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Abstract Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that can lead to major reproductive and metabolic complications. Management of glycemic parameters is an important step to improve the symptoms of PCOS. Objective: This study aims to evaluate the effects of the dietary approaches to stop hypertension (DASH) diet and curcumin (Cur) co-administration on glycemic parameters in normal weight and overweight/obese women with PCOS undergoing in vitro fertilization. Materials and Methods: In this double-blind randomized clinical study, 104 infertile women with PCOS were divided into 4 intervention groups considering treatment conditions and body mass index. They received 500 mg twice daily of Cur or placebo (Pls) along with DASH or a standard diet (St) based on macronutrient composition (52% carbohydrate, 18% protein, and 30% fat) for 12 wk, (DASH + Cur, DASH + Pls, St + Cur, St + Pls). The effect of these interventions on fasting blood sugar and insulin levels, insulin resistance (IR), and insulin sensitivity were determined. Results: Participants adhered to the intervention protocol ( > 80%). Insulin levels in the supplement intervention (Cur + diet) decreased significantly in the crude model. They remained significant even after adjusting for confounding variables in adjusted models (body mass index classification, energy difference, age, and physical activity levels at the baseline) ( β = -45.3, 95% CI [-73.23, -17.46], p = 0.002). Homeostasis model assessment of IR decreased significantly in the supplement intervention even after controlling for confounding factors in adjusted models. Changes in fasting blood sugar and insulin sensitivity were not significant in either the crude or adjusted models. Conclusion: The study results show that adding Cur to the diet can positively reduce insulin levels, improve IR, and lead to faster recovery of hyperinsulinemia. Cur supplementation with a healthy diet has synergistic beneficial effects on glycemic parameters. Larger clinical trials with longer durations are needed to confirm these results.

Abstract Background: Since thyroid hormones have an essential role in energy production, early development of the human placenta, embryo development, and implantation, abnormalities in thyroid function can significantly affect pregnancy outcomes. Objective: The present study aimed to investigate the effect of higher thyroid-stimulating hormone (TSH) levels in the normal range in euthyroid women with unexplained infertility. Materials and Methods: In this cross-sectional study, we evaluated the data for 300 euthyroid women aged between 18 and 39 yr with normal TSH levels ( ≤ 5 mIU/L) referred to Yazd Reproductive Sciences Institute, Yazd, Iran from December 2018-March 2021 in 2 groups: the case group (with unexplained infertility) and the control group (with male factor infertility). Finally, age, body mass index, and serum levels of TSH were extracted from participants' medical records and compared between groups. Results: The mean age and TSH level of participants were 31.52 ± 3.52 yr and 1.24 ± 2.59 mIU/L, respectively. 142 women (47.3%) had TSH < 2.5, and 158 women (52.7%) had TSH ≥ 2.5 mIU/L. The women with unexplained infertility had significantly higher TSH levels than controls in the same normal range (0.62 vs. 0.64 mIU/L, p < 0.001). Although a more significant proportion of women in the case group had TSH levels > 2.5 mIU/L, we did not find a significant association between TSH levels and age or body mass index. Conclusion: Women with unexplained infertility have a higher level of serum TSH in the normal range ( ≥ 2.5 mIU/L) than the control group. So, the effect of TSH treatment on these women should be considered.

Abstract Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases with major reproductive and metabolic complications with an impact on public health. Hyperandrogenism and chronic inflammation have been suggested as the leading cause of pathophysiology and clinical manifestations associated with PCOS. It seems that the altered expression of genes involved in the synthesis of pro-inflammatory cytokine and androgens contribute to the promotion of PCOS. Objective: This trial aims to determine the effects of dietary approaches to stop hypertension (DASH) and standard diets with and without curcumin supplementation on the gene expression of interleukin -1 alpha(IL1α), 5α reductase and androgenic and glycemic profile among PCOS patients, who are candidates for in vitro fertilization. Materials and Methods: 96 infertile women with PCOS, aged 18-40 yr, will participate in this randomized, placebo-controlled clinical trial. Based on treatment conditions and body mass index, the participants will be randomly divided into 4 equal groups using a randomized block design. They will receive a DASH or standard diet containing 52% carbohydrate, 18% protein, and 30% total fat, with the same prescribed sodium, plus 500 mg twice daily curcumin or placebo for 12 wk. The mRNA expression of IL-1 α , 5 α reductase, and androgenic and glycemic profiles will be measured at baseline and at the end of the study. Conclusion: Concomitant administration of DASH diet and curcumin supplementation may reduce IL-1 α , 5 α reductase gene expressions, and improve glycemic and androgenic profiles.

Background: Assembling an artificial ovary needs supporting the in vitro growth of cumulus cells, and finally, follicles. This study aimed to determine the appropriate cocktail for culture of cumulus cells (CCs).Methods: CCs were collected from healthy women and cultured with 9 cocktails of basal media, supplemented with 10% and 20% fetal bovine serum (FBS) and 1% and 2% human serum albumin (HSA). Ovarian cells were isolated from cortex, medulla, and hilum, and their conditioned media (CM) were collected. Expression of GDF9 in ovarian cells was evaluated. CCs were treated with various concentrations of CMs from ovarian cells and mesenchymal stem cells. Also, they were cultured with various concentrations of supplements including L-Glutamine, bovine serum albumin (BSA), HSA, insulin transferrin selenium (ITS), Follitropin alfa, and Pregnyl. Also, they were treated with various concentrations of follicular fluids (FFs), collected from patients with different infertility etiologies. Finally, CCs proliferation and culture stability were evaluated.Results: All the ovarian cells expressed GDF9. DMEMF12 + 20% FBS was the most suitable cocktail for CCs. 20% FBS was superior to 10% FBS. HSA alone could not support the growth of CCs. The CMs of (cortical + hilar + medullar) cells and FFs from healthy women caused higher CCs proliferation. 17 mM/l L-Glutamine, 24 mg/ml BSA, 20 mg/ml HSA, 10 ng/ml ITS, 300 mIU/ml Follitropinα, and 3.5 IU/ml Pregnyl led to higher CCs proliferation.Conclusion: Supplementation of the basal medium with CMs, serums, FFs, hormones, ITS and L-Glutamine, can better support the culture of CCs.

