Virulence characterization and clonal analysis of uropathogenic Escherichia coli metallo-beta-lactamase-producing isolates.

BACKGROUND: Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infection (UTI); however, treatment of UTI has been challenging due to increased antimicrobial resistance (AMR). One of the most important types of AMR is carbapenem resistance (CR). CR bacteria are known as an important threat to global public health today. Class B metallo-beta-lactamases (MBLs) are one of the major factors for resistance against carbapenems. We aimed to investigate the characteristics of UPEC isolates producing MBL. METHODS: A cross-sectional study was conducted from October 2018 to December 2019 in Ahvaz; Iran. UPEC isolates were identified by biochemical and molecular methods. Metallo-beta-lactamase-producing isolates were detected using modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) tests. MBL genes, phylogenetic group, and virulence genes profile of carbapenem resistant isolates were determined. Conjugation assay and plasmid profiling were conducted to evaluate the ability of transferring of CR to other E. coli isolates. Clonal similarity of isolates were assessed using Enterobacterial intergenic repetitive element sequence (ERIC)-PCR. RESULTS: Among 406 UPEC isolates, 12 (2.95%) carbapenem-resistant were detected of which 11 were phenotypically MBL-producing strains. Four isolates were resistant to all investigated antimicrobial agents and were considered possible pandrug-resistant (PDR). blaNDM, blaOXA-48, blaIMP-1, and blaIMP-2 genes were found in 9, 5, 1, and 1 isolates, respectively. Among 30 virulence genes investigated, the traT, fyuA followed by fimH, and iutA with the frequency of 8 (66.7%), 8 (66.7%), 7 (58.3%), and 7 (58.3%) were the most identified genes, respectively. Siderophore production was the main virulence trait among carbapenem-resistant UPEC isolates. Except for two, all other isolates showed weak to moderate virulence index. In all recovered isolates, CR was readily transmitted via plasmids to other isolates during conjugation experiments. CONCLUSION: MBL and carbapenemase genes, especially blaNDM and blaOXA-48 are spreading rapidly among bacteria, which can be a threat to global public health. Therefore monitoring the emergence and dissemination of new AMR is necessary to continuously refine guidelines for empiric antimicrobial therapy. Understanding the mechanisms of resistance and virulence in this group of bacteria can play an effective role in providing new therapeutic methods.

Antimicrobial resistance and metallo-beta-lactamase producing among commensal Escherichia coli isolates from healthy children of Khuzestan and Fars provinces; Iran.

BACKGROUND: The emergence of metallo-ß-lactamase (MBL)-producing isolates is alarming since they carry mobile genetic elements with great ability to spread; therefore, early detection of these isolates, particularly their reservoir, is crucial to prevent their inter- and intra-care setting dissemination and establish suitable antimicrobial therapies. The current study was designed to evaluate the frequency of antimicrobial resistance (AMR), MBL producers and identification of MBL resistance genes in Escherichia coli strains isolated from fecal samples of the healthy children under 3 years old. A total of 412 fecal E. coli isolates were collected from October 2017 to December 2018. The study population included healthy infants and children aged < 3 years who did not exhibit symptoms of any diseases, especially gastrointestinal diseases. E. coli isolates were assessed to determine the pattern of AMR. E. coli isolates were assessed to determine the pattern of AMR, the production of extended spectrum ß-lactamase (ESBL) and MBL by phenotypic methods. Carbapenem-resistant isolates were investigated for the presence of MBL and carbapenemase genes, plasmid profiling, and the ability of conjugation. RESULTS: In sum, AMR, multi-drug resistance (MDR) and ESBL production were observed in more than 54.9, 36.2 and 11.7% of commensal E. coli isolates, respectively. Out of six isolates resistant to imipenem and meropenem, four isolates were phenotypically detected as MBL producers. Two and one E. coli strains carried the blaNDM-1 and blaVIM-2 genes, respectively and were able to transmit imipenem resistance through conjugation. CONCLUSION: Our findings showed that children not exposed to antibiotics can be colonized by E. coli isolates resistant to the commonly used antimicrobial compounds and can be a good indicator for the occurrence and prevalence of AMR in the community. These bacteria can act as a potential reservoir of AMR genes including MBL genes of pathogenic bacteria and lead to the dissemination of resistance mechanisms to other bacteria.

