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Background: Steroid hormones (i.e., estradiol, progesterone, and testosterone) are considered to play a crucial role in the regulation of women’s sexual desire and sexual attraction to sexual stimuli throughout the menstrual cycle. However, the literature is inconsistent, and methodologically sound studies on the relationship between steroid hormones and women’s sexual attraction are rare. Methods: This prospective longitudinal multisite study examined estradiol, progesterone, and testosterone serum levels in association with sexual attraction to visual sexual stimuli in naturally cycling women and in women undergoing fertility treatment (in vitro fertilization, IVF). Across ovarian stimulation of fertility treatment, estradiol reaches supraphysiological levels, while other ovarian hormones remain nearly stable. Ovarian stimulation hence offers a unique quasi-experimental model to study concentration-dependent effects of estradiol. Hormonal parameters and sexual attraction to visual sexual stimuli assessed with computerized visual analogue scales were collected at four time points per cycle, i.e., during the menstrual, preovulatory, mid-luteal, and premenstrual phases, across two consecutive menstrual cycles (n = 88 and n = 68 for the first and second cycle, respectively). Women undergoing fertility treatment (n = 44) were assessed twice, at the beginning and at the end of ovarian stimulation. Sexually explicit photographs served as visual sexual stimuli. Results: In naturally cycling women, sexual attraction to visual sexual stimuli did not vary consistently across two consecutive menstrual cycles. While in the first menstrual cycle sexual attraction to male bodies, couples kissing, and at intercourse varied significantly with a peak in the preovulatory phase, (all p ≤ 0.001), there was no significant variability across the second cycle. Univariable and multivariable models evaluating repeated cross-sectional relationships and intraindividual change scores revealed no consistent associations between estradiol, progesterone, and testosterone and sexual attraction to visual sexual stimuli throughout both menstrual cycles. Also, no significant association with any hormone was found when the data from both menstrual cycles were combined. In women undergoing ovarian stimulation of IVF, sexual attraction to visual sexual stimuli did not vary over time and was not associated with estradiol levels despite intraindividual changes in estradiol levels from 122.0 to 11,746.0 pmol/l with a mean (SD) of 3553.9 (2472.4) pmol/l. Conclusions: These results imply that neither physiological levels of estradiol, progesterone, and testosterone in naturally cycling women nor supraphysiological levels of estradiol due to ovarian stimulation exert any relevant effect on women’s sexual attraction to visual sexual stimuli.

The menstrual cycle is characterized by various hormonal alterations and associations with mental and physical conditions have been postulated. Among endocrine factors, the androgen system has been a target of major interest in males and to a lesser extent in females and may influence emotion, cognition, behavior and somatic factors. Only few studies investigated alterations of these parameters throughout the menstrual cycle and there is a lack of studies exploring a link towards epigenetic and genetic regulation. This multisite longitudinal study examines behavioral parameters including affectivity, stress perception and various diary parameters of mental and physical well-being in conjunction with testosterone and LH plasma levels in 87 menstruating women. Additionally, Cysteine-Adenenine-Guanin (CAG) repeat length and methylation of the androgen receptor gene collected at four time points across two cycles comprising the menstrual, pre-ovulatory, mid-luteal and premenstrual phase were assesed. There was a significant increase of LH and testosterone plasma levels during the pre-ovulatory phase as well as a decrease of methylation of the androgen receptor at mid-luteal phase. Subjective ratings of physical condition and sexual interest peaked during the pre-ovulatory phase and the former correlated negatively with the androgen receptor gene methylation level. This longitudinal study shows alterations of the androgen system including epigenetic measurements throughout the menstrual cycle. While a link between peripheral testosterone and sexual activity and between increased physical condition and an upregulation of testosterone receptor protein expression can be assumed, the majority of parameters remained unchanged. These initial findings need validation by subsequent studies.

Purpose To evaluate the use of wearable sensors for prediction of intraamniotic infection in pregnant women with PPROM. Materials and methods In a prospective proof of principle study, we included 50 patients diagnosed with PPROM at the University Hospital Zurich between November 2017 and May 2020. Patients were instructed to wear a bracelet during the night, which measures physiological parameters including wrist skin temperature, heart rate, heart rate variability, and breathing rate. A two-way repeated measures ANOVA was performed to evaluate the difference over time of both the wearable device measured parameters and standard clinical monitoring values, such as body temperature, pulse, leucocytes, and C-reactive protein, between women with and without intraamniotic infection. Results Altogether, 23 patients (46%) were diagnosed with intraamniotic infection. Regarding the physiological parameters measured with the bracelet, we observed a significant difference in breathing rate (19 vs 16 per min, P P = .03) in women with intraamniotic infection compared to those without during the 3 days prior to birth. In parallel to these changes standard clinical monitoring values were significantly different in the intraamniotic infection group compared to women without infection in the 3 days preceding birth. Conclusion Our results suggest that wearable sensors are a promising, noninvasive, patient friendly approach to support the early detection of intraamniotic infection in women with PPROM. However, confirmation of our findings in larger studies is required before implementing this technique in standard clinical management.