Abstract Background: Endometrial polyps are one of the most common gynecological disorders with a high frequency among infertile women. Hysteroscopic polypectomy remains the gold standard for the treatment of endometrial polyps. As alternative treatments, few drugs have been evaluated to date. Objective: To investigate the possible effect of misoprostol on the elimination of endometrial polyps. Materials and Methods: In this clinical trial we examined 30 infertile women whose endometrial polyps were confirmed by transvaginal ultrasound with saline injection. All women were administered 400 mg of misoprostol: 200 mg orally and 200 vaginally. 8 hr later, sonography with saline injection was performed again and all women were examined for the presence or absence of endometrial polyps. Finally, the diagnosis was confirmed for all women using hysteroscopy. The main outcome of this study was the elimination of endometrial polyps after misoprostol administration. Results: The average size of the endometrial polyps was 14.33 ± 4.26 mm, with a range of 7-22 mm. After misoprostol administration, in 12 out of the 30 women who had shown endometrial polyps in the initial examination, no polyp was found. At follow-up it was found that the smallest endometrial polyp that had been eliminated was 8 mm and the largest was 22 mm. Conclusion: The findings of our study revealed that misoprostol can remove up to 40% of endometrial polyps. This drug has the potential to be used as a safe and low-cost first-line treatment before performing hysteroscopic polypectomy.

Abstract Background: Preoperative anxiety is a common event in patients expecting surgery. Education can play an important role in reducing the negative effects of anxiety on the response to treatment. Therefore, identifying the appropriate method is important. Objective: The aim of this study was comparing the effects of nursing versus peer-based education on the preoperative anxiety in infertile women. Materials and Methods: In this randomized clinical trial, 198 eligible infertile women were evaluated in three groups (n = 66/each): the nurse-educated, peer-educated, and the controls. The Spielberger State-Trait Anxiety Inventory was filled out by all participants for measuring the patient anxiety at the time of hospital admission and prior to surgery. Participants in the nurse-educated and peer-educated groups received a group education program by a nurse or peer, respectively, after the initial completion of the Spielberger State-Trait Anxiety Inventory. Results: The mean score anxiety was 44.47, 46.92, and 42.60 at the time of hospital admission and 39.38, 41.06, and 43.42 prior to surgery in nurse-educated, peer-educated, and the control groups, respectively. There was a significant difference in the mean score of anxiety in each group before and after the intervention (p < 0.0001). However, the difference between the groups was not significant. Conclusion: Our findings demonstrate that nursing and peer education programs both reduce the preoperative anxiety. Hence, optimal use of the peer's potential regarding the compensation for staff shortage for preoperative education as well as investigating the effect of individual education is suggested for further studies.

Abstract Endometriosis is major gynecological disease that affects over 10% of women worldwide and 30%-50% of these women have pelvic pain, abnormal uterine bleeding and infertility. The cause of endometriosis is unknown and there is no definite cure mainly because of our limited knowledge about its pathophysiology at the cellular and molecular levels. Therefore, demystifying the molecular mechanisms that underlie endometriosis is essential to develop advanced therapies for this disease. In this regard, HOX genes are remarkable because of their critical role in endometrial development and receptivity during implantation, which is attributed to their ability to mediate some of the sex steroid functions during the reproductive period. Access to the expression profiles of these genes would provide the necessary information to uncover new genes for endometriosis and assist with disease diagnosis and treatment. In this study we demonstrate an altered expression pattern for the HOX clusters (A-D) and their cofactors in both eutopic and ectopic conditions compared to control tissue biopsies. Remarkably, most of the intensive changes occurred in eutopic samples from endometriosis patients compared to control tissue biopsies. Pathway analysis revealed the involvement of differentially expressed genes in cancer that correlate with an association between endometriosis and cancer. Our results suggest critical roles for the HOX cluster and their cofactors in endometriosis pathophysiology.

Background: Endometrioma is a common high-recurrence gynecological disease that affects infertility. Surgical resection using laparotomy or laparoscopy is applied as a standard treatment. Moreover, sclerotherapy is reported to be effective as a non-invasive method for treating endometrioma. Objective: To evaluate whether the ethanol retention or aspiration after sclerotherapy improve pregnancy outcome in infertile women with endometrioma. Materials and Methods: In a retrospective study, hospital records of 43 women with recurrent or bilateral endometrioma who had been undergone transvaginal ultrasound sclerotherapy were reviewed. They were selected to receive either ethanol for 10 min, ethanol injection, irrigation, and then aspiration or total retention without aspiration based on the surgeon's decision. The participants were followed-up for 3, 6 and 12 months for natural or artificial conception as well as for cyst recurrence. Results: Chemical pregnancy was positive in 52% of the women in the aspiration group and 53.8% in the retention group. Ongoing pregnancy (44% vs 46.2%, p = 0.584) and live birth (40% vs 46.2%, p = 0.490) were reported marginally higher in the retention group compared with the aspiration group, and the differences were not statistically significant. Moreover, the recurrence rate were found to be 48.1% and 37.5% in the aspiration and retention groups, respectively (p = 0.542). The cysts size in the retention group was significantly correlated to the recurrence rate. Conclusion: Both the aspiration and left in situ of ethanol 95% sclerotherapy have the similar impact on the treatment of ovarian endometrioma regarding pregnancy and recurrence rate. However, larger randomized studies with strict inclusion criteria are needed.

