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BackgroundType-1 diabetes (T1D) occurs following autoimmune-induced pancreatic beta cells death. Among several treatment modalities, Mesenchymal Stem Cells (MSCs) transplantation is promising for autoimmune disorders due to immunomodulation, regeneration, and migration to damaged tissue upon systemic injection. This study assessed the safety and efficacy of intravenous injection of autologous bone marrow-derived MSCs in newly diagnosed T1D patients. MethodsAfter receiving informed consent, 21 patients who met the study criteria were enrolled and randomly assigned to receive either MSCs or placebo. Each patient in the experimental group received two doses of MSCs and followed for at least one year post-transplantation. ResultsThe results have shown that this transplantation is safe and significantly reduces the number of hypoglycemic episodes. MSCs transplantation improved glycated hemoglobin (HbA1c), shifted serum cytokine patterns from pro-inflammatory to anti-inflammatory, increased the number of regulatory T-cells in the peripheral blood, and improved quality of life. Early transplantation of MSCs significantly improved HbA1c and C-peptide levels and shifted pro-inflammatory cytokines to anti-inflammatory cytokines. Also, exercise combined with MSCs transplantation improved glycemic and immunologic indices. ConclusionsIn conclusion, autologous MSC transplantation is safe and effective, and its early transplantation is a promising treatment in newly-diagnosed T1D children suffering from hypoglycemic episodes. Trial registrationThis clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the identifier IRCT ID: IRCT2016070428786N1 registered on August 20, 2016 (Retrospectively registered) (https://en.irct.ir/trial/23256) and at the U.S. National Institutes of Health (ClinicalTrials.gov) with the related identifier NCT04078308 registered on September 6, 2019 (Retrospectively registered). (https://clinicaltrials.gov/ct2/show/NCT04078308)

BackgroundType-1 diabetes (T1D) occurs following autoimmune-induced pancreatic beta cells death. Among several treatment modalities, mesenchymal stem cells (MSCs) transplantation is promising for autoimmune disorders due to immunomodulation, regeneration, and migration to damaged tissue upon systemic injection. This study assessed the safety and efficacy of intravenous injection of autologous bone marrow-derived MSCs in newly diagnosed T1D patients.MethodsAfter receiving informed consent, 21 patients who met the study criteria were enrolled and randomly assigned to receive either MSCs or placebo. Each patient in the experimental group received two doses of MSCs and was followed for at least one-year post-transplantation.ResultsThe results have shown that this transplantation is safe and significantly reduces the number of hypoglycemic episodes. MSCs transplantation improved glycated hemoglobin (HbA1c), shifted serum cytokine patterns from pro-inflammatory to anti-inflammatory, increased the number of regulatory T-cells in the peripheral blood, and improved quality of life. Early transplantation of MSCs significantly improved HbA1c and C-peptide levels and shifted pro-inflammatory cytokines to anti-inflammatory cytokines. Also, exercise combined with MSCs transplantation improved glycemic and immunologic indices.ConclusionsTaken together, autologous MSC transplantation is safe and effective, and its early transplantation is a promising treatment in newly diagnosed T1D children suffering from hypoglycemic episodes.Trial registration: This clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the identifier IRCT ID: IRCT2016070428786N1 registered on August 20, 2016 (Retrospectively registered) (https://en.irct.ir/trial/23256) and at the U.S. National Institutes of Health (ClinicalTrials.gov) with the related identifier NCT04078308 registered on September 6, 2019 (Retrospectively registered). (https://clinicaltrials.gov/ct2/show/NCT04078308).

We evaluated the predictive value of serum anti-Müllerian hormone (AMH) levels for improved menstrual cycles in response to dietary management in women with polycystic ovary syndrome (PCOS). In addition, we assessed the effect of a restricted calorie diet for 12 weeks on serum AMH levels. This intervention study was carried out at Rohan Institute, Tehran, Iran from 2013 to 2015. A total of 105 overweight and obese women with PCOS and reproductive impairment participated in a 12-week weight loss program (WLP). The serum AMH levels, weight, and menstrual cyclicity were assessed at baseline and post-intervention for all of the participants. A total of 90 patients completed the 12-week WLP. Of the 90 patients, 65 (72.2%) responded to the intervention with improvements in menstrual cyclicity. There were no significant differences in terms of age, baseline AMH levels, and other hormone profiles between responders and nonresponders. Responders had a significantly lower baseline body mass index (BMI) and waist circumference compared with nonresponders. These factors were the clinical predictors for a menstrual response after the intervention. The AMH levels did not significantly change after 12-week WLP despite the overall reduced weight; however, women who responded with improved reproductive function had a greater reduction in AMH levels.

