Astaxanthin treatment decreases pro-inflammatory cytokines and improves reproductive outcomes in patients with polycystic ovary syndrome undergoing assisted reproductive technology: A randomized clinical trial.

RESEARCH QUESTION: In a randomized, triple-blind, placebo-controlled clinical trial (RCT), we investigated the effect of astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and assisted reproductive technology (ART) outcomes in 44 infertile Polycystic Ovary Syndrome (PCOS) patients. DESIGN: Patients with PCOS were randomly divided into two groups. The intervention group received 6 mg AST, and the control group received placebo daily for 8 weeks. Blood samples were obtained from all patients before and after intervention and follicular fluid (FF) was collected during the ART procedure. Interleukin (IL) -6, IL-1ß were evaluated from serum samples and FF and OS markers (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD], and reactive oxygen species [ROS]) were measured from FF. The groups were compared for ART outcomes as well. RESULTS: A significant decrease in IL-6 and IL-1ß concentrations (both, P = < 0.01) serum levels was found following AST treatment. FF cytokine levels and OS markers did not differ significantly between the groups. Reproductive outcomes, including the number of oocytes retrieved (P = 0.01), the MII oocyte count (P = 0.007), oocyte maturity rate (MII %) (P = 0.02) and number of frozen embryos (P = 0.03) significantly improved after intervention. No significant differences were found in chemical, clinical and multiple pregnancies between the groups. CONCLUSIONS: AST pretreatment may modify inflammation and improve ART outcomes in PCOS infertile patients. Further investigations are recommended to verify these findings.

High Anti-Müllerian Hormone Strongly Correlates with Reproductive Outcomes in Women Undergoing Assisted Reproduction.

BACKGROUND: In a retrospective cohort of 881 women with gynecologic and unexplained infertility, we aimed to study the relationship between serum AMH levels and ART outcomes. This retrospective cohort includes 881 infertile women aged 20 - 45 who underwent their first fresh autologous non-preimplantation genetic diagnosis ART cycles between 2012 and 2020. METHODS: We assessed the correlation between AMH levels and reproductive outcomes among infertile women with different causes of infertility (including endometriosis, polycystic ovary syndrome (PCOS), and unexplained infertility). RESULTS: We found a strong correlation between high AMH levels and reproductive outcomes independent of age and the cause of infertility in women undergoing ART. In all patients with gynecologic and unexplained infertility, higher AMH correlated with the improved number of oocytes (p < 0.001), MII oocytes (p < 0.001), good-quality embryos (p < 0.001), chemical pregnancy rate (p < 0.001 in women < 37; and p = 0.002 in women over 37), clinical pregnancy rate (p < 0.05), and live birth rate (p = 0.05). CONCLUSIONS: Serum AMH concentrations can be invaluable for predicting ovarian reserve and reproductive outcomes in young and advanced-age infertile patients undergoing ART. However, it should not be used as the sole predictive marker for disqualifying infertile women from ART treatment. Further large cohort studies are warranted to determine an exact cutoff point for AMH to provide an accurate ART success prediction.

The modulating effects of vitamin D on the activity of ß-catenin in the endometrium of women with endometriosis: a randomized exploratory trial.

AIMS: The aim of this prospective study was to investigate the effects of vitamin D on the expression and activity of ß-catenin, as the key molecule of the Wnt/ß-catenin signaling pathway, in endometriosis women. MATERIALS AND METHODS: Thirty four infertile women with stage III or IV endometriosis were randomly divided to two groups. The control group received the routine treatment and the treatment group, beside the routine protocol, received 50000 IU vitamin D weekly for 12-14 weeks. Blood and endometrial tissue were collected from both groups before and after the intervention. Protein and Gene expression levels of ß-catenin were assessed by Western blotting and Real-Time PCR, respectively. RESULTS: Compared to before intervention, the expression of active form of ß-catenin reduced significantly within treatment group (p = .000), in addition, the difference between control and treatment groups (p = .012) was significant after intervention, too. Also, the ratio of active/total form of ß-catenin protein expression was significantly decreased within the treatment group at the end of intervention period (p = .000). CONCLUSIONS: It seems vitamin D can change the activity of ß-catenin protein in the endometrial cells of endometriosis patients. Further studies on the therapeutic potential of vitamin D in modifying the ß-catenin activity in endometriosis patients are warranted. CLINICAL TRIAL REGISTRATION NUMBER: IRCT2015081823678N1. TRIAL REGISTRATION DATE: 29 September 2015.

