***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND : Management of repeated implantation failure despite transfer of good- quality embryos still remains a dilemma for ART specialists . Scrapping of endometrium in the nontransfer cycle has been shown to improve the pregnancy rate in the subsequent IVF/ET cycle in recent studies . AIM : The objective of this r and omized controlled trial ( RCT ) was to determine whether endometrial injury caused by Pipelle sampling in the nontransfer cycle could improve the probability of pregnancy in the subsequent IVF cycle in patients who had previous failed IVF outcome . SETTING : Tertiary assisted conception center . DESIGN : R and omized controlled study . MATERIAL S AND METHODS : 100 eligible patients with previous failed IVF despite transfer of good- quality embryos were r and omly allocated to the intervention group and control groups . In the intervention group , Pipelle endometrial sampling was done twice : One in the follicular phase and again in the luteal phase in the cycle preceding the embryo transfer cycle . OUTCOME MEASURE : The primary outcome measure was live birth rate . The secondary outcome measures were implantation and clinical pregnancy rates . RESULTS : The live birth rate was significantly higher in the intervention group compared to control group ( 22.4 % and 9.8 % P = 0.04 ) . The clinical pregnancy rate in the intervention group was 32.7 % , while that in the control group was 13.7 % , which was also statistically significant ( P = 0.01 ) . The implantation rate was significantly higher in the intervention group as compared to controls ( 13.07 % vs 7.1 % P = 0.04 ) . CONCLUSIONS : Endometrial injury in nontransfer cycle improves the live birth rate , clinical pregnancy and implantation rates in the subsequent IVF-ET cycle in patients with previous unsuccessful IVF cycles Stopping r and omized trials early because of an apparent benefit is a growing phenomenon . A recent systematic review found that the number of r and omized trials stopped early for benefit has more than doubled since 1990 ( 1 ) . To protect and promote the interests of trial participants , investigators may feel ethically obligated to stop a trial early because of the unexpected harm or apparent benefit of a study treatment . If a study treatment 's benefit far outweighs its adverse effects , is it not unethical to continue enrolling patients in a trial in which , as is typically the case , patients have a 50 % chance of receiving a placebo or an inferior treatment ? In this article , we argue that stopping a r and omized trial early for apparent benefit is often unethical and can be justified only under restricted circumstances . If the scientific community were to accept our arguments , then the approach that investigators , institutional review boards , and data monitoring committees take to the practice of stopping trials early for apparent benefit would substantially change . Ethical Considerations Emanuel and colleagues ( 2 ) describe a framework of 7 requirements for determining whether clinical research is ethical . We use this framework to identify and assess the ethical issues raised by stopping trials early because of apparent benefit ( Table ) . Table . Ethical Violations Result ing from Stopping a Trial Early for Apparent Benefit Scientific Validity The purpose of a trial of alternative interventions is to generate an estimate of treatment effect that closely approximates the true effect and is not misleading . This requires application of scientific procedures that yield valid and reliable data and thus minimize both systematic and r and om error . A systematic review of r and omized trials stopped early for apparent benefit ( 1 ) found that many of the trials yielded implausibly large treatment effects ; the median relative risk was 0.53 . Apparent large treatment effects occurred much more frequently when trials accrued only a small number of events . The odds of a treatment effect larger than the overall median relative risk of 0.53 was 28 times greater ( 95 % CI , 11 to 73 ) among trials in which fewer than the median of 66 events accrued than among trials in which more events accrued . These results , which are consistent with predictions from statistical theory ( 3 ) , suggest that stopping trials early for apparent benefit will systematic ally overestimate treatment effects . The scientific validity of trials that are stopped early is further compromised when trials yield inconclusive data about outcomes that did not influence trial truncation but are nonetheless important to patients , such as disease-free survival , symptom control , quality of life , and adverse effects of treatment . For example , a trial of vitamin E supplementation in premature newborns that was stopped early because of an apparent reduction in  intracranial hemorrhage  ( 4 ) failed to detect the increase in sepsis associated with vitamin E supplementation that subsequent trials identified ( 5 ) . Social or Scientific Value and Favorable RiskBenefit Ratio It is underst and able that investigators focus their ethical obligations on research participants . Such focus , however , risks neglecting obligations to society . The tendency of truncated trials to overestimate the effect of a treatment on the end point that result ed in trial truncation and to yield insufficient data about other important outcomes endangers the wider community to whom the results will be applied ( 6 ) . On review ing the results of a truncated trial , astute clinicians might appropriately conclude that the benefits of the intervention remain uncertain . However , less skeptical clinicians might assume that the results are true and inappropriately expose patients to the intervention and its unknown harms . Consider the results of a trial in which the investigators continued to enroll patients even though prespecified criteria for early stopping were met . Two interim analyses of a r and omized trial of 5 versus 4 courses of chemotherapy in patients with acute myeloid leukemia ( 7 ) found apparent large benefits to the 5-course regimen ( relative odds reduction of 53 % [ CI , 23 % to 71 % ; P= 0.003 ] in the first analysis and 45 % [ CI , 20 % to 62 % ; P= 0.0002 ] in the second analysis ) . Finding these results too good to be true , the data monitoring committee recommended continuing the trial , which ultimately showed a trend in favor of the 4-course regimen . Had the investigators terminated the trial in accordance with their stopping rule , subsequent patients with leukemia may have experienced the toxicity of an additional course of chemotherapy without benefit . Harm result ing from the misleading findings of truncated trials can be compounded if the findings influence the recommendations of clinical practice guideline panels . Investigators conducting a trial that involved patients undergoing vascular surgery ( 8) stopped the trial early when 2 of 53 patients r and omly assigned to receive the -blocker bisoprolol and 18 of 59 control patients had major cardiovascular events ( relative risk reduction , 90 % [ CI , 59 % to 98 % ] ) . These results contributed to recommendations by the American Heart Association and the American College of Cardiology favoring administration of -blockers to patients with cardiac risk factors who were undergoing noncardiac surgery ( 9 ) . However , these results contradict those of 2 much larger subsequently published trials , neither of which suggested that -blockers reduce cardiac risk in patients undergoing noncardiac surgery ( 10 , 11 ) . Further social detriment may occur when clinicians compromise the ability of others to conduct more definitive studies by placing undue confidence in the results of a truncated trial . Investigators ( including 2 contributors to this article ) who obtained funding for a trial of -blockers in noncardiac surgery with an enrollment target of 10000 patients ( 12 ) faced challenges in persuading clinicians that the question remained unanswered . Participant Consent and Respect for Participants Key prerequisites for informed consent include the participant 's decision-making capacity and voluntariness and whether he or she had received adequate information to decide that participation in the research was in alignment with his or her values and goals . However , informed consent is not a single event , but it is an ongoing collaboration between participants and investigators . When important changes occur during a trial , investigators should inform participants of the changes . One justification for stopping a trial early for benefit is to inform study participants of the preliminary results and offer them the superior treatment . According to this argument , uncertainty about the relative merits of alternative interventions ( equipoise ) has been lost and informed clinicians and patients will overwhelmingly choose the superior treatment ( 13 ) . However , as we have pointed out , the astute clinician or patient may remain skeptical about a treatment 's apparent benefits if the findings come from a truncated trial . Unfortunately , many clinicians and even more patients probably will not have the knowledge and underst and ing to appropriately interpret the results . Disclosing interim results to study participants may therefore prove misleading . Furthermore , if investigators were to continue a trial after informing patients of the interim results , patients would be unblinded and may cross over or leave the trial . These behaviors create problems in interpreting trial results by further weakening inferences about the efficacy and safety of the intervention and compromising the ethical requirement of scientific validity . Finally , stopping a trial early does not guarantee that current and potential trial participants will receive the apparently beneficial treatment ( assuming that one believes they should ) . Studies of dissemination of new treatments reveal that long delays , such as those between reports of r and omized trials and recommendations of experts in review articles and textbooks , are common ( 14 ) . Continuing a 2-group trial gives participants at least a 50 % chance of receiving the experimental treatment , whereas if the trial is stopped early , the probability that participants will receive the treatment due to rapid dissemination is likely to be considerably less than 50 % . Independent Review Trials