Background: A repeat dose of Gonadotropin-releasing Hormone (GnRH) agonist could provide long duration of luteinizing hormone (LH) surge and amplitude appropriately. Objective: Improvement in oocyte maturity could be obtained by a repeat dose of GnRH agonist. Materials and Methods: In this randomized double-blinded study, 120 women with polycystic ovarian syndrome and serum estradiol level (E2) > 3000 who were candidate for in vitro fertilization with Antagonist protocol were enrolled between July 2018 and July 2019. Participants were randomized in two groups - and final oocyte maturation was triggered with two doses: In group A, a repeat dose of 0.1 mg, 12 hr. after the first dose and in group B, 0.2 mg SC triptorelin (decapeptyl) 35 hr. prior to oocyte retrieval. Serum Estradiol, LH, and progesterone concentration were measured on the trigger day. Serum LH measurement was done three times in both groups. The outcomes were oocyte yield, meiosis (M) I, MII, Maturity rate, germinal vesicle (GV) rate, 2 pronuclear, embryo yield, ovarian hyper stimulation syndrome rates. Results: Maturity rate (p = 0.89), MI (p = 0.38), MII (p = 0.89), and GV oocytes (p = 0.38) were not statistically different between the two study groups. LH levels measured at 12 hr post-trigger did not relate statistically significant with maturity rate in our participants (p = 0.96). No empty follicular syndrome was reported. Conclusion: Although, the second dose of GnRH agonist after 12 hr since the first dose could provide duration of LH surge and amplitude and as a result no empty follicular syndrome was seen, the maturity rate, MI, MII, and GV oocytes were not different between the two study groups.

Introduction: Monthly regeneration of endometrium after cyclical mensturation confirmed the ability of specific population of the cells that presence in the basalis layer and undergone consecutive hormonal changes that could prepared the endometrial layer for probable implantation. These cells, known as, stem cell. The aim of this study was the isolation and culture of human endometrial derived mesenchymal stem/stromal cells (EnMSCs). Methods: .In this study, human endometrial tissues were collected after fully-informed patient consent, which attended the Research and Clinical Center for Infertility. After washing and enzymatic treatment, EnMSCs were isolated and cultured in vitro. Results: Cells from endometrium were successfully isolated using enzymatically treatment and mechanically dissociation, then cultured and expanded for several passages for further characterization and evaluations. Endometrium derived cells were morphologically similar to mesenchymal stem/stromal cells (MSCs). Conclusion: The results of the present study confirm previous reports in vitro studies for the isolation and culture of human EnMSCs. Endometrial tissue is a part of uterus with available source of MSCs with self-renewal and differentiation capacity that undergoes a cyclical regeneration every month in normal women’s life span. In this regard, human EnMSCs could be used for future novel therapeutic methods in regenerative medicine for treatment of uterine-factor infertile patients, which can lead to recurrent pregnancy loss (RPL) and finally resolve of surrogacy problems.

Background The goal of this study was to investigate oocyte maturation, fertilization and pregnancy rates among infertile women, by concomitant follicle stimulating hormone (FSH) administration at the time of human chorionic gonadotropin (hCG) trigger, compared to hCG trigger alone. Materials and Methods In this prospective randomized controlled trial, 109 infertile women between the ages of 20 and 40 years, received gonadotropin-releasing hormone (GnRH) antagonist and fresh embryo transfer. Following the procedure, the subjects were randomly divided into two groups on the oocyte-triggering day. In the experimental group, final oocyte maturation was achieved by 5000 IU hCG plus 450 IU FSH. In the control group, however, oocyte triggering was performed by 5000 IU hCG, only. The primary outcome was clinical pregnancy and the secondary out- comes included oocyte recovery rate, oocyte maturity rate, fertilization proportion rate, fertilization rate, implantation rate and chemical pregnancy rate. Results Fifty-four women were appointed to the group with the FSH bolus injection at the time of hCG trigger and 55 women were assigned to the hCG alone group. Women in the FSH group had a significantly higher metaphase II (MII) oocyte (7.17 ± 3.50 vs. 5.87 ± 3.19), 2 pronuclear embryos (2PNs) (5.44 ± 3.20 vs. 3.74 ± 2.30) and total em- bryos (4.57 ± 2.82 vs. 3.29 ± 2.13) compared to hCG alone group, respectively. Furthermore, fertilization rate (0.75 ± 0.19 vs. 0.68 ± 0.25), implantation rate (14.2 vs. 8.5%) as well as clinical (27.9 vs. 15.9%) and chemical (32.6 vs. 20.5%) pregnancy rates were higher in the FSH group, but no statistically significant difference was found (P > 0.05). Conclusion Combination of FSH and hCG for oocyte triggering improves oocyte maturity and fertilization propor- tion rates without increasing the chance of implantation, chemical and clinical pregnancy rates (Registration number: IRCT2017082724512N5).