Diet and The Risk of Endometriosis in Iranian Women: A Case-Control Study.

BACKGROUND: Endometriosis is one of the most common pelvic diseases associated with dyspareunia, pelvic pain, and infertility. The primary aim of this study is to evaluate the role of diet on the risk of endometriosis among Iranian women. MATERIALS AND METHODS: This case-control study was conducted in two health research centres between 2015 and 2016. There were 207 women with endometriosis (case) and 206 women without endometriosis (control) who were evaluated by laparoscopy. The women were asked about their frequency of consumption per week of portions of selected dietary items in the Iranian diet in the year before the interview. RESULTS: The results indicated that intake of green vegetables (odds ratio [OR]=0.39, 95% confidence interval [CI]=0.21-0.74, Ptrend=0.004), red meat (OR=0.61, 95% CI=0.41-0.91, Ptrend=0.015) and dairy products (milk [OR=0.65, 95% CI=0.47-0.92, Ptrend=0.014], cheese [OR=0.53, 95% CI=0.37-0.76, Ptrend<0.001]), fresh fruit (OR=0.68, 95% CI=0.50-0.93, Ptrend=0.015) and grain legumes (OR=0.59, 95% CI=0.47-0.77; Ptrend<0.001) had a significant association with lower risk of endometriosis. Consumption of carrots, green tea, fish, eggs and oil was not significantly related to the risk of endometriosis. CONCLUSION: This study suggests that certain types of dietary components may be related to the risk of endometriosis.

Association of Signal Transducer and Activator of Transcription 4 rs10181656 Polymorphism With Rheumatoid Arthritis and Systemic Sclerosis in Khuzestan Province in Southwestern Iran.

OBJECTIVES: This study aims to investigate the association of polymorphism rs10181656 (C>G) of signal transducer and activator of transcription 4 (STAT4) gene with rheumatoid arthritis (RA) and systemic sclerosis (SSc) in the southwest of Iran as well as the probable relationship between the polymorphism with clinical features and disease activity parameters in both diseases. PATIENTS AND METHODS: A total of 200 patients (120 with RA [21 males, 99 females; mean age 44.83 years; range, 16 to 75 years] and 80 with SSc [13 males, 67 females; mean age 44.3 years; range, 30 to 75 years]) and 120 healthy controls (25 males, 95 females; mean age 46.93 years; range, 30 to 75 years) were recruited in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. A set of genotypes was confirmed by sequencing. RESULTS: A statistically significant association was detected between STAT4 rs10181656 polymorphism and RA (p=0.007). No significant correlation was detected between STAT4 rs10181656 polymorphism and SSc (p=0.357). None of the clinical features (anti-cyclic citrullinated peptide, rheumatoid factor) or disease activity parameters (limited cutaneous SSc, diffuse cutaneous SSc) showed any correlation with the genotype distribution of the STAT4 rs10181656 polymorphism in RA or SSc patients. CONCLUSION: Our findings suggest an association between RA susceptibility and STAT4 rs10181656 polymorphism. However, no significant association was found between the mentioned polymorphism and SSc. Clinical features and disease activity parameters did not show any association with the polymorphism.

The Association between ABO and Rh Blood Groups and Risk of Endometriosis in Iranian Women.