Background: Inflammatory responses within the peritoneal cavity may result in endometrial dysfunction in women with endometriosis. The true causes of this disease remain poorly understood. It is hypothesized that downstream toll-like receptors (TLRs) inflammatory cytokines in response to pathogens may be associated with endometriosis. So, this study was aimed at evaluating the expression of TLRs signaling and endometriosis-associated inflammatory responses. Methods: Totally, 20 infertile endometriosis patients and 20 normal women undergoing controlled ovarian stimulation were enrolled. The cellular pellet and supernatant were obtained by centrifugation of follicular fluid (FF). Evaluation of TLRs and their signaling pathway gene expression was performed on cellular pellets using quantitative-PCR. The supernatant was used for determination of cytokine protein expression by ELISA. The results are expressed as mean±SEM and a p

BackgroundChlamydia trachomatis (CT) infection is often mentioned as a silent disease. Reactive oxygen species (ROS) can also cause Sperm apoptosis and have negative impact on Sperm parameters. The objectives of this study were to elucidate the association between Sperm parameters and ROS caused by CT infections resulting in male Infertility as well as evaluating the role of antibiotic therapy.Materials and methodsA total of 848 infertile males having normal and abnormal Sperm parameters were included. After Semen sampling, the CT IgA were measured by Elisa and confirmed by Nested PCR. ROS was determined by Chemiluminescence. After treatment under the direct supervision of the private urologists. Then, the second Semen samples were taken and subjected to tests on Sperm parameters and ROS levels as assessed again.ResultsThe levels of ROS and morphology were improved following the treatments (PConclusionsOur findings indicate that CT infection and Sperm parameters were associated with the rate of ROS in infertile men. However, after treatment, ROS value dropped allowing the recovery of certain Sperm parameters. Antibiotic therapy can improve some Semen quality parameters and treat the male Infertility.Reza Azmakan, rezaazmakan@yahoo.com, Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran, https://orcid.org/0000-0001-6718-3348.

Numerous evidences suggested that microRNAs (miRs) could play an active and significant role during spermatogenesis. Cysteine-rich secretory protein (CRISP3) has a role in inflammatory response and is extremely over-expressed in adolescents with varicocele seminal plasma and modified semen analysis. Nowadays, the miRs expression's association with their target genes is well recognized. The aim of this study was evaluating the association of CRISP3 and four candidate miRs among teratozoospermia (TZ) infertile men. First, we have selected four miRs, miR-182-5p, miR-192-5p, miR-204-5p, and miR-493-5p bioinformatically. After that, RNA was extracted from semen samples of 21 TZ patients and 20 normozoospermia (Norm). Then, their expression levels were assessed using real-time polymerase chain reaction method. In the next step, we quantified the expression of two CRISP3 protein isoforms, targeted by these miRs, using western blotting. According to our results, up-regulation of miR-182-5p, miR-192-5p, and miR-493-5p was observed. MiR-182-5p, miR-192-5p, and miR-493-5p showed good AUC values which can be introduced as possible biomarkers of TZ. In addition, the expression level of the CRISP3 glycosylated (31 kDa) isoform was significantly lower in TZ patients than Norm ones. Notably, in TZ patients, there was a possibly positive correlation of glycosylated CRISP3 expression with normal sperm morphology. According to our results, CRISP3 protein can play a significant role in male infertility especially in maturation formation of spermatozoa. Also, deregulation of the studied miRs, miR-182-5p, miR-92-5p, and miR-493-5p, can suggest a regulatory network between these miRs and CRISP3 isoforms and suggest their regulatory roles in male infertility.

This case-control study was designed to evaluate the impact of endometriosis and the presence of endometrioma (OMA) per se on the serum anti-Müllerian hormone (AMH) level and also to compare the in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) outcomes after therapeutic surgery in endometriosis patients, according to the localisation of endometriosis lesions. One hundred and fifty two infertile women ≤40 years with suspicious symptoms were surgically evaluated to detect the aetiology of infertility at the Royan Institute during this study and, in parallel, 131 patients with a male factor infertility diagnosis were considered as the control group. The serum AMH level and IVF/ICSI outcomes were compared according to the nature and extension degree of endometriosis lesions. The results demonstrated that the existence of a deep infiltrating endometriosis (DIE) with and without OMA was associated with a significant decrease in AMH level, antral follicle count and ovarian sensitivity index (OSI) (p .001 and p = .007, respectively). The multivariable logistic regression analysis adjusted for confounding factors indicated that the OSI and the existence of DIE with and without OMA were a significant predictive variable for clinical pregnancy and for live birth. On the basis of our results, the severity of endometriosis and the location of its lesions could affect an ovarian reserve and the ovarian stimulation outcomes. Impact Statement What is already known on this subject? Previous studies have evaluated the impact of endometrioma (OMA) on ovarian reserve and the assisted reproduction technology (ART) outcomes and controversial results have been reported; therefore, it seems that this topic still needs further research. What the results of this study add? In the present study, the effect of endometriosis lesions' localisation on ovarian reserve and the success rate of the in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle after therapeutic surgery were compared with that of the control group. It was found that the existence of a deep infiltrating endometriosis (DIE) with and without OMA was associated with a significant decrease in the anti-Müllerian hormone (AMH) level, antral follicle count, ovarian sensitivity index (OSI), clinical pregnancy and live birth rates. What the implications are of these findings for clinical practice and/or further research? The results of this study has a practical value in the decision making process for the ovarian stimulation protocol in patients with the different severity of endometriosis and the counselling regarding the success rate of IVF or ICSI/embryo transfer cycles.

