:0.021], dominant [AG + GG/AA, 1.57(1.09-2.27), P:0.016], recessive [GG/AA+AG, 2.18(1.04-4.56), P:0.036] and log-additive models [1.51(1.12-2.02), P:0.006]. C20orf54 rs13042395 was not associated with ESCC under any genetic model. RUNX1 rs2014300 was associated with risk of ESCC assuming codominant [AG/GG, 0.63(0.41-0.97), P:0.018], dominant [AG + AA/GG, 0.59 (0.39-0.89), P:0.010] and log-additive models [0.61 (0.42-0.87), P: 0.005]. Meta-analysis found significant associations between rs2274223 and ESCC under all analyzed genetic models. However, meta-analysis stratified by ethnicity showed a significant association in Asians but not non-Asian populations. No significant association was found for rs13042395 in meta-analysis. This study provided first evidence for association of GWAS-identified variants with risk of ESCC in an Iranian cohort.

Evidences from a Systematic Review and Meta-Analysis Unveil the Role of MiRNA Polymorphisms in the Predisposition to Female Neoplasms.

Breast (BCa) and gynecological (GCa) cancers constitute a group of female neoplasms that has a worldwide significant contribution to cancer morbidity and mortality. Evidence suggests that polymorphisms influencing miRNA function can provide useful information towards predicting the risk of female neoplasms. Inconsistent findings in the literature should be detected and resolved to facilitate the genetic screening of miRNA polymorphisms, even during childhood or adolescence, and their use as predictors of future malignancies. This study represents a comprehensive systematic review and meta-analysis of the association between miRNA polymorphisms and the risk of female neoplasms. Meta-analysis was performed by pooling odds-ratios (ORs) and generalized ORs while using a random-effects model for 15 miRNA polymorphisms. The results suggest that miR-146a rs2910164 is implicated in the susceptibility to GCa. Moreover, miR-196a2 rs11614913-T had a moderate protective effect against female neoplasms, especially GCa, in Asians but not in Caucasians. MiR-27a rs895819-G might pose a protective effect against BCa among Caucasians. MiR-499 rs3746444-C may slightly increase the risk of female neoplasms, especially BCa. MiR-124 rs531564-G may be associated with a lower risk of female neoplasms. The current evidences do not support the association of the remaining polymorphisms and the risk of female neoplasms.

The Effectiveness of Herbal Mixture Supplements with and without Clomiphene Citrate in Comparison to Clomiphene Citrate on Serum Antioxidants and Glycemic Biomarkers in Women with Polycystic Ovary Syndrome Willing to be Pregnant: A Randomized Clinical Trial.

This paper aimed to evaluate the effect of herbal mixture (Mentha spicata, Zingiberofficinale, Cinnamomumzeylanicum, and Citrussinensis) only and along with clomiphene citrate (CC) compared to CC on serum antioxidants, glycemic status, menstrual regulation, and rate of pregnancy. This single-blind randomized clinical trial was carried out on 60 infertile participants with polycystic ovary syndrome (PCOS) willing to be pregnant. They were randomly allocated into group 1 (n = 20) who received routine dose of CC pills (50-150 mg) for three menstrual cycles from the fifth day of menstruation for five days; group 2 (n = 20) who consumed herbal mixture daily (700 mg); and group 3 (n = 20) who used up herbal mixture along with CC for 3 months. Catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), fasting blood sugar (FBS), insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were measured in their blood samples. No statistically significant differences were observed between the three groups in terms of socio-demographic characteristics. After intervention, however, the levels of CAT in group 2 (adjusted mean difference (aMD): = 9.0; confidence interval (CI) 95% = 1.1-16.9) and group 3 (aMD = 12.2; CI 95% = 4.5-19.9), GPx in group 2 (aMD = 986.1; CI 95% = 141.1-1831.1) and group 3 (aMD = 1781.2; CI 95% = 960.7-2601.8), and SOD in group 2 (aMD = 55.1; CI 95% = 26.0-84.2) increased. While FBS in group 3 (aMD = -8.7; CI 95% = -14.7 to -2.7), insulin in group 2 (aMD = -5.6; CI 95% = -10.8 to -0.4), and HOMA-IR in group 2 (aMD = -1.3; CI 95% = -2.4 to -0.2) significantly decreased compared to the group 1. To summarize, herbal mixture supplements along with CC have beneficial effects on serum antioxidant levels, as well as glycemic biomarkers of infertile PCOS, menstrual regulation, and pregnancy rate.

Association of mir-196a-2 rs11614913 and mir-149 rs2292832 Polymorphisms With Risk of Cancer: An Updated Meta-Analysis.

