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Official websites use. Share sensitive information only on official, secure websites. In this study, a simple and reliable method by gas chromatograph—mass spectrometry GC—MS was developed for the fast and regular identification of 3, 4-MDMA impurities in ecstasy tablets. In so doing, 8 samples of impurities were extracted by diethyl ether under alkaline condition and then analyzed by GC—MS. The results revealed high MDMA levels ranging from The experimental results indicated the acceptable time window without interfering peaks. Consequently, the intense MDMA levels would support the police to develop a simple quantification of impurity in Ecstasy tablets. A worldwide consumption of the well-known synthetic drugs club drugs increased annually. It is available in various forms on the drug market, mainly as tablets, capsules or powder, all called ecstasy. The Ecstasy tablets mostly contain amphetamine-type stimulants including 3, 4-methylenedioxymethamphetamine MDMA , 3, 4-methylenedioxyamphetamine MDA , methamphetamine MA and ketamine Keta , etc 4 , 5. The term is used more generally for all amphetamine type substances sold in form of tablets in the illicit market. Amphetamines and other related derivatives are powerful stimulants of the central nervous system and one of the most highly addictive drugs. The majority of people take MDMA orally, most often in tablet or capsule form. MDMA poisoning features are due to release of endogenous catecholamines particularly norepinephrine and dopamine and block their reuptake into presynaptic vesicles. MDMA produce profoundly positive feelings and empathy for others, that it eliminates anxiety. Furthermore, MDMA overdose is characterized by persistent psychosis, high blood pressure, panic attack, and in more severe cases, loss of consciousness, seizures and a marked rise in body temperature. In some cases, at high doses, it can cause convulsions, loss of consciousness, coma, and hyperthermia respectively 6 - 8. Due to the widespread abuse of amphetamine, drug testing for amphetamines is routinely done in forensic toxicology. So, introduction of new and fast determination method is essential 9. Detailed impurity information has been reported on the drugs seized in countries such as Australia 10 , Thailand 11 , Philippines 12 , Korea and Japan respectively Hence, a rapid, precise and reproducible methodology is required for the quantitative and qualitative determination of drugs for forensic science. These methods are time-consuming, especially concerning diagnosis, since often require the use of more ones analytic method to find the amphetamine drugs. Another advantage is that the technique is trouble-free to do and may be easily available in health centers, as opposed to other methods that are more expensive such as LC—MS—MS 17 and therefore not accessible to all diagnostic centers including local antinarcotics police. A general disadvantage of quantitation based on in vivo detection is relatively lower abundance for ones of the chemical derivatization of samples resulting lower coverage. GC-MS methods are often preferred for quantitative determination. To the best of our knowledge, the use of different methods did not provides sensitive and selective detection of amphetamine containing tablets, with the exception of 3,4-MDMA. This study was aimed to describe a GC—MS method for impurity profiling, after a simple liquid—liquid extraction. The first aim was to develop a fast, routine, quantitative and qualitative GC-MS method for confirmation of the presence of 3, 4- MDMA in the sized drugs. The ecstasy tablets seized in Ahwaz-Iran were examined and the data matrices were analyzed. This method evidently makes possible a simple identification of impurity in Ecstasy tablets. The second aim was to study GC-MS pattern of 3. All ecstasy samples discussed were obtained in tablet forms. The samples were confiscated by the Ahwaz-Iran antinarcotics police. The 8 random samples were categorized into 4 groups and analyzed. The tablets weighed from 0. All standard solutions were prepared with doubly distilled water. The analyses were performed on an Agilent GC system. Helium was used as the carrier gas at a flow rate of 0. Then the final temperature held for 15 min. The MS system was operated in electron impact mode. EI was used as ionization mode at 70 eV. The measurements were carried out in the selected ion monitoring mode in three time windows. MS scanning was performed at the range of 35— amu. GC-MS was used for determination of chemical profile of the tablets. A total of 8 samples of ecstasy tablets were studied from each kind of four provided samples, collected randomly from seizures at year. These samples were chosen from more than samples of ecstasy tablets seized in local antinarcotics police. These samples were divided into four groups according to their physical and appearance characteristics such as shape, break line, color, weight, diameter and thickness. Ecstasy tablets were ground and homogenized. Then, 5 mg of the powdered tablets was dissolved in 2 mL distilled water. The mixing was followed by addition of 2 mL pre-distilled diethyl ether. The solution was mixed 10 min and centrifuged at rpm. The ether layer was then separated and was transferred into a glass insert of GC micro vial for automatic sampling and dried. GC—MS analysis was carried out to identify the impurities. In order to avoid impurity degradation, the extracts were prepared and injected on the same day. Due to the increasing number of drug cases, as well as the widening globalization of illicit drugs, law enforcement agencies worldwide have adopted the strategy of profiling of drug impurities. They consist of a large variety of active ingredients and some contain a mixture of MDMA and one or more amphetamine-type drug s such as ketamine with apoptotic and neurodegenerative activities Amphetamine drugs are strongly controlled in most countries. Analytical information derived from the analysis of the illicit drugs, is important for legal and intelligence purposes. Liquid—liquid extraction LLE is a classical