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Since paroxysmal nocturnal haemoglobinuria (PNH) was first described in 1881, the diagnosis and follow-up patients diagnosed with the illness has remained an area of concern, with several different techniques of varying sensitivity having been described in the literature for both the diagnosis and monitoring treatment of the disease. PNH is a rare and life-threatening disease that manifests symptoms of haemolytic anaemia. Hence, a quick and reliable technique for precise diagnosis would be crucial. PNH patients who have previously been diagnosed with aplastic anaemia or myelodysplastic syndrome carry small PNH clones and for more than a century traditional method with low sensitivity was used for such patients. In 2010, the International Clinical Cytometry Society described a highly sensitive method for detection and quantification of different types of PNH clones using multi-colour flow cytometry. In this method, a three-colour flow cytometer is essential to detect PNH affected cells amongst monocytes and granulocytes. This started a new era in the diagnosis of patients who carry small clones of PNH cells. Before this, flow cytometric analysis was used only for detection of PNH cells amongst erythrocytes. By using flow cytometry instruments with more light sources, the sensitivity of detection and quantification of PNH clones would be augmented. However, standardisation and crosstalk compensation would be the most concerning issue. For the first time in Iran, we set up and standardised multi-colour flow cytometry technique to detect PNH cells in erythrocytes and leukocytes at Payvand medical laboratory.

Objective To compare the effect of gonadotropin-releasing hormone (GnRH) agonist microdose flare-up and GnRH agonist flare-up protocols among women with poor ovarian reserve undergoing intracytoplasmic sperm injection (ICSI) cycles. Methods Randomized controlled trial study among 131 women with poor ovarian reserve who underwent ICSI cycles at a single center in Tehran, Iran, between September 2008 and May 2014. Eligible women were randomly assigned to either the microdose flare-up (n=66) or flare-up (n=65) protocol. The primary outcome measure was live birth rate. Results Both groups were comparable in cycle cancellation, mean number of dominant follicles, retrieved oocytes, and metaphase II oocytes. Number of stimulation days (P=032) and endometrial thickness (P=0.001) were significantly higher, and gonadotropin dose was non-significantly higher (P=0.075) in the microdose flare-up group than in the flare-up group. No difference in clinical pregnancy, implantation, or abortion rate was observed between the two protocols. Live birth was higher in the microdose flare-up group than in the flare-up group (P=0.036). Conclusion The microdose flare-up protocol seemed to be superior to the flare-up protocol, but it required a higher dose of gonadotropins and a longer duration of stimulation. Further prospective clinical trials of the microdose flare-up protocol are recommended. CLINICALTRIALS.GOV: NCT01006954.

Purpose: The question that remains is, does changing the type of luteal phase support (LPS) improve the pregnancy outcomes in patients with poor ovarian response (POR) diagnosis?. Therefore, this study was designed to investigate and compare the efficiency of different methods of luteal phase support (progesterone alone or hCG alone and the combination of progesterone with hCG) in these patients.Methods: This randomized clinical trial evaluated three hundred seventy five patients who were diagnosed as POR on the basis of Bologna criteria undergoing intracytoplasmic sperm injection- embryo transfer (ICSI-ET) cycles at Royan institute from November 2015 to June 2019. The patients were allocated randomly into three different LPS groups on the day of oocyte pickup. In first group, 1500 IU of hCG IM on the ET day, as well as 4 days after that were administrated. In the second group, the patients received 1500 IU of hCG IM on the ET day, as well as 3 and 6 days after the ET along with vaginal suppositories 400 mg twice daily. For the third group, only vaginal suppositories twice daily was administrated from the day of oocyte pick up until the pregnancy test day.The clinical pregnancy, miscarriage and live birth rates were the main outcomes. Results: The data analysis showed that the three groups were comparable. In the following, there is no significant difference in terms of implantation, clinical pregnancy, and miscarriage and live birth rates among groups. The twin pregnancy rate in the hCG-only group was higher than those of in the other two groups, although this difference was not statistically significant (P=0.06).Conclusion: The type of LPS does not improve the pregnancy and live birth rates in POR patients. A multi-center clinical trial is warranted to confirm or refute these findings.Trial registration: The study was registered in the clinicaltrial.gov site on 14 June 2015. (NCT02798653 at www. clinicaltrials.gov, registered prospectively).

