Effectiveness of mindful self-compassion therapy on psychopathology symptoms, psychological distress and life expectancy in infertile women treated with in vitro fertilization: a two-arm double-blind parallel randomized controlled trial.

OBJECTIVES: Infertility is a prominent problem affecting millions of couples worldwide. Recently, there has been a hightened emphasis on elucidating the subtle linkages between infertility treatment leveraging assisted reproductive technology and the complex realm of psychological challenges, as well as efforts in implementation of psychological interventions.The Mindful Self-Compassion (MSC) program seeks to improve self-compassion, compassion for others, mindfulness, and life satisfaction while reducing depression, anxiety, and stress. In the current study, an MSC intervention was performed on infertile women (IW) undergoing in vitro fertilization (IVF) to assess the effectiveness of this intervention in reducing psychological distress and psychopathological symptoms and enhancing life expectancy. METHODS: Fifty-seven IW undergoing IVF were randomly allocated to two groups: MSC (n = 29) or treatment as usual (TAU; n = 28). Participants in MSC met once a week for two hours for eight weeks and attended a half-day meditation retreat. The Synder's Hope questionnaire and the Revised 90-Symptom Checklist (SCL-90-R) were used as the primary outcome measures. Data were obtained before the intervention, immediately after the intervention, and two months post-intervention. Repeated measures of ANCOVA and paired t-tests in all assessment points were used to compare the MSC and the TAU groups in outcomes. RESULTS: In the MSC group, hopelessness, anger-hostility, anxiety, interpersonal sensitivity difficulties, and depression were significantly reduced compared with the TAU group, and those improvements persisted at the two-month follow-up. Reliable change index revealed that the MSC group's gains were both clinically significant and durable. CONCLUSIONS: MSC can facilitate higher life satisfaction and mental well-being for IW undergoing IVF by reducing psychological distress, psychopathological symptoms, and hopelessness. These encouraging findings call for more research into the effectiveness of mindfulness-based therapies in addressing psychological problems among IW undergoing IVF.

Effect of vitamin K2 administration on depression status in patients with polycystic ovary syndrome: a randomized clinical trial.

BACKGROUND: Patients with Polycystic ovary syndrome (PCOS) are predisposed to the development of several mental comorbidities such as depression. According to several studies, PCOS can be managed by improving insulin sensitivity. The insulin-sensitizing effect of vitamin K has been reported in recent studies. Therefore, in the current trial, we assessed the effect of administrating vitamin K2 (Menaquinone-7) on depression status in women afflicted with PCOS. METHODS: Eighty-four PCOS women were allocated into the intervention and comparison groups; the intervention group (n = 42) administered 90 µg/day Menaquinone-7, and the comparison group (n = 42) consumed placebo capsules (containing avesil) for 8 weeks. In this randomized, double blind, placebo-controlled clinical trial, depression status was measured by BECK depression inventory-II (BDI-II) before and after 8 weeks of intervention. RESULTS: Consumption of Menaquinone-7 in comparison with the placebo capsules significantly improved depression status (P = 0.012). CONCLUSION: This clinical study reported the advantageous effect of Menaquinone-7 administration on depression status in PCOS patients. Trial registration The present study was registered at http://www.IRCT.ir on 06/06/2018 (registration number: IRCT20170916036204N5).

Delayed cord clamping for prevention of intraventricular hemorrhage in preterm neonates: a randomized control trial.