BACHGROUND: Endometriosis is a common gynaecological disease that affects quality of life for women. Several studies have revealed that both environmental and genetic factors contribute to the development of endometriosis. The aim of this study was to investigate the distribution of ABO and Rh blood groups in Iranian women with endometriosis who presented to two referral infertility centers in Tehran, Iran. MATERIALS AND METHODS: In this case-control study, women who referred to Royan Institute and Arash Women's Hospital for diagnostic laparoscopy between 2013 and 2014 were assessed. Based on the laparoscopy findings, we categorized the women into two groups: endometriosis and control (women without endometriosis and normal pelvis). Chi-square and logistic regression tests were used for data analysis. RESULTS: In this study, we assessed 433 women, of which 213 patients were assigned to the endometriosis group while the remaining 220 subjects comprised the control group. The most frequent ABO blood group was O (40.6%). The least frequent blood group was AB (4.8%). In terms of Rh blood group, Rh+ (90.1%) was more frequent than Rh- (9.9%). There was no significant correlation between ABO (P=0.091) and Rh (P=0.55) blood groups and risk of endometriosis. Also, there was no significant difference between the two groups with regards to the stage of endometriosis and distribution of ABO and Rh blood groups (P>0.05). CONCLUSION: Although the O blood group was less dominant in Iranian women with endometriosis, we observed no significant correlation between the risk of endometriosis and the ABO and Rh blood groups. Endometriosis severity was not correlated to any of these blood groups.

Longitudinal Assessment of Serum Creatinine Levels on Graft Survival After Renal Transplantation: Joint Modeling Approach.

BACKGROUND: Chronic kidney disease (CKD) is a major public health problem. The eventual outcome of CKD is end-stage renal disease (ESRD). Early diagnosis and proper management play an important role in preventing CKD progression to ESRD. Dialysis and kidney transplantation are the only treatment options available for patients suffering from ESRD. OBJECTIVES: This study was designed to investigate the etiological role of recipient and donor characteristics on serum creatinine changes within the follow-up period, graft failure risk, and the impact of longitudinal serum creatinine levels on graft survival after renal transplantation. PATIENTS AND METHODS: This study was carried out at the department of nephrology, Baqiyatallah hospital, Baqiyatallah University, Tehran, Iran, between April 2005 and December 2008. During that time period, 461 patients who had undergone renal transplantation were entered in the current study. Time to graft loss and serum creatinine levels at each visit were the primary data gathered for the study. A joint modeling of survival and longitudinal nonsurvival data was used to assess the association between the two processes and investigate the influential factors. RESULTS: Median follow-up time was 6.80 months. A linear decreasing trend in serum creatinine level over time was found (P < 0.001). The results showed a positive correlation between serum creatinine levels and risk of graft failure (P < 0.001). CONCLUSIONS: The major finding of this study is that one unit increase in serum creatinine level suggests an increased risk of graft failure of up to four times.

Evaluation of Risk Factors Associated with Endometriosis in Infertile Women.

BACKGROUND: Endometriosis affects women's physical and mental wellbeing. Symptoms include dyspareunia, dysmenorrhea, pelvic pain, and infertility. The purpose of this study is to assess the correlation between some relevant factors and symptoms and risk of an endometriosis diagnosis in infertile women. MATERIALS AND METHODS: A retrospective study of 1282 surgical patients in an infertility Institute, Iran between 2011 and 2013 were evaluated by laparoscopy. Of these, there were 341 infertile women with endometriosis (cases) and 332 infertile women with a normal pelvis (comparison group). Chi-square and t tests were used to compare these two groups. Logistic regression was done to build a prediction model for an endometriosis diagnosis. RESULTS: Gravidity [odds ratio (OR): 0.8, confidence interval (CI): 0.6-0.9, P=0.01], parity (OR: 0.7, CI: 0.6-0.9, P=0.01), family history of endometriosis (OR: 4.9, CI: 2.1-11.3, P<0.001), history of galactorrhea (OR: 2.3, CI: 1.5-3.5, P=0.01), history of pelvic surgery (OR: 1.9, CI: 1.3-2.7, P<0.001), and shorter menstrual cycle length (OR: 0.9, CI: 0.9-0.9, P=0.04) were associated with endometriosis. Duration of natural menstruation and age of menarche were not correlated with subsequent risk of endometriosis (P>0.05). Fatigue, diarrhea, constipation, dysmenorrhea, dyspareunia, pelvic pain and premenstrual spotting were more significant among late-stage endometriosis patients than in those with early-stage endometriosis and more prevalent among patients with endometriosis than that of the comparison group. In the logistic regression model, gravidity, family history of endometriosis, history of galactorrhea, history of pelvic surgery, dysmenorrhoea, pelvic pain, dysparaunia, premenstrual spotting, fatigue, and diarrhea were significantly associated with endometriosis. However, the number of pregnancies was negatively related to endometriosis. CONCLUSION: Endometriosis is a considerable public health issue because it affects many women and is associated with the significant morbidity. In this study, we built a prediction model which can be used to predict the risk of endometriosis in infertile women.