Effects of resveratrol on VEGF & HIF1 genes expression in granulosa cells in the angiogenesis pathway and laboratory parameters of polycystic ovary syndrome: a triple-blind randomized clinical trial.

OBJECTIVES: Management options for PCOS, as the most prevalent endocrine disorder in women of reproductive age, using natural supplements have a high priority for physicians, especially based on the etiological pathways. Therefore, this study was conducted to describe the effect of resveratrol on the angiogenesis pathway, for management of PCOS through assessing VEGF, HIF1 gene expression, and laboratory parameters. METHODS: In this triple-blind RCT, PCOS was confirmed in ICSI candidates based on the Rotterdam criteria. Sixty-two patients that met the inclusion criteria were randomly assigned to two groups. All patients took resveratrol 800 mg/day or placebo for 40 days orally from the beginning of their previous menstruation cycle until the oocyte retrieval day. The serum levels of different hormones were measured, and the expression of HIF1 & VEGF genes was quantified by real-time PCR. RESULTS: As for the laboratory hormone assay in 61 PCOS patients, a significant mean difference was seen in the FSH, LH, TSH, and testosterone between the two groups (P < 0.05). The results showed a reduction in the expression of VEGF & HIF1 genes under the effect of resveratrol in the granulosa cells (P = 0.0001). The number of mature oocytes, cleavage rate, fertilization rate, and fertility rate were not significantly different between the two groups (P > 0.05), but the high-quality oocyte rate and high-quality embryo rate were higher in the resveratrol group (P < 0.05). CONCLUSIONS: Based on the results, resveratrol may improve some outcomes of PCOS patients, probably through changing the serum levels of some sex hormones and expression of VEGF & HIF1 genes in the angiogenesis pathway of granulosa cells.

The role of antioxidants in sperm freezing: a review.

Cryopreservation of spermatozoa is becoming more important because of new clinical requirements and current clinical practice. Despite the success of sperm cryopreservation this routinely used procedure induces serious detrimental changes in sperm function. Some researchers believe that cryopreservation is associated with DNA fragmentation and DNA single strand breaks in sperm. Mechanisms of cryodamage to human spermatozoa are thought to be multifactorial including: cold shock, osmotic stress, intracellular ice crystal formation, oxidative stress, and combinations of these conditions. Additives showing antioxidative properties reported to reduce the impact of ROS-induced and cold shock damages. Many studies exist as regards the effects of antioxidants on the cryopreservation aimed at improving the quality of post-thaw semen. Hence, this review will clarify results of recent applications of various antioxidants used in numerous research efforts to improve cryopreservation of spermatozoa. This review is to increase the understanding of the roles of these antioxidants concerning mechanisms which enhance resistance to cryodamage of spermatozoa.

Menstrual disturbances and hormonal changes in women workers exposed to a mixture of organic solvents in a pharmaceutical company.

BACKGROUND: Chemicals are among risk factors that can affect women's reproductive system. This study is aimed to investigate the association of occupational exposure to a mixture of organic solvents with menstruation disturbances and hormonal changes among female workers. METHODS: Female workers of a pharmaceutical company were divided into three groups of non-exposed, lowexposed and highly-exposed to a mixture of organic solvents (formaldehyde, phenol, N-hexane, and chloroform) based on workplace measurements. Menstrual disturbances (in terms of short cycles, long cycles, irregular cycles, and bleeding or spotting between periods) and mean of hormone levels (including follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone, prolactin, estrogen and progesterone levels) were compared between these three groups. For investigating associations, logistic regression was performed. RESULTS: Our study showed that mean length of cycles, duration of bleeding, and amount of flow and also prevalence of long cycles, irregular cycles, and bleeding or spotting between periods were higher in exposed groups (p≤0.05). Odds ratio for prevalence of menstrual disturbances in the low exposure group and high exposure group were 9.69 (p=0.001) and 3.40 (p=0.002) respectively compared to the reference group. Estrogen and progesterone levels were not affected (p> 0.05), but other hormones levels were significantly disturbed in the exposed groups compared with the non-exposed group (p=0.001). CONCLUSION: Occupational exposure to the mixture of organic solvents may be associated with the increase of menstrual disorders and hormonal changes in female workers. Based on our findings, periodic evaluation of reproductive system of female workers in pharmaceutical companies is recommended.

