Vasodilators for women undergoing fertility treatment.

BACKGROUND: Since 1978, when Patrick Steptoe and Robert Edwards achieved the birth of the first test tube baby, assisted reproductive techniques have been refined and improved. However, the rate of successful pregnancies brought to term has barely increased. Therefore closer evaluation of the interventions is needed along with working towards improving uterus receptivity. Vasodilators have been proposed to increase endometrial receptivity, thicken the endometrium and favour uterine relaxation, all of which could improve uterine receptivity and enhance the chances for successful assisted pregnancies. OBJECTIVES: To evaluate the effectiveness and safety of vasodilators in women undergoing fertility treatment. SEARCH METHODS: We searched the following electronic databases, trial registers and websites: the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of controlled trials, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, Web of Knowledge, the Open System for Information on Grey Literature in Europe (OpenSIGLE), the Latin American and Caribbean Health Science Information Database (LILACS) and ClinicalTrials.gov. The search was conducted in February 2014. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) of vasodilators alone or in combination with other treatments compared with placebo or with other agents in women undergoing fertility treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, assessed the risk of bias and extracted data. Risk ratios (RRs) were calculated using the numbers of events in the control and intervention groups of each study. Study data were combined using a random-effects model, and evidence quality was assessed using Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) methods. MAIN RESULTS: Ten studies with a total of 797 women were included in this review. Most of the studies were judged as having an unclear risk of bias. Three studies reported live births, two reported vasodilator-related side effects, 10 reported clinical pregnancies (diagnosed by differing criteria) and four reported other side effects (multiple gestation, miscarriage, ectopic pregnancy).Overall, no evidence suggested that treatment with vasodilators increased live birth rates compared with placebo or no treatment (RR 1.18, 95% confidence interval (CI) 0.82 to 1.69, P value 0.37, three RCTs, 350 women, I(2) = 0%, moderate-quality evidence). This indicates that among women undergoing fertility treatment who have a 24% chance of live birth without the use of vasodilators, between 19% and 40% will achieve live birth with the use of vasodilators.No evidence was found of a difference between vasodilators and placebo or no treatment in the incidence of treatment side effects (RR 1.63, 95% CI 0.33 to 7.93, P value 0.55, two RCTs, 258 women, I(2) = 32%, low-quality evidence). Nor did any evidence show a difference between them in terms of multiple gestation, spontaneous abortion/miscarriage or ectopic pregnancy rates. However few relevant data were available.Overall, treatment with vasodilators was associated with an increased clinical pregnancy rate compared with placebo or no treatment (RR 1.38, 95% CI 1.00 to 1.92, P value 0.05, eight RCTs, 717 women, I(2) = 0%, low-quality evidence). However, confidence intervals do not rule out no effect of the intervention, and when studies of vasodilators combined with another medication (vitamin E or oestrogen) were excluded, the effects of treatment with vasodilators alone on clinical pregnancy rates were more uncertain.The evidence was of low or moderate quality, and the main limitations were imprecision and lack of clarity about study methods. Risk of publication bias could not be assessed because of the low number of identified studies. AUTHORS' CONCLUSIONS: Evidence was insufficient to show that vasodilators increased the live birth rate in women undergoing fertility treatment. However, low-quality evidence suggests that vasodilators may increase clinical pregnancy rates in comparison with placebo or no treatment. Evidence was insufficient to show whether any particular vasodilator, administered alone or in combination with other active medications, was superior, and evidence was insufficient to allow the review authors to reach any conclusions regarding adverse effects. Adequately powered studies are needed so that each treatment can be evaluated more accurately.

Physicians and patients' motivations to perform elective single or double-embryo transfers: A nationwide survey.