BACKGROUND: Intraventricular hemorrhage (IVH) is a common condition in preterm neonates and is responsible for substantial adverse neurodevelopmental outcome in preterm neonates. Prevention of IVH is an important intervention for better neurological outcome in these preterm neonates. AIMS AND OBJECTIVE: This study aimed to determine whether delayed cord clamping (DCC) was superior to immediate cord clamping (ICC) for the prevention of IVH in preterm neonates. PATIENTS AND METHODS: In this two centered prospective double-blind randomized controlled trial, eligible neonates with gestational age from 26 to 34 weeks were randomized to receive either ICC (cord clamped in 10-15 s) or DCC (cord clamped in 30-45 s) groups. The grading and severity of IVH were evaluated by cranial ultrasound scan done on the 3-4th and 7-10th days after birth. RESULTS: Among the 148 enrolled neonates, 79 were in the ICC group and 69 were in the DCC group. There was no difference in maternal and neonatal baseline characteristics except the neonates in the DCC group weighed more (ICC 1528.77 ± 365.5 g vs. DCC 1658.11 ± 419.52 g; p = .047) at birth. There was no significant difference in the incidence of any grade of IVH in both groups (ICC 12.8% vs. DCC 14.5%; p = .745). There was a significantly higher incidence of grade I IVH (ICC 2.5% vs. DCC 13%; p = .024) in the DCC group. The incidence of grade II IVH (ICC 5.1% vs. DCC 0%; p = .123); grade III IVH (ICC 3.8% vs. DCC 1.4%; p = .623); and grade IV IVH (ICC 1.3% vs. DCC 0%; p>.999) were comparable between the two groups. The incidence of a significant IVH (grades II, III, and IV) was significantly less in the DCC group (ICC 10.1% vs. DCC 1.4%, p = .036). The mean initial hemoglobin levels were significantly higher in neonates enrolled in DCC (15.41 ± 2.1 vs. 16.46 ± 2.45 g/dL; p = .007). There was a significant reduction in the number of days of hospital stay (ICC 18.78 ± 15.42 vs. DCC 13.21 ± 16.16; p = .002). There was no difference in initial hematocrit, platelet count, maximum bilirubin level, and Apgar score (p>.05). CONCLUSIONS: Although there was no reduction in any grade of IVH, the incidence of significant IVH (grades II, III, and IV) was significantly decreased with the use of DCC in preterm neonates. Delayed cord clamping also resulted in a significant increase in birth weight, higher hemoglobin levels, and shorter hospital stays without any increase in the risks of hyper-bilirubinemia, low Apgar score, and neonatal mortality. TRIAL REGISTRY: IRCT2014031116936N1, https://www.irct.ir/trial/15707.

The impact of GSTM1 and GSTT1 polymorphisms on susceptibility to gestational diabetes in Iranian population.

BACKGROUND: Gestational diabetes mellitus (GDM) is characterized as a common metabolic disorder during pregnancy which is associated with glucose intolerance and insulin resistance. Genetic predisposition could contribute to the development of GDM. METHODS: We conducted a case-control study to inspect the impact of GSTM1 and GSTT1 polymorphism on GDM susceptibility in Iranian population. The population consisted of 149 pregnant women with GDM as cases, and 138 healthy pregnant women without any history of GDM as controls. Polymerase chain reaction-restriction fragment length polymorphism method was applied to determine the GSTM1 and GSTT1 gene polymorphisms. RESULTS: There were statistically significant differences between the cases and controls in terms of age (p = .005), BMI (p < .001), family history of gestational diabetes (p < .001), FBS (p = .001), TG (p ≤ .001), and HDL (p = .003). However, no significant differences were observed in TC (p = .078) and LDL (p = .062). There were significant differences between GSTM1 polymorphism (Null and present) in the case and controls groups [OR (95% CI); 2.3 (1.4-3.7), p < .001]. The distribution of GSTM1-null genotype was found to be significantly higher in GDM patients (68.6%) than the control group (48.5%). No significant variance was detected between GSTT1 polymorphism (Null and present) in the case and controls groups [OR (95% CI); 1.1 (0.6-1.6), p = .088]. The frequency of GSTM1 null/GSTT1 null [OR (95% CI); 2.7 (1.2-5.2), p = .01] and GSTM1 null/GSTT1 present [OR (95% CI); 2.6 (1.4-4.8), p = .002] genotypes significantly differed between the GDM and control groups. CONCLUSION: It seems that GSTM1 null genotype might be considered as GDM risk factor in Iranian population.