Background The role of the screening protocol for viral hepatitis and human immuunodeficiency virus (HIV) infections among infertile couples were seldom investigated. Objective The present study was performed to assess the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV infections among infertile couples referring to infertility clinic of Royan Institute. Materials and methods This analytical cross-sectional study was performed on 21673 infertile couples referring to infertility clinic of Royan Institute between 2009 and 2014. Serological findings for viral hepatitis B, C and HIV infection were gathered herewith demographic data of the study participants through the study checklist. Ultimately, 302 couples who had at least one positive result in their serological tests were included in the statistical analysis. Results The HBV and HCV infections prevalence among study participants were 0.57% and 0.148% respectively; only two cases had HIV infection. HBV and HCV infections prevalence had significant association with the gender of participants, but there was no significant relationship between these infections and infertility types. Conclusion Viral hepatitis infections screening among infertile couples undergoing assisted reproductive techniques needs more attention.

Infertility affects approximately 15% of couples worldwide, an estimated 30% of which is related to male factor infertility. Application of low level laser therapy (LLLT) to improve fertility status is a rapidly growing discipline in medicine. Laser therapy triggers a variety of biological processes through interaction with primary cellular photoacceptors. The present review aims at evaluating the literature available in the MEDLINE/ PubMed on cellular and molecular mechanisms of photobiomodulation in the domains of reproductive and veterinary medicine. We primarily focused on the clinical application of laser treatment on seminal quality, in particular its role in promoting spermatozoa motility, as well as the role of phototherapy in modulating assisted reproduction (ART). Additionally, we investigated the strength of evidence in support of the positive impact of photobiomodulation on facilitating ART.

Background: Chlamydia trachomatis (CT) with damaging effects on sperm quality parameters can often cause infertility in men. Objective: The main objective of this study was to determine the diagnostic value of polymerase chain reaction (PCR) and enzyme linked immuno sorbent assay (ELISA) for screening and detecting CT in semen samples of infertile men. Materials and Methods: In this cross-sectional study, 465 men referring to the clinical laboratory of Royan Institute were chosen for primary screening and detection of the presence of CT. 93 samples were normozoospermia with normal sperm parameters i.e. sperm number, motility and morphology (Asymptomatic) and 372 had abnormal sperm parameters (Symptomatic) in semen analysis. ELISA test was performed as the screening test. Samples with optical density (OD) >0.200 were selected as the case and asymptomatic samples with OD 0.400 as the ELISA positive, the diagnostic value of CT-ELISA positive in symptomatic and asymptomatic infertile patients were 0.019 (7 of 372) and 0.021 (2 of 93), respectively. There was no relationship between the presence of CT infection and different sperm abnormalities. Conclusion: The anti-CT IgA ELISA test may be introduced as an appropriate tool for screening purpose in the seminal plasma to select suspicious samples for PCR confirmatory tests.

Injury to podocytes is a principle cause of initiation and progression of both immune and non-immune mediated glomerular diseases that result in proteinuria and decreased function of the kidney. Current advances in regenerative medicine shed light on the therapeutic potential of cell-based strategies for treatment of such disorders. Thus, there is hope that generation and transplantation of podocytes from induced pluripotent stem cells (iPSCs), could potentially be used as a curative treatment for glomerulonephritis caused by podocytes injury and loss. Despite several reports on the generation of iPSC-derived podocytes, there are rare reports about successful use of these cells in animal models. In this study, we first generated a model of anti-podocyte antibody-induced heavy proteinuria that resembled human membranous nephropathy and was characterized by the presence of sub-epithelial immune deposits and podocytes loss. Thereafter, we showed that transplantation of functional iPSC-derived podocytes following podocytes depletion results in recruitment of iPSC-derived podocytes within the damaged glomerulus, and leads to attenuation of proteinuria and histological alterations. These results provided evidence that application of iPSCs-derived renal cells could be a possible therapeutic strategy to favorably influence glomerular diseases outcomes.

The role of asymptomatic infections caused by Ureaplasma species in male infertility and the efficacy of antibiotics in treatment of this failure is not yet definitely determined. A total of 165 infertile males having abnormal semen parameters (study group) as well as 165 healthy fertile men (control group) were included in this study. Semen samples were taken from all participants and after analyzing, undergone real-time PCR, microbial culture, and reactive oxygen species (ROS) as well as total antioxidant capacity (TAC) assays. Infected individuals of study group were treated with antibiotic. One month after the treatment completion, second semen samples were taken and undergone all the tests mentioned. The frequency of Ureaplasma spp. was significantly higher in the infertile men compared with the fertile ones (36.4% versus 11.5%; p < 0.001). Most of semen parameters were improved (p < 0.05) and reached their normal range, the level of TAC elevated (p < 0.001), and ROS level (p = 0.003) as well as ROS/TAC ratio (p = 0.003) reduced after antibiotic treatment. Moreover, wives of 37 infertile men (61.7%) became pregnant six months after the treatment completion. These findings indicate that Ureaplasma species are correlated with male infertility and that antibiotic therapy can improve the semen parameters and treat the male infertility.