Background: Endometriosis is a disease that affects women of reproductive age. This disease is characterized by the presence of endometrial-like tissues (endometrial or stromal glands) outside the uterus and shows significantly elevated prevalence in industrial regions. Additionally, an interaction between genetics and environmental factors is assumed for the disease. Enzymes belonging to the cytochrome P450 (CYP) family are participated in detoxification process of a wide range of environmental toxins and carcinogens. Thereby, they are good link for the interaction. CYP1A1 which belong to cytochrome P450 (CYPs) superfamily, is a very important gene for the metabolism of carcinogens. Objective: The aim of this study was to analyze the frequency of the MspI polymorphism of CYP1A1 gene and its relation to endometriosis. Materials and Methods: Genomic DNA was isolated from 93 endometriosis women and 139 healthy controls. Genotyping was performed using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results: Frequencies of the TT, TC, and CC genotype of CYP1A1 gene polymorphism in patients were 73.1%, 22.6%, and 4.3%, while frequencies in controls were 74.1%, 22.3%, and 3.6%, respectively. So there was no significant differences between the genotypes in two groups (p=0.961). Conclusion: According to our study, MspI polymorphism of CYP1A1 gene appears to be not associated with the risk of endometriosis in the studied population. However, additional studies, especially with larger sample size are needed to validate these findings.

Background: Endometriosis is a prevalent gynecological disease, with limited known etiology and more researches are required to identify its etiology. In this manner, there is no evidence for expression and function of 3´HOX genes in 4 clusters in the limb and pelvic organs such as the uterus and its disorders (Genes in the HOXA-D clusters are subdivided into 13 paralogous groups). Objective: This study designed to investigate the expression profile of 5 paralogous (1-5) in four clusters of HOX genes (A, B, C, and D) in ectopic and eutopic tissues of women with endometriosis compared to the normal endometrium. Materials and Methods: Samples were obtained from thirty patients (15 with and 15 without endometriosis) of reproductive age with normal menstrual cycles. The same patient provided both eutopic and ectopic tissues and control women were laparoscopically checked for the absence of endometriosis. The expression profile of these HOX genes was investigated by quantitative real-time polymerase chain reaction technique. Results: We observed significant up-regulation of some members of HOXC and D clusters (HOXD1, HOXD3, HOXC4 and HOXC5) in ectopic and eutopic tissues vs. control. Also, our data showed significant down-regulation of all of HOXA and HOXB paralogous except HOXA1 in ectopic tissues versus control. Conclusion: Our data showed specific cluster dependent modulation of the HOX genes expression in endometriosis (over-expression of some HOX genes in cluster C and D and down-regulation of HOX genes in cluster A and B) in ectopic and eutopic tissues compare to control group. Therefore, it is possible that change of expression level of these genes in endometrium plays a role in the pathogenesis of endometriosis.

Abstract Background: Anti-Mullerian hormone (AMH) is considered as a good marker for quantitative evaluation of ovarian response to the stimulation during assisted reproductive technology cycles. Objective: To evaluate the association between serum AMH level and embryo morphokinetics using time-lapse imaging and intracytoplasmic sperm injection (ICSI) outcomes in women with polycystic ovarian syndrome (PCOS). Materials and Methods: We evaluated a total of 547 embryos from 100 women underwent ICSI cycles; 50 women with PCOS and 50 women with tubal factor infertility. Serum AMH level was measured in all participants. Time-laps records were annotated for time to pronuclear fading (tPNf), time to 2-8 cells (t2-t8), reverse cleavage, direct cleavage, and also for the presence of multinucleation. Results: AMH was negatively correlated with t5, t8, and the third cell cycle (p=0.02, p=0.02, and p=0.01; respectively) in PCOS group. AMH had no correlation with embryo kinetics in infertile women with tubal factor infertility. Moreover, AMH level is similar between embryos with and without direct cleavage as well as reverse cleavage and Multinucleation in both groups. The Receiver operating characteristic curves analyses indicated that AMH was not an accurate predictor of clinical pregnancy as well as a live birth (AUC=0.59 [95% CI, 0.42-0.76]) in PCOS women. However, in the women with tubal factor infertility AMH showed a fair prediction value for clinical pregnancy (AUC=0.64 [95% CI, 0.48-0.82]) along with the live birth (AUC=0.70 [95% CI, 0.55-0.85]). Conclusion: Some of the time-lapse embryo parameters may be related to the AMH concentration. However, AMH is not an accurate tool to predict the ICSI outcomes in PCOS women.

Background: The use of embryo cryopreservation excludes the possible detrimental effects of ovarian stimulation on the endometrium, and higher reproductive outcomes following this policy have been reported. Moreover, gonadotropin-releasing hormone agonist trigger in gonadotropin-releasing hormone (GnRH) antagonist cycles as a substitute for standard human chorionic gonadotropin trigger, minimizes the risk of ovarian hyperstimulation syndrome (OHSS) in fresh as well as frozen embryo transfer cycles (FET). Objective: To compare the reproductive outcomes and risk of OHSS in fresh vs frozen embryo transfer in high responder patients, undergoing in vitro fertilization triggered with a bolus of GnRH agonist. Materials and Methods: In this randomized, multi-centre study, 121 women undergoing FET and 119 women undergoing fresh ET were investigated as regards clinical pregnancy as the primary outcome and the chemical pregnancy, live birth, OHSS development, and perinatal data as secondary outcomes. Results: There were no significant differences between FET and fresh groups regarding chemical (46.4% vs. 40.2%, p=0.352), clinical (35.8% vs. 38.3%, p=0.699), and ongoing (30.3% vs. 32.7%, p=0.700) pregnancy rates, also live birth (30.3% vs. 29.9%, p=0.953), perinatal outcomes, and OHSS development (35.6% vs. 42.9%, p=0.337). No woman developed severe OHSS and no one required admission to hospital. Conclusion: Our findings suggest that GnRHa trigger followed by fresh transfer with modified luteal phase support in terms of a small human chorionic gonadotropin bolus is a good strategy to secure good live birth rates and a low risk of clinically relevant OHSS development in in vitro fertilization patients at risk of OHSS.