Cost-Effectiveness Analysis of Different Methods of Treatment of Tubal Ectopic Pregnancy in the South of Iran.

OBJECTIVES: The aim of the study was to evaluate the cost-effectiveness of different methods of treating tubal ectopic pregnancy in the south of Iran. METHODS: This study was an economic evaluation that analyzed and compared the cost-effectiveness and cost utility of 3 treatment methods, including single-dose methotrexate, double-dose methotrexate, and surgery in patients with tubal ectopic pregnancy. In this study, a decision tree model was used. The outcomes included in the model were the percentage of successful treatment and the average utility score of each treatment method. The study was conducted from the social perspective, and a one-way and probabilistic sensitivity analysis was performed to measure the effects of uncertainty. RESULTS: The incremental cost-effectiveness ratio of surgery compared with single-dose methotrexate was positive and equal to $5812 purchasing power parity; moreover, the results of one-way analysis showed the highest sensitivity toward the effectiveness of single-dose methotrexate. Scatter plots also revealed that surgery in 82% and 96% of simulations was at the acceptable region compared with a single-dose and double-dose methotrexate, respectively and was below the threshold. It was identified as a more cost-effective strategy. Furthermore, the acceptability curves showed that in 81.4% of simulations, surgery was the most cost-effective treatment for thresholds less than $20 950 purchasing power parity. CONCLUSIONS: On the basis of the results of this study, surgery can be used as the first line of treatment for ectopic pregnancy. In addition, the best drug strategy was single-dose methotrexate because this strategy reduced costs and increased treatment success and quality-adjusted life-years compared with double-dose methotrexate.

Male subfertility effects of sub-chronic ethanol exposure during stress in a rat model.

BACKGROUND: Stressful conditions increase alcohol consumption in men. Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but the effect of alcohol in a stress condition on male fertility is still relatively poorly understood. This project was undertaken to evaluate the effect of sub-chronic alcohol in a stress condition on male fertility in a rat model. METHODS: Male Sprague-Dawley rats were randomly divided into a control group, a stress group that was exposed to restraint stress, an ethanol group that was injected with ethanol daily, and a stress + ethanol group that was injected with ethanol daily and was exposed to restraint stress, simultaneously. Furthermore, testis tissue was evaluated histomorphometrically and immunohistochemically for apoptosis using a TUNEL assay after 12 days. Epididymis sperm analysis was done. Blood cortisol and testosterone were measured and expression of hypothalamic kisspeptin (Kiss1), RFRP-3, and MC4R mRNA were evaluated. RESULTS: Ethanol exposure during restraint stress did not alter body weight. Ethanol exposure decreased the cellular diameter and area, and stress increased the cellular diameter and area, in comparison with the control group. In the stress group, in comparison with the other groups, the number of seminiferous tubules decreased and the numerical density of seminiferous tubules increased. In addition, ethanol exposure and/or stress reduced semen analysis parameters (sperm viability and motility), but did not change serum testosterone concentrations. Apoptosis increased in spermatogonia with ethanol exposure, but spermatocytes were not affected. Our data present the novel finding that ethanol and stress reduced hypothalamic Kiss1 mRNA expression, while ethanol exposure decreased hypothalamic RFRP-3 and MC4R mRNA expression. CONCLUSIONS: Ethanol decreased cortisol hormone level during the restraint stress condition and attenuated hypothalamic reproductive-related gene expressions. Therefore, ethanol exposure may induce reduction of sperm viability, increased sperm mortality, and increased apoptosis, with long-term effects, and may induce permanent male subfertility.

Comparing four different methods for the management of ectopic pregnancy: A cross-sectional study.

