Abstract
Context
Anti-müllerian hormone (AMH) is produced by granulosa cells of small, growing follicles in the ovary. Serum AMH levels strongly correlate with the number of growing follicles, and ...therefore AMH has received increasing attention as a marker for ovarian reserve. This review summarizes recent findings and limitations in the application of serum AMH in ovarian reserve assessment.
Evidence Acquisition
A PubMed search was conducted to find recent literature on the measurements and use of serum AMH as a marker for ovarian reserve.
Evidence Synthesis
Serum AMH levels are measured to assess the “functional ovarian reserve,” a term that is preferred over “ovarian reserve,” since AMH levels reflect the pool of growing follicles that potentially can ovulate. Serum AMH levels are used in individualized follicle-stimulating hormone dosing protocols and may predict the risk of poor response or ovarian hyperstimulation syndrome but has limited value in predicting ongoing pregnancy. Serum AMH levels are studied to predict natural or disease-related age of menopause. Studies show that the age-dependent decline rates of AMH vary among women. The generalized implementation of serum AMH measurement has also led to an increase in diagnostic assays, including automated assays. However, direct comparison of results remains problematic.
Conclusion
Serum AMH remains the preferred ovarian reserve marker. However, the lack of an international standard for AMH limits comparison between AMH assays. Furthermore, little is known about endogenous and exogenous factors that influence serum AMH levels, which limits proper interpretation of AMH values in a clinical setting.
Biobased polymers and materials are desperately needed to replace fossil-based materials in the world's transition to a more sustainable lifestyle. In this article, Avantium describes the path from ...invention towards commercialization of their YXY
plants-to-plastics Technology, which catalytically converts plant-based sugars into FDCA-the chemical building block for PEF (polyethylene furanoate). PEF is a plant-based, highly recyclable plastic, with superior performance properties compared to today's widely used petroleum-based packaging materials. The myriad of topics that must be addressed in the process of bringing a new monomer and polymer to market are discussed, including process development and application development, regulatory requirements, IP protection, commercial partnerships, by-product valorisation, life cycle assessment (LCA), recyclability and circular economy fit, and end-of-life. Advice is provided for others considering embarking on a similar journey, as well as an outlook on the next, exciting steps towards large-scale production of FDCA and PEF at Avantium's Flagship Plant and beyond.
A caesarean section (CS) can be a life-saving intervention when medically indicated, but this procedure can also lead to short-term and long-term health effects for women and children. Given the ...increasing use of CS, particularly without medical indication, an increased understanding of its health effects on women and children has become crucial, which we discuss in this Series paper. The prevalence of maternal mortality and maternal morbidity is higher after CS than after vaginal birth. CS is associated with an increased risk of uterine rupture, abnormal placentation, ectopic pregnancy, stillbirth, and preterm birth, and these risks increase in a dose–response manner. There is emerging evidence that babies born by CS have different hormonal, physical, bacterial, and medical exposures, and that these exposures can subtly alter neonatal physiology. Short-term risks of CS include altered immune development, an increased likelihood of allergy, atopy, and asthma, and reduced intestinal gut microbiome diversity. The persistence of these risks into later life is less well investigated, although an association between CS use and greater incidence of late childhood obesity and asthma are frequently reported. There are few studies that focus on the effects of CS on cognitive and educational outcomes. Understanding potential mechanisms that link CS with childhood outcomes, such as the role of the developing neonatal microbiome, has potential to inform novel strategies and research for optimising CS use and promote optimal physiological processes and development.
Objective
Patients with breast cancer face cognitive impairment that affects their quality of life; partially attributable to treatment. Our aim was to detail the prevalence and change of cognitive ...impairment during the course of treatment. We also investigated the effect of therapy (chemotherapy CT) vs. radiotherapy and/or endocrine therapy vs. healthy controls).
Methods
This article reviews longitudinal cohort studies published to date in Medline and Embase that (i) assess cognition before and after therapy, (ii) report prevalence cognitive impairment or change, and (iii) use standardized and valid neuropsychological tests. We used the original authors' criteria for cognitive impairment.
Results
The title and of 891 articles were screened, resulting in the identification of 90 potentially relevant articles while applying the eligibility criteria. After full‐text examination, 17 studies were included. Prevalence of cognitive impairment range from 25% before therapy, through 24% after therapy to 21% at maximal 1‐year follow‐up (FU). Compared to their pretreatment cognitive functioning, 24% of patients decline after treatment and 24% at 1‐year FU. Some studies also reported cognitive improvement showing that 15% and 31% of patients improve, respectively. In general, patients undergoing CT have a higher chance of cognitive impairment and decline than no‐CT patients and healthy controls.
