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AbstractBackground Dienogest (DNG) improves endometriosis-associated pain (EAP) and patients’ quality of life; however, the modern cornerstone of the management of endometriosis is the long-term adherence of the patient to medical treatment.Objective To evaluate DNG as a long-term treatment of endometriosis, focusing on patients’ compliance and side effects, also correlating with different phenotypes of endometriosis.Methods This was a cohort study on a group of patients with endometriosis (n = 114) undergoing long-term treatment with DNG. During the follow up visits (12, 24, and 36 months) patients were interviewed: an assessment of EAP was performed by using a visual analogue scale (VAS) and side effects were evaluated by using a specific questionnaire of 15 items.Results At 12 months, 81% were continuing the DNG treatment, with a significant reduction of dysmenorrhea, dyspareunia, dyschezia, dysuria and chronic pelvic pain. Of the 19% that discontinued the treatment: 62% was due to spotting, reduced sexual drive, vaginal dryness, and mood disorders. The improvement of EAP was significant for all endometriosis phenotypes, especially in patients with the deep infiltrating type. At 36 months, 73% of patients were continuing the treatment, showing a significant reduction of EAP through the follow up, along with an increase of amenorrhea (from 77% at 12 months to 93% at 36 months). In a subgroup of 18 patients with gastrointestinal disorders, DNG was administered vaginally at the same dosage, showing similar results in terms of efficacy and tolerability.Conclusions DNG was an effective long-term treatment for all endometriosis phenotypes, with few side effects that caused the discontinuation of the treatment mainly during the first year. Thus, the course of 1-year treatment is a predictive indicator for long-term treatment adherence.

Abstract Purpose Pregorexia is a phenomenon posited to occur in the peripartum, characterized by an attempt to counter pregnancy’s physiological changes in body shape through reduced calorie intake or increased physical activity. Methods In this pre-registered systematic review and meta-analysis, body image dissatisfaction and eating psychopathology in the peripartum according to gestational age were formally assessed. PubMed was searched up to May 2023. Selection criteria were represented by studies on body image concerns or eating psychopathology in the peripartum (up to 1 year after delivery). The population needed to include women from the general population or among patients with a history of (or current) eating disorder. For the meta-analysis, 17 studies were included: 10 for body image dissatisfaction (2625 individuals overall), 7 for eating behaviors (2551 individuals overall). The interplay between body image and the following themes was examined in depth: the adoption of breastfeeding, peripartum depression, sociocultural influences on body image, sexual disturbances, experiencing or reporting an altered food intake. Results Progressive dissatisfaction with body image during pregnancy by gestational age was observed, stably elevated for at least 12 months postpartum. Eating psychopathology was observed as elevated only at 12 months in the postpartum, but not during pregnancy. Discussion The current work offers normative values of body image satisfaction and eating psychopathology in the peripartum by gestational age. The relevance of current results was discussed, in order to inform both current clinical practice and future public policies. Level of Evidence Level I—Evidence obtained from: systematic reviews and meta-analyses.

Chagas disease is an endemic parasitosis in Latin America where the main route of transmission is vectorial. In Europe, due to migration phenomena, Chagas disease cases are increasing and the main way of transmission is mother-to-child, perpetuating the infection from one generation to the other. Congenital Chagas disease is in most cases asymptomatic at birth, but, if not diagnosed and treated early, it puts the child at risk of developing severe cardiac and gastrointestinal problems throughout life. According to the Regional Resolution throughout the territory of Tuscany, pregnant women born in continental Latin America (or born to a mother born in that area) should be offered free of charge serological test for Chagas disease during pregnancy or at delivery, with the main objective of controlling and stopping the transmission of the disease.