Background: Ectopic pregnancy (EP) is one of the major causes of maternal mortality during the first trimester of pregnancy. Objective: Four treatment methods for EP including single-dose methotrexate (SD-MTX), double-dose methotrexate, expectant and surgical management were considered. Materials and Methods: In this cross-sectional study, the clinical characteristics of 365 women aged 15-44 yr who had been diagnosed with EP were reviewed from March 2017 to March 2019 in hospitals affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Receiver operating characteristics curves were plotted to determine the cut-off points for size of ectopic mass and beta-human chorionic gonadotropin (ß-hCG) that suitably discriminated between double-dose methotrexate and surgery management. Results: The most common site of EP was adnexa. According to the receiver operating characteristics analysis, surgery was the best plan for the women with an ectopic mass > 34.50 mm in diameter or with an initial ß-hCG level > 6419 mIU/ml. The ß-hCG levels in the women successfully treated with SD-MTX were significantly lower than in those with failed treatment (p = 0.02). The SD-MTX group had a higher success rate and significantly shorter duration of hospitalization, and so this was a more effective medical treatment in comparison with the double-dose protocol. Conclusion: Surgery is proposed as the best option for the cases with large ectopic mass or high ß-hCG level. SD-MTX had a higher success rate and shorter hospital stay than the double-dose protocol, and so was found to be an efficient and safe alternative. Further randomized clinical trials with larger sample sizes are recommended to validate the current results.

Beneficial health effects of Menaquinone-7 on body composition, glycemic indices, lipid profile, and endocrine markers in polycystic ovary syndrome patients.

OBJECTIVE: The aim of this study was to investigate the effect of oral vitamin K2 (Menaquinone-7 [MK-7]) on clinical and biochemical parameters in polycystic ovary syndrome (PCOS) patients. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, 84 PCOS patients were randomly assigned into the treatment (90 µg Menaquinone-7 daily for 8 weeks) and placebo groups. Insulin resistance, lipid profile, endocrine biomarkers, and body composition of the participants were measured before and after the intervention. This study was performed in Ghadir Mother & Child Hospital affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. RESULTS: Menaquinone-7 supplementation, when compared to placebo, significantly decreased serum fasting insulin (p = .002), homeostasis model of assessment insulin resistance (p = .002), and homeostasis model of assessment ß-cell function (p = .02) in addition to a significant increase in quantitative insulin sensitivity check index (p = .001). Also, MK-7 administration led to significant declines in serum triglyceride (p = .003) and dihydrotestosterone (DHT; p = .03) levels, free androgen index (p < .001), waist circumference (p = .03), and body fat mass (p < .001) as well as significant increases in skeletal muscle (p < .001) and sex hormone binding globulin (SHBG, p < .001). CONCLUSIONS: This study highlights the beneficial effects of MK-7 on insulin resistance, fat mass, skeletal muscle, and serum levels of triglyceride, DHT, and SHBG in PCOS patients. Therefore, it seems that MK-7 supplementation might be an appropriate additive treatment for PCOS patients.

Founder Effect of KHDC3L, p.M1V Mutation, on Iranian Patients with Recurrent Hydatidiform Moles.

BACKGROUND: Recurrent hydatidiform moles (RHMs) are an unusual pregnancy with at least two molar gestations that are associated with abnormal proliferation of trophoblastic tissue and a failure in the embryonic tissues development. Three maternal-effect genes, including NLRP7, KHDC3L, and PADI6 have been identified as the cause of RHMs. The present study aimed to understand the association of a founder mutation with the incidence and prevalence of a disease in different individuals of a population. METHODS: 14 unrelated Iranian patients with recurrent reproductive wastage, including at least two HMs, entered this study. In order to find a possible mutation in KHDC3L, all the 14 samples were Sanger sequenced. For haplotype analysis, three single nucleotide polymorphisms (SNPs) were selected with highest Minor Allele Frequency along KHDC3L. RESULTS: A common KHDC3L mutation with the same haplotype was identified in four out of 14 patients with RHM. Regarding the present study, c.1A>G is the highest reported mutation in KHDC3L so far and is also the first report of the homozygous state that has led to RHM. CONCLUSION: c.1A>G mutation in KHDC3L is the highest reported mutation around the world. Our data also demonstrated the presence of founder effects for this particular mutation in Iranian populations. These data suggest that the high frequency of this mutation is potentially responsible for a higher rate of RHM in Iran.