Background Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. Objective and rationale We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Search methods Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. Outcomes We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a central action of estrogens to increase the satiating potency of the gastrointestinal hormone cholecystokinin. Another mechanism involves a decrease in the preference for sweet foods during the follicular phase. Genetic defects in brain α-melanocycte-stimulating hormone-melanocortin receptor (melanocortin 4 receptor, MC4R) signaling lead to a syndrome of overeating and obesity that is particularly pronounced in women and in female animals. The syndrome appears around puberty in mice with genetic deletions of MC4R, suggesting a role of ovarian hormones. Emerging functional brain-imaging data indicates that fluctuations in ovarian hormones affect eating by influencing striatal dopaminergic processing of flavor hedonics and lateral prefrontal cortex processing of cognitive inhibitory controls of eating. There is a dearth of research on the neuroendocrine control of eating after menopause. There is also comparatively little research on the effects of ovarian hormones on EE, although changes in ovarian hormone levels during the menstrual cycle do affect resting EE. Wider implications The markedly greater obesity burden in women makes understanding the diverse effects of ovarian hormones on eating, EE and body adiposity urgent research challenges. A variety of research modalities can be used to investigate these effects in women, and most of the mechanisms reviewed are accessible in animal models. Therefore, human and translational research on the roles of ovarian hormones in women's obesity and its causes should be intensified to gain further mechanistic insights that may ultimately be translated into novel anti-obesity therapies and thereby improve women's health.

STUDY QUESTION Is fatigue a frequent symptom of endometriosis? SUMMARY ANSWER Fatigue is an underestimated symptom of endometriosis as it affects the majority of women with endometriosis, but it is not widely discussed in literature. WHAT IS KNOWN ALREADY Fatigue can be a symptom of endometriosis causing major distress impacting the daily activities and quality of life of women with endometriosis. However, few studies with large sample sizes have investigated fatigue as a symptom of endometriosis. STUDY DESIGN, SIZE, DURATION The study was designed as a multi-center matched case-control study. Recruitment took place at hospitals and private practices in Switzerland, Germany and Austria between 2010 and 2016. Data was collected from 1120 women, 560 of them with endometriosis. The women with endometriosis were matched to 560 control women in regard to age ±3 years and ethnic background. PARTICIPANTS/MATERIALS, SETTING, METHODS Diagnosis of women with endometriosis had to be surgically and histologically confirmed. Surgical exclusion or absence of any endometriosis-identifying symptoms was required for control subjects. Materials included surgical and histological reports as well as data retrieved from a self-administered questionnaire. This study focused on the symptom fatigue in endometriosis. Relationships of variables were established by regression analysis and associations were quantified as odds ratios. MAIN RESULTS AND THE ROLE OF CHANCE Frequent fatigue was experienced by a majority of women diagnosed with endometriosis (50.7% versus 22.4% in control women, P < 0.001). Fatigue in endometriosis was associated with insomnia (OR: 7.31, CI: 4.62-11.56, P < 0.001), depression (OR: 4.45, CI: 2.76-7.19, P < 0.001), pain (OR: 2.22, CI: 1.52-3.23, P < 0.001), and occupational stress (OR: 1.45, CI: 1.02-2.07, P = 0.037), but was independent of age, time since first diagnosis and stage of the disease. LIMITATIONS, REASONS FOR CAUTION Women with asymptomatic endometriosis cannot be excluded in the control group which would lead to underestimation of our results. The study's design allows no evaluation of causal effects. WIDER IMPLICATIONS OF THE FINDINGS As fatigue is experienced by numerous women with endometriosis, it needs to be addressed in the discussion of management and treatment of the disease. In addition to treating endometriosis, it would be beneficial to reduce insomnia, depression, pain and occupational stress in order to better manage fatigue. STUDY FUNDING/COMPETING INTEREST(s) There was no additional funding received for this study and no conflict of interest. TRIAL REGISTRATION NUMBER ClinicalTrials.gov, NCT 02511626.

Therapeutic use of mesenchymal stem cells (MSCs) for tissue repair has great potential. MSCs from multiple sources, including those derived from human umbilical matrix, namely Wharton’s jelly, may serve as a resource for obtaining MSCs. However, low in vivo engraftment efficacy of MSCs remains a challenging limitation. To improve clinical outcomes using MSCs, an in-depth understanding of the mechanisms and factors involved in successful engraftment is required. We recently demonstrated that 17β-estradiol (E2) improves MSCs in vitro proliferation, directed migration and engraftment in murine heart slices. Here, using a proteomics approach, we investigated the angiogenic potential of MSCs in vivo and the modulatory actions of E2 on mechanisms involved in tissue repair. Specifically, using a Matrigel® plug assay, we evaluated the effects of E2 on MSCs-induced angiogenesis in ovariectomized (OVX) mice. Moreover, using proteomics we investigated the potential pro-repair processes, pathways, and co-mechanisms possibly modified by the treatment of MSCs with E2. Using RT-qPCR, we evaluated mRNA expression of pro-angiogenic molecules, including endoglin, Tie-2, ANG, and VEGF. Hemoglobin levels, a marker for blood vessel formation, were increased in plugs treated with E2 + MSCs, suggesting increased capillary formation. This conclusion was confirmed by the histological analysis of capillary numbers in the Matrigel® plugs treated with E2 + MSC. The LC-MS screening of proteins obtained from the excised Matrigel® plugs revealed 71 proteins that were significantly altered following E2 exposure, 57 up-regulated proteins and 14 down-regulated proteins. A major result was the association of over 100 microRNA molecules (miRNAs) involved in cellular communication, vesicle transport, and metabolic and energy processes, and the high percentage of approximately 25% of genes involved in unknown biological processes. Together, these data provide evidence for increased angiogenesis by MSCs treated with the sex hormone E2. In conclusion, E2 treatment may increase the engraftment and repair potential of MSCs into tissue, and may promote MSC-induced angiogenesis after tissue injury.