Background Menstrual cycle has a significant impact on women’s health from different perspectives, both physically and psychologically. The assessment of menstrual-related distress is of pivotal clinical interest, especially in women with chronic exposure to abnormal bleeding or pain. The Menstrual Distress Questionnaire (MEDI-Q) is a new tool originally developed in Italian that comprehensively evaluates menstrual-related distress.Objective To validate the English version of the MEDI-Q in an English-speaking population.Methods The study consisted of two phases: an initial translation phase of the original Italian version of the MEDI-Q, and a data collection phase to validate the new English version among 288 native English-speaking women.Results The English version of MEDI-Q showed excellent psychometric properties, with high internal consistency (Cronbach’s alpha = 0.84) and test-retest reliability (intraclass correlation coefficient = 0.95). Construct validity was supported by significant correlations between MEDI-Q scores and scores on measures of psychological distress and premenstrual symptoms.Conclusions The English version of the MEDI-Q is a valid and reliable instrument for the assessment of menstrual distress and its impact on psychological well-being. This tool can be utilized in research and clinical settings to comprehensively investigate the impact of menstruation on various populations, identify and monitor menstruation-related disorders promptly and effectively, and to evaluate the effectiveness of targeted treatments for menstrual distress.

Objective In the 24-week, phase 3 LIBERTY 1 (L1) and LIBERTY 2 (L2) trials, relugolix combination therapy (relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethisterone acetate 0.5 mg)) reduced uterine fibroid (UF)-associated symptoms. This post hoc analysis assessed safety and efficacy of relugolix-CT in European women from L1/L2.Methods Premenopausal women (aged 18–50 years) with UF-associated heavy menstrual bleeding (HMB) were randomized 1:1:1 in L1 (N = 388) and L2 (N = 382) to relugolix-CT or placebo for 24 weeks, or delayed relugolix-CT (relugolix 40 mg then relugolix-CT; 12 weeks each). Primary endpoint: proportion of responders (menstrual blood loss (MBL)

Background Sexual health is a major concern in women with endometriosis, however only a few controlled studies have examined this with validated instruments. The effect of hormonal treatments on sexual function in endometriosis is also an underrated topic. The aim of this study was to investigate sexual function of patients with endometriosis by a specific tool to better evaluate their sexual function (including different domains), and the influence of hormonal treatment or surgery on these parameters. Methods An observational, cross-sectional, multicentre study was conducted in a group (n=194) of sexually active, women aged 25–45 years old, with surgical or ultrasonographic diagnosis of endometriosis, referred to the Endometriosis Center of Careggi University Hospital or Negrar di Valpolicella. Sexual function was assessed by administering the Female Sexual Function Index (FSFI), which assesses the domains of desire, arousal, lubrication, orgasm, satisfaction and pain. FSFI scores were compared to those of a control group (n=58) and according to the treatment received by patients with endometriosis. Results Ovarian endometriosis was present in 50 patients (25.8%), deep infiltrating endometriosis in 65 patients (33.5%) and both in 79 patients (40.7%). Adenomyosis coexisted in 102 patients (52.6%). Women with endometriosis reported a mean total FSFI score of 18.3 [4.2-25.8] (< 26.55), indicating female sexual dysfunction (FSD) in all patients. At multivariate analysis, after adjusting for confounders (BMI and hormonal therapy), women with endometriosis presented significantly lower scores than controls in all the FSFI (p

Background: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. Methods: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). Results: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. Conclusions: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.

The leading route of Chagas disease transmission in nonendemic countries is congenital. However, policies concerning screening, prevention, and management of congenital Chagas disease are rare in these settings. Since 2012, serological screening for Chagas disease should be provided for pregnant women at risk in Tuscany, Italy according to a Regional resolution. Due to difficulties in the implementation, in November 2019, a checklist aimed at identifying pregnant women at risk for Chagas disease was introduced in digital clinical records at Careggi University Hospital, Florence, Italy. In order to evaluate the effectiveness of the “Chagas checklist”, data about the number of deliveries by women at risk and their screening coverage between 2012 and June 2022 were collected. Out of 1348 deliveries by women at risk, 626 (47%) Trypanosoma cruzi serology tests were performed during the study period. The annual screening coverage increased from an average of 40.3% between 2012 and 2019 to 75.7% between 2020 and June 2022, underlining the big impact of the checklist. Four Chagas disease serological tests out of 626 (0.6%) resulted positive, corresponding to 2 affected women. No cases of congenital transmission occurred. The study showed that a simple digital tool led to a tangible improvement in the coverage of the screening program; its application in a setting where digital charts are available will contribute to the control and elimination of congenital Chagas disease.