Swimming modifies the effect of noise stress on the HPG axis of male rats.

BACKGROUND: Few studies have examined the effect of noise pollution on the hypothalamic-pituitary-gonadal (HPG) axis. In this study, the effects of noise pollution and swimming on the HPG hormone axis of male rats were investigated. METHODS: Forty male Sprague Dawley rats were assigned to four groups of equal size, including control (C), swimming (S), noise (N), and noise with swimming (NS). Serum levels of GnRH, LH, FSH, and testosterone were measured through blood samples taken 48 h following the last session of treatment. The main treatment programs of voluntary swimming and noise stress were performed 5 days per week over 7 weeks. RESULTS: Serum levels of GnRH, LH, FSH, and testosterone decreased after exposure to the noise compared with the S and C groups, while in the S group, all hormone levels were higher than those in the C and N groups. Hormone levels of the SN group were higher than those in the N group but lower than those in the C group. CONCLUSIONS: Long-term exposure to noise is known to have a negative impact on male sex hormones, while submaximal swimming exercise is likely to reduce these effects and improve HPG axis hormones.

Analysis of the frequencies and functions of CD4+CD25+CD127low/neg, CD4+HLA-G+, and CD8+HLA-G+ regulatory T cells in pre-eclampsia.

Most of the investigations on regulatory T cells (Treg) have focused on CD4+CD25+Foxp3+ Treg cells. Although new subsets of these cells such as CD4+CD25+CD127low/neg, CD4+HLA-G+, and CD8+HLA-G+ Treg cells have been introduced, documents regarding these populations are limited or controversial in case of pregnancy and pre-eclampsia (PE). Here, we investigated the frequencies of the three aforementioned Treg cell subsets in the peripheral blood of non-pregnant (n = 15), healthy pregnant, and preeclamptic women (n = 17 in each group) using flow cytometry. We also assessed the ability of the isolated CD4+CD25+CD127low/neg and CD4+HLA-G+ Treg cells to suppress responder T cells proliferation and cytokine secretion using CFSE dye dilution and ELISA technique. Our results showed that the frequency of CD4+CD25+CD127low/neg Treg cells was significantly lower in preeclamptic women (p =  0.001). Also, this subset negatively correlated with both systolic (R= - 0.401, p =  0.004) and diastolic (R= - 0.541, p =  0.001) blood pressures. Regarding CD4+HLA-G+ and CD8+HLA-G+ Treg cells, the mean percentages of these cells were significantly higher in the context of normal pregnancy (p <  0.01). Finally, our results in the functional assay experiments did not show statistically significant differences between groups (p ≥  0.05), but they reveal a shift toward the lower suppressive capacity of CD4+CD25+CD127low/neg and CD4+HLA-G+ Treg cells in preeclamptic patients which might be clinically important. In conclusion, a significant decrease in the frequency of Treg cell subsets and also a shift toward the lower suppressive capacity of these cells in preeclamptic patients may lead to immunological maladaptation in the context of PE.

A Novel Mutation in NLRP7 Related to Recurrent Hydatidiform Mole and Reproductive Failure.

BACKGROUND: Hydatidiform mole (HM) is an abnormal human pregnancy with excessive trophoblastic proliferation and abnormal embryonic development, dividing into two complete HM (CHM) and partial HM (PHM) groups. One subcategory of the CHMs is recurrent and familial, which is known as biparental HM (BiHMs) or recurrent HM (RHM). NLRP7, KHDC3L and PADI6 are maternal-effect genes involved in RHMs. NLRP7 is a major gene responsible for RHMs. This study was performed on patients with molar pregnancies and miscarriage. The aim of this study was to genetic screen for mutations in NLRP7 and KHDC3L genes in an affected woman with previous history of 5RHM and the sibling with history of miscarriage. MATERIALS AND METHODS: In this experimental study, DNA was extracted from blood samples. KHDC3L and NLRP7 were polymerase chain reaction (PCR) amplified. The PCR products were purified and Sanger sequenced. RESULTS: In this study, there is no mutation in KHDC3L gene but a novel mutation was identified in the NACHT domain of NLRP7 gene. Patient with five recurrent moles had this mutation in the homozygous state while her sister with one miscarriage and one normal child showed this mutation in the heterozygous state. CONCLUSION: In this study, we identified a new mutation in NLRP7 gene of a patient with recurrent HM. Following egg donation, this patient has a normal boy. The sister of this patient with heterozygous mutation has a spontaneous abortion and one normal child that confirm the impact of a defective allele of NLRP7 on reproductive wastage in a recent finding.