Background: Human platelet antigens (HPAs) are part of platelet GP complexes have the potential to contribute to the autoantibody production. Moreover, these antigens demonstrate different patterns of distribution on different ethnic groups and variation in some types of diseases. This study was objected to determine the incidence of HPA-1 to -5 and -15 polymorphisms in the Iranians suffering from primary Immune thrombocytopenic purpura (ITP). Materials and Methods: In this case-control investigation, 30 patients by definite primary ITP were randomly selected and enrolled in the study. HPA genotyping was performed implicating by the Single Specific Primer PCR (SSP-PCR). For the control group, data of recently published gene polymorphism among Iranian Blood donors were deployed for comparison. Results: The incidence of HPA-1 to -5 and -15 polymorphisms in the Iranian patients with primary ITP was found to be: HPA-1a/1a: 0.933, HPA-1a/1b: 0.067, HPA-2a/2a: 0.133, HPA-2a/2b: 0.867, HPA-3a/3a: 0.2, HPA-3a/3b: 0.533, HPA-3b/3b: 0.267, HPA-4a/4a: 1, HPA-5a/5a: 0.967, HPA-5a/5b: 0.330, HPA-15a/15a: 0.166, HPA-15a/15b: 0.667 & HPA-15b/15b: 0.167. Conclusion: This study provides special new data on the distribution of HPA allele among the Iranians ITP patients.Furthermore, it might useful toccharacterize understanding more presizely about ITP and HPA distribution. However, further studies concerning platelet immunology are needed to do help on best practice on management of immune diseases triggered by platelet antibodies.

Aim To evaluate the effect of adjuvant low-dose aspirin therapy on clinical pregnancy rate and uterine perfusion in women undergoing frozen-thawed embryo transfer (FET) cycles. Methods This study was performed as a pilot randomized, double-blind placebo-controlled trial, from May 2012 to February 2015. Overall, 60 available eligible women who were candidates for FET were randomly assigned to two groups receiving either 100 mg oral aspirin (n =30) or placebo (n =30). The primary outcome measure was clinical pregnancy rate. Secondary outcome measures were pulsatility index (PI), resistance index (RI), implantation rate, live birth rate and miscarriage rate. Results There was no significant difference in endometrial thickness, PI and RI. However, the study group had higher rates of clinical pregnancy, implantation, live birth (P = 0.042, P = 0.031 and P = 0.007, respectively) and lower rate of miscarriage (P = 0.020) as compared to the control group. Twin birth rate was comparable between the two groups. Conclusion Our pilot study demonstrated that administration of low-dose aspirin in FET cycles results in better pregnancy, implantation and live birth rates without changing the uterine hemodynamics or endometrial thickness. However, further randomized clinical studies in larger populations are needed to confirm these findings.

Background Spermatozoa interactions with fallopian tubes may influence fertilization. The purpose was to investigate cytokines, chemokines and growth factors expression from human fallopian tube epithelial cells (OE-E6/E7) exposed to spermatozoa. Methods Fresh semen samples were obtained from 10 healthy normozoospermic men. Sperms were prepared and co-cultured with OE-E6/E7. The cell line without spermatozoa was considered as the control group. Afterwards, Expression of 84 cytokines from OE-E6/E7 cell line in the presence and absence of spermatozoa were measured using PCR-array. Quantitative PCR was performed on seven genes to confirm the results of PCR-array analysis. Differentially expressed genes were subjected to www.geneontology.org and www.pantherdb.org to perform GO enrichment and panther pathway analysis. The concentration of IL-8, IL-10, IL-1B and BMP-4 in culture medium were analyzed by ELISA. Results Sperm interaction with the epithelial cells resulted in a significant increase in expression of TGF-β2, BMP-4, IL-10, IL-9, and CD40LG markers. Moreover, expression of IL-16, IL-17F, SPP-1, CXCL-13, MSTN, IL-1A, IL-1B, IL-8, BMP-7, CSF-2, CSF-3, VEGF-A, OSM, LTA, TNF, TNFRSF11B, TNFSF11, CCL-11, CCL-20, CCL-24, CCL-3, CCL-8, CX3CL1 and CXCL-9 were considerably reduced in presence of spermatozoa. Panther pathway analysis discovered 3 pathways for upregulated genes including gonadotropin-releasing hormone receptor, TGF-beta and interleukin signaling pathways. Furthermore, 9 pathways were detected for down-regulated genes. Inflammation signaling pathway which is mediated by chemokine and cytokine contains the most number of genes. Conclusion This study indicates that sperm modifies expression of cytokines, chemokines and growth factors from OE-E6/E7. Moreover, altered genes expression are toward higher survival chance of the spermatozoa.