Conclusions
This study shows that one out of four breast cancer patients shows cognitive impairment prior to treatment administration CT and a significant number of patients decline during the course of disease, suggesting that cognitive impairment is not exclusively related to CT and/or no‐CT therapies. This study shows that assessment of cognitive functioning, ideally over time, is crucial and may help the implementation of personalized rehabilitation pathways.
•We claim that the core of the Dark Triad is equivalent to most conceptions of “evil”.•We test 5 competing theories that claim to capture the core of the Dark Triad (i.e., the core of “evil”).•We ...find that the HEXACO model of personality best accounts for the core of the Dark Triad.•We position these results into the broader theoretical picture, including life history theory.
Understanding the nature of “evil” has been challenging for a number of reasons. A productive psychological approach to this problem has been to study antisocial traits associated with negative outcomes. One such approach has grouped together three antisocial personalities known as the “Dark Triad”: Machiavellianism, Narcissism, and Psychopathy. Researchers have proposed various models to account for the common core of these antisocial personalities – a core that might well be considered the psychological equivalent of the core of “evil” – and these models have not been directly compared, to date. We conducted two studies (total N>700) to compare the utility of the various models using Canonical Correlation Analyses (CCAs). Results confirm that the HEXACO personality model (and, in particular, the Honesty–Humility factor) is not only the most theoretically parsimonious model, it also best accounts for the empirical overlap between these constructs that represents the core of the Dark Triad. Results also support the idea that the core of the Dark Triad represents an alternative life history strategy.
Excessive fat accumulation in the body causes overweight and obesity. To date, research has confirmed that there are two types of adipose tissue with opposing functions: lipid-storing white adipose ...tissue (WAT) and lipid-burning brown adipose tissue (BAT). After the rediscovery of the presence of metabolically active BAT in adults, BAT has received increasing attention especially since activation of BAT is considered a promising way to combat obesity and associated comorbidities. It has become clear that energy homeostasis differs between the sexes, which has a significant impact on the development of pathological conditions such as type 2 diabetes. Sex differences in BAT activity may contribute to this and, therefore, it is important to address the underlying mechanisms that contribute to sex differences in BAT activity. In this review, we discuss the role of sex hormones in the regulation of BAT activity under physiological and some pathological conditions. Given the increasing number of studies suggesting a crosstalk between sex hormones and the hypothalamic-pituitary-adrenal axis in metabolism, we also discuss this crosstalk in relation to sex differences in BAT activity.
In the mid-20th century, Hemolytic Disease of the Fetus and Newborn, caused by maternal alloimmunization to the Rh(D) blood group antigen expressed by fetal red blood cells (i.e., "Rh disease"), was ...a major cause of fetal and neonatal morbidity and mortality. However, with the regulatory approval, in 1968, of IgG anti-Rh(D) immunoprophylaxis to prevent maternal sensitization, the prospect of eradicating Rh disease was at hand. Indeed, the combination of antenatal and post-partum immunoprophylaxis is ~99% effective at preventing maternal sensitization to Rh(D). To investigate global compliance with this therapeutic intervention, we used an epidemiological approach to estimate the current annual number of pregnancies worldwide involving an Rh(D)-negative mother and an Rh(D)-positive fetus. The annual number of doses of anti-Rh(D) IgG required for successful immunoprophylaxis for these cases was then calculated and compared with an estimate of the annual number of doses of anti-Rh(D) produced and provided worldwide. Our results suggest that ~50% of the women around the world who require this type of immunoprophylaxis do not receive it, presumably due to a lack of awareness, availability, and/or affordability, thereby putting hundreds of thousands of fetuses and neonates at risk for Rh disease each year. The global failure to provide this generally acknowledged standard-of-care to prevent Rh disease, even 50 years after its availability, contributes to an enormous, continuing burden of fetal and neonatal disease and provides a critically important challenge to the international health care system.
