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Background: Endometriosis is an idiopathic gynecological condition affecting women with pelvic pain and infertility in reproductive ages. Due to preventive and therapeutic effects of soy isoflavones (SI) and broccoli extract (BE) on tumor angiogenesis, inflammation and oxidative stress and since endometriosis is accompanied by chronic inflammation, in this study, we aim to evaluate the potential role of these compounds on the pathological scores of endome-triosis and also consider the expression level of the gene markers of autophagy, apoptosis, and oxidative stress in an endometriosis rat model. Materials and Methods: In the present experimental study, 45 mature female Sprague- Dawley rats weighing 220 ± 20 g at the age of eight weeks with surgically induced endometriosis was divided into five groups and treated for six weeks with normal saline (control group), BE, SI, BE+SI by oral gavage, and also Diphereline intramuscularly. The histopathological scores of the endometrial implants (0, 1, 2, 3: no, poorly, moderately and well-preserved epithelial layers, respectively) and the mRNA expression level of Bcl-2, Bax, Caspase-3, Beclin-1, Lc3, and Sod within peritoneal tissue were compared among the groups. Results: Pathologic scores of the implants in the Diphereline (1.2 ± 0.27) and BE+SI (1.2 ± 0.41) groups were declined significantly in comparison with the control group (2.08 ± 0.44) (P≤0.001). In the endometriotic structures, the mRNA expression levels of our target genes were improved significantly (P≤0.01) in comparison with the control group. Conclusion: The findings of the current study demonstrated that the simultaneous consumption of a certain amount of broccoli extract and SI can be considered as a promising therapeutic strategy for treatment of endometriosis. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the effects of carob (Ceratonia siliqua L.) pod extract (CPE) on the viability of human endometrial mesenchymal stromal/stem cells (EnMSCs) and its impact on mRNA and protein expressions of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B), histone deacetylase 1 (HDAC1), matrix metalloproteinase-2 (MMP2), and cyclooxygenase-2 (COX-2) in endometriotic patients. Materials and Methods: In this experimental study, EnMSCs were derived from endometrium of patients with ovarian endometrioma (OMA-EnMSCs group) and deep infiltrative endometriosis (DIE) samples of 10 endometriosis-associated infertility (EAI) women (E-EnMSCs group) and compared to EnMSCs derived from the endometrium of an endometriosis-free, normal woman as the control group (C-EnMSCs). The metabolic activity of the control and case groups were evaluated by treating them with different concentrations of CPE. Cell viability was analysed by MTT. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to evaluate the expression of specific genes at the mRNA and protein levels, respectively. Results: Treatment with 0.8 and 2 μg/mL of CPE downregulated COX-2 and HDAC1 in the E-EnMSC group compared to the C-EnMSCs group. Treatment with 0.8 μg/mL of CPE also decreased MMP2 and DNMT3B gene expressions. The COX-2 and DNMT3A genes were significantly upregulated after treatment with 2 μg/mL of CPE. Expressions of the COX-2, HDAC1, DNMT1, DNMT3A, and DNMT3B peptides decreased in the all three groups after treatment with 0.8 and 2 μg/mL of CPE. Gas chromatography-mass spectroscopy (GC-MS) analysis of CPE identified 14 bioactive compounds. Molecular docking showed the best position of each bioactive compound on the different target proteins that are involved in the process of apoptosis in EnMSCs. Conclusion: In vitro and in silico analyses of CPE bioactive compounds show that they may downregulate the cell inflammatory pathway involved in the pathophysiology of endometriosis. [ABSTRACT FROM AUTHOR]