technique that has been often used for carrying out the extraction of many compounds from various kinds of samples. Most laboratories prefer using liquid—liquid extraction for sample preparation. GC—MS is recently the most used method for the determination of drugs which allows working with complex matrixes leading to high specificity along with sensitivity. GC-MS method showed full advantage of the high resolution for impurities using multiple points of selectivity for identification based on the match of retention time and mass spectrum of an unknown peak with that of the standard Figure 1 , 2 and 3. The internal standard method was used to construct the calibration curve. Acceptable linear regression was obtained for calibration curves Table 1. The proposed fragmentation for monitoring of 3, 4- MDMA and typical MS spectra profile for the analysis of tablet sample A and internal standard down. The proposed fragmentation for monitoring of Ketamine and typical MS spectra profile for the analysis of tablet sample B up and internal standard down. In order to show the specificity of GC-MS method in Amphetamines measurement, the determinations were carried out in two series; with and without solvent. Only a peak was seen in solution. This peak was not observed in solvent. This feature shows the selectivity of GC-MS method in the amphetamine determination. After construction calibration curves for target compounds, the proposed procedure described above was applied to determine the target analytes in tablet samples. Typical MS spectrum of the diethyl ether extracts of drug samples are shown in Figure 2 - 4. With using information are listed in Table 1 , the amount of present compounds were calculated. Table 2 is shown data of amount impurities found, as a result of GC—MS analysis. The amount of MDMA was different in all samples. The proposed fragmentation for monitoring of Metamphetamine and typical MS spectra profile for the analysis of tablet sample C up and internal standard down. The sensitivity of the MDMA analysis and the specificity of peaks are improved 3 , 5 - 6. The peaks of derivatives are particularly desirable when the mass spectrum of the underivatized molecules is of low diagnostic value. Multi-drug combinations were found only in one tablet sample. In this study, the range of tablets weight was 0. The range of MDMA content was percent mean 90 mg. The tablet weight usually ranges from 40 to mg. The content is differing regionally. MDMA Identification was accomplished by comparing the retention time and mass spectrum of tablet A with standard spectrum. Comparing the retention time MDMA identification was accomplished by comparing the retention time and mass spectrum of standard spectrum. Amphetamine identification was accomplished by comparing the retention time at 1. The MDMA content in tablet samples were ranging from 60— mg. The range of tablets was mg. The MDMA levels were ranging from The results of this study showed MDMA levels ranging from GC technique is a fast analysis that recently coupled with MS. The GC method is not suitable for samples requiring extensive derivitization, as well as for complex samples such as seized samples for an effective separation of the large number of ingredients. The throughput and coverage of unknown samples were significantly improved by this coupling. The efficiency of the extraction process and the identity of MDMA peak were verified This method requires long run times. These times are less in GC-MS. GC-MS provide an appropriate method for large numbers of chemical including abuse drugs in a complex mixture. This technique unifies the separation power and sensitivity of a GC-FID with the analyte specificity of a spectroscopic technique. Therefore this method is able to provide highly specific spectral data on individual compounds in a complex mixture of compounds without prior separation. The present study showed the simultaneous quantification of amphetamine, 3,4-methylenedioxymethamphetamine MDMA , Amphetamine AM and ketamine in tablets. In this research, we used a simple liquid—liquid extraction prior GC-MS analysis. The sample preparation procedures prior to GC include several steps. In order to obtain high extraction recoveries of the drugs, some variables such as pH, extraction time and organic solvent were investigated and optimized. The method was optimized following a one-at-a time variable approach using the peaks area as analytical signals. This study has demonstrated the successful application of GC-MS method for the quantitative and qualitative determination of the multiple illicit drugs. This method is a rapid detective tool in the clinical emergency management. All experiments were applicable in less than half-hour. The experiments require low levels of the sample. The preparation method is minimal and simple. This work not only provides information about MDMA content of ecstasy tablets, but also develops a new method for the fast and regular identification of 3, 4-MDMA impurities in ecstasy tablets. Chemical profiling is able to provide more reliable information than the physical characteristics of the tablets. Also, impurity profiling could reveal the hidden information on the clandestine MDMA laboratory. The Information about the impurities in methamphetamine allowed identification of the drug synthetic routes. We are actively pursuing the identities of the unknown impurities via synthetic approach and will report the outcomes of our efforts in next publication. The study was carried out by Tahere Safarpour as her MSc. The authors thank the staffs of the Faculty of Rasht Azad University and Faculty of Pharmacy, Jundishapur University for their help during carrying out the study. This study was supported by the Research affairs of Jundishapur University. As a library, NLM provides access to scientific literature. Iran J Pharm Res. Find articles by Amir Jalali. Find articles by Amir Hatamie. Find articles by Tahere Saferpour. Find articles by Alireza Khajeamiri. Find articles by Tahere Safa. Find articles by Foad Buazar. Received Sep; Accepted Mar. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.

