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Shame plays a central role in psychosocial functioning, being a transdiagnostic emotion associated with several mental health conditions. According to the evolutionary biopsychosocial model, shame is a painful and difficult emotion that may be categorized into two distinct focal components: external and internal shame. External shame is focused on the experience of the self as seen in a judgemental way by others, whereas internal shame is conceptualized as self-focused negative evaluations and feelings about the self. The current study aimed to develop the External and Internal Shame Scale (EISS) to assess in a single measure these two dimensions. The study was conducted in a community sample comprising 665 participants (18 to 61 years old). Three models were tested through confirmatory factor analysis. One higher order factor (global shame) with two lower order factors (external and internal shame) revealed a good fit to the data. The scale reliability and its association with other related constructs measures were also addressed. Additionally, gender differences on shame were explored. Results showed that EISS subscales and global score presented good internal consistency, concurrent validity and were associated with depressive symptoms. Regarding gender differences, results revealed that women presented significantly higher scores both in external and internal shame. The EISS showed to be a short, robust and reliable measure. The EISS allows the assessment of the specific dimensions of external and internal shame as well as a global sense of shame experience and may therefore be an important contribution for clinical work and research in human psychological functioning.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder often leading to anovulatory infertility. PCOS pathophysiology is still unclear and several potential genetic susceptibility factors have been proposed. The effect of polymorphisms in two genesrelated to follicular recruitment and development, the follicle-stimulating hormone receptor ( ) and the estrogen receptor 1 ( ), have been studied in different populations with contradictory results. To evaluate the influence of rs6166 (c.2039A>G) and of rs2234693 (Pvull c.453-397 T > C) polymorphisms on PCOS risk, phenotype, and response to controlled ovarian stimulation (COS). Genotyping of the rs6166 and the rs2234693 polymorphisms was performed in PCOS women and a control group undergoing in vitro fertilization (IVF). Demographic, clinical, and biochemical data, genotype frequency, and IVF outcomes were compared between groups. We evaluated 88 PCOS women and 80 controls. There was no significant difference in the genotype distribution of rs6166 polymorphism between PCOS women and controls (AA 31.8%/AS 48.9%/SS 19.3% in PCOS women vs AA 37.5%/AS 40.0%/SS 22.5% in controls; p = 0.522). The same was true for the rs2234693 (CC 24.1%/CT 46.0%/TT 29.9% in PCOS women vs CC 18.8%/CT 48.8%/TT 32.5% in controls; p = 0.697). In PCOS women, we found higher follicle-stimulating hormone (FSH) levels on the third day of the menstrual cycle associated with the SS variant of the polymorphism (9.2 vs 6.2 ± 1.6 and 5.6 ± 1.6 mUI/mL; p = 0.011). We did not find other associations between the baseline hormonal parameters, antral follicle count, and response measures to COS with or genotypes. We found, however, a need for higher cumulative doses of FSH for COS in patients with the SS variant of the rs6166 polymorphism (1860.5 ± 627.8 IU for SSvs 1498.1 ± 359.3 for AA and 1425.4 ± 474.8 for SA; p = 0.046 and p = 0.046). Our data suggest that in the population,  rs6166and polymorphisms do not influence the risk of developing PCOS nor do they influence the patient's phenotype and IVF success. However, the SS variant of the rs6166 polymorphism may be associated with FSH resistance requiring higher FSH doses for COS.