Loboob as a traditional drug in Iranis known for its beneficial effects on busulfan-induced oligospermia. In this experimental study, protective effects of loboob (a Persian traditional remedy) on sexual hormones, antioxidant levels and stereological changes of testis tissue were evaluated in an oligospermia rat model induced by busulfan. Fifty male rats were randomly divided into five different groups: control, received no treatments; and the other groups administrated with a single dose of busulfan (10 mg/kg body weight). After 30 days, these groups were treated with 0, 35, 70 or 140 mg/kg/day of loboob for 60 days. Blood samples were collected for hormone and antioxidant enzyme assays. Unbiased stereology was performed on testis tissues to evaluate the volume of different parts of the testis and the number of various testis cells. Data indicated that FSH, LH and MDA were increased, and testosterone, catalase, SOD were decreased in the busulfan group, while treatment with loboob at 70 and 140 mg/kg significantly improved these parameters (P <0.05). Treatment with 70 and 140 mg/kg of loboob ameliorated the germinal epithelium volume, types A and B spermatogonia, spermatocytes, elongated and round spermatids, and Sertoli cells in the seminiferous tubules (P <0.05). High concentration of loboob also improved testis weight and volume, and leydig cell number (P <0.05). Thus, loboob is more effective for the recovery of seminiferous tubules and their cells than for the interstitial tissue. Loboob with various antioxidants, minerals and vitamins could overcome the side effects of busulfan. [ABSTRACT FROM AUTHOR]

Objectives: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women. Hyperinsulinemia and insulin resistance are normally observed in PCOS patients and metformin is used to treat this disease. The evidence indicates that the opioid system plays a role in the pathogenesis of the PCOS. Based on the above-mentioned explanation, the present study evaluated the role of opioid antagonist (naltrexone) in PCOS-induced infertility compared to metformin. Materials and Methods: Totally, 120 patients afflicted with PCOS were assigned to three groups based on Rotterdam diagnostic criteria, with a body mass index (BMI) of 25-30 kg/m2. The first group received naltrexone (50 mg/d) for 8 weeks. In addition, the second group were injected with metformin 1000 and then 1500 mg/d for the first and seventh weeks, respectively. Finally, the third group entered the intrauterine insemination (IUI) without prior therapeutic treatment. Then, the groups were compared in terms of the amount of estradiol produced per day of human chorionic gonadotropin injection and the total amount of gonadotropin needed, the number and size of the adult follicles, the number of days of taking the drug, and incidence of pregnancy-induced abo Results: Based on the results, the mean of infertility duration was not significant among the three groups (P = 0.782). Further, the mean fasting insulin level between the metformin and control groups represented a significant difference (P = 0.045). The average number of days to trigger patients in the 3 groups was not significant (P = 0.346). Although the average number of follicles between metformin and naltrexone groups was not significant, it was higher in the naltrexone group. Finally, the average BMI of the naltrexone group after the treatment was lower compared to before treatment (P ≥ 0.001). Conclusions: In general, the number of receiving days and the dose of the drug in the naltrexone group was lower compared to the metformin group. Furthermore, the number of mature follicles in both ovaries and the serum estradiol level in the naltrexone group was higher compared to the metformin group. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance (IR) occurs in 50-70% of women with polycystic ovary syndrome (PCOS) and can be applied as a prediabetic feature in PCOS. Objective: In this study, indirect methods including fasting blood sugar (FBS), fasting insulin (FI), FBS/FI ratio, and quantitative insulin sensitivity check index (QUICKI) were compared with the homeostasis model assessment of insulin resistance (HOMA-IR) as a standard technique. The association of IR to sex hormone-binding globulin (SHBG) and several hormones was also analyzed. Materials and Methods: This cross-sectional study was performed on 74 PCOS women. Sensitivity and specificity of each IR method was calculated based on HOMA-IR. Hormonal profiles of the patients were compared between the groups with defined normal and abnormal values of IR. Results: Triglyceride levels had a positive association with FBS and HOMA-IR (p = 0.002 and p = 0.01, respectively) with a negative association to QUICKI and SHBG (p = 0.02 and p = 0.02, respectively). SHBG showed a significant negative association with FBS (p = 0.001). Dehydroepiandrosterone sulfate showed a positive association with FI (p = 0.002). Seven PCOS women showed abnormal SHBG levels (< 36 nmol/L) while expressed normal values of the rest of the studied variables. FI and QUICKI had the highest sensitivity while FBS/FI and QUICKI had the highest specificity when HOMA-IR was applied as a standard test. Conclusion: SHBG and triglyceride had a significant negative and positive association with IR, respectively. HOMA-IR followed by FI and QUICKI is the most sensitive test for the detection of IR. SHBG levels can be a helpful biomarker for the diagnosis of PCOS. [ABSTRACT FROM AUTHOR]