The modulating effects of astaxanthin on apoptosis in women with polycystic ovarian syndrome: A randomized clinical trial.

Objective: Astaxanthin (ASX) is a lipid-soluble keto-carotenoid with several biological effects. These effects may benefit polycystic ovarian syndrome (PCOS) patients. Imbalanced apoptosis/anti-apoptosis signaling has been considered the major pathogenesis of PCOS. In a randomized clinical trial, we tested the impact of ASX on the apoptotic pathway in PCOS granulosa cells (GCs). The present study hypothesizes that ASX may improve apoptosis in PCOS patients. Materials and Methods: This trial recruited patients with confirmed PCOS. A total of 58 patients were randomly assigned to take ASX (12 mg) or placebo for 8 weeks. Aspirated follicular fluid (FF) and blood samples were taken from both groups to measure BAX and BCL2 protein expression. Following FF aspiration, GCs from both groups were obtained; Real-Time PCR and Western blotting were used to evaluate the apoptotic pathway's gene and protein expression levels in GCs.BAXBCL2. Results: In GCs analysis, ASX reduced DR5 gene and protein expression after 8 weeks compared to placebo(p<0.05). Also, Caspase8 (p>0.05) and BAX (p<0.05) gene expression declined, although the difference was not statistically significant for Caspase8. Besides,ASX treatment contributed to an elevated BCL2 gene expression in GCs(p<0.05). In FF and serum analysis, a statistically significant increase was found in BCL2 concentration in the ASX group (p<0.05). Moreover, a reduction in BAX level was confirmed in both FF and serum of the ASX group; however, this change was not significant in the serum (p>0.05). Conclusion: It seems that ASX consumption among women with PCOS improved serum and FF levels of apoptotic factors and modulated genes and protein expression of the apoptosis pathway in GCs. Nevertheless, further investigations are needed to reveal the potential role of this compound in PCOS treatment.

Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial.

BACKGROUND: This study was designed to examine the effect of resveratrol on mitochondrial biogenesis, oxidative stress (OS), and assisted reproductive technology (ART) outcomes in individuals with polycystic ovary syndrome (PCOS). METHODS: Fifty-six patients with PCOS were randomly assigned to receive 800 mg/day of resveratrol or placebo for 60 days. The primary outcome was OS in follicular fluid (FF). The secondary outcome involved assessing gene and protein expression related to mitochondrial biogenesis, mitochondrial DNA (mtDNA) copy number, and adenosine triphosphate (ATP) content in granulosa cells (GCs). ART outcomes were evaluated at the end of the trial. RESULTS: Resveratrol significantly reduced the total oxidant status (TOS) and oxidative stress index (OSI) in FF (P = 0.0142 and P = 0.0039, respectively) while increasing the total antioxidant capacity (TAC) (P < 0.0009). Resveratrol consumption also led to significant increases in the expression of critical genes involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) and mitochondrial transcription factor A (TFAM) (P = 0.0032 and P = 0.0003, respectively). However, the effect on nuclear respiratory factor 1 (Nrf-1) expression was not statistically significant (P = 0.0611). Resveratrol significantly affected sirtuin1 (SIRT1) and PGC-1α protein levels (P < 0.0001 and P = 0.0036, respectively). Resveratrol treatment improved the mtDNA copy number (P < 0.0001) and ATP content in GCs (P = 0.0014). Clinically, the resveratrol group exhibited higher rates of oocyte maturity (P = 0.0012) and high-quality embryos (P = 0.0013) than did the placebo group. There were no significant differences between the groups in terms of chemical or clinical pregnancy rates (P > 0.05). CONCLUSIONS: These findings indicate that resveratrol may be a promising therapeutic agent for patients with PCOS undergoing assisted reproduction. TRIAL REGISTRATION NUMBER: http://www.irct.ir ; IRCT20221106056417N1; 2023 February 09.

