Marian Showell

The impact of body mass index on semen parameters and reproductive hormones in human males: a systematic review with meta-analysis

BACKGROUND It has been suggested that body mass index (BMI), especially obesity, is associated with subfertility in men. Semen parameters are central to male fertility and reproductive hormones also play a role in spermatogenesis. This review aimed to investigate the association of BMI with semen parameters and reproductive hormones in men of reproductive age. METHODS MEDLINE, EMBASE, Biological Abstracts, PsycINFO and CINAHL databases and references from relevant articles were searched in January and February 2009. Outcomes included for semen parameters were sperm concentration, total sperm count, semen volume, motility and morphology. Reproductive hormones included were testosterone, free testosterone, estradiol, FSH, LH, inhibin B and sex hormone binding globulin (SHBG). A meta-analysis was conducted to investigate sperm concentration and total sperm count. RESULTS In total, 31 studies were included. Five studies were suitable for pooling and the meta-analysis found no evidence for a relationship between BMI and sperm concentration or total sperm count. Overall review of all studies similarly revealed little evidence for a relationship with semen parameters and increased BMI. There was strong evidence of a negative relationship for testosterone, SHBG and free testosterone with increased BMI. CONCLUSIONS This systematic review with meta-analysis has not found evidence of an association between increased BMI and semen parameters. The main limitation of this review is that data from most studies could not be aggregated for meta-analysis. Population-based studies with larger sample sizes and longitudinal studies are required.

Methodological Quality of Systematic Reviews in Subfertility: A Comparison of Two Different Approaches

Background Systematic reviews are used widely to guide health care decisions. Several tools have been created to assess systematic review quality. The measurement tool for assessing the methodological quality of systematic reviews known as the AMSTAR tool applies a yes/no score to eleven relevant domains of review methodology. This tool has been reworked so that each domain is scored based on a four point scale, producing R-AMSTAR. Methods and Findings We aimed to compare the AMSTAR and R-AMSTAR tools in assessing systematic reviews in the field of assisted reproduction for subfertility. All published systematic reviews on assisted reproductive technology, with the latest search for studies taking place from 2007–2011, were considered. Reviews that contained no included studies or considered diagnostic outcomes were excluded. Thirty each of Cochrane and non-Cochrane reviews were randomly selected from a search of relevant databases. Both tools were then applied to all sixty reviews. The results were converted to percentage scores and all reviews graded and ranked based on this. AMSTAR produced a much wider variation in percentage scores and achieved higher inter-rater reliability than R-AMSTAR according to kappa statistics. The average rating for Cochrane reviews was consistent between the two tools (88.3% for R-AMSTAR versus 83.6% for AMSTAR) but inconsistent for non-Cochrane reviews (63.9% R-AMSTAR vs. 38.5% AMSTAR). In comparing the rankings generated between the two tools Cochrane reviews changed an average of 4.2 places, compared to 2.9 for non-Cochrane. Conclusion R-AMSTAR provided greater guidance in the assessment of domains and produced quantitative results. However, there were many problems with the construction of its criteria and AMSTAR was much easier to apply consistently. We recommend that AMSTAR incorporates the findings of this study and produces additional guidance for its application in order to improve its reliability and usefulness.

Methodological quality of systematic reviews in subfertility: a comparison of Cochrane and non-Cochrane systematic reviews in assisted reproductive technologies

STUDY QUESTION Are there differences in the methodological quality of Cochrane systematic reviews (CRs) and non-Cochrane systematic reviews (NCRs) of assisted reproductive technologies? SUMMARY ANSWER CRs on assisted reproduction are of higher methodological quality than similar reviews published in other journals. WHAT IS KNOWN ALREADY The quality of systematic reviews varies. STUDY DESIGN, SIZE AND DURATION This was a cross-sectional study of 30 CR and 30 NCR systematic reviews that were randomly selected from the eligible reviews identified from a literature search for the years 2007-2011. MATERIALS, SETTING AND METHODS We extracted data on the reporting and methodological characteristics of the included systematic reviews. We assessed the methodological quality of the reviews using the 11-domain Measurement Tool to Assess the Methodological Quality of Systematic Reviews (AMSTAR) tool and subsequently compared CR and NCR systematic reviews. MAIN RESULTS AND THE ROLE OF CHANCE The AMSTAR quality assessment found that CRs were superior to NCRs. For 10 of 11 AMSTAR domains, the requirements were met in >50% of CRs, but only 4 of 11 domains showed requirements being met in >50% of NCRs. The strengths of CRs are the a priori study design, comprehensive literature search, explicit lists of included and excluded studies and assessments of internal validity. Significant failings in the CRs were found in duplicate study selection and data extraction (67% meeting requirements), assessment for publication bias (53% meeting requirements) and reporting of conflicts of interest (47% meeting requirements). NCRs were more likely to contain methodological weaknesses as the majority of the domains showed <40% of reviews meeting requirements, e.g. a priori study design (17%), duplicate study selection and data extraction (17%), assessment of study quality (27%), study quality in the formulation of conclusions (23%) and reporting of conflict of interests (10%). LIMITATIONS, REASONS FOR CAUTION The AMSTAR assessment can only judge what is reported by authors. Although two of the five authors are involved in the production of CRs, the risk of bias was reduced by not involving these authors in the assessment of the systematic review quality. WIDER IMPLICATIONS OF THE FINDINGS Not all systematic reviews are equal. The reader needs to consider the quality of the systematic review when they consider the results and the conclusions of a systematic review. STUDY FUNDING/COMPETING INTEREST(S) There are no conflicts with any commercial organization. Funding was provided for the students by the summer studentship programme of the Faculty of Medical and Health Sciences of the University of Auckland.