may have stopping rules that allow early termination because of genuine ( although misguided ) ethical concerns . However , investigators , trial sponsors , journals , and patients may all have additional motives for stopping trials early for apparent benefit . For example , truncated trials that report a large treatment effect tend to be published in the most prestigious medical journals ( 1 ) , which enhances the careers of the investigators and increases the likelihood that they will receive grants . Funding agencies have an interest in stopping trials early to minimize research costs . Pharmaceutical and for-profit sources that financially support trials are interested not only in controlling costs but also in the publicity and market share that result from reporting a trial stopped early for apparent benefit . Medical journals are interested in these trials because of publicity and citations , which result in increased journal impact factor , prestige , and advertising revenue . And patients and their advocates are motivated to stop a trial early when the experimental intervention is promising in order to hasten delivery of the intervention to clinical practice . All of these motives may affect investigators ' decisions and encourage an inappropriately early stop to a trial . These considerations m and ate that institutional review boards and data monitoring committees underst and the principles outlined in this article and insist on appropriate st and ards for stopping a trial early for apparent benefit to maintain the ethical integrity of clinical trials . Aim : To evaluate the effect of local injury to the endometrium during spontaneous menstrual cycles before in vitro fertilization ( IVF ) treatment on implantation and pregnancy rates in women with recurrent implantation failure ( RIF ) . Methods : In a prospect i ve r and omized controlled trial ( RCT ) , a total of 36 patients , with RIF undergoing IVF  , were r and omized to two groups . In 18 patients , endometrial biopsies were performed using a pipelle curette on days 9–12 and 21–24 of the menstrual cycle preceding IVF treatment . In 18 control patients , a cervical pipelle was performed . Results : The implantation rate ( 2.08 % versus 11.11 % ; p = 0.1 ) , clinical ( 0 % versus 31.25 % ; p < 0.05 ) and live births rates ( 0 % versus 25 % ; p = 0.1 ) were lower in the experimental group compared with controls . Conclusion : Our RCT did not find any benefit from local injury to the endometrium in women with a high number of RIFs . Further studies are warranted to better define the target population of patients who may benefit from this procedure OBJECTIVE To investigate the effect of endometrial injury on the clinical pregnancy rate in normoresponders undergoing long agonist protocol intracytoplasmic sperm injection ( ICSI ) cycles with single embryo transfer . STUDY DESIGN Prospect i ve case-control study . METHODS One hundred and eighteen women ( age < 35 years , normoresponders with Grade I or II embryos for transfer ) were included . Women in the intervention group ( n=56 ) underwent endometrial biopsy on Day 3 of the menstrual cycle following downregulation . Women in the control group ( n=62 ) did not undergo endometrial biopsy . RESULTS The clinical and embryological characteristics were comparable in the two groups , and no significant difference was found in the fertilization rates ( 66.32 % in the intervention group vs. 70.23 % in the control group ) . The clinical pregnancy rate was 48.2 % in the intervention group and 29.0 % in the control group ( p=0.025 ) . Endometrial injury may increase the clinical pregnancy rate ( odds ratio 2.27 ) . The ' take home baby ' rates were 33.9 % and 17.7 % in the intervention and control groups , respectively ( p=0.035 ) . CONCLUSION Assisted reproductive technology treatment that is preceded by endometrial injury may increase the clinical pregnancy rate in women undergoing long agonist protocol ICSI cycles with single embryo transfer OBJECTIVE To study whether an injury-induced inflammation might be the mechanism underlying the favorable effect of endometrial biopsy on the implantation rate in in vitro fertilization ( IVF ) patients . DESIGN Controlled clinical study . SETTING A medical center IVF unit and a research institute . PATIENT(S ) Women undergoing IVF who had previous failed treatment cycles . INTERVENTION(S ) Endometrial sample s were collected from two groups of patients on day 21 of their spontaneous menstrual cycle . The experimental , but not the control group underwent prior biopsy treatment on days 8 or/ and 11 to 13 of that same cycle . MAIN OUTCOME MEASURE(S ) Abundance of immune cells 
    Output:
    
Moderate- quality evidence indicates that endometrial injury performed between day 7 of the previous cycle and day 7 of the embryo transfer ( ET ) cycle is associated with an improvement in live birth and clinical pregnancy rates in women with more than two previous embryo transfers .
There is no evidence of an effect on miscarriage , multiple pregnancy or bleeding .
The procedure is mildly painful .
Endometrial injury on the day of oocyte retrieval is associated with a reduction of clinical and ongoing pregnancy rates .