Background: In women with rheumatic diseases (RDs) menstruation-related disorders have never been investigated. The aim of this study was to evaluate gynecological symptoms/disorders in fertile age women with RDs.Materials and methods: All patients (n = 200) filled up a self-administered questionnaire on their gynecological history, menstrual cycle pattern, menstrual-related symptoms, and quality of life (QoL). The RD group was then compared to a control group of 305 age-matched fertile age women.Results: Among patients with RDs, 58% had arthritis, 40% connective tissue diseases (CTDs), and 1.5% systemic vasculitis. No differences were observed between CTDs and arthritis, except for a family history of HMB which was more common among women with CTDs (p < .01). When compared to controls, women with RDs reported more frequent heavy menstrual bleeding (HMB) during adolescence (51.7 and 25.4%, respectively; p = .0001) and adult life (37.7 and 25.9%, respectively; p = .0065). Also, dysmenorrhea in adolescence was significantly more common among cases (55.6 and 45.4%, respectively; p = .0338). Gynecological pain (dysmenorrhea, non-menstrual pelvic pain, dyspareunia, dysuria, and dyschezia) in patients with RDs was more frequent than in controls (p = .0001, .0001, .0001, .0001, .0002, respectively). Considering women who reported moderate and severe symptoms in RDs, dysmenorrhea and dyspareunia remain significantly more frequent in women with RDs than in controls (p = .0001; p = .0022; respectively). QoL scores were significantly reduced in women with RDs, either in physical (p = .0001) and mental domains (p = .0014) of short-form 12.Conclusion: Women affected by RDs frequently presented menstruation-related disorders; thus, female patients with RDs should be questioned about gynecological symptoms and referred to the gynecologist for an accurate evaluation.

Undifferentiated connective tissue disease (UCTD) is characterized by signs and symptoms suggestive of a connective tissue disease (CTD), but not fulfilling criteria for a specific CTD. Although UCTD is probably the most common rheumatic disease diagnosed in pregnant women, data about disease course during pregnancy and perinatal outcomes are very limited. Compared to other CTDs, UCTD seems to have milder clinical manifestations in pregnancy. Its natural history is related to disease activity at conception. In fact, if the disease is in a state of remission or minimal activity at conception, pregnancy outcomes are generally good. On the contrary, patients who become pregnant in a moment of high disease activity and/or who have multiple antibodies positivity show an increased risk of disease flares, evolution to a definite CTD and obstetric complications, such as fetal growth restriction, preeclampsia and preterm birth. Therefore, a preconception assessment is essential in women with UCTD to evaluate maternal and fetal risks, to initiate interventions to optimize disease activity, and to adjust medications to those that are least harmful to the fetus. The aim of the present study was to review the available literature about pregnancy course, maternal and fetal outcomes and therapeutic approaches of pregnant women with UCTD.