BACKGROUND The measurement of circulating anti-Müllerian hormone (AMH) has been applied to a wide array of clinical applications, mainly based on its ability to reflect the number of antral and ...pre-antral follicles present in the ovaries. AMH has been suggested to predict the ovarian response to hyperstimulation of the ovaries for IVF and the timing of menopause, and to indicate iatrogenic damage to the ovarian follicle reserve. It has also been proposed as a surrogate for antral follicle count (AFC) in the diagnosis of polycystic ovary syndrome (PCOS). METHODS This paper is a summary of presentations at a European Society of Human Reproduction and Embryology campus workshop on AMH, with literature cited until September 2013. Published peer-reviewed medical literature about AMH was searched through MEDLINE and was subjected to systematic review and critical assessment by the panel of authors. RESULTS Physiologically, recent data confirm that AMH is a follicular gatekeeper limiting follicle growth initiation, and subsequently estradiol production from small antral follicles prior to selection. AMH assays continue to evolve and technical issues remain; the absence of an international standard is a key issue. The dynamics of circulating AMH levels throughout life can be split into several distinct phases, with a peak in the early 20s before a decline to the menopause, with a strong and positive correlation with non-growing follicle recruitment. There is a more complex rise during childhood and adolescence, which is likely to be more reflective of different stages of follicle development. AMH shows limited short-term variability, but the influence of states such as prolonged oral contraceptive use need to be considered in clinical assessment. There are only very limited data on relationships between AMH and natural fertility at different stages of reproductive life, and while it has a relationship to age at menopause the marked variability in this needs further exploration. AMH may be useful in assessing the need for fertility preservation strategies and detecting post-chemotherapy or surgical damage to the ovarian reserve. Long-term follow-up of patients to ascertain fully the value of post-cancer serum AMH in predicting long-term ovarian function is required. There is a linear relationship between AMH and oocyte yield after ovarian stimulation, which is of value in predicting ovarian hyperstimulation. AMH can also identify 'poor responders', but it seems inappropriate at present to withhold IVF purely on this basis. Women with PCOS show markedly raised AMH levels, due to both the increased number of small antral follicles and intrinsic characteristics of those granulosa cells, and this may contribute to anovulation. The value of AMH in the diagnosis of PCOS remains controversial, but it may replace AFC in the future. CONCLUSIONS For the first time in female reproductive biology, it is possible to measure the submerged part of the iceberg of follicle growth, i.e. the intrinsic, so-called 'acyclic' ovarian activity. An international standard for AMH and improved assay validity are urgently needed to maximize the clinical utility of this very promising biomarker of ovarian function in a large array of clinical situations, both in childhood and adulthood.
Primary ovarian insufficiency (POI) affects ∼1% of women before 40 years of age. The recent leap in genetic knowledge obtained by next generation sequencing (NGS) together with animal models has ...further elucidated its molecular pathogenesis, identifying novel genes/pathways. Mutations of >60 genes emphasize high genetic heterogeneity. Genome-wide association studies have revealed a shared genetic background between POI and reproductive aging. NGS will provide a genetic diagnosis leading to genetic/therapeutic counseling: first, defects in meiosis or DNA repair genes may predispose to tumors; and second, specific gene defects may predict the risk of rapid loss of a persistent ovarian reserve, an important determinant in fertility preservation. Indeed, a recent innovative treatment of POI by in vitro activation of dormant follicles proved to be successful.
The mechanisms underlying the formation of the ovarian reserve are generally well conserved, from Drosophila to mammals. Owing to this high degree of conservation, factors shown to regulate the ovarian reserve in mouse models are all potential candidates for identifying mutations associated with POI in humans.
With the generation of genetically modified mice, much insight has been gained into the mechanisms that control the formation of the ovarian reserve and trigger the activation of primordial follicles.
Comparison with animal models is complicated by the fact that the phenotype of complete gene deletion in knockout models may not be mimicked by single gene mutations.
Recently innovative treatment for POI based on in vitro activation of the dormant primordial follicular pool has been developed.
Obesity, usually characterized by the body mass index (BMI), is a risk factor for hand osteoarthritis (OA). We investigated whether adipose tissue and abdominal fat distribution are associated with ...hand OA.
The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45 to 65 years, including 5315 participants (53% women, median BMI 29.9 kg/m²). Fat percentage and fat mass (FM) (kg) were estimated using bioelectrical impedance analysis. The waist-to-hip ratio (WHR) was calculated. In 1721 participants, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (cm²) were assessed using abdominal MR imaging. Hand OA was defined according to the ACR criteria.
Hand OA was present in 8% of men and 20% of women. Fat percentage was associated with hand OA in men (OR 1.34 (95% CI 1.11 to 1.61)) and women (OR 1.26 (1.05 to 1.51)), as was FM. WHR was associated with hand OA in men (OR 1.45 (1.13 to 1.85)), and to a lesser extent in women (OR 1.17 (1.00 to 1.36)). Subgroup analysis revealed that VAT was associated with hand OA in men (OR1.33 (1.01 to 1.75)). This association increased after additional adjustment for FM (OR 1.51 (1.13 to 2.03)).
Fat percentage, FM and WHR were associated with hand OA. VAT was associated with hand OA in men, suggesting involvement of visceral fat in hand OA.