T Cell Subsets Profiling in Unexplained Infertile Women with Successful and Unsuccessful in Vitro Fertilization Outcome: Focus on the Effect of Seminal Plasma.

Unexplained infertility (UI) is one of the most common diagnoses in the fertility care. Seminal plasma (SP) plays a crucial role in the regulation of female immune responses and the success of a pregnancy. In vitro fertilization (IVF) is a well-known method for the treatment of UI. In this study, we aimed to investigate the effect of SP on the differentiation of T helper (Th) cell subsets and the relationship between these subsets with the rate of IVF success in a group of women complicated with UI compared to those with normal pregnancy. This study was conducted on 20 UI couples (ten with successful and ten with unsuccessful IVF outcome) and 10 fertile couples as the control group. Four color flow cytometry technique was used to detect Th cell subsets in the peripheral blood mononuclear cells (PBMC) with or without stimulation by SP. Results indicated that the frequencies of IL-17+ and Foxp3+ T cells after incubation with SP was significantly increased in couples with unsuccessful IVF outcome as compared to successful and healthy groups (p<0.05). Additionally, a positive correlation was observed between Th1 and Th2 cells in the unsuccessful IVF group (R=0.6, p=0.03). In summary, the results of the present study demonstrated that exposure to SP might increase Th17 and Treg cell frequencies in infertile women with unsuccessful IVF, and might also balance inflammatory to regulatory responses to finally tune-up the Th1/Th2/Th17/Treg balance and support the success of IVF.

Association between Interleukin-32 and Interleukin-17A Single Nucleotide Polymorphisms and Serum Levels with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is correlated with low-grade chronic inflammation. Interleukin-17A (IL-17A) and Interleukin-32 (IL-32) are two members of the pro-inflammatory cytokines which act as significant components of the immune system during certain inflammatory diseases. Along with immunological processes, genetic factors play major roles in predisposition to PCOS. There are myriad single nucleotide polymorphisms (SNPs) within IL-17A and IL-32 genes that may affect their production and the susceptibility of individuals to PCOS. The objective of the present research was to investigate the association between IL-17A (rs2275913) and IL-32 (rs9927163, rs4786370) SNPs, and also their serum levels with susceptibility to PCOS in a group of Iranian women. In this case-control study, 150 PCOS patients (mean age of 29.1 years) and 150 healthy women (mean age of 26.1 years) were analyzed in terms of IL-17A and IL-32 SNPs via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Furthermore, serum levels of IL-17A and IL-32 cytokines were measured through the use of ELISA method. There were significant differences between PCOS and healthy women regarding IL-17A rs2275913 alleles, genotypes frequencies (p=0.005, and 0.01, respectively) and the allelic distribution of IL-32 rs9927163 SNP (p=0.03). Additionally, significant differences were indicated between two groups concerning the AG genotype against AA+GG genotypes (p=0.009) and the GG genotype against AA+AG genotypes (p=0.006) in IL-17A rs2275913 SNP. In the matter of IL-32 gene SNPs, GC haplotype frequency was significantly different between patients and controls (p=0.05). Furthermore, IL-32 serum level was not significantly different between the two studied groups and the serum level of IL-17A was not detectable. In conclusion, IL-17A and IL-32 SNPs might be associated with predisposition to PCOS in Iranian women.