Background: Accumulating evidence suggests that functional dysregulations of miRNAs, especially miR-196a-2 and miR-149, in cancers could be attributed to polymorphisms in miRNA sequences. This study was aimed at clarifying the association of mir-196a-2 rs11614913 and mir-149 rs2292832 with cancer risk by performing an updated meta-analysis of genetic association studies. Methods: PubMed, Embase, Scopus, and ScienceDirect databases were searched until 9 April 2018 to identify eligible studies. Studies should meet the following criteria to be included in the meta-analysis: evaluation of genetic association between rs11614913 and/or rs2292832 and susceptibility to cancer; A case-control design; Written in English; Availability of sufficient data for estimating odds ratio (OR) and its 95% confidence interval (95%CI). Studies that met the following criteria were excluded: review articles, meta-analysis, abstracts or conference papers; duplicate publications; studies on animals or cell-lines; studies without a case-control design; studies that did not report genotype frequencies. Pooled ORs and 95% CIs were estimated using a total of 111 studies (41,673 cases and 49,570 controls) for mir-196a rs11614913 and 44 studies (15,954 cases and 19,594 controls) for mir-149 rs2292832. Stratified analysis according to quality scores, genotyping method, ethnicity, broad cancer category and cancer type was also performed. Results: Mir-196a-2 rs11614913 T allele was associated with decreased cancer risk in overall population. The association was only significant in Asians but not Caucasians. In subgroup analysis, significant associations were found in high quality studies, gynecological cancers, ovarian, breast, and hepatocellular cancer. Mir-149 rs2292832 was not associated with cancer risk in overall population and there were no differences between Asians and Caucasians. However, the T allele was associated with a decrease risk of gastrointestinal tract cancers under the heterozygote model and an increased risk of colorectal cancer under the recessive model. Conclusions: The present meta-analysis suggests that mir-196a-2 rs11614913 may contribute to the risk of cancer especially in Asians. Mir-149 rs2292832 may modulate the risk of gastrointestinal tract cancers especially colorectal cancer. This study had some limitations such as significant heterogeneity in most contrasts, limited number of studies enrolling Africans or Caucasians ancestry and lack of adjustment for covariates and environmental interactions.

Overview of CD24 as a new molecular marker in ovarian cancer.

Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women. The high mortality rate is due to lack of early symptoms, late diagnosis, limited treatment options, and also emerging of drug resistance. Todays, molecular markers have become promising in tumor-targeted therapy. Several molecular markers have been known in OC immunotherapy. Identification of the specific molecular markers with prognostic significance is interested. CD24 is a small sialoglycoprotein which is localized in lipid rafts through its glycosylphosphatidylinositol (GPI) anchor. It has been reported that CD24 is overexpressed in many cancers including OC. Also, CD24 is identified as a cancer stem cell marker in OC. The CD24 expression is associated with the development, invasion, and metastasis of cancer cells. The exact role of CD24 in cancer cells is not clearly understood. Recently, CD24 has been identified as an independent prognostic marker of survival in patients with OC. In this study, we reviewed the molecular targets in OC immune-targeted therapy and also presented an overview of the new molecular marker CD24 and its association with the OC by reviewing the recent literature.

Psychosocial Factors Associated with Polycystic Ovary Syndrome: a Case Control Study.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a disorder in women of reproductive age. Psychosocial factors can play a role in PCOS. METHODS: To determine the psychosocial factors associated with PCOS in a case control study, 742 PCOS cases were compared to 798 women without PCOS for psychiatric disorders and social conditions. The data were collected using a validated questionnaire of the Minnesota Multiphasic Personality Inventory (MMPI). The Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire (DSM-IV) was used to diagnose major psychopathological disorders and other depressive and anxiety syndromes. The suspected psychopathology was evaluated by a clinical psychiatrist. RESULTS: There was a significant difference between cases and controls in education level (71.8% vs. 80.4%; (P<0.001), and employment status (60% vs. 53%; P=0.01) (respectively). Chronic anxiety (35.7% vs. 26.8%; P<0.001), depression (18.9% vs. 7.9 %; P<0.001), anxiety disorders (7.7% vs. 3.3%; P<0.001), and personality disorders (2.9% vs. 1.7%; P=0.01), were higher in the PCOS patients compared controls, respectively. CONCLUSION: The results showed that chronic anxiety and depression were the most pscycologic pattern in PCO patients. Lower educational level and unemployment were higher in the cases than controls.

Hormonal and metabolic effects of polyunsaturated fatty acid (omega-3) on polycystic ovary syndrome induced rats under diet.