Injury to podocytes is a principle cause of initiation and progression of both immune and non-immune mediated glomerular diseases that result in proteinuria and decreased function of the kidney. Current advances in regenerative medicine shed light on the therapeutic potential of cell-based strategies for treatment of such disorders. Thus, there is hope that generation and transplantation of podocytes from induced pluripotent stem cells (iPSCs), could potentially be used as a curative treatment for glomerulonephritis caused by podocytes injury and loss. Despite several reports on the generation of iPSC-derived podocytes, there are rare reports about successful use of these cells in animal models. In this study, we first generated a model of anti-podocyte antibody-induced heavy proteinuria that resembled human membranous nephropathy and was characterized by the presence of sub-epithelial immune deposits and podocytes loss. Thereafter, we showed that transplantation of functional iPSC-derived podocytes following podocytes depletion results in recruitment of iPSC-derived podocytes within the damaged glomerulus, and leads to attenuation of proteinuria and histological alterations. These results provided evidence that application of iPSCs-derived renal cells could be a possible therapeutic strategy to favorably influence glomerular diseases outcomes.

Background Viral hepatitis is one of the health problems which have the effects on the health issues. It seems that hepatitis B virus (HBV) and hepatitis C virus (HCV) infection have negative impacts on the semen quality and male infertility rate. Objective In this study, we aimed to evaluate the effects of HBV and HCV on sperm quality among Iranian infertile men referred to Royan Institute Reproductive Biomedicine Research Center between 2003 and 2014. Materials and Methods This retrospective case-control study included 112 HBV positive infertile men and 47 HCV positive infertile men as case group and 112 HBV negative and HCV negative matched infertile men as a control group. All semen analysis and viral parameters assessment was performed in the central laboratory with the same method and instruments. Results Sperm count among infertile men with HBV and HCV infection was significantly lower than control group [the mean of the total sperm count 100.95░±░118.59, 118.22░±░141.18, 166.27░±░151.25 (p░

Introduction: In recent years a great deal of effort has been made to improve the culture medium which can be used for different cell culturing and Folliculogenesis. PL (Platelet Layset) with a high percentage of growth factors and also microelements can be effective on the growth of follicle and oocyte. Material and method: Preantral follicles were collected from 12 to 14 days female NMRI mice and cultured in culture medium with a different supplement as the serum for 12 days. The different serums were, 5% and 10% FBS as the control groups and the experimental groups were enriched by 5% PL, 10% PL and a combination of 5% PL and 5% FBS. The growth and development of follicle and oocyte was monitored and also the amount of Estradiol (E2) and progesterone (P4) was detected in different mediums on days 9 and 12 of culturing. Result: Oocytes had a significant growth in all medium compared to day zero and reached to the size of a mature oocyte (p < 0.05). Although survival rate after one day had significant decrease in all medium compared to 5% FBS (p < 0.05), after 12 days of culturing, the best survival rate belonged to 5% PL. Progesterone secretion increased in experimental groups significantly (p < 0.05) while Estradiol secretion in 5% and 10% PL decreased in half of control groups. Discussion: This result demonstrates that PL can be a considerable supplement that can be added to the culture medium or a good replacement for FBS as serum used in Folliculogenesis.

Cysteine-Rich Secretory Protein 2 (CRISP2) plays an important role in the morphology and motion of male ejaculated spermatozoa. The association of its expression with some miRNAs is also well known. The aim of this study was to determine the expression of CRISP2 and mir-582 in the seminal plasma fluid and spermatozoa of three groups of infertile men and the possible association of their expressions. In this experimental study, the expression of CRISP2 in seminal plasma fluid and spermatozoa of 17 men with asthenozoospermia, 15 men with teratozoospermia, 17 men with teratoasthenozoospermia, and 18 infertile individuals with normozoospermia were measured using western blotting. Then by using bioinformatics studies, miR-582-5p was nominated as a CRISP2-associated miRNA, and its expression was evaluated by means of Real-Time PCR. Comparison of expression of CRISP2 and miRNA-582 in the studied groups was analyzed by t-test and Mann-Whitney U test. The expression of CRISP2 showed a significant reduction in the spermatozoa and seminal plasma fluid of all three groups, (p 0.05). MiR-582-5p expression significantly increased in teratozoospermia patients (0.05), and significantly decreased in teratoasthenozoospermia patients (p 0.05). Meanwhile, changes in the expression of miR-582-5p in teratoasthenozoospermia individuals was associated with a decrease in the expression of CRISP2, which could represent the potential role of miR-582-5p in regulation of CRISP2 expression in teratoasthenozoospermia individuals.