Background: Currently, there is little evidence to guide clinical management of pregnancies after stillbirth. Our study aims to evaluate the pregnancy outcome in pregnant women with a previous stillbirth, by applying a standardized protocol for etiologic investigations and subsequent treatment of the underlying etiology. Methods: A retrospective cohort study on a group of 100 women with history of stillbirth, occurred in single pregnancy between 2005 and 2021, was performed. All patients were followed up in their subsequent pregnancies (n = 153) in a tertiary university hospital. During the preconception period causes of stillbirth were investigated and a correction of modifiable risk factors was encouraged with a multidisciplinary approach. Data about pregnancy management, obstetric complications, gestational age at delivery, mode of delivery and neonatal outcomes were collected. Results: The analysis of previous stillbirth revealed that, by using the ReCoDe classification, the most common identifiable causes of death were fetal growth restriction (21%), placental abruption (11%) and “other placenta insufficiencies” (26.7%), whereas 15.8% of stillbirth was unexplained. Out of 153 subsequent pregnancies, 131 (85.62%) resulted in live births, 15 (9.8%) in a first trimester miscarriage, and 7 (4.57%) in second trimester miscarriage; no cases of stillbirth recurrence occurred. Obstetric complications in subsequent pregnancies included gestational diabetes (21.4%), gestational hypertensive disorders (6.1%), intrahepatic cholestasis of pregnancy (3.8%), fetal growth restriction (7.6%) and preterm birth (19.8%). The mean gestational age at delivery was 38 weeks with a mean birth weight of 2886.63 g. Conclusions: Our experience is encouraging as reflecting good outcomes in terms of live birth rate in the subsequent pregnancies, with no cases of recurrence. These results are probably due to extensive preconception investigations with a multidisciplinary approach. A preconception evaluation is, thus, essential to improve maternal and fetal outcome in case of history of stillbirth, aiming to minimize the risk of recurrence.

Objectives: Endometriosis is an inflammatory disease characterized by a frequent association with gynecologic and systemic comorbidities. Our aim was to evaluate which gynecologic and systemic comorbidities occur in women affected by endometriosis and their impact on quality of life and global health. Mechanism: A literature search of the PubMed, Cochrane Library, Scopus and Web of Science databases was performed to identify the relevant studies published before December 31, 2021. We selected clinical studies, systematic reviews, and meta-analyses in English. Findings in Brief: Endometriosis is strongly associated with gynecologic (adenomyosis, uterine fibroids, polycystic ovarian syndrome-PCOS) and systemic (autoimmune, inflammatory, psychiatric and neurological disorders) comorbidities that impair women quality of life and global health through multiple mechanisms, influencing everyday life and work activities. Conclusions: Endometriosis is a chronic disease, impairing multiple functioning areas and affecting women’s health and everyday life. Considering the co-existence of multiple both gynecological and non-gynecological disorders, endometrisois needs a multidisciplinary approach. Thus, specialized referral centres are warranted for a personalized management, focused on patient symptoms and comorbidities.

Introduction: Endometriosis is a gynecological disease with a severe impact on quality of life. The aim of this study is to assess mental health status in a group of women with endometriosis, investigating their clinical history, pain symptoms and systemic comorbidities. Methods: An observational cross-sectional study was performed on a group of Italian Caucasian women with endometriosis (n = 134). All patients filled the ‘Patient Health Questionnaire’ (PHQ), a self-administered screening tool for mental health disorders. The characteristics of endometriosis, pain symptoms and their severity, the presence and types of comorbid systemic disorders were added into the same survey. Results: According to PHQ algorithms, 59% of patients were affected by at least one psychiatric disorder, with a significant correlation with pain symptoms (p = 0.0026). Patients with severe pain showed a higher incidence of multiple psychiatric disorders (p = 0.026) and somatoform disorder than those with mild pain (p = 0.0009). There was no correlation between the presence of psychiatric disorders and age, BMI, parity, infertility, need for surgery, number of intervention, localization of endometriotic lesions and systemic comorbidities. Discussion: Women with endometriosis showed a high frequency of PHQ results positive for psychiatric disorders, with a significant association with pain severity.

