Effect of intrauterine granulocyte-colony stimulating factor administration on in vitro fertilization outcome in women with moderate-to-severe endometriosis: An RCT

Background: Nearly 25-50% of infertile women have endometriosis. There are reports of disorders in the expression of granulocyte colony-stimulating factor (G-CSF) receptors in women with endometriosis. Objective: To examine the effect of intrauterine administration of G-CSF in in vitro fertilization (IVF) cycles on the fertility rate of infertile women with moderate-to-severe endometriosis. Materials and Methods: This clinical trial was conducted on 66 infertile women with moderate-to-severe endometriosis, undergoing IVF and intracytoplasmic sperm injection (ICSI). The participants were allocated into two groups via simple randomization: the G-CSF (n = 27) and control (n = 39) groups. In the G-CSF intervention group, on the oocyte pick-up day, immediately after an ovarian puncture, 300 μg of G-CSF was injected through a transcervical catheter under abdominal ultrasound guide to visualize flushing into the uterine cavity. Women in the control group received no intervention. The two groups were evaluated for clinical pregnancy. Results: No significant difference was noted in the demographic characteristics of the two groups. The rate of clinical pregnancy was 28.2% in the control group and 25.9% in the G-CSF group, indicating no significant difference (p = 0.83). Conclusion: The results showed that the intrauterine injection of G-CSF had no effects on pregnancy in women with stage-3/4 endometriosis undergoing IVF. Key words: G-CSF, In vitro fertilization, Endometriosis, Pregnancy

Letrozole as co-treatment agent in ovarian stimulation antagonist protocol in poor responders: A double-blind randomized clinical trial

Background: Ovarian stimulation (OS) for poor ovarian response (POR) patients is still a major challenge in assisted reproductive techniques. Aromatase inhibitors as co-treatment in antagonist protocol are suggested to these patients, but there are controversial reports. Objective: To evaluate the effectiveness Letrozole (LZ) as adjuvant treatment in gonadotropin-releasing hormone (GnRH)-antagonist protocol in POR patients undergoing in vitro fertilization/intracytoplasmic sperm injection cycles. Materials and Methods: This double-blind randomized clinical trial was conducted in Arash women’s hospital. One hundred sixty infertile women with POR based on Bologna criteria were allocated into two groups randomly: LZ + GnRH-antagonist (LA) and placebo + GnRH-antagonist (PA) groups. In the experimental group, the patients received 5 mg LZ on the first five days of OS with 150 IU of recombinant human follicle-stimulating hormone (rFSH) and 150 IU of human menopausal gonadotropin (HMG). The cycle outcomes were compared between groups. Results: The total number of retrieved oocytes and the metaphase II oocytes in LA-treated group were significantly higher than those in the control group (p = 0.008, p = 0.002). The dosage of hMG used and the duration of OS and antagonist administration in LZ-treated group were significantly lower than those of the control group. The number of patients with no oocyte, in the control group, was higher than the LZ-treated group, and the clinical pregnancy rate in LA-treated group (25%) was higher than the control group (18%); however, the differences were not significant statistically. Conclusion: Adding 5 mg of LZ to rFSH/hMG antagonist protocol may improve the in vitro fertilization/intracytoplasmic sperm injection cycle outcome in POR patients. Key words: Letrozole, Ovarian reserve, Primary ovarian insufficiency, Ovulation induction, Fertilization in vitro, Aromatase inhibitors

Natural cycle versus modified natural cycle for endometrial preparation in women undergoing frozen-thawed embryo transfer: An RCT