Background Premature ovarian failure (POF) is characterized by the loss of ovarian activity before the age of 40 years. Stem cell therapy has the capability to create a regenerative microenvironment and is a proposed treatment for POF-related infertility due to the presence of renewal folliculogenesis and germ cells in the adult ovaries. In this study, we assessed the safety, feasibility, efficacy and dose adjustment of autologous adipose-derived stromal cells (ADSCs) and their ability to improve ovarian function in POF patients. Methods This study was a non-randomized clinical trial, phase I. Nine women with a definitive diagnosis of POF were divided into three groups (n = 3 per group) that received either 5 × 106, 10 × 106, or 15 × 106 autologous ADSCs suspension transplanted in the one ovary. Participants were followed-up at 24 h after the transplantation, and at 1 and 2 weeks, and 1, 2, 3, 6, and 12 months after the transplantation. The primary objective was to evaluate the safety of ADSCs transplantation. Secondary objectives included the effects of ADSCs transplantation on the resumption of menstruation, hormones level (Follicle-stimulating hormone (FSH) and anti-Müllerian hormone), ovarian function (Antral follicle count and ovary volume by ultrasonography evaluation) as well as dose escalation. Results Participants had not shown any early-onset possible side effects and secondary complications during follow-up. The menstruation resumption was observed in four patients which established for several months. In the 15 × 106 group, two POF patients had a return of menstruation second months after the intervention. Two other POF patients in 5 × 106 and 10 × 106 cell groups reported menstruation resumption at 1 month after the intervention. We observed decreased serum FSH levels of less than 25 IU/l in four patients. In two patients in 5 × 106 and 10 × 106 cell groups, serum FSH showed an inconsistent decline during a 1 year follow up after ADSCs transplantation. The ovarian volume, AMH, and AFC were variable during the follow-up and no significant differences between cell groups (p > 0.05). Conclusions We showed the intra-ovarian embedding of ADSCs is safe and feasible and is associated with an inconsistent decline in serum FSH. This should be further investigated with a large RCT. Trial registration NCT02603744, Registered 13 November 2015 - Retrospectively registered, http://www.Clinicaltrials.gov

Objective In vitro fertilization (IVF) is one of the most efficient approaches within the context of assisted reproductive technology (ART) to treat infertility. High pregnancy rates have become the major index of successful IVF in clinical studies. It is not clear yet which factors are certainly responsible for IVF success, as various outcomes were obtained in different IVF centers with different settings. In this study, we aimed to address controversies in the interpretation of promising results of IVF with respect to preimplantation genetic screening (PGS). Materials and Methods In this retrospective case series study, we built a dataset containing data from 213 IVF patient candidates for PGS (654 embryos) with blastomere biopsy at day 3 and trophectoderm biopsy in day 5, referred to Royan Institute, Tehran, Iran from 2015 to 2018. Next, the data were analyzed to find influential factors affecting success rate of ART cycles. Results Data analyses showed that regardless of PGS indications (ART failures, recurrent miscarriage, chromosomal abnormalities, etc.), the pregnancy rate is influenced by maternal and embryonic factors such as the age of mother as well as quantity and quality of transferred embryos. Furthermore, genotyping of embryos using array comparative genomic hybridization (aCGH) depicted the highest rate of chromosomal aberrations for chromosomes 1, 16 and 19 while the lowest frequency for chromosomes 11 and 17. Similarly, we detected 463 genetically abnormal embryos by aCGH, among which only 41.9% could be detected by classical fluorescent in situ hybridization (FISH) method. Conclusion This study not only highlighted the advantages of aCGH over the FISH method in detection of chromosomal abnormalities, but also emphasized the importance of genetic abnormality as an indication for determination of IVF success rate.