Abstract Background A unique standardized national dataset on adolescent girls (21 regions) participating in the Italian Health Behaviour in School-aged Children Study (HBSC) was used to investigate the correlation between body mass index (BMI) and age at menarche. Methods Two independent nationally representative survey datasets: one on 15-year-olds (n = 6907, in 21 regions, year 2013/2014) and one on 11-year-olds (n = 10,128, in 20 regions, year 2009/2010) were analysed. The survey instrument was a self-report questionnaire. Median age at menarche and 95% confidence intervals (CIs) were estimated by means of Kaplan–Meier analysis. Hierarchical models were used to assess the relationship between BMI and age at menarche (months). “Region-level obesity” was measured as the prevalence of overweight/obesity (%) in each region. Results Region-level median age at menarche ranged between 12 years/3 months and 13 years/4 months. Region-level prevalence of overweight among 15-year-old girls ranged between 4 and 19%. Age at menarche was inversely associated with individual BMI (unstandardized regression coefficient beta = − 0.70; 95% CI, − 0.84 to − 0.56). Individual- and class-level measures of BMI accounted for 50% of the region-level variance in age at menarche. Conclusions The results show that overweight in childhood is in relation with the early puberty in girls. Future surveys may take into account this report to clarify if overweight is the cause or consequence of early menarche.

ObjectiveMaternal characteristics and OGTT values of pregnancies complicated by gestational diabetes mellitus (GDM) were evaluated according to treatment strategies. The goal was to identify different maternal phenotypes in order to predict the appropriate treatment strategy.MethodsWe conducted a retrospective study among 1,974 pregnant women followed up for GDM in a tertiary referral hospital for high-risk pregnancies (Careggi University Hospital, Florence, Italy) from 2013 to 2018. We compared nutritional therapy (NT) alone (n = 962) versus NT and insulin analogues (n = 1,012) group. Then, we focused on different insulin analogues groups: long acting (D), rapid acting (R), both D and R. We compared maternal characteristics of the three groups, detecting which factors may predict the use of rapid or long-acting insulin analogue alone versus combined therapy.ResultsAmong women included in the analysis, 51.3% of them needed insulin therapy for glycemic control: 61.8% D, 28.3% combined D and R, and 9.9% R alone. Age >35 years, pre-pregnancy BMI >30, family history of diabetes, previous GDM, altered fasting plasma glucose (FPG), hypothyroidism, and assisted reproductive technologies (ART) were identified as maternal variables significantly associated with the need of insulin therapy. Altered 1-h and 2-h glucose plasma glucose level at OGTT, age >35 years, and previous GDM were found as independent predicting factors for the use of combined therapy with rapid and long acting analogues for glycemic control. On the contrary, pre-pregnancy BMI

PCOS is one of the most common endocrine disorders and NAFLD is one of its most dangerous metabolic consequences. The diagnosis of NAFLD is not a practical task and the condition is at risk of being overlooked. The use of simpler but still reliable surrogate markers is necessary to identify women with a high likelihood of NAFLD. The aim of this study was to evaluate the clinical correlates of NAFLD Liver Fat Score (NAFLD-LFS) in women with oligomenorrhea and/or hirsutism. Furthermore, the study aimed to evaluate whether, among the hormonal parameters evaluated in such women, possible hallmarks of NAFLD may be identified. To this purpose, 66 women who attended our Outpatient Clinic for oligomenorrhea and/or hyperandrogenism were included in the study. In order to validate the results obtained in the first cohort, a second independent sample of 233 women evaluated for female sexual dysfunction (FSD) was analyzed. In cohort 1, NAFLD-LFS positively correlated with metabolic and inflammatory parameters. Among the hormone parameters, NAFLD-LFS showed no significant relationships with androgens but a significant negative correlation with SHBG (p