Astaxanthin ameliorates inflammation, oxidative stress, and reproductive outcomes in endometriosis patients undergoing assisted reproduction: A randomized, triple-blind placebo-controlled clinical trial.

Purpose: In a randomized, triple-blind, placebo-controlled clinical trial (RCT) including 50 infertile women with endometriosis candidate for assisted reproductive techniques (ART), we studied the effect of Astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and early pregnancy outcomes. Methods: Before and after 12 weeks of AST treatment (6 mg per day), blood serum and follicular fluid (FF) samples were collected from 50 infertile women with endometriosis stage III/IV undergoing ART. Pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and OS markers (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], and total antioxidant capacity [TAC]) were measured in the serum and FF. ART outcomes were also compared between the groups. Results: Increased serum levels of TAC (398.661 ± 57.686 vs. 364.746 ± 51.569; P = 0.004) and SOD (13.458 ± 7.276 vs. 9.040 ± 5.155; P = 0.010) were observed after AST therapy in the treatment group. Furthermore, serum MDA (14.619 ± 2.505 vs. 15.939 ± 1.512; P = 0.031) decreased significantly following antioxidant treatment. In addition, significantly lower serum levels of IL-1ß (4.515 ± 0.907 vs. 6.8760 ± 0.8478; P = 0.000), IL-6 (5.516 ± 0.646 vs. 5.0543 ± 0.709; P = 0.024) and TNF-α (2.520 ± 0.525 vs. 2.968 ± 0.548; P = 0.038) were observed after AST treatment. In addition, AST supplementation led to an improved number of oocytes retrieved (14.60 ± 7.79 vs. 9.84 ± 6.44; P = 0.043), number of mature (MII) oocytes (10.48 ± 6.665 vs. 6.72 ± 4.3; P = 0.041), and high-quality embryos (4.52 ± 2.41 vs. 2.72 ± 2.40; P = 0.024). Conclusion: AST pretreatment can modulate inflammation and OS in endometriosis-induced infertile patients. ART outcomes also improved after 12 weeks of AST therapy. Our results suggest that AST can be a potential therapeutic target for infertile patients with endometriosis undergoing ART.

Association of dietary total antioxidant capacity, alternative healthy eating index, and dietary inflammatory index with semen quality in men seeking infertility treatment.

Background: Since the association between dietary quality scores and semen quality remains unclear, we carried out a hospital-based cross-sectional study to investigate the association of Dietary Total Antioxidant Capacity (dTAC), Dietary Inflammatory Index (DII), and Alternative Healthy Eating Index (AHEI) scores with semen quality in men seeking infertility treatment. Methods: This study enrolled 210 men with unexplained or idiopathic infertility. Semen samples were collected and analyzed according to the WHO 2010 criteria. Dietary data was collected using a 168-item semi-quantitative food frequency questionnaire (FFQ) developed for Tehran Lipid and Glucose Study. Multivariable logistic regression models were used to estimate the relationship between dTAC, AHEI, and DII scores with abnormal semen in crude and adjusted models. Results: There were no significant differences across quartile categories of the dTAC, AHEI, and DII scores regarding semen parameters. There was a trend toward a significant direct association between DII and abnormal semen risk (p = 0.01). Infertile men in the highest quartile of DII had a 2.84 times higher risk of abnormal semen in the crude model (OR: 3.84; 95% CI: 1.64-8.95); such that remained after adjusting for several potential confounders. There was no significant association between dTAC or AHEI and the risk of abnormal semen in infertile men, either before or after adjusting for potential confounders. Total energy (p = 0.05), fat (p = 0.02), saturated fat (p = 0.02), mono-saturated fat (p = 0.009), Thiamine (Vitamin B1) (p = 0.02), Niacin (Vitamin B3) (p = 0.03), Calcium (p = 0.01), and Selenium (p = 0.01) were inversely associated with semen normality. Discussion: The study suggests that certain dietary factors may affect semen quality, and the mechanisms underlying the observed associations are likely multifactorial, involving complex interactions between diet, oxidative stress, inflammation, and hormone levels. Further research is required to confirm the results, fully elucidate the mechanisms underlying the associations, and identify specific dietary interventions that may improve male fertility outcomes.