The original version of this article unfortunately contained a mistake. The affiliation of Dr. Adnan Khosravi and Gholamreza Bahoush-Mehdiabadi have been mistakenly "substituted" with each

Study question In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? Summary answer A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. What is known already Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. Study design, size, duration This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. Participants/materials, setting, methods Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. Main results and the role of chance Ongoing pregnancy rate was 12.8% (25/195) for mild ovarian stimulation versus 13.6% (27/199) for conventional ovarian stimulation leading to a risk ratio of 0.95 (95% CI: 0.57-1.57), representing an absolute difference of -0.7% (95% CI: -7.4 to 5.9). This 95% CI does not extend below the predefined threshold of 10% for inferiority. The duration of ovarian stimulation was significantly lower in the mild ovarian stimulation strategy than in the conventional ovarian stimulation strategy (mean difference -1.2 days, 95% CI: -1.88 to -0.62). Also, a significantly lower amount of gonadotropins was used in the mild simulation strategy, with a mean difference of 3135 IU (95% CI: -3331 to -2940). Limitations, reasons for caution A limitation of our study was the lack of data concerning the cryopreservation of surplus embryos, so we are not informed on cumulative pregnancy rates. Another limitation is that we were not able to follow up on the ongoing pregnancies in all centers, so we are not informed on live birth rates. Wider implications of the findings The results are directly applicable in daily clinical practice and may lead to considerable cost savings as high dosages of gonadotropins are not necessary in women with poor ovarian reserve undergoing IVF. A health economic analysis of our data planned to test the hypothesis that mild ovarian stimulation strategy is more cost-effective than the conventional ovarian stimulation strategy is underway. Study funding/competing interests This study was supported by NUFFIC scholarship (the Netherlands) and STDF short-term fellowship (Egypt). Trial registration number NTR2788 (Trialregister.nl). Trial register date 01 March 2011. Date of first patient's enrolment May 2011.

To evaluate the effect of double stimulations during the follicular and luteal phases in women with poor ovarian response (POR) in in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.This prospective clinical study was performed in Royan Institute from October 2014 to January 2016. 121 patients were diagnosed as POR on the basis of Bologna criteria were included. Double stimulations were performed during the follicular and luteal phases by Letrozole, Clomid, hMG and GnRH-agonist. The patients' present cycle outcomes were compared with those of the previous cycle results using appropriate statistical tests.The total of 104 (85.9%) patients completed the stimulation stages. The analysis revealed the number of retrieved oocytes after the first and second stimulations did not differ (P = 0.2); however, the fertilization rate and the number of frozen embryos after the first stimulation were significantly higher than those of in the second stimulation (P 0.001 and P = 0.03), indicating the better quality of retrieved oocytes after the first stimulation. The mean number of MII oocytes and the fertilization rate after Shanghai protocol were higher than those of the previous antagonist protocol with a substantial trend toward significance (P = 0.06), which can be clinically important. The cancellation rate (33%) due to no ovarian response and no embryo formation was still high in these patients.Since the intensity of stimulation in both stages was mild, this protocol can be considered a time-efficient and patient friendly regime; however, more studies are required with emphasis on its cost-effectiveness.