Background: Genital tract infection is one of the causes of male infertility. Several studies have shown a role for human cytomegalovirus (CMV) in this context. In the present study, the prevalence of CMV in a population of male partners of infertile couples was estimated and the impact of CMV on sperm parameters was determined. Methods: In this cross sectional study, CMV DNA and virus copy number were examined in the semen of 150 participants including 80 with normal semen analysis (SA) and 70 with abnormal SA, by quantitative Real-Time PCR. Sperm parameters were compared between CMV positive and negative groups. Comparisons with pvalues under 0.05 were considered significant. Logistic regression was performed to control the effect of some variables with p<0.25 on sperm parameters. Results: CMV DNA was detected in the semen of 28 (18.6%) individuals. 21 men (30%) with abnormal SA and 7 (8.8%) with normal SA were positive for CMV DNA (p=0.001). The mean virus copy number was 883.1±4662.01 for the men with abnormal SA and 2525.7±12680.9 for those with normal SA (p=0.001). Sperm count was (32.1±23.5) x106 in CMV positive and (44.2±24.1) x106 in CMV negative groups (p=0.022). Normal sperm morphology was 2.73±2.83% and 5.99±5.44% in CMV positive and negative groups, respectively (p<0.001). After controlling some variables, the sperm morphology remains the only statistically significant sperm parameter that was reduced by CMV. Conclusion: The higher CMV prevalence in the semen of males with abnormal SA compared to normal SA and significant reduction of sperm morphology in the presence of CMV, are in favor of the negative impact of CMV on male fertility. [ABSTRACT FROM AUTHOR]

Background: Abnormal female immune response is one of the potential causes of unexplained infertility (UI). Seminal plasma (SP) is an important regulator of female immune responses during pregnancy. This study investigated a SP effect on the expression of CD4+ T-cell related cytokines in a group of UI woman candidates for in vitro fertilization (IVF) and healthy fertile women. Materials and Methods: This was a semi experimental study that performed on 20 UI couples (ten unsuccessful and ten successful IVF outcomes) and 10 fertile couples as the healthy group. CD4+ T-cells were separated from peripheral blood mononuclear cells of women by magnetic activated cell sorting technique and incubated with (stimulated condition) or without (unstimulated condition) SP of their husbands. After incubation, real time polymerase chain reaction method was used to investigate interleukin (IL) 23, IL 17, IL 4, IL 10, transforming growth factor (TGF)-β, and interferon (IFN)-γ gene expression. Mann--Whitney U test, Kruskal--Wallis test, and Wilcoxon signed rank test were used for statistical analysis. Results: Baseline TCD4+ mRNA levels of IL 23 (P = 0.03) and TGF-β(P = 0.01) were different between healthy and infertile groups. However, IL-17, IL-4, IFN-γ, and IL-10 were expressed similarly regardless of fertility status. Comparing mRNA expression before and after SP exposure, our results have shown that relative expression of IL-23 significantly increased in successful (P = 0.04) and unsuccessful IVF groups (P = 0.01), whereas IL-10 expression increased only in the IVF failure group (P = 0.01). Conclusion: SP can make a positive effect on IVF outcome through alteration in CD4 + T-cell related cytokines expression, especially IL-10 and IL-23. [ABSTRACT FROM AUTHOR]