Evaluating The Effective Factors in Pregnancy after Intrauterine Insemination: A Retrospective Study.

BACKGROUND: Controlled ovarian hyperstimulation (COH) in conjunction with intrauterine inseminations (IUI) are commonly used to treat infertile couples. In this study we evaluated the relationship between IUI outcome and special causes of infertility. We also aimed to examine parameters that might predict success following IUI. MATERIALS AND METHODS: In this cross-sectional study, we included 994 IUI cycles in 803 couples who referred to the infertility Institute. All statistical analyses were performed by using SPSS program, t tests and chi-square. Stepwise multiple linear regression analysis was performed to compare the association between dependent and independent variables. Logistic regression was conducted to build a prediction model of the IUI outcome. RESULTS: Overall pregnancy rate per completed cycle (16.5%) and live birth rate per cycle (14.5%). The mean age in the pregnant group was significantly lower than that of the non-pregnant group (P=0.01).There was an association between cause of infertility and clinical pregnancies (P<0.001). Logistic regression identified four significant factors in determining the success of the IUI [menstrual irregularites (OR:2.3, CI:1.6-3.4, P<0.001), duration of infertility (OR:0.8, CI:0.8-0.9, P<0.001), total dose of gonadotropin (OR:1.02, CI:1.003-1.04, P=0.02) and semen volume (OR:1.1, CI:1.008-1.2, P=0.03)] which were the most predictive of IUI success. CONCLUSION: Our study defined prognostic factors for pregnancy in COH+IUI. These variables can be integrated into a mathematical model to predict the chance of pregnancy rate in subsequent COH+IUI cycles.

New single nucleotide polymorphism G5508A in the SEPT12 gene may be associated with idiopathic male infertility in Iranian men.

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<0.05 was considered as statistically significant. RESULTS: Genotype analysis indicated that G5508A polymorphic SEPT12 alleles were distributed in three peaks of frequency in both control and diseases groups. Categorization of the alleles into (GG), (GA), (AA) types revealed a significant difference between infertile patients (azoospermic and asthenospermic) and normal controls (p=0.005). CONCLUSION: According to our finding we suggest that G5508A polymorphism in SEPT12 gene can affect spermatogenesis in men, the opinion needs more investigation in different populations.

A randomized controlled trial evaluating the effect of ethinyl estradiol during clomiphene citrate cycles among women with polycystic ovary syndrome.

OBJECTIVE: To investigate the effects of low-dose ethinyl estradiol (EE) on the clinical pregnancy rate among women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with clomiphene citrate (CC). METHODS: Between March 12, 2011, and February 10, 2013, a randomized, double-blind, placebo-controlled trial was conducted at the Royan Institute Research Center, Tehran, Iran, among women with PCOS who were aged 25-30 years, were undergoing their first intrauterine insemination cycle, and had a history (≥2 years) of infertility, oligomenorrhea, or amenorrhea. Participants were randomly allocated to receive EE (0.05 mg daily for 5 days) or placebo, co-administered with CC cycles (100 mg daily for 5 days). The primary outcome was clinical pregnancy rate. Analyses were per protocol: patients who discontinued the intervention were excluded. RESULTS: Analyses included 45 women who received CC and EE, and 50 women who received CC and placebo. The number of women who achieved a clinical pregnancy was higher among participants who received CC and EE (13 [29%]) than among those in the control group (5 [10%]; P =0 .02). No adverse effects of EE were reported. CONCLUSION: The combination of CC and EE seems to increase the clinical pregnancy rate among women with PCOS undergoing intrauterine insemination. ClinicalTrials.gov:NCT01219101.