Introduction Endometriosis is an inflammatory condition, affecting mainly women of reproductive age. Leptin is a regulator of food intake and energy expenditure, posing pleiotropic actions, and regulating immunity and fertility. The aim of this study was to systematically review the literature regarding leptin concentrations in biological fluids and tissues of women with endometriosis, and to investigate and propose a possible role of leptin in the pathophysiology of endometriosis. Materials and methods A systematic search of the literature was conducted in two electronic databases (MEDLINE, COCHRANE) and grey literature for original research articles on humans, published in any language. Results Twenty-nine studies with 1291 women with endometriosis and 1664 controls were included in the systematic review. Peritoneal fluid and follicular fluid leptin concentrations were higher in endometriosis compared with control group [mean difference (MD) 7.10, 95 % confidence interval (CI) 4.76 to 9.44 ng/mL, 18 studies), (MD 1.35, 95 % CI 0.54–2.17 ng/ml, 2 studies) respectively. No differences were evident in serum (MD 0.92, 95 % CI -0.84 to 2.68 ng/mL, 12 studies) or plasma (MD -0.95, 95 % CI -4.63 to 2.72 ng/mL, 3 studies) between the groups. No meta-analysis was conducted for ovarian tissue leptin (2 studies). Conclusions This meta-analysis provided evidence for increased leptin concentrations in both peritoneal fluid and follicular fluid of women with endometriosis compared with control; these differences were not present in the serum or plasma. The above results support a potential pathophysiologic role for leptin in the local microenvironment while declines its use as a blood diagnostic marker. Furthermore, we propose a possible role of leptin in the pathophysiology of endometriosis.

Autocrine/paracrine factors generated in response to 17β-estradiol (E2) within the fallopian tube (FT) facilitate fertilization and early embryo development for implantation. Since cyclic AMP (cAMP) plays a key role in reproduction, regulation of its synthesis by E2 may be of biological/pathophysiological relevance. Herein, we investigated whether cAMP production in FT cells (FTCs) is regulated by E2 and environmental estrogens (EE’s, xenoestrogens and phytoestrogens). Under basal conditions, low levels of extracellular cAMP were detectable in bovine FTCs (epithelial cells and fibroblasts, 1:1 ratio). Treatment of FTCs with forskolin (AC, adenylyl cyclase activator), isoproterenol (β-adrenoceptor agonist) and IBMX (phosphodiesterase (PDE) inhibitor) dramatically (&gt, 10 fold) increased cAMP, whereas LRE1 (sAC, soluble AC inhibitor) and 2’,5’-dideoxyadenosine (DDA, transmembrane AC (tmAC)) inhibitor decreased cAMP. Comparable changes in basal and stimulated intracellular cAMP were also observed. Ro-20-1724 (PDE-IV inhibitor), but not milrinone (PDE-III inhibitor) nor mmIBMX (PDE-I inhibitor), augmented forskolin-stimulated cAMP levels, suggesting that PDE-IV dominates in FTCs. E2 increased cAMP levels and CREB phosphorylation in FTCs, and these effects were mimicked by EE’s (genistein, 4-hydroxy-2’,4’,6’-trichlorobiphenyl, 4-hydroxy-2’,4’,6’-dichlorobiphenyl). Moreover, the effects of E2 and EE were blocked by the tmAC inhibitor DDA, but not by the ERα/β antagonist ICI182780. Moreover, BAPTA-AM (intracellular-Ca2+ chelator) abrogated the effects of E2, but not genistein, on cAMP suggesting differential involvement of Ca2+. Treatment with non-permeable E2-BSA induced cAMP levels and CREB-phosphorylation, moreover, the stimulatory effects of E2 and EEs on cAMP were blocked by G15, a G protein-coupled estrogen receptor (GPER) antagonist. E2 and IBMX induced cAMP formation was inhibited by LRE1 and DDA suggesting involvement of both tmAC and sAC. Our results provide the first evidence that in FTCs, E2 and EE’s stimulate cAMP synthesis via GPER. Exposure of the FT to EE’s and PDE inhibitors may result in abnormal non-cyclic induction of cAMP levels which may induce deleterious effects on reproduction.

Pericytes facilitate blood–brain barrier (BBB) integrity, however, the mechanisms involved remain unclear. Hence, using co-cultures of human cerebral microvascular endothelial cells (ECs) and vascular pericytes (PCs) in different spatial arrangements, as well as PC conditioned media, we investigated the impact of PC-EC orientation and PC-derived soluble factors on EC barrier function. We provide the first evidence that barrier-inducing properties of PCs require basolateral contact with ECs. Gene expression analysis (GEA) in ECs co-cultured with PCs versus ECs alone showed significant upregulation of 38 genes and downregulation of 122 genes. Pathway enrichment analysis of modulated genes showed significant regulation of several pathways, including transforming growth factor-β and interleukin-1 regulated extracellular matrix, interferon and interleukin signaling, immune system signaling, receptor of advanced glycation end products (RAGE), and cytokine–cytokine receptor interaction. Transcriptomic analysis showed a reduction in molecules such as pro-inflammatory cytokines and chemokines, which are known to be induced during BBB disruption. Moreover, cytokine proteome array confirmed the downregulation of key pro-inflammatory cytokines and chemokines on the protein level. Other molecules which influence BBB and were favorably modulated upon EC-PC co-culture include IL-18 binding protein, kallikrein-3, CSF2 CSF3, CXCL10, CXCL11 (downregulated) and IL-1-R4, HGF, PDGF-AB/BB, PECAM, SERPIN E1 (upregulated). In conclusion, we provide the first evidence that (1) basolateral contact between ECs and PCs is essential for EC barrier function and integrity, (2) in ECs co-cultured with PCs, the profile of BBB disrupting pro-inflammatory molecules and cytokines/chemokines is downregulated, (3) PCs significantly modulate EC mechanisms known to improve barrier function, including TGF-β regulated ECM pathway, anti-inflammatory cytokines, growth factors and matrix proteins. This human PC-EC co-culture may serve as a viable in vitro model for investigating BBB function and drug transport.