Unexplained infertility (UI) is one of the most common diagnoses in the fertility care. Seminal plasma (SP) plays a crucial role in the regulation of female immune responses and the success of a pregnancy. In vitro fertilization (IVF) is a well-known method for the treatment of UI. In this study, we aimed to investigate the effect of SP on the differentiation of T helper (Th) cell subsets and the relationship between these subsets with the rate of IVF success in a group of women complicated with UI compared to those with normal pregnancy. This study was conducted on 20 UI couples (ten with successful and ten with unsuccessful IVF outcome) and 10 fertile couples as the control group. Four color flow cytometry technique was used to detect Th cell subsets in the peripheral blood mononuclear cells (PBMC) with or without stimulation by SP. Results indicated that the frequencies of IL-17+ and Foxp3+ T cells after incubation with SP was significantly increased in couples with unsuccessful IVF outcome as compared to successful and healthy groups (p<0.05). Additionally, a positive correlation was observed between Th1 and Th2 cells in the unsuccessful IVF group (R=0.6, p=0.03). In summary, the results of the present study demonstrated that exposure to SP might increase Th17 and Treg cell frequencies in infertile women with unsuccessful IVF, and might also balance inflammatory to regulatory responses to finally tune-up the Th1/Th2/Th17/Treg balance and support the success of IVF. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to compare the effects of Glycyrrhiza glabra (Licorice), a cyclooxygenase- 2 inhibitor (Celecoxib) and a gonadotropin-releasing hormone analog (Diphereline®), with a control group on endometrial implants in rats. Materials and Methods: In this experimental study, endometriosis was induced in rats by auto transplantation and after confirmation, the rats were divided into 4 groups that were treated for 6 weeks with normal saline (0.5 ml/day, orally), licorice extract (3000 mg/kg/day, orally), celecoxib (50 mg/kg, twice a day, orally) or diphereline (3 mg/kg, intramuscularly). At the end of treatments, the mean area, volume, histopathology and hemosiderin-laden macrophage (HLM) counts of the endometrial implants were evaluated and compared among the four groups. Results: The mean area, volume and HLM counts of the implants in the licorice group were significantly lower than those of the control group (P<0.001). The histopathologic grades of endometrial implants were significantly decreased by licorice compared to the control group (P<0.001). There was no significant change in the mentioned parameters in rats treated with celecoxib compared to the control group. Diphereline was the most potent agent for suppressing the growth of endometrial implants in terms of all of the above-mentioned parameters. Conclusion: Licorice decreased the growth and histopathologic grades of auto-transplanted endometrial implants. However, while celcoxib had no significant effect, diphereline showed the highest potency for decreasing the endometrial growth. Licorice may have the potential to be used as an alternative medication for the treatment of endometriosis. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is correlated with low-grade chronic inflammation. Interleukin-17A (IL-17A) and Interleukin-32 (IL-32) are two members of the pro-inflammatory cytokines which act as significant components of the immune system during certain inflammatory diseases. Along with immunological processes, genetic factors play major roles in predisposition to PCOS. There are myriad single nucleotide polymorphisms (SNPs) within IL-17A and IL-32 genes that may affect their production and the susceptibility of individuals to PCOS. The objective of the present research was to investigate the association between IL-17A (rs2275913) and IL-32 (rs9927163, rs4786370) SNPs, and also their serum levels with susceptibility to PCOS in a group of Iranian women. In this case-control study, 150 PCOS patients (mean age of 29.1 years) and 150 healthy women (mean age of 26.1 years) were analyzed in terms of IL-17A and IL-32 SNPs via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Furthermore, serum levels of IL-17A and IL-32 cytokines were measured through the use of ELISA method. There were significant differences between PCOS and healthy women regarding IL-17A rs2275913 alleles, genotypes frequencies (p=0.005, and 0.01, respectively) and the allelic distribution of IL-32 rs9927163 SNP (p=0.03). Additionally, significant differences were indicated between two groups concerning the AG genotype against AA+GG genotypes (p=0.009) and the GG genotype against AA+AG genotypes (p=0.006) in IL-17A rs2275913 SNP. In the matter of IL-32 gene SNPs, GC haplotype frequency was significantly different between patients and controls (p=0.05). Furthermore, IL-32 serum level was not significantly different between the two studied groups and the serum level of IL-17A was not detectable. In conclusion, IL-17A and IL-32 SNPs might be associated with predisposition to PCOS in Iranian women. [ABSTRACT FROM AUTHOR]