Relationship between Religious Orientation, Anxiety, and Depression among College Students: A Systematic Review and Meta-Analysis.

BACKGROUND: Religious obligation helps people to develop mental health by creating internal commitment to special rules. This meta-analysis aimed to determine the relationship between religious orientation and anxiety among college students. METHODS: Major scientific databases including PubMed, Web of Science, Science Direct, EBSCO, ProQuest and PsycINFO were searched for original research articles published 1987-2016. A random effect model was used to combine Correlation coefficient. All analyses were performed using Stata MP. RESULTS: After screening of 7235 documents, 13 articles including 5620 participants met inclusion criteria in this meta-analysis. Correlation coefficient was -0.08 (95% CI= -0.19, -0.03) which indicated with increasing religious orientation, anxiety and depression reduced (P<0.001). Characteristics such as sex, geographic region, and type of religions were potential sources of heterogeneity. Based on fill-and-trim method the adjusted pooled r was obtained, -0.06 (95% CI= -0.16, -0.04). CONCLUSION: There was a weakness relationship between religious orientation and mental anxiety and depression. Therefore, it needs to improve knowledge of student about advantages of religious orientation.

Effect of low-dose aspirin on the development of ovarian hyperstimulation syndrome and outcomes of assisted reproductive techniques in the women with PCOS, a randomized double-blinded clinical trial.

OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is a major complication of assisted reproductive technologies (ART). Polycystic ovary syndrome (PCOS) is a risk factor for OHSS. The aim of this randomized clinical trial (RCT) was to study the effect of low-dose aspirin (LDA) on the development of OHSS and ART outcomes in PCOS during ART. MATERIALS AND METHODS: This double-blinded placebo controlled RCT was performed on 232 PCOS infertile women in their first ART cycles during 2010-2016. LDA and placebo capsules were prepared, packed and specified by code numbers in similar shapes. One package was given to every woman and asked to take one capsule/day since the 21st day of her cycle prior to the gonadotropin stimulation. Gonadotropin releasing hormone agonist long protocol and triggering by human chorionic gonadotropin were used. Development of moderate to severe OHSS and their ART outcomes were documented then the codes were broken and data analyzed. Chi-square and Mann-Whitney U tests were used for the statistical analyses. RESULTS: Eighteen cases that did not follow the study design were excluded. 214 cycles remained for the final analyses with 109 cases in LDA and 105 in the placebo group. Rate of the moderate to severe OHSS in LDA group was 34.9% compared to 30.5% in placebo group (P = 0.494). Fertilization rate was 71.8% vs 65.1% (P = <0.001) and the mean number of grade III embryos were 3.28 ± 3.53 vs 1.46 ± 1.42 (P = 0.014) in LDA and placebo groups, respectively. The mean number of the oocytes in different grades, total and frozen embryos also implantation and clinical pregnancy rates were not different between the groups. CONCLUSION: Moderate to Severe OHSS was not decreased but fertilization rate and the mean number of poor quality embryos were increased in LDA arm. REGISTRATION NUMBER: IRCT 201105216541N1.

Comparing The Effects of Glycyrrhiza glabra Root Extract, A Cyclooxygenase-2 Inhibitor (Celecoxib) and A Gonadotropin-Releasing Hormone Analog (Diphereline) in A Rat Model of Endometriosis.