Background: Studies have evaluated different endometrial preparation methods, but the optimal frozen-thawed embryo transfer (FET) cycle strategy in terms of the in-vitro fertilization outcome is still debated. Objective: To compare the natural versus modified natural cycles for endometrial preparation in women undergoing FET. Materials and Methods: This study was designed as a randomized clinical trial, and it was performed at the Arash women’s hospital between August 2016-2018. Hundred and forty eligible participants were enrolled in this study and were randomly divided into 2 groups by using the block randomization method, including true natural FET (n = 70) and modified natural FET (mNFET) (n = 70) cycles. Both groups were monitored for endometrial thickness and follicular size; simultaneously spontaneous luteinizing hormone surge using urinary luteinizing hormone testing kits. The mNFET group received 5000 IU of human chorionic gonadotropin injection to trigger final follicular maturation. Luteal support by vaginal progesterone (cyclogest 400 mg twice daily) was used in true natural FET from the day of transfer until the 10th wk of pregnancy. Chemical and clinical pregnancy and abortion rates were considered as the primary outcomes. Results: There were no differences in the participants’ baseline characteristics between groups. There was no difference in clinical pregnancy and abortion rate between the 2 groups, while the implantation rate was significantly higher in the mNFET group (29.2% vs. 17.6%; p = 0.036). Conclusion: The results demonstrated that both types of natural cycles were similar in pregnancy outcomes, while modified cycles might be associated with a higher implantation rate. Key words: Embryo transfer, In vitro fertilization, Pregnancy rate, Live birth, Human chorionic gonadotropin

CHANGE IN FREQUENCY OF ACUTE AND SUBACUTE EFFECTS OF ECSTASY IN A GROUP OF NOVICE USERS AFTER 6 MONTHS OF REGULAR USE

Background: Recent research trends are to specify the relation between patterns of ecstasy use and side effects, possibility of dependency, tolerance and long term neurocognitive damage. The objective of this study was to assess the impact of regular ecstasy use on its acute and subacute effects. Subjects and methods: At the first stage, we recruited 120 subjects. If participants continued regular use of ecstasy in this period, they were asked to participate in the second stage of the research 6 months later. Thirty-five subjects attended the second stage of the study, 5 of which were excluded because they had less than 5 drug experiences during the last 6 months. At last, we recruited 30 novice ecstasy users by means of the snowball technique in Tehran, Iran. The pattern of use and experienced effects of ecstasy was documented at the beginning and after 6 months of regular consumption with a self administered questionnaire. Results: Little or no change was observed in acute effects. Those subacute effects that had considerable increase in frequency were anxiety, depression, aggression, memory impairment, poor concentration and learning problems. Conclusion: Small change in acute effects suggests low possibility of tolerance after at least 6 months of regular use. Our results support long term neurocognitive damage and mood impairment with ecstasy use

Pregnancy outcomes in women with adenomyosis, undergoing artificial endometrial preparation with and without gonadotropin-releasing hormone agonist pretreatment in frozen embryo transfer cycles: An RCT

Background: Selecting a suitable and preferable method for endometrial preparation in frozen embryo transfer (FET) cycles for women with adenomyosis is still challenging in infertility treatment. Objective: To compare 2 artificial endometrial preparation regimens with and without gonadotropin-releasing hormone agonist (GnRHa) pretreatment in women with adenomyosis undergoing FET cycles. Materials and Methods: This randomized clinical trial study was conducted on 140 adenomyosis cases who underwent FET cycles at Arash Women’s hospital, Tehran, Iran from May 2020 to March 2021. Participants were randomly allocated into hormonal replacement therapy (HRT) and HRT+GnRHa pretreatment groups (n = 70/each). Endometrial preparation with 2-6 mg daily estradiol was started in the HRT+GnRHa group, taking after down-regulation with the GnRHa. Within the HRT group, the same dose of estradiol was commenced within the early follicular stage. The main (chemical and clinical pregnancy rates) and auxiliary results (twin pregnancy, miscarriage, and live birth rates) were compared between groups. Results: The demographic characteristics and severity of adenomyosis, endometrial thickness, and pattern at starting progesterone administration were similar in the 2 groups, and triple-line endometrium was found to be the dominant pattern in both groups (p = 0.65). No significant differences were observed in chemical, clinical, and twin pregnancy rates as well as miscarriage and live birth rates between groups (p = 0.71, p = 0.81, p = 0.11, and p = 0.84, respectively). However, the total estrogen dose and duration of estrogen consumption were significantly higher in the pretreatment group (p = 0.001, and p = 0.003). Conclusion: These results indicated that the hormonal endometrial preparation with estrogen and progestin for FET cycles is as efficacious as a protocol involving preceding pituitary suppression with a GnRHa. Further large randomized clinical studies are required to confirm these findings. Key words: Adenomyosis, Embryo transfer, Hormone replacement therapy, Gonadotropin-releasing hormone