Mixed-phenotype acute leukemia (MPAL) is the infrequent type of acute leukemia characterized by immunophenotypic and/or cytochemical features of both lineages, but the diagnosis of this disease still is a challenge. In this study, we analyzed immunophenotyping, cytochemistry and frequency of MPAL patients to better diagnosis of MPAL characteristics according to WHO 2016 criteria for the first time in Iran. In this retrospective study, 27 patients were diagnosed as MPAL based on WHO 2016 criteria during 2014–2017. Flow cytometric immunophenotyping was performed on PB and BM samples evaluation of different CD marker expressions in MPAL subsets. RT-PCR was performed for the analyses of BCR/ABL1 fusion in MPAL subsets. Among 27 cases, (70.4%) 19 cases were B + My, (22.22%) 6 cases were T + My, and 2 cases (7.40%) were B + T + My. CD34, CD19, HLA-DR, TdT, CD22, iMPO were positive in majority of B + My cases. CD45, iMPO, iCD3, CD7, CD2 and CD5 were positive in majority of T + My cases. HLA-DR, TdT, CD10, CD22, iCD79a, iMPO, CD45, iCD3, CD7, CD3, CD2, CD5 were positive in majority of B + T + My cases. BCR/ABL1 fusion was positive for 3 cases (11.1%) of p190 fusion and 2 cases (7.4%) of p210 fusion in B + My cases. WHO 2016 criteria are the current standard for diagnosing MPAL. Also, evaluation of TdT, CD2, CD5, CD7 expressions by flow cytometry in EGIL criteria is useful for the better diagnosis of MPAL subsets. In addition, evaluation of BCR/ABL1 and MLL rearrangements in patients should be part of standard work-up in MPAL.

To evaluate the effect of adjuvant low-dose aspirin therapy on clinical pregnancy rate and uterine perfusion in women undergoing frozen-thawed embryo transfer (FET) cycles.This study was performed as a pilot randomized, double-blind placebo-controlled trial, from May 2012 to February 2015. Overall, 60 available eligible women who were candidates for FET were randomly assigned to two groups receiving either 100 mg oral aspirin (n =30) or placebo (n =30). The primary outcome measure was clinical pregnancy rate. Secondary outcome measures were pulsatility index (PI), resistance index (RI), implantation rate, live birth rate and miscarriage rate.There was no significant difference in endometrial thickness, PI and RI. However, the study group had higher rates of clinical pregnancy, implantation, live birth (P = 0.042, P = 0.031 and P = 0.007, respectively) and lower rate of miscarriage (P = 0.020) as compared to the control group. Twin birth rate was comparable between the two groups.Our pilot study demonstrated that administration of low-dose aspirin in FET cycles results in better pregnancy, implantation and live birth rates without changing the uterine hemodynamics or endometrial thickness. However, further randomized clinical studies in larger populations are needed to confirm these findings.

To assess the influence of intrauterine human chorionic gonadotropin (hCG) before embryo transfer on the clinical pregnancy and live birth rates after vitrified-warmed embryo transfer (ET) in programmed cycles. This study was a single-blind randomized clinical trial for eligible patients underwent frozen ET cycles with long-term hormonal GnRH agonist protocol for endometrial preparation. Immediately prior to ET, the women were randomly divided into three groups. In the experimental group, 7–10 min before embryo transfer, 500 IU of hCG with a 40 μL of culture medium was injected into the uterus. In the first control (sham) group, 7–10 min before ET just 40 μL of culture medium intrauterine was infused. In the second control group, no intervention was done. The pregnancy outcomes were compared in the three groups using appropriate statistical tests. Finally, 180 patients allocated into three groups. There was no significant difference in terms of patients ‘characteristics among three groups. No significant difference was found in terms of clinical pregnancy among three groups. The miscarriage rate in control group (0%) was significantly lower than those of in the sham and hCG groups (9.8% and P = 0.01, 6.6% and P = 0.04, respectively). In addition, live birth rate (39.3%) in control group was significantly higher than those of in the sham and hCG groups (16.4% and P = 0.005, 23% and P = 0.051, respectively). It was found that intrauterine injection of 500 IU hCG before vitrified-warmed ET at cleavage stage has no beneficial effect on pregnancy outcome and is not suggested. NCT02355925.

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.

Objectives: This study aimed to assess the influence of coasting duration on the number and quality of oocytes and fertilization rate in male factor infertile women and those with polycystic ovary syndrome (PCOS). Methods: In this prospective observational follow-up study, 114 patients undergoing coasting (53 women with male factor infertility and 61 women with PCOS) were evaluated at the Royan Institute Research Center, Iran, between 2010 and 2012. Results: The results were analyzed according to the coasting periods of 1�4 days. In normal females, the number of oocytes retrieved was significantly reduced after the second day (p = 0.004). In addition, a statistically significant drop was observed in the number of metaphase II oocytes and fertilization rate after the third day (p = 0.006 and p = 0.006, respectively). No significant differences were observed in the number and quality of oocytes retrieved and fertilization rate with regard to coasting days in PCOS patients. Conclusion: Coasting with duration of more than three days should be performed with caution in normal females who are at risk of developing ovarian hyperstimulation syndrome. © 2016, Oman Medical Specialty Board. All Rights Reserved.

