Resumption of pituitary and ovarian activity post-partum: endocrine and ultrasonic observations in bromocriptine-treated women

The resumption of pituitary and ovarian activity was investigated by hormonal measurements and ultrasound scanning in 45 healthy post-partum women who were treated with bromocriptine. Bromocriptine, 50 mg (Parlodel LAR) was administered within 24 h post-partum. Plasma luteinizing hormone, follicle stimulating hormone, oestradiol, progesterone and prolactin concentrations were measured repeatedly and correlated with ultrasound measurements. Forty-one of the 45 women completed the study. A prompt fall in prolactin levels to normal (non-pregnant) values was observed within 24 h post-partum. Hereafter, a rapid return of the normal menstrual cycle was observed. Endocrine evidence of ovulation was obtained in 19/41 women within 1 month post-partum. Ultrasound measurements started at day 10 and were repeated regularly in 40 women. Ultrasound evidence of ovulation was found in 25/40 women. Ultrasound findings appeared not to correspond with the hormonal measurements. It is concluded that the resumption of pituitary and ovarian secretory functions post-partum is not always paralleled by a concomitant recovery of normal follicular growth and ovulation. Application of a progesterone threshold to judge resumption of ovulation post-partum should be reconsidere

The influence of social factors on gender health

Male births exceed female births by 5-6% (for a sex ratio at birth of 1.05-1.06) while a women's life expectancy, on a global scale, is about 6 years longer. Thus within various age groups the male:female ratio changes over time. Until age 50 years men outnumber women; thereafter their numbers show a sharp decline. Consequently at age 80 years, there are many more women than men. An estimated 25% of this male excess mortality is due to biological causes, the rest being explained by behavioural, cultural and environmental factors. For both women and men, the main health risks related to lifestyle are smoking, alcohol, unhealthy diet and physical inactivity. In the year 2010, overweight (BMI: 25-29 kg/m2) and obesity (BMI: >30 kg/m2) were responsible for over 3 million deaths, with similar relative risks in men and women for overweight and obesity. Smoking and alcohol are the major causes of the global gender gap in mortality. For women in some parts of the world however pregnancy is also hazardous. On a global scale, in 2013 about 300 000 deaths were related to pregnancy, with sub-Saharan Africa registering the highest maternal mortality: over 500 maternal deaths per 100 000 births. Additional woman's health risks arise from gender discrimination, including sex-selective abortion, violence against women and early child marriage. Providers should be aware of the effect that these risks can have on both reproductive and general health. © 2016 The Author

Towards Endometriosis Diagnosis by Gadofosveset-Trisodium Enhanced Magnetic Resonance Imaging

Endometriosis is defined as the presence of endometrial tissue outside the uterus. It affects 10–15% of women during reproductive age and has a big personal and social impact due to chronic pelvic pain, subfertility, loss of work-hours and medical costs. Such conditions are exacerbated by the fact that the correct diagnosis is made as late as 8–11 years after symptom presentation. This is due to the lack of a reliable non-invasive diagnostic test and the fact that the reference diagnostic standard is laparoscopy (invasive, expensive and not without risks). High-molecular weight gadofosveset-trisodium is used as contrast agent in Magnetic Resonance Imaging (MRI). Since it extravasates from hyperpermeable vessels more easily than from mature blood vessels, this contrast agent detects angiogenesis efficiently. Endometriosis has high angiogenic activity. Therefore, we have tested the possibility to detect endometriosis non-invasively using Dynamic Contrast-Enhanced MRI (DCE-MRI) and gadofosveset-trisodium as a contrast agent in a mouse model. Endometriotic lesions were surgically induced in nine mice by autologous transplantation. Three weeks after lesion induction, mice were scanned by DCE-MRI. Dynamic image analysis showed that the rates of uptake (inwash), persistence and outwash of the contrast agent were different between endometriosis and control tissues (large blood vessels and back muscle). Due to the extensive angiogenesis in induced lesions, the contrast agent persisted longer in endometriotic than control tissues, thus enhancing the MRI signal intensity. DCE-MRI was repeated five weeks after lesion induction, and contrast enhancement was similar to that observed three weeks after endometriosis induction. The endothelial-cell marker CD31 and the pericyte marker α-smooth-muscle-actin (mature vessels) were detected with immunohistochemistry and confirmed that endometriotic lesions had significantly higher prevalence of new vessels (CD31 only positive) than the uterus and control tissues. The diagnostic value of gadofosveset-trisodium to detect endometriosis should be tested in human settings