Background: Management of poor-responding patients is still major challenge in assisted reproductive techniques (ART). Delayed-start GnRH antagonist protocol is recommended to these patients, but little is known in this regards. Objective: The goal of this study was assessment of delayed-start GnRH antagonist protocol in poor responders, and in vitro fertilization (IVF) outcomes. Materials and Methods: This randomized clinical trial included sixty infertile women with Bologna criteria for ovarian poor responders who were candidate for IVF. In case group (n=30), delayed-start GnRH antagonist protocol administered estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin. Control group (n=30) treated with estrogen priming antagonist protocol. Finally, endometrial thickness, the rates of oocytes maturation, , embryo formation, and pregnancy were compared between two groups. Results: Rates of implantation, chemical, clinical, and ongoing pregnancy in delayed-start cycles were higher although was not statistically significant. Endometrial thickness was significantly higher in case group. There were no statistically significant differences in the rates of oocyte maturation, embryo formation, and IVF outcomes between two groups. Conclusion: There is no significant difference between delayed-start GnRH antagonist protocol versus GnRH antagonist protocol.

This paper summarizes the proceedings of a 1 day national symposium entitled “Reproductive biology, stem cells biotechnology and regenerative medicine” held at Shahid Sadoughi University of Medical Sciences, Yazd, Iran on 3rd March 2016. Here, we collected the papers that presented and discussed at this meeting by specialists that currently researched about the overlaps of the fields of reproductive biology and stem cells and their applications in regenerative medicine.

Background: Implantation failure is one of the most important factors limiting success in IVF treatment. The majority of trials have demonstrated favorable effect of endometrial injury on implantation success rate especially in women with recurrent implantation failure, while some studies failed to detect any benefit. Objective: The purpose of our trial was to explore whether endometrial injury in luteal phase prior to frozen-thawed embryo transfer cycles would improve pregnancy outcomes? Materials and Methods: We conducted a prospective controlled trial of 93 consecutive subjects at a research and clinical center for infertility. All women were undergone frozen-thawed embryo transfer (FTE) cycles. Women in the experimental group underwent endometrial biopsy with a Pipelle catheter in luteal phase proceeding FET cycle. Primary outcomes were implantation and clinical pregnancy rates and secondary outcomes were chemical, ongoing and multiple pregnancy and miscarriage rates. Results: 45 subjects who underwent endometrial injury (EI) were compared with 48 control group which did not include any uterine manipulation. There were no significant differences in baseline and cycle characteristics between two groups. The difference in implantation rate was trend to statistically significance, 11.8% in EI group vs. 20.5% in control group (p=0.091). The chemical, clinical and ongoing pregnancy rates were lower in EI group compared with control group but not statistically significant. The multiple pregnancy rate and miscarriage rate also were lower in EI group compared with control group. Conclusion: Based on results of this study, local injury to endometrium in luteal phase prior to FET cycle had a negative impact on implantation and clinical pregnancy rates.

Background: Despite of higher pregnancy rate after frozen embryo transfer (FET) which is accepted by the majority of researches, the safety of this method and its effect on neonatal outcome is still under debate. Objective: The aim of this study was to evaluate pregnancy and neonatal outcome of FET compare to fresh cycles. Materials and Methods: In this study,1134 patients using fresh ET and 285 women underwent FET were investigated regarding live birth as primary outcome and gestational age, birth weight, gender, multiple status, ectopic pregnancy, still birth and pregnancy loss as secondary outcomes. Results: Our results showed that there is no difference between FET and fresh cycles regarding live birth (65.6% vs. 70.4% respectively). Ectopic pregnancy, still birth and abortion were similar in both groups. The mean gestational age was significantly lower among singletons in FET group compared to fresh cycles (p=0.047). Prematurity was significantly elevated among singleton infants in FET group (19.6%) in comparison to neonates born after fresh ET (12.8%) (p=0.037). Conclusion: It seems that there is no major difference regarding perinatal outcome between fresh and frozen embryo transfer. Although, live birth is slightly increased in fresh cycles and prematurity was significantly increased among singleton infants in FET group

Objective: Toll like receptors (TLRs) are one of the main components of the innate immune system. It has been reported that expression of these receptors are altered in the female reproductive tract (FRT) during menstrual cycle. Here we used a fallopian tube epithelial cell line (OE-E6/E7) to evaluate the effect of two sex hormones in modulating TLR expression. Materials and Methods: In this experimental study, initially TLR gene expression in OEE6/ E7 cells was evaluated and compared with that of fallopian tube tissue using quantitative real time-polymerase chain reaction (qRT-PCR) and immunostaining. Thereafter, OE-E6/E7 cells were cultured with different concentrations of estradiol and progesterone, and combination of both. qRT-PCR was performed to reveal any changes in expression of TLR genes as a result of hormonal treatment. Results: TLR1-10 genes were expressed in human fallopian tube tissue. TLR1-6 genes and their respective proteins were expressed in the OE-E6/E7 cell line. Although estradiol and progesterone separately had no significant effect on TLR expression, their combined treatment altered the expression of TLRs in this cell line. Also, the pattern of TLR expression in preovulation (P), mensturation (M) and window of implantation (W) were the same for all TLRs with no significant differences between P, M and W groups. Conclusion: These data show the significant involvement of the combination of estradiol and progesterone in modulation of TLR gene expression in this human fallopian tube cell line. Further experiments may reveal the regulatory mechanism and signalling pathway behind the effect of sex hormones in modulating TLRs in the human FRT.

