Rheumatoid arthritis (RA) is an inflammatory disease typically affecting the joints, but the systemic inflammatory process may involve other tissues and organs. Many extra-articular manifestations ...are recognized, which are related to worse long outcomes. Rheumatoid nodules are the most common extra-articular feature, found in about 30% of patients. Secondary Sjögren's syndrome and pulmonary manifestations are observed in almost 10% of patients, also in the early disease. Active RA with high disease activity has been associated with an increased risk of such features. Male gender, smoking habit, severe joint disease, worse function, high pro-inflammatory markers levels, high titer of rheumatoid factor, and HLA-related shared epitope have been reported as clinical predictors of occurrence of these rheumatoid complications. In addition, there is a little evidence deriving from randomized controlled trials in this field, thus the therapeutic strategy is mainly empiric and based on small case series and retrospective studies. However, considering that these extra-articular manifestations are usually related to the more active and severe RA, an aggressive therapeutic strategy is usually employed in view of the poor outcomes of these patients.
The extra-articular features of RA remain, despite the improvement of joint damage, a major diagnostic and therapeutic challenge, since these are associated with a poor prognosis and need to be early recognized and promptly managed.
Bisphenol-A (BPA) has been reported to be associated to female infertility. Indeed, BPA has been found to be more frequently detected in infertile women thus leading to hypothesize a possible effect ...of BPA on natural conception and spontaneous fecundity. In addition, in procedures of medically assisted reproduction BPA exposure has been found to be negatively associated with peak serum estradiol levels during gonadotropin stimulation, number of retrieved oocytes, number of normally fertilized oocytes and implantation. BPA deleterious effects are more critical during perinatal exposure, causing dysregulation of hypothalamic-pituitary-ovarian axis in pups and adults, with a precocious maturation of the axis through a damage of GnRH pulsatility, gonadotropin signaling and sex steroid hormone production. Further, BPA exposure during early lifestage may have a transgenerational effect predisposing the subsequent generations to the risk of developing BPA related disease. Experimental studies suggested that prenatal, perinatal and postnatal exposure to BPA can impair several steps of ovarian development, induce ovarian morphology rearrangement and impair ovarian function, particularly folliculogenesis, as well as can impair uterus morphology and function, in female adult animal and offspring. Finally, studies carried out in animal models have been reported the occurrence of endometriosis-like lesions after BPA exposure. Moreover, BPA exposure has been described to encourage the genesis of PCOS-like abnormalities through the impairment of the secretion of sex hormones affecting ovarian morphology and functions, particularly folliculogenesis. The current manuscript summarizes the evidence regarding the association between BPA exposure and female infertility, reviewing both clinical and preclinical studies.
Air pollution is a cause of concern for human health. For instance, it is associated with an increased risk for cancer, cardiovascular and respiratory disorders. In vitro and in vivo studies ...suggested that air pollutants could act as endocrine disruptors, promote oxidative stress and exert genotoxic effect. Whether air pollution affects female infertility is under debate. The aim of the present study was to conduct a systematic review of studies that evaluated the impact of air pollution on female infertility. We systematically searched the MEDLINE (PubMed) and SCOPUS databases to identify all relevant studies published before October 2017. No time or language restrictions were adopted, and queries were limited to human studies. We also hand-searched the reference lists of relevant studies to ensure we did not miss pertinent studies. The risk of bias and quality assessment of the studies identified were performed using the Newcastle-Ottawa Scale. Primary outcomes were conception rate after spontaneous intercourse and live birth rate after in vitro fertilization (IVF) procedures. Secondary outcomes were first trimester miscarriage, stillbirths, infertility, number of oocytes and embryo retrieved. Eleven articles were included in the analysis. We found that in the IVF population, nitrogen dioxide and ozone were associated with a reduced live birth rate while particulate matter of 10 mm was associated with increased miscarriage. Furthermore, in the general population, particulate matter of 2.5 mm and between 2.5 and 10 mm were associated with reduced fecundability, whereas sulfur dioxide
carbon monoxide and nitrogen dioxide might promote miscarriage and stillbirths. The main limitation of our findigns resides in the fact that the desegn of studies included are observational and retrospective. Furthermore, there was a wide heterogenity among studies. Although larger trials are required before drawing definitive conclusions, it seems that air pollution could represent a matter of concern for female infertility.