Comparison of N-Terminal Pro B-Natriuretic Peptide and Echocardiographic Indices in Patients with Mitral Regurgitation

Introduction Echocardiographic indices can form the basis of the diagnosis of systolic and diastolic left ventricular (LV) dysfunction in patients with Mitral regurgitation (MR). However, using echocardiography alone may bring us to a diagnostic dead-end. The aim of this study was to compare N-Terminal pro B-natriuretic peptide (BNP) and echocardiographic indices in patients with mitral regurgitation. Methods 2D and Doppler echocardiography and BNP serum level were obtained from 54 patients with organic mild, moderate and severe MR. Results BNP levels were increased with symptoms in patients with mitral regurgitation (NYHAI: 5.7 ± 1.1, NYHAII: 6.9 ± 1.5, NYHAIII: 8.3 ± 2 pg/ml, P < 0.001). BNP plasma level were significantly correlated with MPI (myocardial performance index) (r = 0.399, P = 0.004), and following echocardiographic indices: LVEDV (r = 0.45, P < 0.001), LVESV (r = 0.54, P < 0.001), LVEDD (r = 0.48, P < 0.001), LVESD (r = 0.54, P < 0.001), dp/dt (r = −0.32, P = 0.019) and SPAP (r = 0.4, P = 0.006). Conclusion The present study showed that BNP may be useful in patients with MR and may confirm echocardiographic indices

Raloxifene adjunctive therapy for postmenopausal women suffering from chronic schizophrenia: a randomized double-blind and placebo controlled trial

BACKGROUND: Cumulative evidence from epidemiological, preclinical and clinical studies suggests estrogens may have psychoprotective effects in schizophrenic patients. Selective Estrogen Receptor Modulators could have therapeutic benefits in schizophrenia for both sexes without being hazardous to gynecological tissues or having feminizing effects. Few studies have been conducted regarding the effects of raloxifene on postmenopausal women suffering from schizophrenia. We conducted this placebo-controlled trial to compare the add-on effect of raloxifene to risperidone versus risperidone with placebo. METHODS: This was an 8-week, parallel-group, placebo-controlled trial undertaken at two universities affiliated psychiatric Hospitals in Iran. Forty-six postmenopausal women with the definite diagnosis of schizophrenia were enrolled in the study. Patients received risperidone (6 mg/day in 3 divided doses) combined with either placebo (N = 23) or 120 mg/day of raloxifene (N = 23) for 8 weeks. Patients were assessed by a psychiatrist at baseline and at 2 and 8 weeks after the start of medical therapy. Efficacy was defined as the change from baseline to endpoint in score on Positive and Negative Syndrome Scale (PANSS). RESULTS: For PANSS scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 1.77, p = 0.18]. For positive subscale scores, there was marginal significant interaction between intervention type and time [F (2, 47) = 2.93, p = 0.06] and there was substantial main effect for time [F (2, 47) = 24.39, p = 0.001] within both groups showing reduction in positive subscale scores across the three time periods. In addition, the main effect comparing two types of intervention was significant [F (1, 48) = 3.78, p = 0.02]. On the other hand, for negative subscale scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 1.43, p = 0.23]. For general subscale scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 0.03, p = 0.86]. CONCLUSIONS: According to our findings, raloxifene as an adjunctive treatment to risperidone was only superior in improvement of positive symptoms and it was not effective in treating negative and general psychopathology symptoms. TRIAL REGISTRATION: The trial was registered at the Iranian registry of clinical trials: IRCT201205131556N4