STUDY QUESTION What is the recommended management for women and transgender men with regards to fertility preservation (FP), based on the best available evidence in the literature? SUMMARY ANSWER The ESHRE Guideline on Female Fertility Preservation makes 78 recommendations on organization of care, information provision and support, pre-FP assessment, FP interventions and after treatment care. Ongoing developments in FP are also discussed. WHAT IS KNOWN ALREADY The field of FP has grown hugely in the last two decades, driven by the increasing recognition of the importance of potential loss of fertility as a significant effect of the treatment of cancer and other serious diseases, and the development of the enabling technologies of oocyte vitrification and ovarian tissue cryopreservation (OTC) for subsequent autografting. This has led to the widespread, though uneven, provision of FP for young women. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 November 2019 and written in English were included in the review. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE This guideline aims to help providers meet a growing demand for FP options by diverse groups of patients, including those diagnosed with cancer undergoing gonadotoxic treatments, with benign diseases undergoing gonadotoxic treatments or those with a genetic condition predisposing to premature ovarian insufficiency, transgender men (assigned female at birth), and women requesting oocyte cryopreservation for age-related fertility loss. The guideline makes 78 recommendations on information provision and support, pre-FP assessment, FP interventions and after treatment care, including 50 evidence-based recommendations—of which 31 were formulated as strong recommendations and 19 as weak—25 good practice points and 3 research only recommendations. Of the evidence-based recommendations, 1 was supported by high-quality evidence, 3 by moderate-quality evidence, 17 by low-quality evidence and 29 by very low-quality evidence. To support future research in the field of female FP, a list of research recommendations is provided. LIMITATIONS, REASONS FOR CAUTION Most interventions included are not well studied in FP patients. As some interventions, e.g. oocyte and embryo cryopreservation, are well established for treatment of infertility, technical aspects, feasibility and outcomes can be extrapolated. For other interventions, such as OTC and IVM, more evidence is required, specifically pregnancy outcomes after applying these techniques for FP patients. Such future studies may require the current recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides clinicians with clear advice on best practice in female FP, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in FP. STUDY FUNDING/COMPETING INTEREST(S) The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. R.A.A. reports personal fees and non-financial support from Roche Diagnostics, personal fees from Ferring Pharmaceuticals, IBSA and Merck Serono, outside the submitted work; D.B. reports grants from Merck Serono and Goodlife, outside the submitted work; I.D. reports consulting fees from Roche and speaker’s fees from Novartis; M.L. reports personal fees from Roche, Novartis, Pfizer, Lilly, Takeda, and Theramex, outside the submitted work. The other authors have no conflicts of interest to declare. DISCLAIMER This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.) †ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.

Background It is estimated that around 70% of Type 2 Diabetes Mellitus patients (T2DM) have Non-Alcoholic Fatty Liver Disease (NAFLD). Awareness and education are amongst the major shortcomings of the public health response to the increasing threat of NAFLD. Characterizing the specific NAFLD-related information needs of particular high-risk metabolic communities, for instance, T2DM patients, might aid in the development of evidence-based health promotion strategies, ultimately promoting NAFLD-awareness, treatment adherence and therapeutic success rates. Methods Semi-structured interviews with T2DM patients were conducted to gain insight into their awareness of NAFLD, including its relationship with insulin resistance and T2DM. Results Awareness of NAFLD as a disease entity, as well as its progression to end-stage liver disease or its relationship with other metabolic conditions, including insulin resistance and T2DM was low. Surveillance behaviours were also suboptimal and perceptions on the self-management knowledge and praxis regarding lifestyle intervention components of T2DM treatment seemed detached from those of NAFLD. Conclusions Our findings could inform the integration of NAFLD-related content in T2DM health promotion strategies. Rising awareness on NAFLD progression and its relationship with T2DM using culturally and community-relevant constructs might facilitate the development of primary and secondary prevention programmes to promote the adherence to lifestyle interventions by influencing NAFLD threat perceptions.