It is recognized that FMR1 premutation expansions are associated with premature ovarian failure (POF), but their role in diminished ovarian reserve (DOR) is not clearly established. Moreover, the impact of smaller repeats at the boundary of premutation and normal is less clear. Therefore, we have compared the frequency of these intermediate (45-54 repeats) and premutation (55) sized FMR1 CGG repeats among a patients group including 188 DOR and 173 POF women and 200 controls. FSH and LH concentrations were also compared between intermediate and premutation ranges in patients. The 5' UTR of FMR1 gene was amplified using PCR. The numbers of trinucleotide repeats were confirmed by the Sanger sequencing method. The frequency of premutation was higher in POF and DOR patients in comparison with controls, but the difference in the incidence of intermediate alleles was not statistically significant among these groups. The mean level of serum FSH was higher in patients with premutation than patients with intermediate alleles. Based on the current evidence, we concluded that intermediate-sized FMR1 CGG repeat alleles should not be considered as a high-risk factor for POF and DOR.

Objective The diminished ovarian reserve (DOR) is a condition characterized by a reduction in the number and/or quality of oocytes. This primary infertility disorder is usually accompanied with an increase in the follicle-stimulating hormone (FSH) levels and regular menses. Although there are many factors contributing to the DOR situation, it is likely that many of idiopathic cases have genetic/epigenetic bases. The association between the FMR1 premutation (50-200 CGG repeats) and the premature ovarian failure (POF) suggests that epigenetic disorders of FMR1 can act as a risk factor for the DOR as well. The aim of this study was to analyze the mRNA expression and epigenetic alteration (histone acetylation/methylation) of the FMR1 gene in blood and granulosa cells of 20 infertile women. Materials and Methods In this case-control study, we analyzed the mRNA expression and epigenetic altration of the FMR1 gene in blood and granulosa cells of 20 infertile women. These women were referred to the Royan Institute, having been clinically diagnosed as DOR patients. Our control group consisted of 20 women with normal antral follicle numbers and serum FSH level. All these women had normal karyotype and no history of genetic disorders. The number of CGG triplet repeats in the exon 1 of the FMR1 gene was analyzed in all samples. Results Results clearly demonstrated significantly higher expression of the FMR1 gene in blood and granulosa cells of the DOR patients with the FMR1 premutation compared to the control group. In addition, epigenetic marks of histone 3 lysine 9 acetylation (H3K9ac) and di-metylation (H3K9me2) showed significantly higher incorporations in the regulatory regions of the FMR1 gene, including the promoter and the exon 1, whereas tri-metylation (H3K9me3) mark showed no significant difference between two groups. Conclusion Our data demonstrates, for the first time, the dynamicity of gene expression and histone modification pattern in regulation of FMR1 gene, and implies the key role played by epigenetics in the development of the ovarian function.

To investigate the effect of late follicular administration of low dose hCG on oocyte maturity in poor responding women undergoing intracytoplasmic sperm injection (ICSI).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.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.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).

Background: The aim of this study was to compare prenatal outcome of intra cytoplasmic sperm injection (ICSI) pregnancies with pregnancies obtained through in vitro fertilization (IVF).Materials and Methods: Retrospectively 532 pregnancies of ART cycles were assessed during 1999-2000. The main outcome measured including abortions, ectopic pregnancies, prematurity, low birth weight, cesarean section, prenatal mortality and malformation compared between IVF and ICSI groups.Results: The mean age was similar in both IVF and ICSI groups, as well as treatment protocols, and the number of transferred embryos. There were significant differences in duration of infertility, and times of ART cycles between groups (p0.05). Prenatal mortality was also similar between groups.Conclusion: In conclusion, perinatal outcome after ICSI showed similarity in the number of pathologies in comparison with IVF.