Impact of Pharmaceutical Impurities in Ecstasy Tablets: Gas Chromatography-Mass Spectrometry Study

Buying MDMA pills online in Rasht

Official websites use. Share sensitive information only on official, secure websites. Despite substantial improvements in the success of treatments through assisted reproduction technologies ART , live birth rates remain constantly low, and practitioners are seeking aetiologic treatments to improve the outcomes. Local inflammatory response is believed to contribute to implantation failure, where prostaglandins may increase uterine contractions and decrease uterine receptivity, decreasing the possibility of an IVF cycle leading to successful embryo transfer. They are often offered in clinical practice to improve ART outcomes, but current robust evidence on their efficacy is lacking. We designed the search using standard Cochrane methods and performed it on databases from their inception to 20 February There were no restrictions by language or country of origin. We used standard methodological procedures recommended by Cochrane. We performed statistical analysis using Review Manager 5. We found 11 RCTs women suitable for inclusion in the review. Most studies were at unclear or high risk of bias. The main limitations in the overall quality of the evidence were high risk of bias, unexplained heterogeneity and serious imprecision and indirectness. There were no data on our primary outcome — live birth per woman randomised — in any review comparisons. The results were similar when two studies were excluded due to high risk of bias. Concerning the secondary outcomes, we are uncertain of an effect on clinical pregnancy rates RR 1. There were no cases of congenital anomalies during antenatal ultrasound screening of the women in one study. Only one study compared piroxicam with indomethacin: we are uncertain of an effect on ongoing pregnancy RR 1. Similar results were reported for clinical pregnancy RR 1. This is based on available data from RCTs, where very low quality evidence showed that there is no single outcome measure demonstrating a benefit with their use. Despite both clinical and laboratory efforts and improvements in the success of these treatments, pregnancy rates remain low. Local inflammatory response is believed to cause implantation difficulties for the embryo, through the action of prostaglandins. These substances mainly cause a differentiated local inflammatory response and uterine contractions during embryo transfer, inhibiting the embryo from implanting successfully. In clinical practice, they are often offered to improve ART outcomes, but evidence is based on various types of studies. Thus because there is lack of clear evidence, their efficacy and safety still remain controversial. In this Cochrane Review we have summarised the available evidence on the use of NSAIDs in infertile women undergoing IVF, in an attempt to identify gaps and limitations in our current understanding. We searched for and included studies irrespective of language and country of origin. Two review authors independently selected and evaluated studies, extracted data, and attempted to contact the authors of studies for which data were missing. We found 11 studies women ; data were not available in one study, so we analysed data on patients; two studies were published as abstracts in international conference reports; and we found one ongoing trial that met our inclusion requirements. Only one study compared piroxicam with indomethacin: we are uncertain of an effect on ongoing pregnancy and on miscarriage. This is based on available data from randomised controlled trials, where no single outcome reported in the studies demonstrated a benefit with their use. This is because of several limitations including poorly reported study methods, imprecision, small study numbers and low numbers of events reported. An IVF cycle involves ovulation stimulation, oocyte retrieval, fertilisation and embryo transfer Speroff With the exception of fertilisation, each of these steps may lead to pain, with a localized inflammatory response and, sometimes, uterine contractions. Studies involving the use of aspirin in ART have not been considered, since a previous review showed clear evidence of no effect of aspirin for this purpose Siristatidis In cells, these enzymes are involved in the synthesis of prostaglandins. Prostaglandins are a group of chemicals produced by various cells in the body. They promote inflammation, pain and fever. The two main adverse drug reactions linked with NSAIDs are gastrointestinal and renal effects, and are associated with the different roles and tissue localisations of each COX isoenzyme Baigent ; Green ; Hawkey Each step of an ART cycle, with the exception of fertilisation, may lead to pain due to the inflammatory reaction. This reaction leads to the production of inflammatory cytokines, which in excess may be detrimental Chaouat Similarly, it is known that an inflammatory response produces prostaglandins locally, which may increase uterine contractions and also decrease uterine receptivity. These products are inexpensive and simple to use, yet remain controversial because of a lack of robust evidence for their efficacy and safety. In this Cochrane Review we have summarised the available evidence on the use of NSAIDs in subfertile women who are undergoing ART and tried to identify any gaps or limitations in our current understanding. Our aim is to provide a clear view on the effectiveness of this pharmacological intervention in order to encourage or disprove its clinical application. All randomised controlled trials, published or unpublished, comparing the relative effectiveness or safety