Background The postponement of parenthood may increase the number of couples experiencing infertility and prolonged time to pregnancy. Previous research has revealed that childless people are not well informed regarding fertility, which may threat their childbearing intentions. This study aimed to examine fertility knowledge and childbearing intentions held by Portuguese people and their use and perceived usefulness of information sources on fertility. Methods Participants were recruited using a random-route domiciliary approach. A total of 2404 individuals aged 18–45 were asked to complete a structured questionnaire evaluating socio-demographic characteristics, childbearing intentions, fertility knowledge and information-gathering sources regarding fertility. Results In total, 95.5% of the participants indicated the desire to have children in the future, and 61.7% reported that having children would contribute to life satisfaction. Most of the participants expressed the desire to have two children in the future. The discrepancy between the numbers of planned and desired children was higher in men, in participants with lower education levels, in professionally active participants and in the unemployed participants. Relationship stability seemed to be more important in influencing childbearing decisions than financial stability or family support. Participants’ knowledge regarding fertility was poor. Women, the participants who were older than 25, the participants with longer education and the participants with higher income exhibited the greatest levels of knowledge of fertility, although this knowledge was only slightly enhanced in these subgroups. Also, the participants overestimated both the chances of spontaneous pregnancy and the success rates of assisted reproduction techniques. Finally, the results revealed that websites were the main information sources used by the participants and only 18.0% of the participants had previously discussed fertility issues with their doctors. Conclusions Although Portuguese men and women reported the desire to have children in the future, their knowledge regarding fertility and infertility risk was poor. In addition, participants used more general sources of information, such as website, but not specialized sources, such as their doctors. There is a real need to work with general practitioners to empower them to provide adequate fertility information to every childless patient.

Shame is a universal emotion, albeit having a bewildering constellation of causes, valuations, and behavioural consequences that differ across social ecologies. This transdiagnostic emotion may be categorized into two distinct components: external and internal shame. The External and Internal Shame Scale (EISS) has proven to be a brief and reliable instrument to assess external and internal shame, as well as a global sense of shame. The current study aims to corroborate the validity of the EISS and expand its utility, by investigating its dimensionality and testing its measurement invariance in samples from five eclectic countries from Europe, East and Southeast Asia and Australia. Differences in EISS scores across the five countries were also explored. This cross-national study included 1405 participants recruited in community samples of adults from Portuguese, French, Australian, Singaporean and Japanese populations, who completed the EISS in four different languages. An hierarchical model with two factors (external and internal shame) loading on one global factor (global shame) revealed good fit to the data in the total sample and in each of the five countries’ samples, and the instrument showed good reliability across countries. The EISS factorial structure also proved to be invariant across countries. Differences in global shame, external and internal shame scores were found between the countries. By supporting the factorial structure, reliability and measurement invariance of the EISS across countries, this study contributes to expand the use of the EISS across nations and in different languages, both in research and clinical settings.

Background Breast cancer is the most common cancer in young women. Fortunately current survival rates of BC are significant which makes future fertility very important for quality of life of BC survivors. Chemotherapy carries a significant risk of infertility in BC patients so it is important to support fertility preservation decisions in premenopausal women. Amenorrhea has long been used as a surrogate marker of infertility in cancer patients but more reliable ovarian reserve (OR) markers are available. This study aimed to prospectively measure levels of OR in a cohort of young women with breast cancer exposed to chemotherapy, to identify adverse reproductive health outcomes in this population and to assess the influence of patient and treatment-related factors in those outcomes. Methods This prospective observational study included premenopausal women with breast cancer aged 18–40 years at diagnosis and proposed for (neo) adjuvant chemotherapy. Patients were evaluated before, during and a minimum of 9 months after the end of chemotherapy. Reproductive health outcomes: menses, hormonal and ultrasound OR markers, recovery of ovarian function and Premature Ovarian Insufficiency (POI). Results A total of 38 patients were included (mean age 32.9 ± 3.5 years). Levels of OR significantly decreased during the study. At the last follow up, 35 patients had AMH below the expected values for age; eight presented postmenopausal FSH; ten had not recovered their ovarian function and five met the defined criteria for POI. Age and baseline AMH were positively correlated with AMH at the last follow-up. AMH levels were higher in the group of patients treated with trastuzumab and lower in those under hormonal therapy, at the last follow-up. Conclusions Significant effects of systemic treatments on several reproductive outcomes and a strong relation of those outcomes with patient’s age and baseline level of AMH were observed. Our results point to a possible lower gonadotoxicity when treatment includes targeted therapy with trastuzumab. Also, this investigation highlights the lack of reliable OR markers in women under hormonal therapy.