Objective To examine the predictive value of serum estradiol and progesterone on the day of human chorionic gonadotropin (hCG) administration and embryo transfer for clinical pregnancy rate in modified natural-cycle frozen embryo transfer (NC-FET). Methods In a longitudinal prospective study, all eligible women who underwent NC-FET cycles with hCG triggering in Royan Institute, Tehran, Iran, from June 1, 2015, to December 31, 2016, were evaluated. Serum estradiol and progesterone levels were measured at menstrual cycle initiation, on day of trigger with hCG, on day of embryo transfer, and in pregnant women every 7 days until the observation of a gestational sac with embryonic heartbeat. Results In total, 101 modified natural FET cycles were assessed, and the clinical pregnancy and live birth rates achieved were 34 (33.6%) and 32 (31.6%), respectively. The changes in estradiol level during early pregnancy showed an increase by an average of 200 pg/mL per week. Multivariable logistic regression analysis showed that only the estradiol level on the hCG day was a significant predictive variable for clinical pregnancy following NC-FET (P=0.04). Conclusion Estradiol level on the day of hCG trigger predicted the clinical pregnancy rates after modified NC-FET; this likely mirrored the developmental competence of the corpus luteum and an appropriate luteal structure-function.

Male infertility is mostly related to semen and spermatozoa, and any diagnosis or treatment requires the investigation of the motility patterns of spermatozoa. The movements of spermatozoa are fast and involve collision and occlusion with each other. In order to extract the motility patterns of spermatozoa, multi-target tracking (MTT) of spermatozoa is necessary. One of the most important steps of MTT is data association, in which the newly arrived observations are used to update the previous tracks. Dynamic Bayesian network (DBN) is a powerful tool for modeling and solving various types of problems such as tracking and classification. There can also be a hybrid-DBN (HDBN), in which both continuous and discrete nodes are present. HDBN has a suitable structure for modeling problems that have both discrete and continuous parameters like MTT. In this research, the data association for MTT of human spermatozoa has been studied. The proposed algorithm was tested over hundreds of manually extracted spermatozoa tracks and evaluated using several standard measures. The superior results of the proposed algorithm in comparison to the other well-known algorithms, show that it could be considered as an improved alternative to traditional computer assisted sperm analysis (CASA) algorithms.

To evaluate the effect of controlled ovarian stimulation (COH) with gonadotropins on the serum levels of autoantibodies in the women who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles and to compare basal levels of these autoantibodies between groups according to history of COH. This prospective cohort study was performed from October 2014 to March 2016 in the Royan Institute. The volunteered infertile women with regard to the inclusion criteria, who underwent IVF/ICSI cycles, were recruited. The COH was performed according to standard long GnRH agonist protocol. The mean levels of the autoantibodies including anti-nuclear, anti-smooth muscle, anti-ovarian, anti-mitochondrial, anti β2-glycoprotein I, anti-parietal cell and anti-follicle-stimulating hormone antibodies were measured at three time points: on the 3–5 days of the menstrual cycle, 1 week after starting of COH and the ovum pick-up (OPU) day. Of all participants (n = 189), 73 women had history of COH (group B) and 116 women did not have such history (group A). The analysis indicated that the autoantibodies changes during COH were similar in both groups. COH has no significant impact on the level of autoantibodies during the stimulation cycle. Multiple logistic regression analysis showed that the serum levels of anti-smooth muscle antibody on OPU day was the positive predictive factors for live birth following ART cycles in the studied population. No significant effect of COH on the studied autoantibodies by the time of OPU was found but further studies are required to interpret these results.

Lipopolysaccharides (LPS) from gram negative bacteria stimulate toll-like receptor 4 (TLR4) expression in immune cells. Recent reports state that bone marrow-derived cells such as mesenchymal stem cells (MSCs) also express TLR proteins. Numerous researches have studied the effect of a number of LPSs on TLR4 expression, but no data exists on the effect of LPSs from different strains of one bacterial genus on TLR4 expression. In this study, we investigate the effects of various concentrations of LPS from different Shigella strains on TLR4 expression in human bone marrow (hBM)-MSCs. At the mRNA level, we have found that untreated hBM-MSCs (control) did not express TLR4 compared to the experimental groups. Cells treated with LPS from Shigella flexneri had the highest expression of TLR4, whereas cells treated with LPS from Shigella sonnei had the lowest expression. We observed that LPSs had a dose-dependent effect on TLR4 expression in all of the treatment groups. ELISA findings for interleukin-6 secretion have confirmed mRNA expression results for all treatment groups. Hence, LPS from S. flexneri can be considered as an optimum LPS to stimulate the immune system for vaccine production against shigellosis. Also, TLR activation in hBM-MSCs can modulate their function such as homing.

Objective: This study was performed to evaluate the correlation of hyaluronic acid binding assay (HBA) with conventional semen parameters, lipid peroxidation (LPO), intracellular reactive oxygen species (ROS), DNA fragmentation (DF), DNA maturity and mitochondrial membrane potential (MMP) level in human spermatozoa. Methods: The semen samples were obtained from 98 patients. The seminal plasma was separated for the study of LPO, and the pellet was employed for evaluation of intracellular ROS, DF, nuclear maturity (sperm chromatin structure assay) and MMP through flowcytometry. Results: The correlation and strength of HBA with respect to the studied parameters were estimated by the Pearson coefficient and multiple liner regression tests. While HBA indicated a positive correlation with progressive motility (β-coefficients = 0.449, p < 0.05) and normal morphology (β-coefficients = 2.722, p < 0.01), it had only negative relationship with DNA integrity (high DNA stain ability; β-coefficients = -0.517, p < 0.05). HBA also did not show any important correlation with other conventional and intracellular sperm parameters. Conclusions: The HBA is sensitive to morphological integrity, high progressive motility and nuclear maturation. Nonetheless, HBA is not a reliable test for prediction of sperm intracellular ROS, DF and MMP risks and healthy spermatozoa selection.