Background: Y chromosome deletions (YCDs) in azoospermia factor (AZF) region are associated with abnormal spermatogenesis and may lead to azoospermia or severe oligozoospermia. Assisted reproductive technologies (ART) by intracytoplasmic sperm injection (ICSI) and testicular sperm extraction (TESE) are commonly required for infertility management of patients carrying YCDs. The aim of this study was to estimate the frequency of YCDs, to find the most frequent variant in infertile men candidate for ART and to compare YCD distribution with a control fertile group. The semen parameters, hormonal profiles and ART outcomes of the infertile group were studied. Materials and Methods: This case-control study consisted of 97 oligozoospermic or non-obstructive azoospermic (NOA) infertile men, who had undergone ART, as the case group and 100 fertile men as the control group. DNA samples were extracted from blood samples taken from all 197 participants and YCDs were identified by multiplex polymerase chain reaction (PCR) of eight known sequence-tagged sites. The chi-square test was used to compare the mean values of hormone and sperm parameters between the two groups. P<0.05 was considered statistically significant. Results: No YCD was detected in the control group. However, 20 out of 97 (20.6%) infertile men had a YCD. AZFc, AZFbc and AZFabc deletions were detected in 15 (75%), four (20%) and one (5%) YCD-positive patients. No fertilization or clinical pregnancy was seen following ICSI in this sub-group with YCD. The mean level of FSH was significantly higher in the group with YCD (28.45 ± 22.2 vs. 4.8 ± 3.17 and 10.83 ± 7.23 in YCD-negative patients with and without clinical pregnancy respectively). Conclusion: YCD is frequent among NOA men and YCD screening before ART and patient counseling is thus strongly recommended. [ABSTRACT FROM AUTHOR]

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovulation induction that usually occurs after gonadotropin stimulation, followed by human chorionic gonadotropin administration, for infertility treatment. The existing knowledge about the pathophysiology, risk factors, and primary and secondary methods for the prevention of OHSS is reviewed in this manuscript. The clinical manifestations and characteristics of mild, moderate, severe, and critical forms of the syndrome are defined. The methods of handling affected cases as outpatient or in-hospital management methods as well as indications for hospitalization are summarized in this review. The clinical and biochemical routes of assessing and monitoring hospitalized patients with OHSS, various drugs and medical treatment strategies including indications for aspiration of the ascitic fluid and pleural effusion, and also rare indications for surgery are briefly explained in this article. Severe OHSS, which two decades ago was considered an iatrogenic life-threatening condition, can now be effectively prevented or managed during the early stages. An OHSS-free clinic can be established nowadays by carefully considering the endocrinology of ovulation and using appropriate and dose-adjusted pharmaceutical agents, which are summarized and discussed in this review. [ABSTRACT FROM AUTHOR]

Our aim is to assess the effect of cinnamon powder capsules on insulin resistance, anthropometric measurements, glucose and lipid profiles, and androgens of women with polycystic ovarian syndrome (PCOS). Out of 80 women that were diagnosed as PCOS by Rotterdam Criteria, 66 were enrolled in this randomized double-blind placebo-controlled clinical trial. All of the PCOS women were taking medroxy progesterone acetate 10 mg/day for the last 10 days of their menstrual cycles. The cases were randomly allocated to 2 groups. The women in the first group were treated by cinnamon powder capsules 1.5 g/day in 3 divided doses for 12 weeks and the second group by similar placebo capsules. Anthropometric measurements, fasting blood sugar, fasting insulin, blood glucose 2 hr after taking 75 g oral glucose, HbA1c, testosterone, dehydroepiandrosterone sulphate, homeostatic model assessment for insulin resistance, triglyceride, and cholesterol (low-density