Risk factors for ectopic pregnancy: A case-control study.

BACKGROUND: Ectopic pregnancy (EP) is a condition presenting as a major health problem for women of childbearing age. This study aimed to identify potential risk factors for EP and to evaluate the contribution of the risk factors associated to EP. MATERIALS AND METHODS: This retrospective nested case-control study was conducted from 2006 to 2011. In case group, there were a total of 83 women diagnosed with EP, while in the control group; there was a total of 340 women who gave birth. The basic recorded information included surgical, gynecological, obstetrics, sexual, contraceptive, and infectious histories; demographic characteristics; smoking habits; fertility markers; as well as reproductive outcome after EP. The association between EP and the factors studied was analyzed by logistic regression. RESULTS: The findings reveal that the following factors were associated with increased risk of EP, including: Maternal age (odds ratio [OR] =1.11, confidence interval [CI] [1.06-1.16], P < 0.0001), spouse's cigarette smoking (OR = 1.73, CI [1.05-2.85], P = 0.02), gravidity (OR = 1.50, CI [1.25-1.80], P < 0.0001), prior spontaneous abortions (OR = 1.93, CI [1.11-3.36], P = 0.01), history of EP (OR = 17.16, CI [1.89-155.67], P = 0.01), tubal blockage (OR = 10.85, CI [2.02-58.08], P = 0.01), use of intrauterine device (IUD) (OR = 4.39, CI [1.78-10.81], P = 0.001), tubal damage (OR = 2.704, CI [1.26-5.78], P = 0.01), first pregnancy interval (OR = 1.01, CI [1.00-1.02], P < 0.0001) and history of infertility (OR = 6.13, CI [2.70-13.93], P < 0.0001). CONCLUSION: By identifying risk factors being amenable to modification, such as cigarette smoking and use of IUD and first pregnancy interval the effective risk-reduction strategies can be devised.

Impact of the endometrioma on ovarian response and pregnancy rate in in vitro fertilization cycles.

BACKGROUND: Our objective was to evaluate the effect of ovarian endometrioma on ovarian stimulation outcomes in in vitro fertilization cycles (IVF). MATERIALS AND METHODS: In this prospective cohort study, we followed 103 patients who underwent intra-cytoplasmic sperm injection (ICSI) procedures over a 24-months period. The study group consisted of 47 infertile women with either unilateral or bilateral ovarian endometrial cysts of less than 3 cm. The control group consisting of 57 patients with mild male factor infertility was candidate for ICSI treatment during the same time period as the study groups. Both groups were compared for number of oocytes retrieved, grades of oocytes, as well as embryo quantity and quality. RESULTS: Our results showed similar follicle numbers, good embryo grades (A or B) and pregnancy rates in the compared groups. However, patients with endometrioma had higher gonadotropin consumption than the control group. The mean number of retrieved oocytes in patients with endometrioma was significantly lower than control group (6.6 ± 3.74 vs. 10.4 ± 5.25) (p<0.001). In addition, patients with endometrioma had significantly lower numbers of metaphase II (MII) oocytes (5 ± 3.21) than controls (8.2 ± 5.4) (p<0.001). In patients with unilateral endometrioma, there were no significant differences in main outcome measures between normal and involved ovaries in the patients with endometrioma. CONCLUSION: Patients with ovarian endometrioma had poor outcome. They showed poor ovarian response with lower total numbers of retrieved oocytes and lower MII oocytes during the stimulation phase; however, it does not affect the total number of embryos transferred per patient, quality of embryos, and pregnancy rate per patient.

Effect of 830-nm diode laser irradiation on human sperm motility.