Motivation Model-based approaches to safety and efficacy assessment of pharmacological drugs, treatment strategies or medical devices (In Silico Clinical Trial, ISCT) aim to decrease time and cost for the needed experimentations, reduce animal and human testing, and enable precision medicine. Unfortunately, in presence of non-identifiable models (e.g. reaction networks), parameter estimation is not enough to generate complete populations of Virtual Patients (VPs), i.e. populations guaranteed to show the entire spectrum of model behaviours (phenotypes), thus ensuring representativeness of the trial. Results We present methods and software based on global search driven by statistical model checking that, starting from a (non-identifiable) quantitative model of the human physiology (plus drugs PK/PD) and suitable biological and medical knowledge elicited from experts, compute a population of VPs whose behaviours are representative of the whole spectrum of phenotypes entailed by the model (completeness) and pairwise distinguishable according to user-provided criteria. This enables full granularity control on the size of the population to employ in an ISCT, guaranteeing representativeness while avoiding over-representation of behaviours. We proved the effectiveness of our algorithm on a non-identifiable ODE-based model of the female Hypothalamic-Pituitary-Gonadal axis, by generating a population of 4 830 264 VPs stratified into 7 levels (at different granularity of behaviours), and assessed its representativeness against 86 retrospective health records from Pfizer, Hannover Medical School and University Hospital of Lausanne. The datasets are respectively covered by our VPs within Average Normalized Mean Absolute Error of 15%, 20% and 35% (90% of the latter dataset is covered within 20% error). Availability and implementation. Our open-source software is available at https://bitbucket.org/mclab/vipgenerator Supplementary information Supplementary data are available at Bioinformatics online.

Youths are particularly at risk of experiencing sexual victimization but research tends to focus on the most violent forms (i.e. rape or child sexual abuse) and on female cases. This study aimed at identifying factors associated to different types of unwanted sexual experiences (USE) among young females and males as well as estimating probabilities of experiencing sexual victimization among gender. Data were drawn from a cross-sectional survey on sexual health and behaviors using a nationally representative sample of youths aged 24–26 living in Switzerland. Respondents (N = 5290) were divided in three categories of reported USE, ordered by conceptualized severity. The fourth group was constituted of those never having experienced any. Weighted bivariate and multivariate analyses were performed using demographic characteristics and risk behavior indicators. At the multivariate level, the higher the severity of USE, the higher the number of associated factors, revealing the complexity of this issue. Females had a higher probability of experiencing sexual victimization than of never experiencing any, with a probability of two out of three. They faced higher probabilities of sexual victimization than males, although males’ probability of USE were not as marginal as expected, further considering that they are found to face higher rates of non-disclosure than females. USE is a complex issue, and the level of complexity increases in parallel with its severity. Although it is much more frequent among females, males report highers rates than expected. When investigating sexual victimization, there is a need to consider the diverse forms of USE and adopt a gendered approach in order to better comprehend sexual victimization and effectively intervene on the social, legal, and public health levels to prevent sexual victimization among youths.

STUDY QUESTION Does follicular flushing increase the number of mature oocytes in monofollicular IVF? SUMMARY ANSWER Follicular flushing increases the number of mature oocytes in monofollicular IVF. WHAT IS KNOWN ALREADY Flushing increases neither the oocyte yield nor the pregnancy rate in polyfollicular IVF or in poor responder patients. In monofollicular IVF, the effect of flushing has so far been addressed by two studies: (i) a prospective study with minimal stimulation IVF demonstrated an increased oocyte yield, and (ii) a retrospective study with natural cycle (NC)-IVF showed an increased oocyte yield and an increased transfer rate. STUDY DESIGN, SIZE, DURATION Randomized controlled trial including 164 women who were randomized for either aspiration with or without flushing from 2016 to 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS Infertile women 18–42 years of age with an indication for IVF treatment at a university-based infertility unit. Women undergoing monofollicular IVF were randomized to either follicular aspiration only or follicular aspiration directly followed by five follicular flushes at a 1:1 ratio. The intervention was done without anaesthesia, using a gauge 19 single-lumen needle. Flushing volume was calculated (sphere formula) based on the size of the follicle. MAIN RESULTS AND THE ROLE OF CHANCE A total of 164 women were included; 81 were allocated to ‘aspiration only’ and 83 to additional ‘flushing’. Primary analysis was based on the intention-to-treat: oocyte yield, defined as the collected mature oocyte rate, was higher (n = 64/83, 77.1%) in the flushing group compared to the aspiration only group (n = 48/81, 59.3%, adjusted risk difference (RD): 18.2% (95% CI 3.9–31.7%), P-value = 0.02). In the flushing group, most oocytes were retrieved within the first three flushes (63/83, 75.8%). Fertilization rate was higher in the flushing group (n = 53/83, 63.9% vs n = 38/81, 46.9%; adjusted RD: 16.8% (96% CI 1.5–31.4%), P = 0.045). Transfer rate was also higher in the flushing group (n = 52/83, 62.7% vs n = 38/81, 46.9%; RD: 15.71 (95% CI 0.3–30.3%)), but the difference was not significant (P = 0.06). The clinical pregnancy rate n = 9/83 versus n = 9/81 (RD: −0.3% (95% CI −9.9% to 9.5%)) and live birth rate n = 7/83 versus n = 8/81 (RD: −1.5% (95% CI −10.4% to 7.1%)) were not significantly different between the flushing and the aspiration group. The median duration of the intervention was significantly longer with flushing (2.38 min; quartiles 2.0, 2.7) versus aspiration only (0.43 min; quartiles 0.3, 0.5) (P LIMITATIONS, REASONS FOR CAUTION Blinding of the procedure was not possible. WIDER IMPLICATIONS OF THE FINDINGS Our study proved that flushing of single follicles in NC-IVF increases the oocyte yield. In contrast to polyfollicular IVF flushing seems to be beneficial in a monofollicular setting if the technique used in our study (single-lumen needle, 5 flushings with flushing volume adaptation) is applied. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the financial sources of the division and in part by a research grant provided by NMS Biomedical SA, Switzerland. The company did not have any roles in design or conduct of the study or in the preparation of the manuscript. The authors have no other conflicts of interest. TRIAL REGISTRATION NUMBER Clinicaltrials.gov NCT 02641808. TRIAL REGISTRATION DATE 29 December 2015 DATE OF FIRST PATIENT’S ENROLMENT 22 August 2016