Outcome reporting across randomised controlled trials evaluating therapeutic interventions for pre‐eclampsia

Standardising outcome collection and reporting in pre‐eclampsia trials requires an appraisal of current outcome reporting.

Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation

Randomised trials and their syntheses in meta‐analyses offer a unique opportunity to assess the frequency and severity of adverse reactions.

Management of ovarian stimulation for IVF: narrative review of evidence provided for World Health Organization guidance

In this paper, a review of evidence provided to the World Health Organization (WHO) guideline development, who prepare global guidance on the management of ovarian stimulation for women undergoing IVF, is presented. The purpose of ovarian stimulation is to facilitate retrieval of multiple oocytes during a single IVF cycle. Availability of multiple oocytes compensates for inefficiencies in subsequent stages of the cycle, which include oocyte maturation, IVF, embryo culture, embryo transfer, and implantation. Multiple embryos can be transferred in most women, and spare embryos can be frozen to allow for future chances of pregnancy without the need for repeated ovarian stimulation and oocyte retrieval. Our evidence synthesis team addressed 10 clinical questions on management of ovarian stimulation for IVF, prepared a narrative review of the evidence and drafted recommendations to be considered through WHO guideline development processes. Our main outcome measures were live birth, clinical pregnancy, and ovarian hyperstimulation syndrome.

A systematic review of primary outcomes and outcome measure reporting in randomized trials evaluating treatments for pre-eclampsia

An evaluation of outcome reporting is required to develop a core outcome set.

Pharmacologic intervention for retained placenta: a systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness and safety of pharmacologic interventions for the treatment of retained placenta (when the placenta remains undelivered after 30 minutes of active management of the third stage of labor). DATA SOURCES: We searched: 1) Cochrane Central Register of Controlled Trials (CENTRAL), 2) Cochrane Pregnancy and Childbirth Groups Trials Register, 3) EMBASE, and 4) MEDLINE from inception to June 2014. METHODS OF STUDY SELECTION: Randomized controlled trials comparing a pharmacologic intervention(s) with a placebo for the treatment of retained placenta were included. TABULATION, INTEGRATION, AND RESULTS: Sixteen randomized controlled trials, including 1,683 participants, were included. Study characteristics and quality were recorded. The meta-analysis was based on random-effects methods for pooled data. There were no statistically significant differences in the requirement to perform manual removal of a placenta in patients treated with oxytocin (55% compared with 60%; relative risk [RR] 0.86, 95% confidence interval [CI] 0.73–1.02; 10 randomized controlled trials [RCTs]), prostaglandins (44% compared with 55%; RR 0.82, 95% CI 0.58–1.15; four RCTs), nitroglycerin (85% compared with 80%; RR 1.06, 95% CI 0.80–1.41; one RCT), or oxytocin and nitroglycerin (52% compared with 79%; RR 0.23, 95% CI 0.01–8.48; two RCTs) compared with placebo. There was limited reporting of secondary outcomes. CONCLUSION: As opposed to the use of oxytocin as part of the active management of the third stage of labor that has been shown to diminish bleeding in the third stage, once the diagnosis of retained placenta has been made, no pharmacologic treatment has been shown to be effective. When retained placenta is diagnosed, immediate manual removal of the placenta should be considered. SYSTEMATIC REVIEW REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews, http://www.crd.york.ac.uk/PROSPERO/, CRD42014010641.

Twenty years of Cochrane reviews in menstrual disorders and subfertility

The past three decades have seen considerable change in the understanding of clinical research methods. There has been an acceptance that RCTs are the best way of establishing treatment effectiveness and a recognition that, while single studies are useful, pooling knowledge from a complete body of work is likely to provide the best evidence. Advances in methodology have been mirrored by the many advances in the field of reproductive medicine, such as assisted reproduction, assessment of male fertility, ovulation induction and laparoscopic surgery. Together, they have led to welcome improvements in the outcomes of fertility treatments. In particular, systematic reviews have become important tools enabling clinicians and patients to make health-care decisions based on evidence from all the available high-quality studies. The move towards identifying and aggregating the highest quality evidence has been led by the Cochrane Collaboration, which this year celebrates 20 years of preparing and publishing systematic reviews. This paper outlines the achievements, progress and challenges of this enterprise to date, with a particular focus on systematic reviews of reproductive medicine.

Clinical trial registration in fertility trials – a case for improvement?

STUDY QUESTION What is the prevalence and source of prospectively and retrospectively registered and unregistered trials in fertility treatments? SUMMARY ANSWER Trial registration is low and does not appear to be changing over the 5 years studied. WHAT IS KNOWN ALREADY Trial registration is associated with lower risk of bias than in unregistered trials. STUDY DESIGN, SIZE, DURATION The Cochrane Gynaecology and Fertility Groups specialised register was searched on 5 November 2015 for randomised controlled trials (RCTs) published from January 2010 to December 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS Eligible trials included randomised women or men for fertility treatments, were published in full text, and written in English. Two reviewers independently assessed trial registration status for each trial, by searching the publication, trial registries, and by contacting the original authors. MAIN RESULTS AND ROLE OF CHANCE Of 693 eligible RCTS, only 44% were registered trials. Of 309 registered trials, 21.7% were prospectively registered, 15.8% were registered within 6 months of first patient enrolment and 62.5% were retrospectively registered trials. Prospective trial registration by country varied from 0% to 100%. The highest frequency of prospective trial registration amongst the top 10 publishing countries was 31% in the Netherlands. LIMITATIONS, REASONS FOR CAUTION Only English language trials were included in this review. WIDER IMPLICATIONS OF THE FINDINGS Prospective trial registration is still low. Journals, funders and ethics committees could have a greater role to increase trial registration. STUDY FUNDING/COMPETING INTERESTS University of Auckland. No competing interests.