Sperm motility is known as an effective parameter in male fertility, and it depends on energy consumption. Low-level laser irradiation could increase energy supply to the cell by producing adenosine triphosphate. The purpose of this study is to evaluate how the low-level laser irradiation affects the human sperm motility. Fresh human semen specimens of asthenospermic patients were divided into four equal portions and irradiated by 830-nm GaAlAs laser irradiation with varying doses as: 0 (control), 4, 6 and 10 J/cm(2). At the times of 0, 30, 45 and 60 min following irradiation, sperm motilities are assessed by means of computer-aided sperm analysis in all samples. Two additional tests [HOS and sperm chromatin dispersion (SCD) tests] were also performed on the control and high irradiated groups as well. Sperm motility of the control groups significantly decreased after 30, 45 and 60 min of irradiation, while those of irradiated groups remained constant or slightly increased by passing of time. Significant increases have been observed in doses of 4 and 6 J/cm(2) at the times of 60 and 45 min, respectively. SCD test also revealed a non-significant difference. Our results showed that irradiating human sperms with low-level 830-nm diode laser can improve their progressive motility depending on both laser density and post-exposure time.

Risk factors associated with endometriosis among infertile Iranian women.

INTRODUCTION: Endometriosis is defined as overgrowth of endometrial tissue outside the uterine cavity. Endometriosis may be asymptomatic or associated with dysmenorrheal symptoms, dyspareunia, pelvic pain, abnormal uterine bleeding and infertility. The aim of this study was to explore the risk factors related to endometriosis among infertile Iranian women. MATERIAL AND METHODS: In this case control study, infertile women referred for laparoscopy and infertility workup to two referral infertility clinics in Tehran, Iran were studied. According to the laparoscopy findings, women were divided into case (women who had pelvic endometriosis) and control (women with normal pelvis) groups. The case group was divided into two subgroups: stage I and II of endometriosis were considered as mild while stage III and IV were categorized as severe endometriosis. A questionnaire was completed for each patient. RESULTS: Logistic regression showed that age, duration of infertility, body mass index (BMI), duration of menstrual cycle, abortion history, dyspareunia, pelvic pain and family history of endometriosis are independent predictive factors for any type of endometriosis. In addition, it was shown that education, duration of infertility, BMI, amount and duration of menstrual bleeding, menstrual pattern, dyspareunia, pelvic pain and family history of endometriosis are independent predictive factors of severe endometriosis. The AUCs for these models were 0.781 (0.735-0.827) and 0.855 (0.810-0.901) for any type of endometriosis and severe endometriosis, respectively. CONCLUSIONS: It seems that any type of endometriosis and severe ones could be predicted according to demographic, menstrual and reproductive characteristics of infertile women.

ICSI Outcome in Infertile Couples with Different Causes of Infertility: A Cross-Sectional Study.

BACKGROUND: Different success rate of Intracytoplasmic Sperm injection (ICSI) has been observed in various causes of infertility. In this study, we evaluated the relation between ICSI outcome and different causes of infertility. We also aimed to examine parameters that might predict the pregnancy success rate following ICSI. MATERIALS AND METHODS: This cross sectional study included1492 infertile women referred to Infertility Center of Royan Institute between 2010 and 2011. We assigned two groups including pregnant (n=504) and non-pregnant (n=988), while all participants underwent ICSI cycles. All statistics were performed by SPSS program. Statistical Analysis was carried out using Chi-square and t test. Logistic regression was done to build a prediction model in ICSI cycles. RESULTS: The overall clinical pregnancy rate in our study was 33.9% (n=1492). There was a statistically significant difference in mean serum concentration on day 3 after application of luteinizing hormone (LH) between the pregnant and the non-pregnant groups (p<0.05). However, There were no significant differences between two groups in the serum concentrations on day 3 after application of the following hormones: folliclestimulating hormone (FSH), thyroid-stimulating hormone (TSH), and metoclopramidestimulated prolactin (PRL) . We found no association between different causes of infertility and clinical outcomes . The number of metaphase II (MII) oocytes, embryo transfer, number of good embryo (grade A, B, AB), total dose of gonadotropin, endometrial thickness, maternal age, number of previous cycle were statistically significant between two groups (p<0.05). CONCLUSION: Our results indicate that ICSI in an effective option in couples with different causes of infertility. These variables were integrated into a statistical model to allow the prediction for the chance of pregnancy following ICSI cycles. It is required that each infertility center gather enough information about the causes of infertility in order to provide more information and better assistance to patients. Therefore, we suggest that physicians prepare adequate training and required information regarding these procedures for infertile couples in order to improve their knowledge.