Background: Genital tuberculosis (GTB) is an important cause of female infertility, especially in developing countries. The positive results of polymerase chain reaction (PCR) in endometrial GTB in the absence of tubal damage raise the possibility of the detection of sub-clinical or latent disease, with doubtful benefits of treatment. Objective: To evaluate the mycobacterium tuberculosis infection in endometrial biopsy samples collected from unexplained infertile women attending Yazd Research and Clinical Center for Infertility by using PCR techniques. Materials and Methods: In this cross sectional study, 144 infertile women with unexplained infertility aged 20-35 years old and normal Histro-saplango graphy findings were enrolled. Endometrial biopsy samples from each participant were tested for mycobacterium tuberculosis detecting by PCR. In 93 patients, peritoneal fluid was also taken for culture and PCR. Results: The PCR results of endometrial specimens were negative in all cases, demonstrating that there was no GTB infection among our patients. Conclusion: Our results showed that GTB could not be considered as a major problem in women with unexplained infertility. Although, studies have indicated that PCR is a useful method in diagnosing early GTB disease in infertile women with no demonstrable evidence of tubal or endometrial involvement.

Background: Recently, motile sperm organelle morphology examination (MSOME) criteria as a new real time tool for evaluation of spermatozoa in intracytoplasmic sperm injection (ICSI) cycles has been considered. Objective: The aim was to investigate the predictive value of MSOME in in vitro fertilization (IVF) in comparison to ICSI cycles and evaluation of the association between MSOME parameters and traditional sperm parameters in both groups. Materials and Methods: This is a cross sectional prospective analysis of MSOME parameters in IVF (n=31) and ICSI cycles (n=35). MSOME parameters were also evaluated as the presence of vacuole (none, small, medium, large or mix); head size (normal, small or large); cytoplasmic droplet; head shape and acrosome normality. In sub-analysis, MSOME parameters were compared between two groups with successful or failed clinical pregnancy in each group. Results: In IVF group, the rate of large nuclear vacuole showed significant increase in failed as compared to successful pregnancies (13.81±9.7vs7.38±4.4, respectively, p=0.045) while MSOME parameters were the same between successful and failed pregnancies in ICSI group. Moreover, a negative correlation was noticed between LNV and sperm shape normalcy. In ICSI group, a negative correlation was established between cytoplasmic droplet and sperm shape normalcy. In addition, there was a positive correlation between sperm shape normalcy and non-vacuolated spermatozoa. Conclusion: The high rate of large nuclear vacuoles in sperm used in IVF cycles with failed pregnancies confirms that MSOME, is a helpful tool for fine sperm morphology assessment, and its application may enhance the assisted reproduction technology success rates.

Background: Recurrent pregnancy loss (RPL) has been defined as two or more miscarriages before 20th week of gestation. It seems that IL-27 may reduce inflammatory responses and affect the survival of the embryo during human pregnancy. IL-27 polymorphisms may influence RPL by altering the levels or the activity of gene product. Objective: We studied for the first time the association of IL-27 -964 A>G single nucleotide polymorphism (SNP) with RPL in Iranian women. Materials and Methods: A case-controlled study was performed on two groups consisting of 150 healthy women with at least one delivery (control group) and 150 women with two or more primary RPLs history (RPL group). The -964 A>G SNP in IL-27 gene was determined by PCR-RFLP technique. Genotype and allele frequencies were compared using 2 tests between two groups. Results: There was no difference between the two groups regarding age of women (29±4.4 [control] vs. 30.84±5.2 years [case]). In the RPL group, the genotype frequencies of -964 A>G polymorphism were AG (49.3%), AA (40%), and GG (10.7%), and in the control group, they were AG (43.3%), AA (48.7%), and GG (8%). There was no significant difference between the genotypes of AA, AG, and GG in two groups (p=0.23). As the frequency of allele A was 64.7% in the RPL group and 70.3% in the control group, the difference in frequency of allele A in -964 A>G between two groups was not significant (p=0.19). Conclusion: Our findings indicate that SNP of -964 A>G in IL-27 gene is not a risk factor for RPL in Iranian women.

Defective spermatogenesis due to the failure in germ cell proliferation and differentiation is the major sign of male infertility pathogenesis; and male factor is involved in up to half of all infertile couples. Testicular torsion is an acute vascular event causing the rotation of the vascular pedicle of the testis, thereby impeding the blood flow to the testis and the scrotal contents. Azoospermia caused by torsion in testis is a common source of impotency, which has not been touched by this approach, yet. Here, we use the capacity of mesenchymal stem cells (MSCs), as multipotent adult stem cells, to revive spermatogenesis in torsion-induced azoospermia. For this purpose, MSCs were extracted from rat bone marrow, cultured and transplanted into torsioned testis. Germ cell specific markers (Oct4, Vasa and c-Kit) were monitored for the differentiation of MSCs after transplantation into the torsion azoospermed testis. This study is a trial evaluation of mesenchymal stem cells in rat torsion testis to follow up the regenerative capacity of stem cells in spermatogenesis revival. These approaches can provide the powerful tools to investigate the basic biology of stem cells for reproductive engineering and infertility treatment.