OBJECTIVE(S): PCOS (polycystic ovary syndrome) produces symptoms in approximately 5% to 10% of women of reproductive age (12-45 years old). It is thought to be one of the leading causes of female subfertility. This study aimed to confirm the role of nutrition containing omega-3 (polyunsaturated fatty acid) on control of experimental PCO induced by estradiol-valerat in rats. MATERIALS AND METHODS:  Wistar female rats (n=40) were allocated into control (n=10) and test groups (n= 30), test group was subdivided into 3 groups: G1, received omega-3 (240 mg/kg/orally/daily); G2 and G3 groups were induced PCO by single injection of estradiol-valerate (16 mg/kg/IM). Group 3 received omega-3 (240 mg/kg/orally/daily) and low carbohydrate feeding for 60 subsequent days; on sixtieth day 5 ml blood samples and ovarian tissues of all rats in the group were removed and prepared for biochemical and hormonal analysis. RESULTS:  Catalase, GPX (Glutathione peroxidase), SOD (Superoxide dismutase) in groups that received omega-3 showed higher levels, but MDA (malondialdehyde) level was significantly decreased (P<0.05) in comparison with other experimental groups. Ovarian weights in both experimental and control groups were similar (P<0.05). Level of serum FSH (follicle stimulating hormone) was decreased, but level of testosterone was significantly increased (P<0.05) in PCO group in comparison with control and omega-3 groups. CONCLUSION: RESULTS revealed that administration of omega-3 plus lower carbohydrate food significantly controlled   PCO syndrome and balanced FSH and testosterone.

Fertility sparing treatment in young patients with early endometrial adenocarcinoma: case series.

OBJECTIVE: The aim of this study was to evaluate fertility-sparing therapy in young patients with endometrial carcinoma. METHODOLOGY: This prospective study was carried out on 8 patients with clinical and radio-graphic stage IA, well differentiated endometrioid adenocarcinoma of the endometrium in Alzahra hospital, Tabriz, Iran. Treatment comprised high-dose megestrol acetate. Dilatation and curettage was repeated every three months. RESULTS: The mean age of the patients was 30 (SD,3.21) years (range 24-35). Of the 8 patients, 7 (87.5%) achieved complete response. The mean time to response was 6.5 months (range 3-9). Of the complete responders, 3 of 7(42.8%) had recurrence; one patient underwent immediate hysterectomy, and 2 were successfully treated with second-line therapy and both subsequently conceived. Conception occurred in 3 of 7 patients (42.8%), in two more than once, However successful pregnancy occurred only in two patients. One patient developed Concomitant ovarian adenocarcinoma. CONCLUSIONS: High dose progestin therapy can be an effective fertility-sparing treatment in young patients with well differentiated stage IA endometrial endometrioid cancer confined to endometrium. However, close follow up is required because of risks of conservative treatment.

The effect of erythropoietin against oxidative damage associated with reperfusion following ovarian detorsion.

OBJECTIVE: To determine the effect of recombinant erythropoietin on serum oxidants and the viability of ischemic ovaries after detorsion. STUDY DESIGN: A non-randomized single-blind clinical trial was conducted from December 2009 to January 2011 in a University Teaching Hospital affiliated with the School of Medicine, Tabriz University of Medical Sciences. Surgery was carried out on 40 patients, aged 18-35 years, with signs and symptoms of ovarian torsion. The patients were divided into two equal groups: group 1 received recombinant erythropoietin 150 IU/kg subcutaneously during the operation and 72 h after detorsion, and group 2 received no medication. Blood samples were taken before and 72 h after detorsion to determine the plasma levels of malondialdehyde, xanthine oxidase, glutathione, superoxide dismutase, nitric oxide, and total antioxidants. In both groups, the arterial and venous blood supply of the ovary and arterial blood flow resistance were evaluated before surgery and 72 h after detorsion of the ovary. The main outcome measures were improving ovarian blood flow and reducing oxidative damage. SPSS 17.0 was used for statistical analyses. RESULTS: The levels of malondialdehyde, glutathione, superoxide dismutase, nitric oxide, and total antioxidants 72 h after detorsion were significantly different between the interventional and non-interventional groups (p<0.001). There was no significant difference in the levels of xanthine oxidase (p=0.13). The difference between groups in the blood flow of the ovary 72 h after surgery was not statistically significant (p=0.61). CONCLUSION: Recombinant erythropoietin was effective in reducing the oxidative damage of ovarian torsion.

Detection of human papillomavirus in the saliva of women with concurrent human papillomavirus related genital lesions.

OBJECTIVE: To determine the association of the human papillomavirus (HPV) subtypes in the saliva of women and HPV-related genital lesions. METHODS: In a cross-sectional study, 104 women with documented genital HPV-related lesions and known HPV status were selected. These cases were examined for the HPV subtypes in their salivary specimens from July 2006 to August 2009 at the Gynecologic Clinics of Alzahra Teaching Hospital, Tabriz, Iran. To detect HPV DNA subtypes of 16, 18, 31, 33, 6, and 11,HPV was genotyped by polymerase chain reaction assay. RESULTS: Type 16 HPV was the most frequently detected subtype in the saliva (29.8%), and cervix (24%). In addition, there was a significant association between the saliva and cervix with co-infection (p=0.009), and between the viral types of salivary and cervical+vulvar samples (p=0.00), and salivary and vulvar samples (p=0.001). On the other hand, there was a significant difference between the cervical and vulvar samples for the viral subtypes (p=0.000). CONCLUSION: The high risk HPV 16 is the most common simultaneous HPV subtype in the saliva and cervix of the cases. Identifying the HPV subtypes in saliva may facilitate recognizing persistent genital infections.