of one of the interventions compared to the other treatment. We did not include the comparison of aspirin versus placebo, as this was the topic of another Cochrane Review Siristatidis Live birth or ongoing pregnancy rate per woman randomised: we defined live birth as delivery of a live fetus after 20 completed weeks of gestation; we defined ongoing pregnancy as a pregnancy beyond 12 weeks of gestation. Miscarriage rate per woman randomised, defined as the number of pregnancies lost before 20 weeks of gestation. Clinical pregnancy rate per woman randomised, defined as evidence of a gestational sac on ultrasound. Adverse effects to the woman per woman randomised: ectopic pregnancy, multiple birth, antenatal and perinatal complications. Adverse fetal effects including fetal anomalies chromosomal, congenital and anatomical abnormalities, preterm labour, growth restriction. Two review authors DV and IM independently conducted a systematic search of the published and unpublished literature. There were no restrictions on language or publication status. We developed the key search terms in accordance with the structured question. We identified synonyms and related terms for each of the PICO elements and added them to the strategy. We identified the relevant subject indexing terms used within individual databases and added them to the strategy as appropriate. We used database facilities, such as truncation, explosion and proximity searching, when they were available. We selected search filters from the ISSG search filter web site, for other databases and to identify systematic reviews www. We sought relevant publications in all languages including full papers and abstracts. Trial registers for ongoing and registered trials: Current Controlled Trials www. PubMed www. Professional societies, organisations and individuals e. We asked external referees who are experts in this field to check the completeness of the search strategy, and to identify any additional, ongoing and planned trials. We handsearched the reference lists from all searched published articles for additional studies. We also contacted experts in the subject area for further references. Similarly, we handsearched the conference proceedings and abstracts not covered in the CGF Specialized Register of Controlled Trials for relevant unpublished reports, theses and any other sources of potentially relevant references or studies, in liaison with the CGF Trials Search Coordinator. This form included details and criteria of all relevant trial characteristics Appendix 9 , Appendix Two review authors AN and DV reviewed titles and abstracts of references for compliance with the inclusion criteria for the review and excluded those considered irrelevant at this screening stage. We sought further information from the study authors when papers contained insufficient information to make a decision about eligibility. We documented the reasons for excluding any studies identified by the search in the ' Characteristics of excluded studies ' table. Two review authors AN and DV independently extracted data from the included studies using the standardized data extraction form Appendix Where there were insufficient data to enable us to make a decision on inclusion or exclusion, we included the trial provisionally and contacted the authors of the trial report for further data on methods or results, or both. AN and CS independently assessed the risk of bias for each trial using Cochrane's 'Risk of bias' assessment tool Higgins We resolved differences of opinion through discussion. We assessed whether adequate steps were taken to reduce the risk of bias across six domains: sequence generation; allocation concealment; blinding of participants, personnel, and outcome assessors ; incomplete outcome data; selective outcome reporting; and other sources of bias. For sequence generation and allocation concealment, we reported the methods used. For blinding, we described who was blinded and the blinding method. For selective outcome reporting, we stated any discrepancies between the methods used and the results, in terms of the outcomes measured or the outcomes reported. For other biases, we described any other trial features that we thought could affect the trial result e. We categorized our judgements as 'low risk of bias', 'high risk of bias', or 'unclear risk of bias', and this information was used to guide our interpretation of the presented data table, which was incorporated into the interpretations of review findings by means of sensitivity analyses. Where our judgement was unclear, we contacted the trial authors for clarification and resolved any differences of opinion through discussion. The 'Risk of bias' tables describe all judgements and present our conclusions; for summaries see Figure 2 and Figure 3. Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies. Methodological quality summary: review authors' judgements about each methodological quality item for each included study. For dichotomous data we used the number of events in the control and intervention groups of each study to calculate the risk ratio RR. There were no continuous data. All analyses were per woman randomised. As we were considering pain as an outcome we anticipated that we would have to convert different pain scales; this, however, was not the case. We assessed the characteristics of the included studies to decide whether there were sufficient similarities — in study populations, methodologies used, comparisons applied vs. If this had been found, we had planned to explore this by means of sensitivity analysis, as described below. We aimed to minimise publication and other biases and their potential