Diversity Arrays Technology (DArT) for Pan-Genomic Evolutionary Studies of Non-Model Organisms

Background: High-throughput tools for pan-genomic study, especially the DNA microarray platform, have sparked a remarkable increase in data production and enabled a shift in the scale at which biological investigation is possible. The use of microarrays to examine evolutionary relationships and processes, however, is predominantly restricted to model or near-model organisms. Methodology/Principal Findings: This study explores the utility of Diversity Arrays Technology (DArT) in evolutionary studies of non-model organisms. DArT is a hybridization-based genotyping method that uses microarray technology to identify and type DNA polymorphism. Theoretically applicable to any organism (even one for which no prior genetic data are available), DArT has not yet been explored in exclusively wild sample sets, nor extensively examined in a phylogenetic framework. DArT recovered 1349 markers of largely low copy-number loci in two lineages of seed-free land plants: the diploid fern Asplenium viride and the haploid moss Garovaglia elegans. Direct sequencing of 148 of these DArT markers identified 30 putative loci including four routinely sequenced for evolutionary studies in plants. Phylogenetic analyses of DArT genotypes reveal phylogeographic and substrate specificity patterns in A. viride, a lack of phylogeographic pattern in Australian G. elegans, and additive variation in hybrid or mixed samples. Conclusions/Significance: These results enable methodological recommendations including procedures for detecting and analysing DArT markers tailored specifically to evolutionary investigations and practical factors informing the decision to use DArT, and raise evolutionary hypotheses concerning substrate specificity and biogeographic patterns. Thus DArT is a demonstrably valuable addition to the set of existing molecular approaches used to infer biological phenomena such as adaptive radiations, population dynamics, hybridization, introgression, ecological differentiation and phylogeography

Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: the TwinSing study

Contains fulltext : 87274.pdf (publisher's version ) (Open Access)BACKGROUND: Pregnancies induced by in vitro fertilisation (IVF) often result in twin gestations, which are associated with both maternal and perinatal complications. An effective way to reduce the number of IVF twin pregnancies is to decrease the number of embryos transferred from two to one. The interpretation of current studies is limited because they used live birth as outcome measure and because they applied limited time horizons. So far, research on long-term outcomes of IVF twins and singletons is scarce and inconclusive. The objective of this study is to investigate the short (1-year) and long-term (5 and 18-year) costs and health outcomes of IVF singleton and twin children and to consider these in estimating the cost-effectiveness of single embryo transfer compared with double embryo transfer, from a societal and a healthcare perspective. METHODS/DESIGN: A multi-centre cohort study will be performed, in which IVF singletons and IVF twin children born between 2003 and 2005 of whom parents received IVF treatment in one of the five participating Dutch IVF centres, will be compared. Data collection will focus on children at risk of health problems and children in whom health problems actually occurred. First year of life data will be collected in approximately 1,278 children (619 singletons and 659 twin children). Data up to the fifth year of life will be collected in approximately 488 children (200 singletons and 288 twin children). Outcome measures are health status, health-related quality of life and costs. Data will be obtained from hospital information systems, a parent questionnaire and existing registries. Furthermore, a prognostic model will be developed that reflects the short and long-term costs and health outcomes of IVF singleton and twin children. This model will be linked to a Markov model of the short-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies to enable the calculation of the long-term cost-effectiveness. DISCUSSION: This is, to our knowledge, the first study that investigates the long-term costs and health outcomes of IVF singleton and twin children and the long-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies

Developing a core outcome set for future infertility research : An international consensus development study