Background: Male infertility is a multifactorial disorder, which affects approximately 10% of couples at childbearing age with substantial clinical and social impact. Genetic factors are associated with the susceptibility to spermatogenic impairment in humans. Recently, SEPT12 is reported as a critical gene for spermatogenesis. This gene encodes a testis specific member of Septin proteins, a family of polymerizing GTP-binding proteins. SEPT12 in association with other Septins is an essential annulus component in mature sperm. So, it is hypothesized that genetic alterations of SEPT12 may be concerned in male infertility. Objective: The objective of this research is exploration of new single nucleotide polymorphism G5508A in the SEPT12 gene association with idiopathic male infertility in Iranian men. Materials and Methods: In this case control study, 67 infertile men and 100 normal controls were analyzed for genetic alterations in the active site coding region of SEPT12, using polymerase chain reaction sequencing technique. Fisher exact test was used for statistical analysis and p

Objective The abdominal form of obesity is prevalent in women with polycystic ovary syndrome (PCOS). Visceral fat accumulation seems to play an important role in etiology of PCOS. In this cross-sectional study we evaluated the association of oxidative stress (OS) induced with PCOS and abdominal obesity in serum and follicular fluid (FF) of infertile women. Study design A total of 80 women younger than 37 years old undergoing an IVF program were studied in the same period of time from September 2012 to October 2013. Blood serum and FF obtained from 40 women with PCOS (diagnosed by the Rotterdam 2004 criteria) and 40 women without PCOS undergoing IVF were evaluated for two OS markers: lipid peroxide (LPO) and total antioxidant capacity (TAC), after puncture. The patients were divided into 4 groups on the basis of presence of PCOS and waist-to-hip ratio (WHR) or abdominal obesity (OA). Results Healthy and PCOS women with abdominal obesity had significantly higher amounts of LPO in the serum and FF as compared with women without abdominal obesity. LPO concentration in FF was significantly lower than in serum and corroborates the hypothesis that the germinal cells have a potent antioxidant mechanism. We also found that LPO concentration in the PCOS group associated with AO had an increasing trend vs. those AO patients without PCOS but this difference was not significant, so the increase in LPO level was approximately independent of PCOS. Based on our results, the association and interaction between PCOS and AO can lead to TAC concentration reduction in patients. Conclusions Abdominal obesity can induce local and systemic oxidative stress in PCOS and non-PCOS patients. We suggest that PCOS-induced disorders are likely to be exacerbated in the presence of abdominal obesity.

This study aimed to assess the possible association of bacterial vaginosis (BV) and early miscarriage in 408 women undergoing intracytoplasmic sperm injection (ICSI) for reasons of male infertility. A vaginal sample was obtained before oocyte retrieval and evaluated for BV-associated bacteria using the Nugent scoring system. The primary outcome was early miscarriage and the secondary outcomes included implantation, pregnancy, late miscarriage, preterm delivery and live birth rates. Chi-square, ANOVA, relative risk and odds ratio were used for data analysis where appropriate. The prevalence of BV was estimated as 7.3%. From 336 patients who had embryo transfer, 138 patients (41.1%) conceived. A total of 17% (n = 23) of pregnant women miscarried during the first trimester: 15 patients (15%) were normal, 4 (17.4%) were intermediate and 4 (26.7%) patients had BV (p = 0.52). The relative risk of early miscarriage in BV patients compared to the non-BV and intermediate group was 1.77 (0.68-4.64, 95% CI). Implantation, pregnancy, preterm delivery and live birth rates were comparable between groups. We conclude that BV does not appear to have an adverse impact on outcomes in women being treated with ICSI for male factor infertility and is not associated with miscarriage and preterm birth.

This study aimed to assess the possible association between ovarian auto-antibodies and poor ovarian response to controlled ovarian hyperstimulation (COH) in patients undergoing intracytoplasmic sperm injection (ICSI) cycles. In total, 42 poor responders and 43 male factor subjects were enrolled in the study and underwent either a standard long gonadotropin-releasing hormone (GnRH) agonist or antagonist protocol. Anti-ovarian, anti-oocyte, anti-zona pellucida (anti-ZP) and anti-gonadotropin antibodies in their sera and follicular fluid (FF) were measured by an enzyme-linked immunosorbent assay technique (ELISA). The mean follicular fluid anti-oocyte antibody [ratio of optical density (OD) sample/OD Control] was significantly higher in poor responders compared to the normal group (2.40 ± 1.55 versus 1.72 ± 0.71, p = 0.012). The linear regression analysis showed an inverse correlation between FF anti-oocyte antibody concentrations and the number of: (i) retrieved oocytes (B = −1.212, r = −0.235, p =...