impact by ensuring a comprehensive search for eligible studies and by being alert for duplication of data. We gave included trials an identity code, comprising the first author and the year published, and listed them in chronological order in forest plots. The review authors planned the following steps if, after confirming data, they detected substantial heterogeneity. Consider completing a subgroup analysis, according to meaningful factors, such as number of embryos transferred, previous failed cycles, maternal age, duration of treatment; and type of COX inhibitors. If we detected substantial heterogeneity, we explored possible explanations in subgroup analyses e. We took any statistical heterogeneity into account when interpreting the results, especially if there was any variation in the direction of effect. We planned sensitivity analyses for the primary outcomes and clinical pregnancy rates to determine whether the conclusions were robust to arbitrary decisions made regarding the eligibility and analysis. These analyses would have included consideration of whether the review conclusions would have differed if:. This table presents the overall quality of the body of evidence for the main review outcomes live birth, ongoing pregnancy, miscarriage, clinical pregnancy, multiple pregnancy, adverse effects for each comparison. We assessed the quality of the studies using five GRADE criteria: study limitations, consistency of effect, imprecision, indirectness, and publication bias Higgins Two authors independently assessed the quality of the evidence for each outcome. We justified, documented, and incorporated judgements about the quality of the evidence high, moderate, low or very low when reporting the results for each outcome. From the database search we located a total of titles and abstracts that we thought might provide data addressing our question of interest. Eleven proved to be duplicates and were not relevant: we excluded them based on the abstract. There was one ongoing study NCT Of the 11 included studies, two were published as abstracts at conferences Asgharnia ; Fekih see Characteristics of included studies. The included studies involved subfertile women undergoing ART; after subtracting the participants studied in Asgharnia , whose data were not available, we analysed data on women. All IVF cycles were fresh, except from one study, which reported on fresh and frozen embryos Moon Six studies were performed on piroxicam administered at a dosage of 10 mg once at 1 to 2 hours before embryo transfer Asgharnia ; Dal Prato ; Firouzabadi ; Kumbasar ; Moon ; Sohrabvand In one study patients received an oral dose of mg of ibuprofen 90 minutes before embryo transfer Fekih ; in a second, flurbiprofen axetil as a single dose 30 minutes before oocyte retrieval Zhao ; and in a third, sodium dilclofenac suppository was administered at a dosage of mg at the end of oocyte retrieval Kailasam Piroxicam was compared with indomethacin, and the exact interventions have been described above Kumbasar In the comparison between piroxicam versus indomethacin, Kumbasar reported ongoing pregnancy, miscarriage and clinical pregnancy. Of the records identified after removal of duplicates, we excluded studies initially on the basis of the abstract Figure 1. We describe the 'Risk of bias' assessments in detail in the 'Risk of bias' tables in Characteristics of included studies , and in Figure 2 and Figure 3. We made the decisions after sending emails to the study authors in an attempt to retrieve further data. Random sequence generation was at unclear risk of bias in three studies Fekih ; Kumbasar ; Sohrabvand ; at high risk of bias in two Asgharnia ; Sohrabvand ; and at low risk in the rest of the included studies. Blinding of participants was at high risk of bias as it was not performed in one study Dal Prato , where authors stated that it was not possible to provide a placebo, and not described in an abstract Asgharnia , and two full text articles Kumbasar ; Sohrabvand Blinding of outcome assessment was at low risk only in one study Zhao , while most of the studies were at high risk. Reporting bias was low in four studies, and high in the two which were published as abstracts Asgharnia ; Fekih No other sources of bias were identified in four studies Dal Prato ; Firouzabadi ; Kailasam ; Zhao See: Table 1 ; Table 2. There were four studies reporting ongoing pregnancy. Four studies reported this outcome: three of them involved the use of piroxicam Dal Prato ; Firouzabadi ; Kumbasar ; one involved the use of indomethacin Kumbasar ; and one involved the use of ibuprofen Fekih A total of seven studies reported on clinical pregnancy. One study used diclofenac Kailasam ; four used piroxicam Dal Prato ; Firouzabadi ; Kumbasar ; Moon ; one study used indomethacin Kumbasar ; one study used flurbiprofen axetil Zhao ; and one used ibuprofen Fekih There were five studies reporting adverse effects in pregnancy. Only one study involving piroxicam reported this outcome Dal Prato There was no certainty of an effect in ectopic pregnancy when piroxicam was compared to placebo RR 0. Only one study involving piroxicam reported this outcome Firouzabadi There was no certainty of an effect in multiple pregnancy rate when piroxicam was compared to placebo RR 2. In the first study, side effects related to indomethacin included headache, gastrointestinal complaints, nausea and dizziness; in the second, although authors reported the presence of muscle cramps in the control group, there were no events observed in the indomethacin group; in the third study, authors reported no side effects in either compared groups. Apart from the fact that side effects were