BACKGROUND: The purpose of this study was to compare the effects of Glycyrrhiza glabra (Licorice), a cyclooxygenase- 2 inhibitor (Celecoxib) and a gonadotropin-releasing hormone analog (Diphereline®), with a control group on endometrial implants in rats. MATERIALS AND METHODS: In this experimental study, endometriosis was induced in rats by auto transplantation and after confirmation, the rats were divided into 4 groups that were treated for 6 weeks with normal saline (0.5 ml/day, orally), licorice extract (3000 mg/kg/day, orally), celecoxib (50 mg/kg, twice a day, orally) or diphereline (3 mg/kg, intramuscularly). At the end of treatments, the mean area, volume, histopathology and hemosiderin-laden macrophage (HLM) counts of the endometrial implants were evaluated and compared among the four groups. RESULTS: The mean area, volume and HLM counts of the implants in the licorice group were significantly lower than those of the control group (P<0.001). The histopathologic grades of endometrial implants were significantly decreased by licorice compared to the control group (P<0.001). There was no significant change in the mentioned parameters in rats treated with celecoxib compared to the control group. Diphereline was the most potent agent for suppressing the growth of endometrial implants in terms of all of the above-mentioned parameters. CONCLUSION: Licorice decreased the growth and histopathologic grades of auto-transplanted endometrial implants. However, while celcoxib had no significant effect, diphereline showed the highest potency for decreasing the endometrial growth. Licorice may have the potential to be used as an alternative medication for the treatment of endometriosis.

Evaluation of IL-17 and IL-35 Serum Levels in Patients with Preeclampsia.

BACKGROUND: Pre-eclampsia (PE) is the most common pregnancy complication affecting 2-8% of all pregnancies. PE could lead to maternal and prenatal morbidity. Imbalanced cytokine network and altered levels of several inflammatory and anti-inflammatory cytokines have been reported in PE. Because of scare information regarding the roles of IL-17 and IL-35 in PE, the current study aimed to investigate the serum level of these cytokines in a group of Iranian women suffering from PE. METHODS: Serum samples were collected from 100 pre-eclamptic and 100 healthy pregnant women. Patients and controls were matched for age, ethnicity and body mass index. The level of IL-35 and IL-17 were evaluated by ELISA technique. T test and one-way ANOVA with Tukey Post-Hoc test were used for analysis and p<0.05 were assumed significant. RESULTS: The serum level of IL-35 was increased in pre-eclamptic subjects as compared with healthy pregnant women (p<0.001). There was no significant difference in the serum level of IL-17 between pre-eclamptic and healthy pregnant women (p=0.73). Moreover, the results of the present study also showed that the pregnant women with severe pre-eclampsia had higher level of IL-35 in their sera when compared to those with mild form of the disease (p<0.001). In addition, the serum level of IL-35 was significantly elevated in women with higher proteinuria (p<0.001). CONCLUSION: Based on the our results, it seems that elevated levels of IL-35 in sera of pre-eclamptic women might work as a marker to evaluate the severity of the preeclampsia.

T Helper Cells Profile and CD4+CD25+Foxp3+Regulatory T Cells in Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is considered as the most common cause of female infertility that affects 4-10% of women in the reproductive age. Previous studies have shown the role of a balanced immune response in a successful pregnancy and fertility. OBJECTIVE: To investigate the T helper cells type 1 (Th1) /Th2/Th17/Treg paradigms in peripheral blood of infertile PCOS compared with normal fertile women. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated at the late follicular phase from 10 PCOS and 10 fertile women. PBMCs were stimulated with PMA and ionomycin in the presence of Berefeldin A as Golgi stop agent to detect intracellular cytokine production (IFN-γ, IL-17, and IL-4) from CD3+CD4+T cells population indicating T helper (Th) cells subsets by flowcytometry. Moreover, regulatory T cells were enumerated using CD25 and Foxp3 markers. RESULTS: In this study, we report that the frequency of Th1 cells was increased compared to Th2 cells in infertile PCOS when considering Th1/Th2 ratio (P=0.05). Analysis of Th17/Th2 ratio showed a significant difference with a bias toward Th17 dominancy in PCOS (P=0.02). The proportion of CD4+CD25+Foxp3+ regulatory T cells was significantly lower in PCOS patients than that of healthy fertile women (P=0.02). CONCLUSION: In summary, Th1 and Th17 bias and reduction of Treg and Th2 cells as regulators of immune responses might be involved in the pathogenesis of PCOS. These results are suggestive of an altered immune response to inflammatory status in PCOS patients, likely causing some complications such as infertility in these patients.