Saffron (Crocus sativus) versus duloxetine for treatment of patients with fibromyalgia: A randomized double-blind clinical trial

Objective: Saffron was found efficient and safe in treatment of neuropsychiatric disorders, in particular depression. We compared the efficacy of saffron with duloxetine in treatment of patients with fibromyalgia. Materials and Methods: In this double-blind parallel-group clinical trial, outpatients with fibromyalgia were randomized to receive either saffron 15 mg or duloxetine 30 mg starting with 1 capsule per day in the first week followed by 2 capsules per day from week 2 until the end of week 8. Participants were men and women aged 18-60 years diagnosed with fibromyalgia based on the American College of Rheumatology 2010 criteria who also had a pain score ≥40 based on visual analogue scale. Participants were excluded in case they had rheumatologic diseases, inflammatory/infectious/autoimmune arthritis, comorbid neuropsychiatric disorders except depressive disorders, pain due to traumatic injuries, drug history of duloxetine or saffron use, current use of psychoactive medications, recent use of muscle relaxants, steroids, opioid analgesics, benzodiazepines, anti-epileptics, or injective analgesics. Primary outcomes included differences in mean score changes from baseline to endpoint between the treatment arms for Hamilton Rating Scale for Depression, Fibromyalgia Impact Questionnaire, and Brief Pain Inventory. Results: Socio-demographic characteristics and baseline scores were similarly distributed between the two treatment arms (2n=46). No significant difference was detected for any of the scales neither in terms of score changes from baseline to endpoint between the two treatment arms (Mean score changes: -4.26 to 2.37; p-values: 0.182-0.900) nor in terms of time´treatment interactions (p-values: 0.209-0.964). Conclusions: Saffron and duloxetine demonstrated comparable efficacy in treatment of fibromyalgia symptoms

Circulating and Endometrial Profiles of miR-145, miR-155-5p, miR-224, MPP-5, and PECAM-1 Expression in Patients with Repeated Implantation Failure: A Case Control Study

Objective: An association between microRNAs (miRNAs) and adhesion proteins expression with repeated implantationfailure (RIF) has been recently reported; however, these findings are controversial. This study aims to evaluatethe endometrial and circulating expressions of miR-145, miR-155-5p, and miR-224 in addition to the endometrialexpressions of membrane protein palmitoylated-5 (MPP-5) and endothelial cell adhesion molecule-1 (PECAM-1) inpatients with RIF compared to control subjects.Materials and Methods: This case-control study was carried out between June 2021-July 2022. Subjects included 17patients with RIF and 17 control subjects, who had previous spontaneous term pregnancy with a live birth, who referredto the Medical Centre of Arash Hospital, Tehran, Iran. Endometrial tissue samples were obtained via hysteroscopyand Pipelle catheter in the RIF and control subjects, respectively. Plasma samples were collected after ovulationin all subjects. The expression levels of MPP5, PECAM-1, miR-224, miR-145, and miR-155-5p were evaluated byquantitative real-time polymerase chain reaction (qRT-PCR). The student’s t test, chi-square, Mann-Whitney U, andanalysis of covariance (ANCOVA) were used for data analyses.Results: RIF patients had less endometrial miR-155-5p expression, and higher endometrial and circulating expressions ofmiR-145 and miR-224 compared to control subjects. Endometrial PECAM-1 and MPP5 expression significantly decreased inpatients with RIF compared to the control group. There was a positive correlation between circulating miR-224 and endometrialmiR-155-5p, and between circulating miR-155-5p and endometrial PECAM-1 expression levels in patients with RIF.Conclusion: The present study suggests that circulating miR-224, endometrial miR-145, and PECAM-1 can bereliable, novel biomarkers for diagnosis of RIF

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding Bill & Melinda Gates Foundation