Background One of the possible negative consequences of sexting is the non-consensual sharing of received-intimate content. This study aimed to determine the characteristics and motives of youths who shared received-intimate images without consent. Methods: Data were obtained from a self-administrated Swiss survey on sexual behaviours among young adults (aged 24–26 years). Out of the 7142 participants, 5175 responded to the question ‘Have you ever shared (forwarding or showing) a sexy photograph/video of someone else (known or unknown) without consent’?; 85% had never shared (Never), 6% had shared once (Once) and 9% had shared several times (Several). Data are presented as relative risk ratios with 95% confidence intervals. Results: Participants who had shared received-intimate content without consent had higher odds of being male [2.73 (2.14–3.47)], foreign-born [1.45 (1.04–2.03)], reporting a non-heterosexual orientation [1.46 (1.10–1.93)], having sent one’s own intimate image [1.76 (1.32–2.34)] and receiving a shared-intimate image of someone unknown [4.56 (3.28–6.36)] or known [2.76 (1.52–5.01)] compared with participants who had never shared. The main reported motivations were for fun (62%), showing off (30%) and failure to realise what they were doing (9%). Conclusions: Given the reported motivations, it appears crucial to remind youths of the seriousness of non-consensual sharing. Although females may also be perpetrators, the behaviour was more prevalent among males. Prevention and education need to consider a broad range of young people in their scenarios. Even if a particular focus on understanding and preventing males’ perpetration must be considered, overall perpetration, including female’s, must be discussed.

We evaluated whether a second semen analysis as suggested by the WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction would improve diagnostic reliability in the evaluation of male infertility.We analyzed a total of 5,132 semen samples from 2,566 men who underwent at least 2 consecutive semen analyses at a university fertility center. Reproducibility and correlation between the first and second analyses were evaluated for sperm concentration, motility and morphology according to the WHO criteria as well as the total motile sperm count.Altogether 51.2% of the second analyses confirmed the initial findings according to WHO criteria and 60% confirmed them when applying total motile sperm count criteria. After finding normozoospermia on the initial analysis 27% of the second semen analyses were pathological. Following a first pathological semen analysis 23% of the second analyses were normal and 77% were pathological. The coefficient of variation ranged from 0.23 to 0.60. The Spearman correlation coefficient was high for sperm concentration (rIn accordance with WHO recommendations 2 consecutive semen analysis should be performed.

Stress is a risk factor for impaired general, mental, and reproductive health. The role of physiological and supraphysiological estradiol concentrations in stress perception and stress processing is less well understood. We, therefore, conducted a prospective observational study to investigate the association between estradiol, stress perception, and stress-related cognitive performance within serial measurements either during the natural menstrual cycle or during fertility treatment, where estradiol levels are strongly above the physiological level of a natural cycle, and consequently, represent a good model to study dose-dependent effects of estradiol. Data from 44 women receiving in vitro fertilization (IVF) at the Department of Reproductive Endocrinology in Zurich, Switzerland was compared to data from 88 women with measurements during their natural menstrual cycle. The German version of the Perceived Stress Questionnaire (PSQ) and the Cognitive Bias Test (CBT), in which cognitive performance is tested under time stress were used to evaluate subjective and functional aspects of stress. Estradiol levels were investigated at four different time points during the menstrual cycle and at two different time points during a fertility treatment. Cycle phases were associated with PSQ worry and cognitive bias in normally cycling women, but different phases of fertility treatment were not associated with subjectively perceived stress and stress-related cognitive bias. PSQ lack of joy and PSQ demands related to CBT in women receiving fertility treatment but not in women with a normal menstrual cycle. Only strong changes of the estradiol level during fertility treatment were weakly associated with CBT, but not with subjectively experienced stress. Our research emphasizes the multidimensional character of stress and the necessity to adjust stress research to the complex nature of stress perception and processing. Infertility is associated with an increased psychological burden in patients. However, not all phases of the process to overcome infertility do significantly increase patient stress levels. Also, research on the psychological burden of infertility should consider that stress may vary during the different phases of fertility treatment. Clinical trial registration: ClinicalTrials.gov # NCT02098668.

ObjectivesEndometriosis is a gynaecological disease most commonly causing severe and chronic pelvic pain as well as an impaired quality of life. The aim of this study was to investigate if and how endometriosis affects choices regarding professional life as well as the quality of daily working life.Design, setting and participantsIn the context of a multicentre case–control study, we collected data from 505 women with surgically/histologically confirmed diagnosis of endometriosis and 505 matched controls. Study participants were recruited prospectively in hospitals and doctors’ practices in Switzerland, Germany and Austria. Using a detailed questionnaire, the study investigated work–life and career choices of study participants.Main outcome measuresAssociations between endometriosis/disease symptoms and limitations in career development as well as ability to work.ResultsWomen with endometriosis were less often able to work in their desired profession than women from the control group (adjusted OR=1.84, 95% CI: 1.15 to 2.94, R2=0.029, p=0.001) and they had to take health-related limitations into consideration in their career decisions to a significantly higher degree than women in the control group (OR=4.79, 95% CI: 2.30 to 9.96, R2=0.063, p2=0.072, p2=0.087, pConclusionsEndometriosis is associated with impairment of professional life, in particular with regard to career choices. Further research to develop strategies to support endometriosis-affected women in realising professional opportunities is recommended.Trial registration numberNCT02511626; Pre-results.

