Vasodilators for women undergoing fertility treatment.

BACKGROUND: The rate of successful pregnancies brought to term has barely increased since the first assisted reproductive technology (ART) technique became available. 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 pregnancy. 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 Gynaecology and Fertility Group (CGF) Specialised Register of controlled trials, the Cochrane Central Register of of Controlled Trials, via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, the Open System for Information on Grey Literature in Europe (OpenSIGLE), the Latin American and Caribbean Health Science Information Database (LILACS), clinical trial registries, and the reference lists of relevant articles. We conducted the search in October 2017 and applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing vasodilators alone or in combination with other treatments versus placebo or no treatment or versus other agents in women undergoing fertility treatment. DATA COLLECTION AND ANALYSIS: Four review authors independently selected studies, assessed risk of bias, extracted data, and calculated risk ratios (RRs). We combined study data using a fixed-effect model and assessed evidence quality using Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) methods. Our primary outcomes were live birth or ongoing pregnancy and vasodilator side effects. Secondary outcomes included clinical pregnancy, endometrial thickness, multiple pregnancy, miscarriage, and ectopic pregnancy. MAIN RESULTS: We included 15 studies with a total of 1326 women. All included studies compared a vasodilator versus placebo or no treatment. We judged most of these studies as having unclear risk of bias. Overall, the quality of evidence was low to moderate for most outcomes. The main limitations were imprecision due to low numbers of events and participants and risk of bias due to unclear methods of randomisation.Vasodilators probably make little or no difference in rates of live birth compared with placebo or no treatment (RR 1.18, 95% confidence interval (CI) 0.83 to 1.69; three RCTs; N = 350; I² = 0%; moderate-quality evidence) but probably increase overall rates of side effects including headache and tachycardia (RR 2.35, 95% CI 1.51 to 3.66; four RCTs; N = 418; I² = 0%; moderate-quality evidence). Evidence suggests that if 236 per 1000 women achieve live birth with placebo or no treatment, then between 196 and 398 per 1000 will do so with the use of vasodilators.Compared with placebo or no treatment, vasodilators may slightly improve clinical pregnancy rates (RR 1.45, 95% CI 1.19 to 1.77; 11 RCTs; N = 1054; I² = 6%; low-quality evidence). Vasodilators probably make little or no difference in rates of multiple gestation (RR 1.15, 95% CI 0.55 to 2.42; three RCTs; N = 370; I² = 0%; low-quality evidence), miscarriage (RR 0.83, 95% CI 0.37 to 1.86; three RCTs; N = 350; I² = 0%; low-quality evidence), or ectopic pregnancy (RR 1.48, 95% CI 0.25 to 8.69; two RCTs; N = 250; I² = 5%; low-quality evidence). All studies found benefit for endometrial thickening, but reported effects varied (I² = 92%) and ranged from a mean difference of 0.80 higher (95% CI 0.18 to 1.42) to 3.57 higher (95% CI 3.01 to 4.13) with very low-quality evidence, so we are uncertain how to interpret these results. AUTHORS' CONCLUSIONS: Evidence was insufficient to show whether vasodilators increase the live birth rate in women undergoing fertility treatment. However, low-quality evidence suggests that vasodilators may slightly increase clinical pregnancy rates. Moderate-quality evidence shows that vasodilators increase overall side effects in comparison with placebo or no treatment. Adequately powered studies are needed so that each treatment can be evaluated more accurately.

Identification and description of controlled clinical trials published in Spanish Gynaecology and Obstetrics journals and risk of bias assessment of trials on assisted reproductive techniques.

OBJECTIVES: To identify and describe controlled clinical trials (CCTs) published in Spanish Gynaecology and Obstetrics journals. In addition, to assess the quality of the CCTs on Assisted Reproduction Techniques (ART) identified in this project. STUDY DESIGN: In order to identify eligible CCTs, all Spanish Gynaecology and Obstetrics journals were handsearched. Handsearching was conducted following the guidelines provided by the Cochrane Collaboration, which state that each journal article must be carefully reviewed, including original articles and other types of studies, letters to the editor, abstracts, and conference presentations. The results of the handsearching process were compared with an electronic search conducted in MEDLINE (PubMed). A descriptive analysis of the main characteristics of the identified CCTs was performed, as well as a methodological assessment of CCTs on ART. RESULTS: Sixteen Gynaecology and Obstetrics journals were identified, four of which have been indexed in MEDLINE at some point, although not currently. The journal with the most CCTs was "Progresos de Obstetricia y Ginecología". A total of 235 CCTs were published in these journals, of which 29 were on ART. Most CCTs (216, 91.9%) were carried out in a hospital setting; 201 (89.4%) were unicentric. Obstetrics was the most studied subspecialty (46.4%). Among CCTs on ART, the risk of bias was predominantly high. CONCLUSIONS: The number of CCTs published in Spanish Gynaecology and Obstetrics journals is limited. CCTs on ART present deficiencies in the report of results and low methodological quality. It is advised that authors and journals adhere to the CONSORT statement and to the Cochrane Collaboration recommendations to reduce risk of bias when designing and disseminating research projects.

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.