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form

Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole genome sequencing consortium to thoroughly characterize the known genetic causes of FTLD-TDP and identify novel genetic risk factors. Through the study of 1,131 unrelated Caucasian patients, we estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.5% and 13.9% of FTLD-TDP patients, respectively. Mutations in TBK1 (1.5%) and other known FTLD genes (1.4%) were rare, and the disease in 57.7% of FTLD-TDP patients was unexplained by the known FTLD genes. To unravel the contribution of common genetic factors to the FTLD-TDP etiology in these patients, we conducted a two-stage association study comprising the analysis of whole-genome sequencing data from 517 FTLD-TDP patients and 838 controls, followed by targeted genotyping of the most associated genomic loci in 119 additional FTLD-TDP patients and 1653 controls. We identified three genome-wide significant FTLD-TDP risk loci: one new locus at chromosome 7q36 within the DPP6 gene led by rs118113626 (pvalue=4.82e-08, OR=2.12), and two known loci: UNC13A, led by rs1297319 (pvalue=1.27e-08, OR=1.50) and HLA-DQA2 led by rs17219281 (pvalue=3.22e-08, OR=1.98). While HLA represents a locus previously implicated in clinical FTLD and related neurodegenerative disorders, the association signal in our study is independent from previously reported associations. Through inspection of our whole genome sequence data for genes with an excess of rare loss-of-function variants in FTLD-TDP patients (n≥3) as compared to controls (n=0), we further discovered a possible role for genes functioning within the TBK1-related immune pathway (e.g. DHX58, TRIM21, IRF7) in the genetic etiology of FTLD-TDP. Together, our study based on the largest cohort of unrelated FTLD-TDP patients assembled to date provides a comprehensive view of the genetic landscape of FTLD-TDP, nominates novel FTLD-TDP risk loci, and strongly implicates the immune pathway in FTLD-TDP pathogenesis

The long-term outcome of 946 consecutive couples visiting a fertility clinic in 2001-2003

Objective: To describe the outcome of fertility work-up, treatment, and dropout in a cohort of subfertile couples in a well-defined area in Western Europe. Design: Prospective cohort study. Setting: Maastricht University Medical Center. Patient(s): Subfertile couples referred by their general physician between 2001 and 2003. Intervention(s): Demographic data, findings of the fertility investigation, and outcome of treatment were entered prospectively into a database. Follow-up was performed until November 2008. Main Outcome Measure(s): Diagnosis, treatment, dropout rate, pregnancy rate, and live-birth rate. Result(s): During the study period, 946 couples were referred, of whom 17% dropped out. Follow-up was complete in 94% of couples. Spontaneous pregnancies occurred in 28% of all couples, and there were 32% treatment-dependent pregnancies. IVF (51% live births in couples treated) and no treatment/expectant management (50%) were the most effective treatments. Conclusion(s): After 5-8 years, 51% of couples referred for subfertility had at least one live birth. (Fertil Steril (R) 2011;96:160-4. (C)2011 by American Society for Reproductive Medicine.

Evidence-based medicine for diagnostic questions

When searching the medical care literature for evidence on a diagnostic test, three questions should be addressed each time a study is found: (1) Is this evidence about a diagnostic test valid? (2) Does the test accurately discriminate between patients who do and patients who do not have a specific disorder? (3) Can the test be applied to this patient who is right now sitting in front of me? We will discuss hysterosalpingography (HSG) as an example of a valid and accurate diagnostic test to be applied in a general population of subfertile couples to assess tubal patency (specificity 0.83). HSG is an unreliable test for diagnosing tubal occlusion however (sensitivity 0.65). If HSG were normal, other investigations could be pursued and diagnostic laparoscopy (LS) only performed if conception had not occurred by a later date. If HSG were abnormal, LS would be needed to confirm or exclude tubal occlusion. Patients with risk factors for pelvic or tubal disease, including an abnormal Chlamydia antibody test (CAT) and those showing abnormalities at pelvic examination, should proceed directly to LS because they are significantly more likely to have pelvic pathology. A completely different issue would be HSG as a prognostic test for the occurrence of pregnancy. In theory, the occurrence of pregnancy may be considered a gold standard; however, in reproductive medicine, with so many causes of subfertility other than tubal pathology, a diagnostic test for one single disorder, if normal, will never be able to accurately predict the eventual occurrence of pregnanc