Background: Fertilization failure is one of the most problems in assisted reproduction technology (ART). Objective: The aim of this study was the evaluation of oocytes activation by addition of calcium ionophore in unfertilized oocytes in ICSI cycles. Materials and Methods: This study was done on 15 ICSI cycles (stimulated with standard long protocol). Mature retrieved oocytes with normal morphology that had no evidence of fertilization 24 hours after ICSI were included in the study. The oocytes with fertilization and unfertilized oocytes with degeneration were excluded from the study. The unfertilized oocytes were washed with GIVF medium and were transferred to GIVF medium that contained 5 μmol of calcium ionophore and were incubated for 10 minutes. Then again oocytes were washed with GIVF medium and consequently were transferred to GIVF medium and were incubated at 37°C in 6% CO2. After 18 hours, the oocytes were examined and activated oocytes were defined with observation of at least one pronucleus or cleaved oocytes. Results: After ovarian stimulation and oocytes retrieval, 175 mature oocytes were obtained and injection of sperm was done for all of them. 114 of 175 oocytes (66%) showed evidence of fertilization after 24 hours. A total of 61 oocytes (34%) showed no evidence of fertilization and 10 oocytes were degenerated and were excluded from the study. Only 51 unfertilized oocytes with normal morphology were selected and were exposed to calcium ionophore. 37 (72.5%) of treated oocytes were fertilized (2PN) and 32 (62.7%) of them showed evidence of cleavage. 6 (11.8%) embryos had good quality. Conclusion: According to our results, oocytes activation with calcium ionophore had an acceptable fertilization rate, however high quality embryos remained low. We propose future studies to evaluate embryo quality.

Background: Conventional IVF and ICSI are two common techniques to achieve fertilization. IVF has long been used for treatment of infertility, although it is not an effective treatment in severe male infertility. The use of ICSI has been expanded in severe male factor and fertilization failure after IVF cycle. In spite of the widespread use of ICSI in patients with non-male factor infertility, there is still little evidence to confirm its effectiveness in this population. Objective: To evaluate assisted reproductive technology outcomes between IVF and ICSI cycles in non-male factor, normoresponder patients. Materials and Methods: A total of 220 non-male factors, normoresponder patients who were indicated for ART were enrolled in this study. The patients received standard long GnRH agonist or GnRH antagonist protocols for ovarian stimulation and after oocytes retrieval, the patients were divided into two groups (IVF and ICSI groups). In IVF group (n=112), all of retrieved oocytes were treated by conventional IVF and in ICSI group (n=88), microinjection (ICSI) was done on all of retrieved oocytes. Results: In IVF group, fertilization and implantation rates were significantly higher than ICSI group (66.22% and 16.67% in IVF group versus 57.46% and 11.17% in ICSI group, respectively). Chemical and clinical pregnancy rates were statistically higher in IVF group as compared with the ICSI group (42.9% vs. 27.3% and 35.7% vs. 21.5%, respectively). Conclusion: According to our study, the routine use of ICSI is not improved fertilization, implantation and chemical pregnancy rates and is not recommended in non-male factor, normozoospermic patients.

Objectives: This study is carried out with the aim of describing the pattern of health-promoting behaviors (HPBs) among middle-aged women and its relevant factors in Iran as a Muslim developing country. Methods: In a cross-sectional study, 483 middle-aged women were selected using cluster random sampling from Yazd city in Central Iran. An adjusted Persian version of Health Promoting Lifestyle Profile II was used for measuring HPBs. The demographic data were collected too. Results: The average score of middle-aged women HPBs was 2.73 ± 0.36 (2.69 ± 2.76, %95). Spiritual growth and physical activity had the highest and the lowest score in HPBs′ dimensions, respectively. HPBs had a positive significant correlation with age (p=0.02) and education level (p=0.001) and a negative significant correlation with number of children (p=0.005). HPBs had a higher level in retired women than employees and housewives. Conclusions: In spite of a desirable level of HPBs in spiritual growth and interpersonal relationship dimensions among this group, their level of HPBs in physical activity and health responsibility dimensions was undesirable. It means that the feature of health among Iranian middle-aged women in a Muslim developing country is different from the industrialized developed and also the non-Muslim countries; hence, they need a different intervention programs.

Background: Endometriosis is one of the most common gynecologic disorders. It is a complex trait and both genetic and environmental factors have been implicated in its pathogenesis. There is growing evidence indicating that exposure to environmental contaminants is a risk factor for endometriosis. Glutathione-S-Transferase M1 (GSTM1) is one of the genes involved in detoxification of endogenous and exogenous compounds. Objective: Several studies have indicated an association between GSTM1 null mutation and endometriosis. In this study, the possible association between the GSTM1 gene null genotype and susceptibility to endometriosis in woman from central and southern Iran was investigated.Materials and Methods: One hundred and one unrelated premenopausal women with endometriosis and 142 unrelated healthy premenopausal women without endometriosis were enrolled in the study. Genomic DNA was extracted from Peripheral blood in all subjects. GSTM1 null genotyping was performed by polymerase chain reaction (PCR).Results: There was no significant difference between frequencies of GSTM1 null genotype in case and control groups (50.5% Vs. 52.1%, p=0.804). Furthermore, this genotype was not associated with severity of endometriosis in our sample (p=0.77). Conclusion: further studies involving gene-environment and gene-gene interactions, particularly combination of GSTM1 and other GST gene family polymorphisms are needed.

