Reduced live birth rates in frozen versus fresh single cleavage stage embryo transfer cycles: A cross-sectional study

Background: Studies have suggested that embryo-endometrial developmental asynchrony caused by slow-growing embryos can be corrected by freezing the embryo and transferring it back in a subsequent cycle. Therefore, we hypothesized that live birth rates (LBR) would be higher in frozen embryo transfer (FET) compared with fresh embryo transfers. Objective: To compare LBR between fresh and FET cycles. Materials and Methods: A cross-sectional analysis of 10,744 single autologous embryo transfer cycles that used a single cleavage-stage embryo was performed. Multivariate analysis was performed to compare LBR between FET and fresh cycles, after correcting for various confounding factors. Sub-analysis was also performed in cycles using slow embryos. Results: Both LBR (19.13% vs 14.13%) and clinical pregnancy (22.48% vs 16.25%) rates (CPR) were higher in the fresh cycle group (p < 0.00). Multivariate analysis for confounding factors also confirmed that women receiving a frozen-thawed embryo had a significantly lower LBR rate compared to those receiving a fresh embryo (OR 0.76, 95% CI 0.68-0.86, p < 0.00). In the sub-analysis of 1,154 cycles using slow embryos, there was no statistical difference in LBR (6.40% vs 6.26%, p = 0.92) or CPR (8.10% vs 7.22%, p = 0.58) between the two groups. Conclusion: This study shows a lower LBR in FET cycles when compared to fresh cycles. Our results suggest that any potential gains in LBR due to improved embryo-endometrial synchrony following FET are lost, presumably due to freeze-thaw process-related embryo damage. Key words: Fresh, Frozen embryo transfer, Live birth, Embryo, Transfer

Feasibility of a multidimensional home-based exercise programme for the elderly with structured support given by the general practitioner's surgery: Study protocol of a single arm trial preparing an RCT [ISRCTN58562962]

<p>Abstract</p> <p>Background</p> <p>Physical activity programmes can help to prevent functional decline in the elderly. Until now, such programmes use to target either on healthy community-dwelling seniors or on elderly living in special residences or care institutions. Sedentary or frail people, however, are difficult to reach when they live in their own homes. The general practitioner's (GP) practice offers a unique opportunity to acquire these people for participation in activity programmes. We conceptualised a multidimensional home-based exercise programme that shall be delivered to the target group through cooperation between GPs and exercise therapists. In order to prepare a randomised controlled trial (RCT), a feasibility study is being conducted.</p> <p>Methods</p> <p>The study is designed as a single arm interventional trial. We plan to recruit 90 patients aged 70 years and above through their GPs. The intervention lasts 12 weeks and consists of physical activity counselling, a home-exercise programme, and exercise consultations provided by an exercise therapist in the GP's practice and via telephone. The exercise programme consists of two main components: 1. a combination of home-exercises to improve strength, flexibility and balance, 2. walking for exercise to improve aerobic capacity. Primary outcome measures are: appraisal by GP, undesirable events, drop-outs, adherence. Secondary outcome measures are: effects (a. motor tests: timed-up-and-go, chair rising, grip strength, tandem stand, tandem walk, sit-and-reach; b. telephone interview: PRISCUS-Physical Activity Questionnaire, Short Form-8 Health Survey, three month recall of frequency of falls, Falls Efficacy Scale), appraisal by participant, exercise performance, focus group discussion. Data analyses will focus on: 1. decision-making concerning the conduction of a RCT, 2. estimation of the effects of the programme, detection of shortcomings and identification of subgroups with contrary results, 3. feedback to participants and to GPs.</p> <p>Conclusion</p> <p>A new cooperation between GPs and exercise therapists to approach community-dwelling seniors and to deliver a home-exercise programme is object of research with regard to feasibility and acceptance. In case of success, an RCT should examine the effects of the programme. A future implementation within primary medical care may take advantage from the flexibility of the programme.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN58562962.</p

Design of the Dutch Obesity Intervention in Teenagers (NRG-DOiT): systematic development, implementation and evaluation of a school-based intervention aimed at the prevention of excessive weight gain in adolescents

BACKGROUND: Only limited data are available on the development, implementation, and evaluation processes of weight gain prevention programs in adolescents. To be able to learn from successes and failures of such interventions, integral written and published reports are needed. METHODS: Applying the Intervention Mapping (IM) protocol, this paper describes the development, implementation, and evaluation of the Dutch Obesity Intervention in Teenagers (DOiT), a school-based intervention program aimed at the prevention of excessive weight gain. The intervention focussed on the following health behaviours: (1) reduction of the consumption of sugar-sweetened beverages, (2) reduction of energy intake derived from snacks, (3) decrease of levels of sedentary behaviour, and (4) increase of levels of physical activity (i.e. active transport behaviour and sports participation). The intervention program consisted of an individual classroom-based component (i.e. an educational program, covering 11 lessons of both biology and physical education classes), and an environmental component (i.e. encouraging and supporting changes at the school canteens, as well as offering additional physical education classes). We evaluated the effectiveness of the intervention program using a randomised controlled trial design. We assessed the effects of the intervention on body composition (primary outcome measure), as well as on behaviour, behavioural determinants, and aerobic fitness (secondary outcome measures). Furthermore, we conducted a process evaluation. DISCUSSION: The development of the DOiT-intervention resulted in a comprehensive school-based weight gain prevention program, tailored to the needs of Dutch adolescents from low socio-economic background