Asherman syndrome is a debatable topic in gynaecological field and there is no clear consensus about management and treatment. It is characterized by variable scarring inside the uterine cavity and ...it is also cause of menstrual disturbances, infertility and placental abnormalities. The advent of hysteroscopy has revolutionized its diagnosis and management and is therefore considered the most valuable tool in diagnosis and management. The aim of this review is to explore the most recent evidence related to this condition with regards to aetiology, diagnosis management and follow up strategies.
Considerable interest has been gathered on the relevant impact of preventable factors, including incorrect lifestyle and unhealthy habits, on female fertility. Smoking, alcohol and addictive drugs ...consumption represent a major concern, given the broad range of diseases which might be favored or exacerbated by these dependable attitudes. Despite the well-characterized effects of prenatal exposure on pregnancy outcomes and fetus health, a substantial proportion of women of reproductive age is still concerned with these habits. At present, the impact of smoke, alcohol and addictive drugs on women fertility, and, particularly, the specific targets and underlying mechanisms, are still poorly understood or debated, mainly due to the scarcity of well-designed studies, and to numerous biases.
The current review will provide a comprehensive overview of clinical and experimental studies in humans and animals addressing the impact of smoke, alcohol and addictive drugs on female fertility, by also embracing effects on ovary, oviduct, and uterus, with particular reference to primary endpoints such as ovarian reserve, steroidogenesis, ovulation and menstrual cycle, oviduct function and uterus receptivity and implantation. A brief focus on polycystic ovary syndrome and endometriosis will be also included.
A Pubmed literature search was performed with selected keywords; articles were individually retrieved by each author. No limitation was set for publication date. Articles in languages other than English were excluded. Additional articles were retrieved from references list of selected manuscripts.
Currently, the most consistent evidences of a detrimental effect of smoke, alcohol and addictive drugs on specific domains of the female reproductive function are provided by experimental studies in animals. Overall, clinical studies suggest that smoking is associated to decreased fertility, although causal inference should be further demonstrated. Studies addressing the effect of alcohol consumption on female fertility provide conflicting results, although the majority reported lack of a correlation. Extremely scarce studies investigated the effects of addictive drugs on female fertility, and the specific actions of selected drugs have been difficult to address, due to multidrug consumption.
Women with impaired ovarian reserve or poor ovarian response (POR) to exogenous gonadotropin stimulation present a challenge for reproductive specialists. The primary reasons relate to the still ...limited knowledge about the POR pathophysiology and the lack of practical solutions for the management of these conditions. Indeed, clinical trials using the current standards to define POR failed to show evidence in favor of a particular treatment modality. Furthermore, critical factors for reproductive success, such as the age-dependent embryo aneuploidy rates and the intrinsic ovarian resistance to gonadotropin stimulation, are not taken into consideration by the current POR criteria. As a result, the accepted definitions for POR have been criticized for their inadequacy concerning the proper patient characterization and for not providing clinicians a guide for therapeutic management. A novel system to classify infertility patients with "expected" or "unexpected" inappropriate ovarian response to exogenous gonadotropins-the POSEIDON criteria-was developed to provide a more nuanced picture of POR and to guide physicians in the management of such patients. The new standards are provoking as they challenge the current terminology of POR in favor of the newly defined concept of "low prognosis." This article provides readers a critical appraisal of the existing criteria that standardize the definition of POR and explains the primary reasons for the development of the POSEIDON criteria.