Background Clinically, acute kidney injury (AKI) is a potentially devastating condition for which no specific therapy improves efficacy of the repair process. Bone marrow mesenchymal stromal cells (BM-MSCs) are proven to be beneficial for the renal repair process after AKI in different experimental rodent models, but their efficacy in large animals and humans remains unknown. This study aims to assess the effect of autologous rhesus Macaque mulatta monkey BM-MSC transplantation in cisplatin-induced AKI. Methods We chose a model of AKI induced by intravenous administration of 5 mg/kg cisplatin. BM-MSCs were transplanted through intra-arterial injection. The animals were followed for survival, biochemistry analysis and pathology. Results Transplantation of 5 × 10 6 cells/kg ameliorated renal function during the first week, as shown by significantly lower serum creatinine and urea values and higher urine creatinine and urea clearance without hyponatremia, hyperkalemia, proteinuria and polyuria up to 84 d compared with the vehicle and control groups. The superparamagnetic iron oxide nanoparticle-labeled cells were found in both the glomeruli and tubules. BM-MSCs markedly accelerated Foxp3+ T-regulatory cells in response to cisplatin-induced damage, as revealed by higher numbers of Foxp3+ cells within the tubuli of these monkeys compared with cisplatin-treated monkeys in the control and vehicle groups. Conclusions These data demonstrate that BM-MSCs in this unique large-animal model of cisplatin-induced AKI exhibited recovery and protective properties.

Background: Ramadan fasting is a religious practice and an exceptional ritual compared to all other religious conventions. The aim of fasting in Ramadan is to establish a proper religious model of self-control and healthy lifestyle. Objectives: The purpose of this study was to compare the biochemical neurohormones between women with polycystic ovary syndrome (PCOS) with and without fasting. Materials and Methods: This study was conducted during July 2011 at the Infertility Center of Royan Institute, and comprised 40 patients diagnosed with PCOS, aged from 20-40 years without any special disease. The study group included 20 women with PCOS and fasting during Ramadan. The control group consisted of 20 non-fasting women with PCOS. The study on the effects of fasting on patients with polycystic ovary syndrome involved demographic data and biochemical stress hormones including cortisol, adrenaline, noradrenaline, beta-endorphin and insulin. Results: In patients with PCOS, mean of cortisol in subjects with and without fasting were 8.2 ± 4.4 and 11.2 ± 4.7, respectively (P = 0.049). Also the respective median of nor-adrenaline in fasting and non-fasting patients were 1273.5 and 1503.5 (P = 0.047). However, no significant differences were found in adrenalin (P = 0.151), beta-endorphin (P = 0.543) and insulin (P = 0.818) between PCOS two groups. Conclusions: This study showed that Ramadan fasting is a well known practice to reduce stress hormones in women with PCOS. So, Ramadan, beside its spiritual benefit is a blessing from God for improving human lifestyle.

This prospective study was performed from June 2012 to June 2014 at Royan Institute to compare the predictive values of serum anti-müllerian hormone (AMH), antral follicle count (AFC) and ovarian response prediction index (ORPI) ([AFC × AMH]/age) for in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle outcomes. Five hundred and fifty women included in the study with male factor and unexplained infertility were the first candidates for IVF/ICSI cycles. Serum AMH level was measured by a commercial ELISA kit and AFC was calculated by a transvaginal ultrasonography on day 2-3 of the menstrual cycle before starting ovarian stimulation. All women underwent IVF/ICSI cycles using a long standard protocol with gonadotropin-releasing hormone agonist. The receiver operating characteristic curves (ROC) analysis showed that both AMH and AFC were good predictors of ovarian response with an area under the curves (AUC) 0.75; even it seems that AFC was being a better predictor. Combining these variables is necessary as ORPI will not improve the prediction value. All the variables had poor predictive ability (AUC0.60) for clinical pregnancy and live birth rates. Logistic regression analysis showed the AMH less than 0.4 ng/ml and quality of transferred embryos were significant predictors for clinical pregnancy rate.

The aim of this study was to evaluate the conventional sperm parameters, level of intracellular reactive oxygen species (ROS), DNA fragmentation (DF) and dysfunction of mitochondrial membrane potential (MMP) after semen preparation techniques with flow cytometry. Semen samples were obtained from 28 men with normal semen analysis according to WHO (world health organization). Each was divided into three equal parts for processing with routine techniques: conventional swim up (CSW), direct swim up (DSW) and density gradient centrifugation (DGC). The conventional sperm parameters were evaluated with computer-assisted sperm analyzer (CASA) and the level of intracellular ROS, dysfunction of MMP and DF were determined with flow cytometry procedure. Conventional sperm parameters such as motility, progressive motility and normal morphology increased after sperm processing by CSW and DGC compared to DSW. A significant increase in intracellular H2O2 (p