Reproductive Outcome following Hysteroscopic Monopolar Metroplasty: An Analysis of 203 Cases.

BACKGROUND: : The aim of this study was to evaluate the reproductive outcome of women with history of infertility or recurrent miscarriage following hysteroscopic septum resection. MATERIALS AND METHODS: :This was a retrospective descriptive study performed on 263 patients, among whom 248 patients were infertile (79% with primary infertility and 21% with secondary infertility) and 15 patients presented with histories of recurrent miscarriage (three or more miscarriages) between 2005 and 2009. All participants underwent hysteroscopic septum resection using monopolar knife electrode. The main outcome measure was reproductive outcome after hysteroscopic metroplasty. RESULTS: The septum was completely removed during the first hysteroscopy in 242 (92%) patients. A residual septum was seen in 21 (8%) patients who required a second sitting of surgery. Three cases were complicated by minor perforations which required no further interventions. One operation complicated with bleeding which was controlled by a Foley catheter. There were no cases of postoperative Asherman's syndrome. Postoperatively, out of 263 patients, outcomes of 203 individuals were analyzed. According to the results, the miscarriage rate reduced significantly from 20.2 to 4.9%. Postoperative ectopic pregnancy rate and preterm labor were lower than prior to septum resection. Term deliveries increased significantly from 2.5 to 33.5%. CONCLUSION: Hysteroscopic septum resection is a safe and effective method for patients with history of infertility or recurrent miscarriage.

Efficacy of low dose hCG on oocyte maturity for ovarian stimulation in poor responder women undergoing intracytoplasmic sperm injection cycle: a randomized controlled trial.

PURPOSE: To investigate the effect of late follicular administration of low dose hCG on oocyte maturity in poor responding women undergoing intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: This prospective randomized pilot trial was performed on 73 poor responders undergoing ICSI, in Reproductive Biomedicine Research Center, Royan Institute, Tehran, Iran. All eligible patients underwent a GnRH-a long protocol and were randomly allocated into three study groups for ovarian stimulation: groupA received recombinant FSH alone, group B received recombinant FSH supplemented by 100 IU hCG. Group C received recombinant FSH supplemented by 200 IU hCG. The main endpoint was the number of metaphase II oocytes retrieved. RESULTS: Of 78 poor responding patients entered to this study, 73 women were considered eligible for enrolment. Of these, 26 women were allocated to receive only recombinant FSH, 24 patients allocated to receive recombinant FSH and 100 IU hCG and 23 patients were assigned to receive recombinant FSH and 200 IU hCG. Number of oocytes retrieved were significantly higher in group B compared to group A (6.5 ± 3.3 versus 4.0 ± 2.3; P = .03). Other cycle and clinical outcomes were comparable between three groups. CONCLUSIONS: The present study demonstrated that adding 100 IU hCG to rFSH in a GnRH agonist cycle in poor responders improve response to stimulation whereas the number of metaphase II oocytes remains comparable between groups. The existence of a possible trend toward higher mature oocytes and lower total dosage rFSH in patients received 100 or 200 IU hCG is probably due to the small sample size that means further large clinical trials in a more homogenous population is required (clinical trial registration number; NCT01509833).

Association of thrombophilia and polycystic ovarian syndrome in women with history of recurrent pregnancy loss.