Melatonin Promotes Differentiation of Human Spermatogonial Stem Cells Cultured on Three-Dimensional Decellularized Human Testis Matrix.

PURPOSE: The use of 3D (3-Dimensional) culture systems supported cell-to-cell and cell-to-extracellular matrix (ECM) interactions, proliferation, and differentiation of SSCs (Spermatogonial stem cells). The potential advantages of ECM-based scaffolds for in vitro spermatogenesis have been indicated in human and animal experiments. Furthermore, the strong antioxidant and anti-inflammatory activities of melatonin have improved in vitro manipulation of human SSCs in culture conditions. MATERIALS AND METHODS: SSCs were isolated from the testis of three dead-brain patients and then propagated for four weeks. The characterization of SSC colonies was done using real-time PCR (Polymerase chain reaction), ICC (Immunocytochemistry), and xenotransplantation to mice model. Decellularization of the human testis was performed using 0.3% sodium dodecyl sulfate (SDS) solution and 1% Triton X-100. Also, various characterizations of DTM (Decellularized testicular matrix ) were carried out using histological staining and DNA content analysis. The optimum dose of melatonin was selected by MTT (Methyl thiazol tetrazolium). SSCs were cultured in 4 groups: control, melatonin, ECM, and ECM-melatonin in a differentiation medium for four weeks. The expression of differentiation genes was evaluated by real-time polymerase chain reaction. In addition, the viability of cultured cells was assessed by MTT assay. RESULTS: The results of ICC and real-time PCR showed the expression of undifferentiated SSC markers (PLZF and GRFA1) in SSC colonies following the 2D culture of isolated SSCs. The presence of testicular ECM components after different staining methods; and the reduction of DNA content confirmed the proper decellularization process. Germ cell apoptosis significantly decreased in melatonin and ECM groups, and the higher viability of SSCs was seen in the ECM-melatonin group. The relative expression of GFRA1 and PRM2 decreased and increased in ECM and ECM-melatonin groups, respectively. CONCLUSION: Our study showed that the addition of melatonin to the human naturally-derived ECM scaffold could provide a suitable platform for inducing the differentiation and preserving the viability of SSCs.

Circulating and Endometrial Profiles of miR-145, miR-155-5p, miR-224, MPP-5, and PECAM-1 Expression in Patients with Repeated Implantation Failure: A Case Control Study.

OBJECTIVE: An association between microRNAs (miRNAs) and adhesion proteins expression with repeated implantation failure (RIF) has been recently reported; however, these findings are controversial. This study aims to evaluate the endometrial and circulating expressions of miR-145, miR-155-5p, and miR-224 in addition to the endometrial expressions of membrane protein palmitoylated-5 (MPP-5) and endothelial cell adhesion molecule-1 (PECAM-1) in patients with RIF compared to control subjects. MATERIALS AND METHODS: This case-control study was carried out between June 2021-July 2022. Subjects included 17 patients with RIF and 17 control subjects, who had previous spontaneous term pregnancy with a live birth, who referred to the Medical Centre of Arash Hospital, Tehran, Iran. Endometrial tissue samples were obtained via hysteroscopy and Pipelle catheter in the RIF and control subjects, respectively. Plasma samples were collected after ovulation in all subjects. The expression levels of MPP5, PECAM-1, miR-224, miR-145, and miR-155-5p were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The student's t test, chi-square, Mann-Whitney U, and analysis of covariance (ANCOVA) were used for data analyses. RESULTS: RIF patients had less endometrial miR-155-5p expression, and higher endometrial and circulating expressions of miR-145 and miR-224 compared to control subjects. Endometrial PECAM-1 and MPP5 expression significantly decreased in patients with RIF compared to the control group. There was a positive correlation between circulating miR-224 and endometrial miR-155-5p, and between circulating miR-155-5p and endometrial PECAM-1 expression levels in patients with RIF. CONCLUSION: The present study suggests that circulating miR-224, endometrial miR-145, and PECAM-1 can be reliable, novel biomarkers for diagnosis of RIF.