Ureaplasma urealyticum is a causative agent of non-gonococcal urethritis and is implicated in the pathogenesis of prostatitis, epididymitis and infertility. The organism is more common in partners of infertile than fertile marriages. U. urealyticum infections not only jeopardize fertility but also pose a risk for infertility treatment and resulting pregnancies. The aim of this study was to determine the prevalence of U. urealyticum and Ureaplasma parvum in semen of infertile and healthy men by polymerase chain reaction (PCR). Semen samples were obtained from infertile patients and healthy controls and were subjected to the routine andrological analysis and PCR. DNA was extracted by the Cadieux method, and analysed by PCR protocol with specific primers for urease and multiple-banded antigen genes. Ureaplasmas were detected significantly by PCR in 12 of 100 (12%) semen specimens from infertile patients and in three of 100 (3%) healthy men. The volume of semen fluid, concentration of sperm cells, and sperm cell with normal morphology were significantly decreased in infertile men. In the group of infertile patients with PCR positive for Ureaplasmas, the volume, count and morphology of semen samples were lower than in the infertile patients with PCR-negative results. U. urealyticum species in semen of infertile men was found to be high (9%) than in healthy controls (1%). Detection rate for U. parvum was 3% in the infertile group and 2% in healthy men. The results indicate that U. urealyticum species is more common in specimens of infertile men. The percentage of normal sperm cells, the volume of semen and the percentage of sperm cells with motility in the PCR positive for U. urealyticum species group were lower than in the PCR positive for U. parvum group.

Objective Although key roles for dietary vitamin E (VITE) and fatty acid (FA) in fertility have been confirmed, limited data are available on the effects of VITE alone, or a constant level of VITE supplemented by dietary omega-6 and omega-3 FAs in combination on male reproduction. Consequently in this paper, the effects of VITE, sunflower oil, fish oil and their combination on rat sperm were investigated. Materials and Methods We divided 50 mature male Wistar rats into 5 groups (n=10) in a experimental completely randomized design for eight weeks: i. Control (CTR): standard diet; ii. Vitamin E diet (VITE): 2 times greater than recommendations; iii. Sunflower oil group (n-6) [gavaged with 0.5 ml/day/rat sunflower oil+VITE diet]; iv. Fish oil group (n-3): [gavaged with 0.5 ml/day/rat fish oil+VITE diet] and v. n-3+n-6 group [gavaged with 0.3 ml fish oil/day/rat+0.2 ml sunflower oil/day/rat+VITE diet]. The sperm parameters were measured by computer assisted semen analyzer (CASA). All data were analyzed with SPSS software. Results Feed intake decreased in groups which were administered sunflower oil compared with the other groups (P

Objective To evaluate the expression of MIF , CD74 , and COX-2 in normal, ectopic, and eutopic endometrium during the menstrual cycle and to assess MIF level in peripheral blood. Design The expressions of MIF , CD74 , and COX - 2 in normal, ectopic, and eutopic endometrium were evaluated with the use of real-time polymerase chain reaction. MIF protein in peripheral blood samples was checked with the use of ELISA. Setting Reproductive biomedicine research center. Patient(s) Sixteen normal women and 20 women with endometriosis. Intervention(s) Ectopic biopsies were obtained with the use of laparoscopic procedure, and eutopic and control biopsies were obtained with the use of Pipelle. Peripheral blood samples were collected before laparoscopy. Main Outcome Measure(s) The expression of MIF , CD74 , and COX-2 in normal, ectopic and eutopic endometrium during the menstrual cycle and the expression level of MIF in peripheral blood samples. Result(s) Relative mRNA expression of MIF , CD74 , and COX-2 were significantly higher in ectopic endometrium than in eutopic and control endometrium. Also, there were significant differences in expression of these genes in normal, ectopic, and eutopic endometrium during the menstrual cycle. Moreover, women with endometriosis had significantly higher circulating levels of MIF compared with control subjects. Conclusion(s) Dynamic expression of MIF , CD74 , and COX-2 during the menstrual cycle could play an essential role in reproduction, inflammation, and endometrium reconstruction. A higher expression of these genes in ectopic endometrium can be considered as a molecular biomarker for endometriosis development and pathophysiology. Also, a high level of MIF in blood serum can act as a biomarker in the diagnosis of endometriosis.

Background: To evaluate diagnostic accuracy of transvaginal sonography and laparoscopy in the diagnosis of endometriosis. Patients and Methods: This was a prospective study of women scheduled for laparoscopy because of infertility assessment. Consecutive patients were assessed prospectively using TVS before laparoscopy and the findings of preoperative TVS were compared with the results obtained by laparoscopy as a gold standard. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy were calculated for the diagnosis of endometriosis. Results: In total, 262 women (mean age 31 + 4.47) had preoperative TVS and laparoscopies. Of these, 78 had endometriosis. Diagnostic accuracy was assessed; the sensitivity and specificity of the TVS in the diagnosis of pelvic endometriosis were 53% and 95%, respectively, and the positive and negative predictive value were 63% and 92%, respectively. The diagnostic accuracy was 88%. Conclusions: TVS is a good test for assessing pelvic endometriosis. Good specificity and sensitivity were obtained in the diagnosis of deep endometriosis. TVS is particularly accurate in detecting deep endometriosis, which could facilitate more effective triaging of women for appropriate surgical care.