Objective The aim of the present study was to determine the prevalence of metabolic syndrome (MS) in infertile Iranian women with polycystic ovary syndrome (PCOS) using the ATPIII criteria. Subjects and methods In this cross-sectional study, 624 women with PCOS were enrolled at a tertiary referral center in Tehran, Iran, between April, 2012 and March, 2013. Diagnosis of MS was according to ATPIII criteria. Also, we divided PCOS patients into following two main groups: (i) with MS (n = 123) and (ii) without MS (n = 501), and then compared variables between two groups. Results The mean age, body mass index (BMI) and waist circumference were 28.6 ± 4.3 years, 26.7 ± 3.7 kg/m2 and 85.2 ± 8.7 cm, respectively. The prevalence of MS was 19.7%. Our findings showed that age, BMI, waist circumference and all metabolic parameters were higher in PCOS women with MS than related values in those without MS. The most and least prevalent forms of MS were low level of high density lipoprotein-cholesterol (HDL-C) and hypertension, respectively. Conclusion It seems the prevalence of metabolic syndrome in our country isn’t as high as western countries. The prevalence rate of MS increased with age and BMI. One of the major cardiovascular risk factors, low level of HDL-C, is the most prevalent metabolic abnormality in our participants.

Purpose: The aim of this prospective, randomized trial was to evaluate the efficacy of Embryo-Glue® as a human embryo transfer medium in IVF/ICSI cycles. Method: A total of 815 nonselected patients undergoing IVF/ICSI treatment between September 2003 and February 2004 were randomly allocated into the test (417 patients) and the control (398 patients) groups. In both groups, embryos were cultured in G-1™ver 3, supplemented with 10% recombinant human albumin. On the day of embryo transfer (day 3), the best or good quality embryos were selected for intrauterine transfer. In the test group, the selected embryos were treated with EmbryoGlue® prior to the transfer, whereas in the control group they were transferred without any treatment. Results: The patients’ characteristics such as age and the number of ART cycles and also the number of patients in each indication of infertility and the number of embryos selected for transfer were all similar between the two groups. In the test group, the clinical pregnancy rate in the tubal factors and the implantation rate in the tubal factors and recurrent implantation failures increased significantly compared with those in the control group. In the test group, life birth and the triplet delivery rates increased significantly compared with those in the control group. Conclusion: EmbryoGlue® is a useful embryo transfer medium, and at least in some infertile patients it can improve clinical implantation and ongoing pregnancy rates.

Purpose: Pelvic inflammatory disease is a rare complication of transvaginal oocyte retrieval. It results in failure of assisted reproductive procedure. Patients: During a 6-year period, 5958 transvaginal ultrasound-guided oocyte retrievals resulted in 10 cases of acute pelvic inflammatory disease (0.12%). Results: Eight of the 10 patients were diagnosed infertile because of endometriosis. Two patients had mild ovarian, three had stage III, and two had stage IV endometriosis. One patient had a 3–4 cm ovarian endometrioma. After treatment, no mortality was encountered among the 10 patients, although none of them conceived. Conclusion: This observation supports the previous reports that endometriosis can raise the risk of pelvic inflammatory disease after oocyte retrieval. More vigorous antibiotic prophylaxis and better vaginal preparation are recommended when oocyte pickup is performed in patients with endometriosis.

The importance of chromosomal abnormalities in etiology of premature ovarian failure (POF) is well known but in many cases, POF still remains idiopathic. We investigated the frequency and type of chromosomal aberrations in Iranian women diagnosed with idiopathic POF. Standard cytogenetic analysis was carried out in a total of 179 patients. Karyotype analysis of these patients revealed that 161 (89.95%) patients had normal female karyotype and 18 (10.05%) patients had abnormal karyotypes. The abnormal karyotypes included sex reverse sex determining region Y (SRY) negative (five Cases), X chromosome mosaicism (five cases), abnormal X chromosomes (three cases), abnormal autosomes (three cases) and X-autosome translocation (two cases). The overall prevalence of chromosomal abnormalities was 10.05% in this first large-scale report of chromosomal aberrations in Iranian women with POF. The results confirm previous observations and emphasis on the critical role of X chromosome abnormalities as one of the possible etiologies for POF.