Background: Human fertility has been declined all over the world. Advanced women’s age is one of the most important factors in determining the success of reproduction and ageing has negative impact on ART outcome and advanced female age decreases the chance of live birth rates achieved using ART, especially after 40 years of age. Objective: To evaluate ART outcomes regarding to pregnancy, abortion, cycle cancellation and live birth rates in women 40 years and older.Materials and Methods: A retrospective study was performed on three hundred-thirteen women undergoing ART cycles in the Madar Hospital in Yazd. Women with age ≥ 40 years who indicated for ART enrolled the study regardless of the infertility type or etiology. In this study, we used data from IVF or ICSI cycles using fresh embryo transfer. Follow up was performed in regard to pregnancy, abortion, cycle cancellation and live birth rates.Results: The mean age of women was 41.87±1.97 years. Chemical pregnancy rate was 8.6% (27/313) per cycle. Clinical pregnancy rate was 3.8% (12/313) per cycle. Spontaneous abortion was observed in 63% (17/27) of patients with positive pregnancy test. The overall cancellation rate was 23.3% per oocytes retrieval. The overall live birth rate per cycle for all women who initiated an ART cycle at age ≥40 years was 3.2% (10/313) that eight of those women were under 42 years old.Conclusion: Based on our results, we suggest that women with age 42 years and above should be advised to use other options, including oocyte donation or adoption

Background Implantation failure is the most important cause of recurrent in vitro fertilization/intra cytoplasmic sperm injection (IVF/ICSI) failure. Several reports suggest that intercourse during the peritransfer period might improve pregnancy rates. This study is designed to determine whether intercourse during the peritransfer period will improve pregnancy and implantation rates in patients undergoing IVF or ICSI. Materials and methods In a randomized control trial study, 390 women with at least five years infertility were evaluated. In the study group, 195 patients had intercourse at least once 12 hours after embryo transfer. Implantation and clinical pregnancy rates were compared with 195 patients in the control group who had no intercourse for the entire assisted reproductive technology (ART) cycle. Results Implantation rate in the study group was 6.5% in comparison with 5.5% for the control group. Clinical pregnancy rates were not significantly higher in study patients when compared to the control group (14.2% and 11.7% respectively). Conclusion The results showed that intercourse during the peritransfer period can not increase pregnancy outcome.

Background: The prevalence of infertility is about 10-15% among the couples overally. Several factors can affect fertility ability of men and women. Chlamydia is a non-motile gram negative obligatory interacellular pathogenic organism. It can cause infections in females as cervicitis, urethritis, endometritis, pelvic inflammatory disease also prostatitis and epidydidimitis in male as well. The aim of this survey is to mention the frequency of infection with Chlamydia in infertile female who were treated in Yazd Research & Clinical Center for Infertility.Materials and Methods: A questionnaire containing some demographic information and clinical features related to the infection was completed for each infertile woman. Specimen of vaginal discharge was collected by well trained nurses using sterile cotton swap from 91 women. Elisa test was done on blood serum. DNA extraction for Chlamydia was carried out using low salt method and PCR was done using MOMP and plasmid primers. DNA sequencing was performed on two PCR products using Chromas LITE ver.2.01 and analyzed by BLAST.Results: Of 91 blood samples collected in this survey, none of them was positive by ELISA. Also there was no positive PCR result. Four PCR products showed a questionable band which was not in the range of Chlamydia. The products underwent DNA sequencing and there were not any finding related to any other micro-organism.Conclusion: However, it is well known that Chlamydia as an infection plays a role in infertility. Nevertheless, there was not evidence of this organism in these infertile patients. It is necessary to design such a survey in larger populations of infertile patients especially on infertile women with tubal infertility and their husbands as well.

The microdose GnRH agonist (GnRH-a) flare protocol may have a particular value for previously poor responders in whom it has been observed to stimulate dramatic increases in serum FSH. The Purpose of this study was to determine the effects of microdose GnRH-a in poor responders. This is a clinical trial with before and after design. This study was done in Research and Clinical Center for Infertility (Shahid Sadoughi University, Yazd, Iran) and Madar Hospital, Yazd, Iran. In this study, 61 poor responders volunteered for in vitro fertilization (IVF) or intracytoplacmic sperm injection (ICSI). The volunteers were divided into two age groups (group A, 20 - 34; group B, 35 - 40) and received low dose oral contraceptive pills for 21 days, then 40µg of subcutaneous buserelin 2 times/day from day 3 of the cycle and human menopausal gonadotropin (hMG) 3 ampoules/day from day 5. Main Outcome measures were number of follicles, oocytes and embryos, and pregnancy rate (PR). These measures were then compared with those of the previous cycle. There were significant differences in all parameters (P < 0.05). Pregnancy occurred in 3 women (5%). There was no significant difference in number of follicles, oocytes and embryo between two age groups (P > 0.05). Use of microdose GnRH-a plus HMG for controlled ovarian hyperstimulation in IVF or ICSI cycles can lead to formation of more follicles, oocyte and embryo in poor responders.