Metabolic risk factors of ovarian cancer: a review.

Ovarian cancer continues to be the leading cause of death from gynecological cancers. Despite inconsistent results, patients with metabolic abnormalities, including obesity and diabetes mellitus (DM), have poorer outcomes, showing a correlation with ovarian cancer incidence and ovarian cancer survival. Since ovarian cancer is the most common cancer in women, and considering the increasing prevalence of obesity and DM, this paper reviews the literature regarding the relationship between the aforementioned metabolic derangements and ovarian cancer, with a focus on ovarian cancer incidence, mortality, and likely mechanisms behind them. Several systematic reviews and meta-analyses have shown that obesity is associated with a higher incidence and poorer survival in ovarian cancer. Although more studies are required to investigate the etiological relation of DM and ovarian cancer, sufficient biological evidence indicates poorer outcomes and shorter survival in DM women with ovarian cancer. A variety of pathologic factors may contribute to ovarian cancer risk, development, and survival, including altered adipokine expression, increased levels of circulating growth factors, altered levels of sex hormones, insulin resistance, hyperinsulinemia, and chronic inflammation. Thus, obesity and DM, as changeable risk factors, can be targeted for intervention to prevent ovarian cancer and improve its outcomes.

The Protective Effect of Sulforaphane against Oxidative Stress through Activation of NRF2/ARE Pathway in Human Granulosa Cells.

OBJECTIVE: Sulforaphane (SFN) is a natural free radical scavenger that can reduce oxidative stress (OS) through mediating nuclear factor (erythroid-derived 2)-like 2 (NF-E2-related factor 2 or NRF2)/antioxidant response element (ARE) signaling pathway and the downstream antioxidant enzymes. Here, we intended to study the role of SFN in OSinduced human granulosa cells (GCs) by investigating the intracellular levels of reactive oxygen species (ROS), cell death, and NRF2-ARE pathway. MATERIALS AND METHODS: This experimental study was conducted on GCs of 12 healthy women who had normal menstrual cycles with no history of polycystic ovary syndrome (PCOS), endometriosis, menstrual disorders, hyperprolactinemia, or hormonal therapy. After isolation of GCs, the MTT assay was performed to explore GCs viability after treatment with SFN in the presence or absence of H2O2. Flow cytometry was utilized to determine the intracellular ROS production and the apoptosis rate. Evaluation of the mRNA and protein expression levels of NRF2 and phase II enzymes including superoxide dismutase (SOD) and catalase (CAT) was performed by quantitative real-time polymerase chain reaction (PCR) and western blotting. Finally, the data were analyzed by SPSS software using One-way ANOVA and the suitable post-hoc test. Significance level was considered as P<0.05. RESULTS: Pretreatment of GCs with SFN attenuated intracellular ROS production and apoptosis rate in the H2O2-exposed cells. Moreover, SFN treatment increased the mRNA expression level of NRF2, SOD, and CAT. Higher expression of NRF2 and SOD was also observed at the protein level. CONCLUSION: Our study demonstrated that SFN protects human GCs against H2O2 induced-OS by reducing the intracellular ROS production and the following apoptosis through a mechanism by which NRF2 increases the antioxidant enzymes such as SOD and CAT. This result may have a potential application in assisted reproduction cycles by improving the quality of GCs and the embedded oocyte, especially in PCOS patients.

A randomized exploratory trial to assess the effects of resveratrol on VEGF and TNF-α 2 expression in endometriosis women.