The global trend of rising (male) infertility is concerning, and the unidentifiable causes in half of the cases, the so-called unknown origin male infertility (UOMI), demands a better understanding and assessment of both external/internal factors and mechanisms potentially involved. In this work, it was our aim to obtain new insight on UOMI, specifically on idiopathic (ID) and Unexplained male infertility (UMI), relying on a detailed evaluation of the male gamete, including functional, metabolic and proteomic aspects. For this purpose, 1114 semen samples, from males in couples seeking infertility treatment, were collected at the Reproductive Medicine Unit from the Centro Hospitalar e Universitário de Coimbra (CHUC), from July 2018–July 2022. Based on the couples’ clinical data, seminal/hormonal analysis, and strict eligibility criteria, samples were categorized in 3 groups, control (CTRL), ID and UMI. Lifestyle factors and anxiety/depression symptoms were assessed via survey. Sperm samples were evaluated functionally, mitochondrially and using proteomics. The results of Assisted Reproduction Techniques were assessed whenever available. According to our results, ID patients presented the worst sperm functional profile, while UMI patients were similar to controls. The proteomic analysis revealed 145 differentially expressed proteins, 8 of which were specifically altered in ID and UMI samples. Acrosin (ACRO) and sperm acrosome membrane-associated protein 4 (SACA4) were downregulated in ID patients while laminin subunit beta-2 (LAMB2), mannose 6-phosphate isomerase (MPI), ATP-dependent 6-phosphofructokinase liver type (PFKAL), STAR domain-containing protein 10 (STA10), serotransferrin (TRFE) and exportin-2 (XPO2) were downregulated in UMI patients. Using random forest analysis, SACA4 and LAMB2 were identified as the sperm proteins with a higher chance of distinguishing ID and UMI patients, and their function and expression variation were in accordance with the functional results. No alterations were observed in terms of lifestyle and psychological factors among the 3 groups. These findings obtained in an experimental setting based on 3 well-defined groups of subjects, might help to validate new biomarkers for unknown origin male infertility (ID and UMI) that, in the future, can be used to improve diagnostics and treatments.

Treatment for pediatric cancer requires periodic and long hospital admissions. The intensity and frequency of the interactions taking place in the treatment setting indicate that this is a context to which children and their families can feel connected. This study’s main goal was to develop the Connectedness to Treatment Setting Scale (CTSS-Pediatric Cancer), a 10-item scale assessing children’s and parents’ connectedness to the health setting where children receive cancer treatment. Participants were 128 dyads of children receiving treatment at two Portuguese public hospitals and their parents. Two exploratory factor analyses with children’s and parents’ data separately and a dyadic confirmatory factor analysis with the whole sample supported a second-order factorial structure of the CTSS-Pediatric Cancer, where three dimensions (Sense of Belonging, Comfort and Emotional Care) loaded onto a total score of connectedness. Findings suggest that the CTSS-Pediatric Cancer is a valid and useful assessment measure.

We aim to validate a European-Portuguese version of the Hypertension Knowledge Test (HKT) questionnaire and examine its factorial structure with a confirmatory factor analysis (CFA). A process of translation and back-translation was performed. A cross-sectional study was developed in which all adult patients taking at least one antihypertensive drug were invited to participate. Data on personal and family history were collected, and the HKT, Strelec, and the Batalla questionnaires were administered. We enrolled 304 patients with a mean age of 68.12±10.83 years. The mean score of HKT was 15.33±2.79. CFA indicated that the construct being tested was unidimensional, and Cronbach’s alpha (α=0.65) showed that the instrument had an acceptable internal consistency. When evaluating concurrent validity, HKT was significantly correlated with the Batalla and Strelec scores. Thus, the Portuguese version of HKT (HKT-pt-PT) can be used either in research or in clinical practice. With this version, a potential standard exists to evaluate knowledge about hypertension, which could avoid the practice of using non-validated questionnaires in Portugal and allow the cross-sectional and longitudinal comparability of studies.