Endometriosis affects various aspects of women's lives. We searched for predictors for patient satisfaction with medical support (PSwMS) in women with endometriosis. The study was designed as a multi-centre retrospective cohort study. We approached women with histologically confirmed endometriosis from 2010 until 2016, comparing women satisfied to women dissatisfied with medical support. We analysed data on characteristics of endometriosis, PSwMS and the influence of disease characteristics on PSwMS. Information on satisfaction with medical support was collected through a standardized questionnaire. After exclusion of 73 women because of inchoately filled in questionnaires, data from 498 women was evaluated. Altogether, it was observed that 54.6% (n = 272) of the study participants were satisfied with medical support and 45.4% (n = 226) were not. Feeling adequately informed by the time of diagnosis (p < 0.001), taking women's mental troubles seriously (p < 0.001) and supporting women in handling their pain (p < 0.001) were significantly associated with satisfaction. We found adequate information to be the most distinctive indicator for PSwMS. Further, acknowledging psychological distress and supporting women in handling their symptoms rather than to alleviate them, positively affect PSwMS. To achieve PSwMS, healthcare providers have to give adequate information on endometriosis and its management.

Core and peripheral body temperatures are affected by changes in reproductive hormones during the menstrual cycle. Women worldwide use the basal body temperature (BBT) method to aid and prevent conception. However, prior research suggests that taking one’s daily temperature can prove inconvenient and subject to environmental factors. We investigate whether a more automatic, non-invasive temperature measurement system can detect changes in temperature across the menstrual cycle. We examined how wrist skin temperature (WST), measured with wearable sensors, correlates with urinary tests of ovulation and may serve as a new method of fertility tracking. One hundred and thirty-six eumenorrheic, non-pregnant women participated in an observational study. Participants wore WST biosensors during sleep and reported their daily activities. An at-home luteinizing hormone (LH) test was used to confirm ovulation. WST was recorded across 437 cycles (mean cycles/participant = 3.21, S.D. = 2.25). We tested the relationship between the fertile window and WST temperature shifts, using the BBT three-over-six rule. A sustained 3-day temperature shift was observed in 357/437 cycles (82%), with the lowest cycle temperature occurring in the fertile window 41% of the time. Most temporal shifts (307/357, 86%) occurred on ovulation day (OV) or later. The average early-luteal phase temperature was 0.33°C higher than in the fertile window. Menstrual cycle changes in WST were impervious to lifestyle factors, like having sex, alcohol, or eating prior to bed, that, in prior work, have been shown to obfuscate BBT readings. Although currently costlier than BBT, the present study suggests that WST could be a promising, convenient parameter for future multiparameter fertility awareness methods.

Circadian and circannual rhythms influence not only the environment, but also human physiology. In times of increasing numbers of couples struggling with infertility, and thus increasing demand for successful assisted reproduction, the aim of our study was to evaluate circadian and circannual rhythms and their association with semen quality. A total of 12 245 semen samples from 7068 men, collected at the andrology laboratory of the Department of Reproductive Endocrinology, University Hospital Zurich, between 1994 and 2015, were uniformly analysed in terms of sperm concentration, total sperm count, progressive motility and normal morphology. On the basis of these four parameters, we retrospectively examined the circadian and circannual changes of semen quality. The Mann-Whitney U test and multiple linear regression analysis were used for the statistical evaluation. The semen samples collected in the early morning before 7:30 a.m. showed the highest levels in sperm concentration, total sperm count and normal morphology, all with statistical significance. Progressive motility did not show any significant alterations based on circadian rhythm. Furthermore, a significant increase in sperm concentration and total sperm count was found in spring, with significant decreases in the summer. The highest percentage of normal morphology was found in summer. For progressive motility, no significant seasonal variation could be demonstrated. Male semen quality varies with both circadian and circannual rhythms. Collection of semen in the early morning, where semen quality was highest, can be used to improve natural fertility as well as fertility resulting from assisted reproduction.

STUDY QUESTION Is maltreatment during childhood (MC), e.g. sexual abuse, physical abuse, emotional abuse and neglect, associated with diagnosis of endometriosis? SUMMARY ANSWER Childhood sexual abuse, emotional abuse/neglect and inconsistency experiences were associated with the diagnosis of endometriosis while no such association was found for physical abuse/neglect and other forms of maltreatment. WHAT IS KNOWN ALREADY Symptoms of endometriosis such as chronic pelvic pain, fatigue and depression, are correlated with MC, as are immune reactions linked to endometriosis. These factors support a case for a potential role of MC in the development of endometriosis. STUDY DESIGN, SIZE, DURATION The study was designed as a multicentre retrospective case-control study. Women with a diagnosis of endometriosis were matched to control women from the same clinic/doctor's office with regard to age (±3 years) and ethnic background. A total of 421 matched pairs were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with endometriosis and control women were recruited in university hospitals, district hospitals, and doctors' offices in Germany, Switzerland and Austria. A German-language version of the Childhood Trauma Questionnaire (CTQ) was used to evaluate MC. Diagnosis of endometriosis was confirmed histologically and classified according to ASRM criteria. MAIN RESULTS AND THE ROLE OF CHANCE Women with endometriosis reported significantly more often than control women a history of sexual abuse (20%/14%, P = 0.0197), emotional abuse (44%/28%, P < 0.0001), emotional neglect (50%/42%, P = 0.0123) and inconsistency experiences (53%/41%, P = 0.0007). No statistically significant differences could be demonstrated for physical abuse/neglect (31%/26%, P = 0.1738). Combinations of different abuse/neglect experiences were described significantly more often in women with endometriosis. Frequencies of other MC, i.e. violence against the mother (8%/7%, P = 0.8222), drug abuse in the family (5%/3%, P = 0.0943), mentally handicapped family members (1%/1%, P = 0.7271), suicidal intentions in the family (6%/4%, P = 0.2879) and family members in prison (1%/1%, P = 0.1597) were not statistically different in women with endometriosis and control women. LIMITATIONS, REASONS FOR CAUTION Some control women might present asymptomatic endometriosis, which would lead to underestimation of our findings. The exclusion of pregnant women may have biased the results. Statistical power for sub-analyses of physical abuse/neglect and sexual abuse was limited. WIDER IMPLICATIONS OF THE FINDINGS A link to MC needs to be considered in women with endometriosis. As there are effective strategies to avoid long-term consequences of MC, healthcare professionals should inquire about such experiences in order to be able to provide treatment for the consequences as early as possible. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER Endo_QoL NCT 02511626.