Resveratrol, a naturally synthesized polyphenolic compound found in some fruits, has anti neoplastic, anti-inflammatory, anti-oxidative, and anti-angiogenic properties. Angiogenesis is an important process in endometriosis which provides blood supply for implantation, proliferation and survival of endometriotic lesions. In this study, we assessed the effects of resveratrol on vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α) expression in the eutopic endometrium of infertile patients with endometriosis within the window of implantation as a randomized exploratory trial. Subjects, who confirmed their endometriosis (stage III-IV) by a pathologist after laparoscopic surgery, were recruited to the present trial. A total of 34 patients were randomly divided into treatment (n = 17) and control (n = 17) groups, beside the routine protocol for treatment of endometriosis, they received resveratrol and placebo (400 mg) for 12-14 weeks, respectively. Endometrial tissue was collected from both groups before and after the intervention in the mid-secretory phase. Gene and protein expression levels of VEGF and TNF-α in the eutopic endometrium were assessed by Real-Time PCR and Western blotting, respectively. VEGF and TNF-α gene and protein levels in the treatment group showed significant decrease following intervention. It seems resveratrol may improve the endometrium of endometriosis patients in window of implantation period by modifying the expression of VEGF and TNF-α but further investigations are needed to reveal the potential role of this compound.

Resveratrol treatment in patients with polycystic ovary syndrome decreased pro-inflammatory and endoplasmic reticulum stress markers.

PROBLEM: Polycystic ovary syndrome (PCOS) is associated with endoplasmic reticulum (ER) stress and pro-inflammatory condition. The aim of the present study was to evaluate the effect of resveratrol treatment on pro-inflammatory and ER stress markers in patients with PCOS. METHOD OF STUDY: Cumulus cells were obtained from 40 patients with PCOS who were divided into two groups: placebo and resveratrol treatment (receiving 800 mg/d for 40 days) groups. Blood samples were obtained from all patients before and after the procedure to evaluate interleukin (IL)-6, IL-1ß, IL-18, TNF-α, NF-κB, and C-reactive protein (CRP). Total RNA was extracted from cumulus cells, and cDNA was synthesized by reverse transcription. Expressions of five genes in ER stress response pathway (ATF4, ATF6, CHOP, GRP78, and XBP1s) were assessed with quantitative real-time PCR. Statistical analysis was performed with Student's t test. RESULTS: After treatment with resveratrol, it was found that serum levels of IL-6, IL-1ß, TNF-α, IL-18, NF-κB, and CRP decreased in the treatment group. In addition, gene expression results showed that the expression levels of ATF4 (P < .05) and ATF6 (P < .001) significantly increased in the resveratrol treatment group, while the expression levels of CHOP, GRP78, and XBP1 (P < .001 for all) significantly decreased. CONCLUSION: Results demonstrated that resveratrol has anti-inflammatory effects through the suppression of NF-κB and NF-κB-regulated gene products. On the other hand, resveratrol can modulate ER stress in granulosa cells (GCs) by altering the expression of genes involved in unfolding protein response (UPR) process. Our findings suggest that ER stress is a potential therapeutic target for patients with PCOS.

Natural cycle versus artificial cycle in frozen-thawed embryo transfer: A randomized prospective trial.

OBJECTIVE: To investigate whether there was a difference in pregnancy outcomes between modified natural cycle frozen-thawed embryo transfer (NC-FET) cycles and artificial cycles (AC)-FET in women who all had regular menstrual cycles. MATERIALS AND METHODS: One hundred seventy patients who met the inclusion criteria and had at least two cryopreserved embryos were included in a prospective randomized controlled trial. Eighty-five patients were randomized based on Bernoulli distribution into the following two groups: 1) Modified NC-FET using human chorionic gonadotropin for ovulation induction and 2) AC-FET, in which endometrial timing was programmed with estrogen and progesterone. The main studied outcome measure was the clinical pregnancy rate per cycle. RESULTS: No significant differences were found between the two groups with regard to the chemical, clinical, and ongoing pregnancy rates (48.2% vs 45.9%, p>0.05; 38.9% vs 35.3%, p>0.05; and 37.6% vs 34.1%, p>0.05, respectively), as well as the live birth or miscarriage rates per cycle (35.3% vs 31.8%, p>0.05; and 1.2% vs 1.2%, p>0.05, respectively). CONCLUSION: These findings suggest that although both FET protocols are equally effective in terms of pregnancy outcomes in women with regular menstrual cycles, NC-FET is more favorable because it requires no medication, has no adverse events, and has a significant cost reduction.

Expression and shedding of CD44 in the endometrium of women with endometriosis and modulating effects of vitamin D: A randomized exploratory trial.