minimal and different among studies, we are unable to account further for this heterogeneity Analysis 1. There were no congenital anomalies reported during antenatal ultrasound screening in both groups Kumbasar One study compared piroxicam with indomethacin Kumbasar There was no certainty of an effect in ongoing pregnancy when piroxicam was compared with indomethacin RR 1. There was no certainty of an effect in miscarriage when piroxicam was compared with indomethacin RR 1. There was no certainty of an effect in clinical pregnancy when piroxicam was compared with indomethacin RR 1. After analysis of the data, we are uncertain of the effect of NSAIDs on ongoing pregnancy, as the studies were at high risk of bias and pooled estimates were imprecise. Three of them involved the use of piroxicam Dal Prato ; Firouzabadi ; Kumbasar ; one involved the use of indomethacin Kumbasar ; and one involved the use of ibuprofen Fekih After analysis of the data, we are uncertain of the effect of NSAIDs on miscarriage, as the studies were at high risk of bias and pooled estimates were imprecise. We did not find different results when we removed data from RCTs with high risk of bias in our sensitivity analysis for miscarriage and when we performed subgroup analysis of ongoing pregnancy according to the type of NSAID used. There were sparse data for adverse fetal effects, quality of life and relief of pain in this comparison. In the second comparison of this review, we found one study comparing piroxicam with indomethacin Kumbasar : we found very low quality evidence of no certainty of an effect in ongoing pregnancy, miscarriage and clinical pregnancy rates. Data on other secondary outcomes set for this review were not available, apart from the adverse fetal effects that were reported as null in both groups. We included 11 studies with data relevant to the review question and a total of women in this Cochrane Review. Women eligible for randomisation had an average age of less than 35 years; they were defined as infertile women with an expected good prognosis in terms of ovarian response after stimulation. These studies reported on outcomes which included ongoing pregnancy and miscarriage amongst primary outcomes and clinical pregnancy, adverse effects to the woman including ectopic and multiple pregnancy, drugs side effects and fetus chromosomal abnormalities and relief of pain amongst secondary outcomes. Of note: none of them reported on live births. All studies were conducted in an urban setting in IVF units in countries around the world. Participants suffered from infertility from the conventional causes and seemed to be good responders. There were no data on high or poor responders, or in specific categories of infertile patients, such as those with recurrent implantation failures. In addition to the published data collected, we retrieved only a small amount of extra details on the trials after communication with authors: a lot of information is therefore missing in many cases. We had no data on the quality of life in the first comparison and in most of the secondary outcomes in the second. We found 28 potentially eligible studies. Of them, 11 studies were eligible for inclusion and 10 for further analysis. The overall quality ranged from very low for the primary outcomes in both comparisons and from very low to low for the secondary outcomes Table 1 ; Table 2 In addition to the published data collected, we retrieved some extra details by communicating authors of the original studies; specified information remained missing in many cases. Of note: one study was published only as a conference abstract. We found very low quality evidence for the secondary outcome of adverse effects, due to serious risk of bias including poor reporting of methods, attrition bias, selective reporting, and other biases, very serious indirectness, very serious imprecision and wide confidence interval. For fetal congenital abnormalities, we found one very low quality trial at high risk of attrition and reporting biases that investigated both review comparisons. It reported no events in either comparison. We made every effort to identify all eligible studies, following standard Cochrane procedures. We did not identify any potential source of bias, except from the fact that very few trial authors responded to our requests for additional information, and that, understandably, the data could not be retrieved for the ongoing trial. There are no similar reviews to date addressing this comparison. These drugs have been linked in the past with 'reversible female infertility' Stone , and are currently used in medical conditions pain due to endometriosis related to infertility Brown , primary dysmenorrhoea Marjoribanks , and in the management of uterine adenomyosis Vannuccini , amongst others. We found little evidence from properly conducted randomised controlled trials RCTs regarding the use of NSAIDs in infertile women undergoing assisted reproduction, in spite of some promising data in the literature, through their physiology and potential action on localized inflammatory response, delaying or preventing ovulation and uterine contractions during an IVF cycle. Individual studies have concluded that there was a reduction in miscarriage rates using ibuprofen and an improvement in clinical pregnancy rates using piroxicam when compared to placebo , but the synthesis of all included studies showed no evidence to support the use of NSAIDs. This could be due to the small number of eligible studies and variations in dose administration and time of treatment commencement across studies. In secondary outcomes for both comparisons, including clinical pregnancy, adverse