The effect of regular walks on various health aspects in older people with dementia: protocol of a randomized-controlled trial

<p>Abstract</p> <p>Background</p> <p>Physical activity has proven to be beneficial for physical functioning, cognition, depression, anxiety, rest-activity rhythm, quality of life (QoL), activities of daily living (ADL) and pain in older people. The aim of this study is to investigate the effect of walking regularly on physical functioning, the progressive cognitive decline, level of depression, anxiety, rest-activity rhythm, QoL, ADL and pain in older people with dementia.</p> <p>Methods/design</p> <p>This study is a longitudinal randomized controlled, single blind study. Ambulatory older people with dementia, who are regular visitors of daily care or living in a home for the elderly or nursing home in the Netherlands, will be randomly allocated to the experimental or control condition. Participants of the experimental group make supervised walks of 30 minutes a day, 5 days a week, as part of their daily nursing care. Participants of the control group will come together three times a week for tea or other sedentary activities to control for possible positive effects of social interaction. All dependent variables will be assessed at baseline and after 6 weeks, and 3, 6, 9, 12 and 18 months of intervention.</p> <p>The dependent variables include neuropsychological tests to assess cognition, physical tests to determine physical functioning, questionnaires to assess ADL, QoL, level of depression and anxiety, actigraphy to assess rest-activity rhythm and pain scales to determine pain levels. Potential moderating variables at baseline are: socio-demographic characteristics, body mass index, subtype of dementia, apolipoprotein E (ApoE) genotype, medication use and comorbidities.</p> <p>Discussion</p> <p>This study evaluates the effect of regular walking as a treatment for older people with dementia. The strength of this study is that 1) it has a longitudinal design with multiple repeated measurements, 2) we assess many different health aspects, 3) the intervention is not performed by research staff, but by nursing staff which enables it to become a routine in usual care. Possible limitations of the study are that 1) only active minded institutions are willing to participate creating a selection bias, 2) the drop-out rate will be high in this population, 3) not all participants will be able to perform/understand all tests.</p> <p>Trial registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1482">NTR1482</a></p

Identification of nine new susceptibility loci for endometrial cancer

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study

The endometrial lymphatic vasculature: Function and dysfunction

The endometrium has a complex and dynamic blood and lymphatic vasculature which undergoes regular cycles of growth and breakdown. While we now have a detailed picture of the endometrial blood vasculature, our understanding of the lymphatic vasculature in the endometrium is limited. Recent studies have illustrated that the endometrium contains a population of lymphatic vessels with restricted distribution in the functional layer relative to the basal layer. The mechanisms responsible for this restricted distribution and the consequences for endometrial function are not known. This review will summarise our current understanding of endometrial lymphatics, including the mechanisms regulating their growth and function. The potential contribution of lymphatic vessels and lymphangiogenic growth factors to various endometrial disorders will be discussed

Endometrial lymphangiogensis

This article briefly summarises some of the more important recent advances in understanding of lymphangiogenesis, and then reviews current knowledge of the lymphatics and lymphangiogenesis in the endometrium. The recent identification of vascular endothelial growth factor-C (VEGF-C) and VEGF-D, as well as specific lymphatic endothelial cell (LEC) markers such as vascular endothelial growth factor receptor-3 (VEGF-R3), lymphatic endothelial hyaluronan receptor-1 (LYVE-1), podoplanin, and prospero-related homeobox-1 (PROX1), has provided the tools to characterize and investigate lymphatic development and function in a wide range of tissues. There are conflicting reports on the distribution of endometrial lymphatics, with some studies reporting lymphatics in the functional zone of human endometrium, others only in the endometrial basalis, and some reporting none at all. Using immunohistochemical methods we have shown that lymphatic vessels of the functionalis were small and sparsely distributed whereas the basalis lymphatics are larger, more frequent and often closely associated with spiral arterioles. Based on comparisons of serial sections, the majority of lymphatic vessels are positive for CD31 but not FVIII or CD34. By comparing CD31 with D2-40 (labels lymphatic endothelial cells) vessel immunostaining, it was estimated that 13% of the vessel profiles in the functionalis, 43% in the basalis and 28% in the myometrium were lymphatics. The lymphangiogenic growth factor VEGF-C is immunolocalized most prominently in the glandular cells, vascular endothelium and some stromal cells in normal cycling endometrium. There is no difference in staining intensity observed between the basalis and functionalis. VEGF-D is immunolocalized throughout the endometrial and myometrial tissues, with no difference in intensity between endometrial glands and stroma or between the basalis and functionalis across the normal cycle. In conclusion, despite an apparently similar distribution of VEGF-C, VEGF-D and VEGF-R3 in endometrial functionalis and basalis, the lymphatic vascular density is 4-5 times higher in the basalis compared to the functionalis. There is also a close association between some lymphatics in the basalis and the spiral arterioles, thus identifying a potential mechanism for a vascular control feedback loop