Endometriosis is an estrogen-dependent disease. The impaired estrogen and progesterone signaling over-activates the Wnt/ß-catenin pathway in endometriosis patients, which can explain the increased invasion potency of endometrial cells derived from the endometrium of women with endometriosis. The regulatory effects of vitamin D on Wnt/ß-catenin pathway were demonstrated by previous studies. According to gene prioritization method, among Wnt target genes, CD44 was in high ranking in relation to endometriosis. The aim of this study is to investigate the expression of CD44 in the endometrium of women with endometriosis and to study the effects of vitamin D on its expression. This prospective study was performed, during a 12 months period from December 2015 to November 2016, on healthy women as the control group (n = 14) and endometriosis patients (n = 34). The endometriosis patients randomly divided into two groups: One group treated according to the routine protocol and the other group, alongside the routine protocol, took 50,000 IU vitamin D weekly for 12-14 weeks. Blood, endometrial fluid, and endometrial tissue samples were obtained from the control group and endometriosis groups before and after the intervention. We used in silico gene prioritization to study the relevance of CD44. The expression of CD44 was evaluated using the techniques of Western blot, real-time polymerase chain reaction, and ELISA. The eutopic endometrium of women with endometriosis in mid-secretory phase expressed significantly higher levels of CD44s, CD44V, and CD44v6. The concentration of soluble CD44 in the serum and endometrial fluid of endometriosis patients was higher than of healthy women. The expression level of CD44s, CD44V, and CD44v6 in the eutopic endometrium as well as the concentration of soluble CD44 in the endometrial fluid was decreased after modification of the circulating levels of 25(OH)D. It seems that the increased expression and extensive shedding of CD44 in eutopic endometrium play a role in the pathogenesis of endometriosis. Vitamin D can control and modify this process at least in part. We suggest more in vivo investigations on the therapeutic potency of vitamin D in endometriosis.

Yoga during pregnancy: The effects on labor pain and delivery outcomes (A randomized controlled trial).

OBJECTIVE: To investigate the effects of an antenatal yoga program on perceived maternal labor pain and delivery outcomes. MATERIAL & METHODS: This randomized control trial was conducted with sixty primiparous women, aged 18-35 years old, who were randomly assigned to either an antenatal yoga program or control groups. Labor pain and discomfort level of the participants were measured using a Visual Analogue Scale at cervical dilatation of 3-4 c and at 2 and 4 h after the initial measurement. Demographic and obstetrical information were collected. The antenatal yoga program consisted of a 1-h supervised yoga class, three times a weekly, starting at 26 weeks gestation. . RESULTS: Participants in control group reported higher pain intensity compared to experimental group at 3-4 cm of dilatation (p = 0.01) and at 2 h after the first and the second measurements (p = 0.000). Mothers in the antenatal intervention group that completed the yoga class required a decreased frequency of labor induction in comparison with control group (p = 0.008). In addition, mode of delivery of the intervention group resulted in a lower percentage of cesarean section than control group (p = 0.002). Lastly, the intervention group experienced a shorter duration of the second and third stages of labor. Interval level data was analyzed by using an independent t-test and chi-square. CONCLUSION: Yoga during pregnancy may contribute to a reduction pain of labor and improved adequacy of childbirth.

Characteristics of menstrual cycle in shift workers.

BACKGROUND: In this study, the characteristics of menstrual cycle in shift workers employed in the pharmaceutical industry are investigated. METHOD: This study was conducted in a pharmaceutical industrial complex in Tehran in 2012. 406 female workers in packaging units were studied on the menstrual cycle characteristics. The studied workers were divided into two groups of shift workers and non-shift workers and were compared in terms of the frequency of menstrual disorder (short-term cycle, long-term cycle, irregular cycle and bleeding during menstrual cycle) as well as hormonal values (FSH, LH, TSH, and Prolactin). RESULTS: The odds ratio (OR) for menstrual disorder in the shift workers was 5.54 (95% CI=2.78-11.02) compared to the non-shift workers. The mean difference of hormonal values (except prolactin) between shift workers and non-shift workers was not significant (P>0.05). CONCLUSION: This study suggests that shift work may disrupt the menstrual cycle.