OBJECTIVE: An association between maternal HELLP syndrome and fetal long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has been proposed. LCHAD catalyzes the third step in the beta-oxidation of fatty acids in mitochondria. Whereas about 75% of LCHAD-deficient patients carry a G-to-C mutation at nucleotide position 1528 (Glu474Gln, E474Q) on both chromosomes, compound heterozygosity for E474Q on one chromosome and a second different LCHAD mutation on the other can be observed in up to 25% of LCHAD-deficiency cases; only very few patients carry two mutations different from E474Q. Genetic analysis of the mother alone is insufficient in case of compound heterozygosity. Since information on the fetal carrier status of the E474Q mutation in maternal HELLP syndrome is rare, we investigated the frequency of the E474Q mutation in families where the mother had HELLP syndrome. METHODS: The occurrence of the E474Q mutation was analyzed by PCR and RFLP in 103 mothers with HELLP syndrome, in 82 children of affected pregnancies and in 21 fathers in families where fetal DNA was not available. In addition, 103 control women with only uncomplicated pregnancies were investigated. RESULTS: The mutation E474Q was not detected in the study population. CONCLUSION: Neither maternal nor fetal heterozygosity for the E474Q mutation is a relevant factor of HELLP syndrome.

An affordable, user-friendly fertility-monitoring tool remains an unmet need. We examine in this study the correlation between pulse rate (PR) and the menstrual phases using wrist-worn PR sensors. 91 healthy, non-pregnant women, between 22–42 years old, were recruited for a prospective-observational clinical trial. Participants measured PR during sleep using wrist-worn bracelets with photoplethysmographic sensors. Ovulation day was estimated with “Clearblue Digital-Ovulation-urine test”. Potential behavioral and nutritional confounders were collected daily. 274 ovulatory cycles were recorded from 91 eligible women, with a mean cycle length of 27.3 days (±2.7). We observed a significant increase in PR during the fertile window compared to the menstrual phase (2.1 beat-per-minute, p

Abortion rates have declined in recent decades; however, the rate of repeat abortion remains high. In order to identify keys to making efficient interventions against repeat abortion, our objectives were: to assess the percentage of repeat abortions in women opting for termination of pregnancy over a period of 1 year; to identify the risk factors for repeat abortion; and to assess the characteristics of women who opted for a further pregnancy termination despite having received standard post-abortion care.A retrospective cross-sectional survey was carried out among 362 women who underwent pregnancy termination during a 1-year period. Women with and without repeat abortion were compared with regard to age, nationality, marital status, parity and use of contraception. In a subsample of 160 women who were available for follow-up over 4 years, those who underwent a further pregnancy termination during the observation period were also analysed qualitatively.The rate of repeat abortion was 30.1% in the survey population. Age and immigrant status were identified as risk factors. The use of long-acting reversible contraception (LARC) was significantly higher after repeat abortion than after a first termination of pregnancy. Among women with repeat abortion in the follow-up group, those with psychological problems tended to discontinue contraception and those with partnership conflicts were prone to using unreliable contraceptive methods.Aside from promoting LARC methods, strategies to reduce repeat abortion should consider the psychosocial risk factors and characteristics of women at risk identified in this study. An interdisciplinary approach including social care and counselling would be the most appropriate means to enable this.

Objective: Although childhood sexual abuse (CSA) may seriously impair childbirth experiences, few systematic evaluations on associations, mediating influences, risk and protective factors are available. As such information is mandatory to improve obstetric care, the present study aimed to provide such data. Methods: The study compared childbirth experiences from 85 women after CSA and at least one pregnancy resulting in a life birth with those from 170 control women matched for nationality, personal age and children's age. Trained specialists from support centers investigated CSA. Obstetrical data were collected from the official personal clinical record of each pregnancy (Mutterpass) and data on CSA as well as childbirth experiences were examined by questionnaires. Results: Childbirth was more often highly frightening (24.7 vs. 5.3%; p < 0.01) and a negative experience (40.7 vs. 19.6%, p < 0.01) in women with a history of CSA than in controls. Multivariate regression models support the hypothesis that at least part of this association was mediated by covariates (specifically, birth preparation classes, presence of a trusted person, participation in medical decision-making, pain relief, emergency during labor and extreme duration of labor), which represent important resources in improving obstetric care. In 41% of women with CSA, memories of traumatic experiences intruded during childbirth, whereas about 58% experienced dissociation. While dissociation may result in loss of contact with obstetric staff, it was also used to reduce labor pain. Conclusion: Childbirth following a history of CSA is associated with particular challenges. Creating a trusting environment by evaluating and integrating individual needs could ameliorate birth experiences.