lipoprotein, high-density lipoprotein, and total) before and after the intervention were evaluated and compared as outcome measures. Fasting insulin (p = .024) and homeostatic model assessment for insulin resistance (p = .014) were reduced after 12 weeks in the cinnamon group compared with the placebo. There was also a significant decrease in low-density lipoprotein in cinnamon group (p = .004) as compared with baseline that caused significant difference with placebo (p = .049). However, changes in other outcome measurements did not lead to statistically significant difference with placebo. The present results suggest that complementary supplementation of cinnamon significantly reduced fasting insulin and insulin resistance in women with PCOS. [ABSTRACT FROM AUTHOR]

Background: Infertility adversely affects quality of life (QoL). The present study aims to evaluate QoL and its associated factors among infertile couples. Materials and Methods: In this cross-sectional study, the Fertility QoL (FertiQoL) instrument was used to measure QoL among 501 volunteer couples who attended the Infertility Clinic at the Mother and Child Hospital, Shiraz, Iran. We used an additional questionnaire to assess participants' demographic and clinical characteristics. The relationship between the scores of QoL to the sociodemographic and treatment data was analysed. Results: The subjects with lower income levels had lower relational, mind/body, emotional, and total core scores. Female participants without academic education had lower scores in the emotional subscale, while the male participants showed lower scores in emotional, mind/body, relational, social, and total QoL domains. Subjects who had undergone any type of treatment, including pharmacological treatment, intrauterine insemination (IUI), intra-cytoplasmic sperm injection (ICSI), and in vitro fertilization (IVF) showed significantly lower scores in the environmental domain. Participants with lower infertility duration obtained significantly greater QoL scores. Finally, tolerability, emotional, and environmental domains were significantly more desirable when the infertility problem was related to a male factor. Conclusion: Infertile couples with shorter duration of infertility and male etiology have higher QoL. Lower academic education, lower income levels, or prior unsuccessful treatments are associated with lower QoL. [ABSTRACT FROM AUTHOR]

Background: Endocrine abnormalities related to polycystic ovary Syndrome (PCOS) are important problems. Objective: To compare serum leptin levels between infertile women with and without PCOS. To rank sensitivity of six indirect methods for detection of insulin resistance (IR) and to evaluate the association between leptin and IR in PCOS group. Materials and methods: This Case-controlled study performed on 189 infertile women referred to Shiraz Mother and Child Hospital during 2012-2015. Ninety-nine PCOS cases according to Rotterdam criteria were compared to 90 cases without PCOS. Serum leptin, body mass index (BMI), several hormones, and their correlation coefficients with leptin were compared. IR in PCOS women was measured by indirect methods, including fasting blood sugar (FBS), fasting insulin (FI), glucose/insulin, homeostatic model assessment of insulin resistance (HOMAIR), quantitative insulin sensitivity check index (QUICKI), and MacAuley index. Association between IR and leptin was evaluated. Independent sample t-test and Pearson's test were used. Results: Infertile women with PCOS had higher BMI (26.47±3.62 vs. 24.82±5.18 kg/m²) and serum leptin levels (41.79±187.89 vs. 19.38±12.57 ng/mL). Leptin showed significant association with weight and BMI in both groups (p<0.001) and to age in non-PCOS group. HOMA-IR showed the highest rate of IR followed by FI and QUICKI methods. The mean leptin levels had positive association with IR assessed by HOMA-IR (p<0.001), QUICKI (p<0.001), FI (p=.002), and FBS (p=0.02). Results: Infertile women with PCOS had higher BMI (26.47±3.62 vs. 24.82±5.18 kg/m²) and serum leptin levels (41.79±187.89 vs. 19.38±12.57 ng/mL). Leptin showed significant association with weight and BMI in both groups (p<0.001) and to age in non-PCOS group. HOMA-IR showed the highest rate of IR followed by FI and QUICKI methods. The mean leptin levels had positive association with IR assessed by HOMA-IR (p<0.001), QUICKI (p<0.001), FI (p=.002), and FBS (p=0.02). [ABSTRACT FROM AUTHOR]