effects to the woman and fetus, the quality varied from low to very low. We are awaiting the results of one ongoing trial, but it is unlikely that these could change the results of our review. We identified 11 studies: two were published in the form of abstracts and there was one ongoing study; data were available for 10 of them, including a total of women. After the synthesis of data, we arrived at no robust conclusions concerning their use. Notably, participants so far have been infertile women, relatively young and identified as normal responders to ovarian stimulation. Other subgroups, such as high or poor responders although in the latter there might be a restriction because of the low number of embryos anticipated , or even women with recurrent implantation failures, could be included in the trials. Accurate documentation of the randomisation, allocation concealment, and blinding methods is highly desirable, so that risks of bias could be eliminated and the quality of the conclusions could be at high levels. In addition to the primary outcomes of live birth and miscarriage, study protocols should include the reporting of other adverse effects, and of crucial secondary outcomes. In addition, we thank the authors of all included studies for supplying further information in response to our queries. We also thank Irene Moridi, Mina Mahdian and Miss Babalwa Zani for their contributions to the protocol and to early drafts of this review. Miscarriage rate was moved to the primary outcomes and clinical pregnancy rate was added to the secondary outcomes to provide a more meaningful approach to the research question. Adverse effects of the drugs administered were considered to have had a temporary effect on the quality of life of the patient, thus these were analysed in the relevant section. We conducted analyses using RR instead of OR because this is our preferred analysis method, as we estimate probability and not odds for the specific question of the review; notably, results were not affected using ORs. AN lead author: writing of the protocol, extracting data of included studies, conducting the analysis and drafting the manuscript. DV: extracting data of included studies, conducting the analysis and developing tables and figures. As a library, NLM provides access to scientific literature. Cochrane Database Syst Rev. Find articles by Atunga Nyachieo. Find articles by Charalampos S Siristatidis. Find articles by Dennis Vaidakis. Collection date This article is an update of the article with doi: Open in a new tab. If no then exclude. If yes go to questions 2 Yes No Unclear 2 Participants a Are participants subfertile women subfertile for any cause who were undergoing any form of assisted reproductive therapy ART which will included IVF, intracytoplasmic sperm injection, ovulation induction and intrauterine insemination? Yes No Unclear If 'no', exclude. Otherwise go to question 3. Yes No Unclear If 'no' to a or b , exclude. Final decision Include if all 'yes' Exclude if any 'no' Unclear Excluded or unclear because: If 'unclear', action taken:. Outcome or subgroup title No. Primary outcomes of the review were addressed Selective reporting reporting bias Unclear risk All data were reported and discussed according to the initially stated objectives of the study authors. No protocol provided Other bias Low risk No apparent evidence of other bias. Primary outcomes of the review were addressed Selective reporting reporting bias Unclear risk No protocol provided Other bias Low risk No evidence of any other source of bias. Not examined the primary outcome of interest of this review Selective reporting reporting bias Low risk None. Authors report all initially planned outcomes, including side effects Other bias Low risk No other sources of bias identified. In all participants, ETs were performed on day 2 following OR Outcomes The rates of implantation, ongoing authors define it after 24 weeks and clinical pregnancy and miscarriage. In the fresh ET cycles, the treatment group 94 cycles received an oral dose of 10 mg of piroxicam Brexin; Kolon Inc. In the frozen—thawed ET cycles, 39 cycles received 10 mg of piroxicam orally treatment group and 39 cycles were treated with placebo control group. Duration of infertility was 6. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Piroxicam compared to Indomethacin for assisted reproductive technology. Described as randomised? If yes go to questions 2. Include if all 'yes' Exclude if any 'no' Unclear. Primary outcomes Live birth Ongoing pregnancy number of pregnancies which continued beyond 12 weeks. Primary outcomes: pregnancy rate Secondary outcomes: mean number of oocyte retrieval metaphase II , 2 pn, embryo cleaved, embryo transferred. Ethics: an informed consent form was obtained from each participant Funding: supported by Azad Islamic university Rasht; Mehr Infertility Institute Sample size: not provided No adverse effects reported due to treatment Protocol of the study not provided, the study was published as an abstract in a conference meeting. Ethics: informed consent; approved by Institutional Review Board Funding: not stated Sample size provided No adverse effects reported due to treatment; ectopic pregnancies were reported Protocol of the study not provided. The randomisation list was provided by an external statistician. No blinding performed 'because it was not possible to provide a placebo', as authors stated. No participant was excluded from the final analysis. Primary outcomes of the review were addressed. All data were reported and discussed according to the initially stated objectives of the study authors. No protocol provided. Inclusion: women undergoing IVF because