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch), Although dyspareunia has a major impact on sexual and general well-being, there are few data on the longitudinal development of its prevalence in representative study groups. Therefore, it was the aim of the present study to fill this gap by evaluating the prevalence of dyspareunia in a representative sample at age 30, 35, 41, and 50. Additional aims were to determine the association between dyspareunia, psychopathological covariates, personality characteristics, and coping resources. Semi-structured interviews with single-item questions on sexual problems in general as well as dyspareunia were used to gain information on 1-year as well as long-time prevalence rates. Psychopathological covariates were explored with the SCL-90-R. The Freiburger Personality Inventory (Freiburger Persönlichkeits Inventar, FPI) assessed personality characteristics. Scales of sense of mastery and self-esteem were used to investigate coping resources. Twelve months prevalence of dyspareunia varied between 4.5 and 6.4% with a mean of 5.6% and a long-time risk of 19.3%. No relation between age and the prevalence rates was found. Dyspareunia was related to psychopathological covariates, especially depression. With respect to personality traits as measured with the FPI only nervousness showed a significant association with dyspareunia, whereas coping resources were unrelated. As dyspareunia is experienced by about 20% of all women, it represents a frequent sexual problem. Therefore, assessment of dyspareunia should be integrated into primary care of women at any age and diagnostic as well as therapeutic strategies should be based on physiological and psychological factors.

During recent years women tend to postpone childbirth to ages when fertility declines. Consequently, an increasing number of women experiences reproductive difficulties and seeks help by assisted reproductive techniques (ART). To investigate the dynamics of age-related fertility in Switzerland we evaluated data from the nationwide FIVNAT-CH statistics on ART as well as from a subsample receiving ART at the Division of Reproductive Endocrinology, University Hospital Zurich. Since 2000 the average age of women receiving ART increased from 34.9 to 36.3 years in Switzerland and since 2006 numbers of annual ART cycles augmented steadily. The percentage of women ⩾40 increased from 17.2% in 2007 to 19.6% in 2011. In the Zurich cohort AMH, the number of oocytes retrieved, the number of fertilized oocytes with two pronuclei, the number of embryos with an adequate cell number, clinical pregnancy rates as well as life birth/ongoing pregnancy rates were lower in the age group ⩾40 years, especially when compared to 33 year-old women. In the nationwide sample pregnancy rates decreased from about 45% at the age of 30 to less than 3% at the age of 45; delivery rates declined from about 38% to nearly 0%. In the Zurich cohort percentages of clinical pregnancies declined from 46% in women ⩽34 years to 21% in women ⩾40 years. In the national sample as well as in the Zurich cohort the percentage of miscarriages increased dramatically from 15.4% and 22% in women ⩽34 years to 38.6% and 33% in women ⩾40 years, respectively. Even in a country with high health standards such as Switzerland fertility is declining with age and ART does not succeed to improve reduced fertility. Rodent and primate models enrich our knowledge on the pathophysiological mechanisms underlying reproductive senescence. As non-infertility specialist physicians as well as the general public are not sufficiently aware of the dramatic reduction of chances for life births in women ⩾40 years, medical counseling as well as schools and media should support the distribution of information future parents need for successful family planning.

Objective: The rising rate of cesarean sections (CS), especially those on maternal request, is an important obstetric care issue. The aim of this two-point cross-sectional study was to evaluate the prevalence of CS and their indications. Methods: We performed a retrospective chart review of the indications of all CS performed at a tertiary care clinic in Switzerland in 2002 and 2008. Chi-square, Student's t and Mann-Whitney U tests were performed to identify significant differences. Results: The number of CS rose from 23.3% (371 out of 1,594 total life births) in 2002 to 27.5% (513 out of 1,866) in 2008 (p=0.005). Of all deliveries, the rate of CS on maternal request and, among these, especially those requested after previous CS, increased significantly (2.1 vs. 5.1% and 0.3 vs. 1.2%, respectively). The number of CS due to previous traumatic birth experience nearly doubled (0.7 vs. 1.2%, not significant). Maternal and fetal complications were rare but not negligible in the subset of low-risk patients requesting CS. Conclusions: The study demonstrated a significant increase in CS on maternal request, especially in case of previous CS. The findings of this study support the need for specific counseling strategies for women requesting delivery by CS

There is growing evidence that hypertensive pregnancy complications and other adverse pregnancy outcomes are associated with the presence of inherited or acquired thrombophilias. As hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome is one of the most severe forms of pre-eclampsia we aimed to assess the prevalence of the factor V Leiden, the prothrombin 20210GA mutation and the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with HELLP syndrome and in their fetuses from the same index pregnancy.The study was performed retrospectively in a case-control design.Seventy-one mother-child pairs with HELLP syndrome and 79 control mother-child pairs with uncomplicated pregnancies were included in the study.Genotyping of the three thrombophilic mutations was performed using the LightCycler technology. The chi-squared test was used for statistical analysis. Main outcome measures were maternal and fetal genotypes and their correlation with clinical parameters.Maternal heterozygosity for factor V Leiden was significantly more prevalent in the HELLP group than in controls (OR 4.45, 95% CI 1.31-15.31). No significant association was observed for maternal prothrombin mutation or MTHFR polymorphism (p=0.894, p=0.189, respectively). The fetal genotype was not associated with HELLP syndrome for any of the three mutations investigated. Analysis of gene-gene interactions and genotype-phenotype correlation with respect to clinical parameters and perinatal outcome revealed no further differences.Our study confirms that women heterozygous for factor V Leiden have an increased risk of developing HELLP syndrome, while the most frequent mutations of the prothrombin and MTHFR gene do not play a major role in the pathogenesis of HELLP syndrome.