OBJECTIVES: To evaluate motivations to perform an elective single embryo transfer (e-SET). METHODS: Cross-sectional surveys to reproductive medicine specialists and to infertile patients undergoing assisted reproductive treatments. RESULTS: In the physician's survey (n = 278), we found that the main reasons for not offering e-SET were the physicians' belief that patients prefer optimizing the pregnancy rates regardless of the potential complications (57.1%). Regarding the decision making process, 76.7% of physicians thought that patients and doctors should make these decisions together and 93.3% would like to have a more formal decision-aid to help with counseling. In the patients' survey (n = 100), 21.3% chose e-SET, while 33% mentioned that complications associated to multiple pregnancies were insufficiently discussed. Among those patients, none chose to have e-SET, while 30% of those who had a full discussion selected e-SET (p = 0.05). CONCLUSIONS: Most physicians did not offer e-SET based on potential patients' negative feelings. Also, almost 30% take important decisions without the patient's participation. Patients that discussed more thoroughly this topic, more frequently selected e-SET. Almost all the physicians surveyed agreed that decision-aids could help in this important shared-decision process. PRACTICE IMPLICATIONS: Decision aids about e-SET vs DET are needed to help patients in the decision making process.

Quality of reporting in infertility journals.

OBJECTIVE: To evaluate whether fertility and top gynecology journals indexed in PubMed require the use of reporting guidelines and to identify the percentage of randomized controlled trials (RCTs) published in 2013 that were written following CONSORT guidelines in the top four fertility journals (by their highest impact factor). DESIGN: Cross-sectional study evaluating instructions for authors and RCTs published in fertility journals. SETTING: Academic institution. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Proportion of instruction-for-authors documents that suggested or required the use of reporting guidelines, and proportion of RCTs published in 2013 that accomplished the CONSORT checklist. RESULT(S): In 47% (16/34) of the journals one or more reporting guidelines were mentioned in the instructions for authors' documents. PRISMA and CONSORT were the most commonly mentioned reporting guidelines. None of the analyzed RCTs completed the 25 items of CONSORT guideline. Sequence generation or allocation concealment was not described in 69% of the studies. One-third of the journals did not publish a flowchart, 72% did not show relative and absolute size-effect measures, and 42% did not use measures of imprecision. In the summaries, 42% did not discuss the limitations of the study and 78% did not mention the generalizability of the results. CONCLUSION(S): Less than half of the analyzed peer-reviewed journals request the authors to use reporting guidelines. Nevertheless, among the top fertility and gynecology journals, reporting guidelines are widely mentioned. Overall, accomplishment of CONSORT items was suboptimal. Editorial boards, reviewers, and authors should join efforts to improve the quality of reporting.

Assessment of research quality in major infertility journals.

OBJECTIVE: To evaluate the level of evidence published in infertility journals with the highest impact factors. DESIGN: Systematic review. We searched in PubMed identifying potential systematic reviews with meta-analysis (SRs) and randomized controlled trials (RCTs) between 2006 and 2010 in the five fertility journals with highest impact factor. SETTING: Academic institution. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): Number and proportion of potential SRs and RCTs published in 2006-2011, and quality assessment of real RCTs published in 2010. RESULT(S): Among evaluated articles, 1.5% and 6.8% were SRs and RCTs. Fertility and Sterility has been the journal with more potential SRs and RCTs, and Human Reproduction Update was the only one with an increasing trend in the number of potential SRs (from 5.3% in 2006 to 24.4% in 2011). Among confirmed RCTs, for each quality assessment item, between 50% and 85% were classified as having low risk of bias, and the most common high risk of bias was related to allocation concealment. Only 23% had a trial registration, which were associated with higher quality assessment classifications. Only 10% of RCTs reported pharmaceutical industry funding. CONCLUSION(S): This is the first study assessing the methodologic quality of publications in the top five fertility journals. More than 90% of all the publications were neither SRs nor RCTs. It is remarkable that the risk of bias was generally low. Enhancing trial registration and funding source statements represent opportunities to improve the quality of reporting. We hope this information is useful to researchers, editorial boards, and clinicians moving forward with research in our field.