PURPOSE: To evaluate the prevalence of thrombophilic disorders in polycystic ovarian syndrome (PCOS) women with history of recurrent pregnancy loss (RPL). MATERIALS AND METHODS: This study was carried out in 184 women with history of RPL, of which 92 of them were diagnosed with PCOS and 92 patients were without known PCOS. The prevalence of thrombophilic disorders was compared between the two mentioned groups. RESULTS: According to the findings, 70.7% of PCOS women with history of RPL had thrombophilic disorders. The prevalence of protein C deficiency was significantly higher in PCOS group compared to the non-PCOS group (21.7% vs. 10.9%, p = 0.04). There was a trend toward higher prevalence of protein S deficiency in PCOS group compared to the control group, but the difference did not reach statistical significance (23.9% vs. 13%, p = 0.05). The prevalence of other thrombophilic disorders such as antithrombin III deficiency, homocysteine elevation, antiphospholipid antibody and Factor V Leiden was comparable between groups. CONCLUSION: The prevalence of thrombophilic disorders was more common in PCOS women than the normal group. The protein C deficiency is associated with PCOS in women with history of RPL. There was a trend toward higher prevalence of protein S deficiency in PCOS women, which needs further study.

Comparative epigenetic analysis of Oct4 regulatory region in RA-induced differentiated NT2 cells under adherent and non-adherent culture conditions.

Oct4 is a POU domain homeobox gene, expressed in undifferentiated embryonal carcinoma and embryonic stem cells and is quickly down-regulated upon induction of differentiation. Transcriptional repression of Oct4 is followed by pronounced epigenetic changes on the regulatory region of the gene. Oct4 has a long upstream regulatory region of about 2,600 bp, consisting of proximal enhancer (PE), distal enhancer (DE), and proximal promoter (PP). In this study, we induced differentiation of a human embryonic carcinoma cell line, NT2, under two different adherent and non-adherent culture conditions, and compared histone modifications as the epigenetic marks on the regulatory region of Oct4 gene after 3 days of differentiation. Using chromatin immunoprecipitation coupled with real-time PCR technique, it was shown that the after induction of differentiation the repressive epigenetic marks of hypoacetylation and methylation on lysine-9 of histone H3 occurred very effectively on the upstream of Oct4, especially in PP region. Also, comparing the two culturing systems it was shown that methylation of lysine-9 of H3 histone was more drastic in PE region of adherent cells rather than suspension cells. This epigenetic profile was in agreement with the difference observed in the expression level of Oct4 in these two culturing systems. The current study clearly shows the effective role of cell culture condition on the epigenetic regulation of gene expression.

The factors affecting the outcome of frozen-thawed embryo transfer cycle.

OBJECTIVE: To determine the impact of the clinical and embryological factors on the pregnancy outcome of frozen-thawed embryo transfer. MATERIALS AND METHODS: The data of 247 frozen-thawed embryo transfer cycles were assessed at Royan Institute from March 2006 to March 2008. Appropriate statistical analysis was performed using Student t test and Chi-square or Fisher exact test. Forward logistic regression was done to predict the individual impact of factors on the success of frozen embryo transfer. RESULTS: According to our results, 1,523 frozen embryos were thawed with a survival rate of 79.8%. The overall chemical and clinical pregnancy rates per embryo transfer cycle were 28.1% and 26.3%, respectively. A total of 71 gestational sacs were implanted (7.9%). The pregnancy outcome was higher in women who were stimulated with the gonadotrophin releasing hormone agonist long protocol, treated by a combination of follicle stimulating hormone and luteinizing hormone, who had endometrial thickness greater than or equal to 8mm on the embryo transfer day, and who had positive fresh-cycle pregnancy test. CONCLUSION: Protocol type, gonadotrophin preparations, fresh-cycle outcome, endometrial thickness and the numbers of obtained oocytes, embryos, and high-quality thawed embryos transferred are the factors affecting pregnancy outcome of frozen-thawed embryo transfer.