Hypo-responsiveness to controlled ovarian stimulation is an undervalued topic in reproductive medicine. This phenomenon manifests as a low follicles output rate (FORT) with a discrepancy between the ...relatively low number of pre-ovulatory follicles which develop following ovarian stimulation as compared to the number of antral follicles available at the start of stimulation. The pathophysiology mechanisms explaining the ovarian resistance to gonadotropin stimulation are not fully understood, but the fact that both hypo-responders and normal responders share similar phenotypic characteristics suggests a genotype-based mechanism. Indeed, existing evidence supports the association between specific gonadotropin and their receptor polymorphisms and ovarian hypo-response. Apart from genotypic trait, environmental contaminants and oxidative stress might also be involved in the hypo-response pathogenesis. The ratio between the number of oocytes collected at the ovum pick up and the number of antral follicles at the beginning of OS Follicle to oocyte index (FOI) is proposed as a novel parameter to assess the hypo-response. Compared with traditional ovarian reserve markers, FOI might reflect most optimally the dynamic nature of follicular growth in response to exogenous gonadotropin. In this review, we contextualize the role of FOI as a parameter to identify this condition, discuss the underlying mechanisms potentially implicated in the pathogenesis of hypo-response, and appraise possible the treatment strategies to overcome hyper-responsiveness to gonadotropin stimulation.
Systemic sclerosis (SSc) is an uncommon autoimmune disease. Aim of the study was to detect the occult cardiac involvement in asymptomatic SSc patients of recent onset (indicative of a more aggressive ...disease) with unenhanced Cardiac Magnetic Resonance (CMR). Our historical prospective study included naïve SSc patients of recent onset. Modified Rodnan Skin Score (mRSS) and Scleroderma Clinical Trial Consortium Damage Index (SCTC-DI) were calculated. Cardiac volumes and global myocardial strain were assessed and also compared with healthy group values. Pericardial involvement was further recorded. Thirty-one patients met inclusion criteria (54 ± 12 years; 1 M). Mean duration of disease was 6.8 years. All patients showed preserved systolic function. Higher incidence of pericardial involvement was founded in patients with disease accrual damage (OR: 9.6, p-value 0.01). Radial and longitudinal strain values resulted significantly different between healthy and SSc patients. GRS and GLS showed an independent predictive validity on damage accrual (HR: 1.22 and 1.47, respectively). Best C-index for disease progression was reached when strain values and pericardial evaluation were added to conventional risk factors (0.97, p-value: 0.0001). Strain analysis by CMR-TT may show a high capability both in identifying early cardiac involvement and stratifying its clinical aggressiveness, regardless of the standard damage indices and CMR contrast-dependent biomarker.
POSEIDON groups 1 and 2 patients respond poorly (<4 oocytes retrieved) or sub-optimally (4-9 oocytes retrieved) to gonadotropin stimulation despite the presence of adequate ovarian parameters, which ...negatively affect their cumulative chances of delivering a baby using Assisted Reproductive Technology. A polygenic trait involving gonadotropins and/or their receptors seems to be the primary pathophysiology mechanism explaining this phenomenon. The clinical management is mainly focused on maximizing oocyte yield as to increase the likelihood of having at least one euploid embryo for transfer. Indices such as FORT (follicle output rate) and FOI (follicle-to-oocyte index) may be used to determine if the ovarian reserve was properly explored during a previous ovarian stimulation. Testing for the presence of common polymorphisms affecting gonadotropins and/or their receptors can also be considered to identify patients at risk of hypo-response. An individualized estimation of the minimum number of oocytes needed to obtain at least one euploid embryo can assist counseling and treatment planning. Among currently existing pharmacological interventions, use of recombinant FSH in preference over urinary gonadotropin preparations, FSH dosage increase, and use of rLH supplementation may be considered -alone or combined- for optimally managing POSEIDON's groups 1 and 2 patients. However, given the recent introduction of the POSEIDON criteria, there is still a lack of studies examining the role of interventions specifically to patients classified as groups 1 and 2, thus making it an area for open research.
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