of tubal, male infertility, unexplained, or endometriosis factors Exclusion: not stated Baseline characteristics: not stated. Intervention: 83 women included in fresh ET cycles received an oral dose of mg of ibuprofen 10 drops ; while in the control group, the same number cycles corresponding to the treatment group were treated with placebo. Outcomes reported: pregnancy and implantation rates Secondary outcomes: abortion rates. Authors state that 'They were randomly divided into treatment and control group' in their abstract, but no further details were provided. Authors state that 'Patients and staff were blinded to the treatment' in their abstract. Pirmary outcomes: clinical pregnancy rate fetal heart at 8 weeks Secondary outcomes: implantation rates, multiple pregnancy, biochemical pregnancy, miscarriage rates. Ethics: written informed consent; approved by Institutional Review Board Funding: not stated Protocol: not stated. Participants and staff were blinded to the treatment, authors stated. No participant was lost and all data were reported. Norethisterone Pharmacia, UK 5 mg twice daily was administered orally for 7 days from day 19 of the preceding cycle to reduce the incidence of functional ovarian cysts Long luteal phase protocol. Ethics: the study was conducted following approval from the local research ethics committee and participants gave written informed consent for all clinical procedures Funding: not mentioned Protocol: not mentioned The study was performed at Centre for Reproductive Medicine, University of Bristol. A block randomisation list was used in order to balance the number receiving diclofenac sodium versus no treatment controls after every 20 women enrolled. Participants and nurses were blinded as regards diclofenac sodium administration. Not examined the primary outcome of interest of this review. Authors report all initially planned outcomes, including side effects. No other sources of bias identified. Intervention: the participants were divided randomly into 3 groups. In all participants, ETs were performed on day 2 following OR. The rates of implantation, ongoing authors define it after 24 weeks and clinical pregnancy and miscarriage. Also, authors reported adverse effects resulting from the use of piroxicam or indomethacin, and congenital anomalies observed during antenatal ultrasound screening. Auhtors stated that the participants were divided randomly into 3 groups, but no further information was available. Primary outcomes: implantation rate and clinical pregnancy rate Secondary outcomes: not reported. Author's response: centralized randomisation process; computer generated. Authors did not address the primary outcomes of interest of this review. Inclusion: women qualifying for IVF between 18 and 36 years and who had an ovulatory cycle between 26 and 35 days; no ovarian cysts; no previous IVF treatments except when this treatment had resulted in an ongoing pregnancy ; no contraindications for the use of indometacin e. Embryo transfer was performed on the 3rd day after OR. Randomisation done using SPSS statistical software with block randomisation. Participants and physicians unaware of treatment allocation. Authors include primary endpoints of this review and side effects. All primary and secondary outcomes were reported including adverse events. Trial funded by pharmaceutical company and the role of the funder was not described The sample size was calculated for the primary endpoint. Primary outcomes: biochemical pregnancy, abdominal muscle cramps Secondary outcomes: not mentioned. Not described and no response from authors on random sequence generation. Author's response: sealed, opaque, sequentially numbered, identical envelopes. Double blind mentioned though not described in detail how it was done. No missing participants, but the primary outcomes of the review were not included. Inclusion: age group of 20 to 35 years old and with ART indication due to tubal factors, ovulation disorders or severe male factor Exclusion: systemic diseases and endometriosis 50 women randomised. Intervention: Group A received piroxicam 10 mg, Tolid Daru, Iran orally 30 minutes before embryo transfer and group B did not use any form of medication which is the conventional method used control group. Mentioned in the text, but no further data are available. No missing participants, but the primary outcomes of the review were not addressed. Participants were prospectively allocated to 2 groups, the flurbiprofen axetil group FA group or the placebo group control group. Primary outcome parameters: pregnancy rate clinical Secondary outcomes: consumption of analgesic rescue, the number and grading of body movements during the procedure, postoperative pain score, and biomarker PGE2 concentration in follicular fluid, consumption of tramadol after being discharged. Provided by sealed envelopes from a nurse who was not involved in the actual conduct of the study. The study coordinator, attending anaesthesiologist, data collection resident, and the participants were all unaware of treatment group assignment. Akande Aldeery Bernabeu Bou Nemer Kadoch Kawachiya Lier Matsota Mesen Mialon Sallam Inadequate and vague description of methodology and results. Sarhan Seidler Shah Nawaz Study type: interventional clinical trial Allocation: randomised Intervention model: parallel assignment Masking: none open label Primary purpose: prevention. Endometrial pathology. Experimental: indomethacin 1 dose of indomethacin mg rectal suppository will be administered 1 to 2 hours before embryo transfer No intervention: no medication No indomethacine before embryo transfer.

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