OBJECTIVE:Whether the use of assisted reproductive technologies (ART) affects the outcome of twin pregnancies is still a matter of debate. Previous studies have evaluated the association between birth weight and ART, without a clear distinction between fetal growth restriction (FGR), a condition at higher risk of adverse outcome, and constitutionally small for gestational age (SGA) fetuses. The aim of this study was to determine whether dichorionic (DC) twin pregnancies obtained by ART have a greater risk of developing FGR, defined by accurate ultrasound criteria, than those spontaneously conceived (SC), and to compare the severity of ultrasound features in the growth restricted fetuses. METHODS:A retrospective study was conducted on DC twin pregnancies delivered between 2010 to 2018 at a tertiary hospital. Twin pregnancies conceived spontaneously were compared with those obtained via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), after exclusion of cases with major fetal or uterine malformations. The primary outcome was the incidence of FGR. Secondary outcome was the rate of SGA neonates, defined by a birth weight less than the 10th percentile. The ultrasound characteristics of the growth restricted fetuses in the two groups were also compared. The groups were compared using univariate and multivariate analyses. RESULTS:Six hundred and seventy-eight DC twin pregnancies were identified. Of these, 367 (54.1%) conceived via IVF/ICSI and 311 (45.9%) conceived spontaneously. The incidence of FGR was not significantly different between the ART and the SC groups (7.9% vs 8.4% respectively, p = 0.76, adjusted OR 0.84, 95% CI 0.53-1.32). Growth restricted fetuses of the two groups showed similar occurrence of an estimated fetal weight less than the 3rd percentile, similar abnormalities in Doppler studies and similar gestational age at diagnosis. There was no difference in the incidence of delivery of an SGA neonate (p = 0.47) or in the rate of maternal complications and preterm delivery between the groups. CONCLUSIONS:Twin pregnancies conceived by assisted reproductive technologies do not have a higher risk of ultrasound-diagnosed FGR than spontaneously conceived twin pregnancies, and fetuses diagnosed with growth restriction in the two groups show similar severity of the ultrasound findings.

Adenomyosis is a benign uterine disorder in which endometrial glands and stroma are pathologically demonstrated in the uterine myometrium and it is considered a specific entity in the PALM-COEIN FIGO (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified – International Federation of Gynecology and Obstetrics) classification of causes of abnormal uterine bleeding (AUB). Although it has always been considered the classic condition of multiparous women over 40 years old who have pain and heavy menstrual bleeding, diagnosed at hysterectomy, the epidemiological scenario has completely changed. Adenomyosis is increasingly identified in young women with pain, AUB, infertility, or no symptoms by using imaging techniques such as transvaginal ultrasound and magnetic resonance. However, there is no agreement on the definition and classification of adenomyotic lesions from both the histopathology and the imaging point of view, and the diagnosis remains difficult and unclear. A uniform and shared reporting system needs to be implemented in order to improve our understanding on imaging features, their relationship with pathogenic theories, and their importance in terms of clinical symptoms and response to treatment. In fact, adenomyosis pathogenesis remains elusive and not a single theory can explain all of the different phenotypes of the disease. Furthermore, adenomyosis often coexists with other gynecological conditions, such as endometriosis and uterine fibroids, increasing the heterogeneity of available data. Treatment requires a lifelong management plan as the disease has a negative impact on quality of life in terms of menstrual symptoms, fertility, and pregnancy outcome and has a high risk of miscarriage and obstetric complications.

ObjectiveTo evaluate the association between the endometriosis phenotype and the age at menarche.DesignAn observational, cross-sectional study using prospectively collected data (Canadian Task Force classification II-2).SettingSingle university tertiary referral center.PatientsTo be eligible, women had to have undergone their 1st complete surgical exeresis of endometriotic lesions. For each patient, a standardized questionnaire was completed the month before the surgery. Endometriotic lesions were classified into 3 phenotypes: superficial peritoneal endometriosis (SUP), endometrioma (OMA), or deep infiltrating endometriosis (DIE). Patients were divided into 3 groups: early menarche (< 12 years), typical menarche (≥ 12 and ≤ 13 years) and late menarche (> 13 years). The groups were compared in terms of general characteristics, medical history, disease phenotype, and disease severity.InterventionsSurgical management for a benign gynecologic condition.Main outcome measure(s)Correlation between the endometriosis phenotype and the age at menarche.Measurements and main resultsFrom January 2004 to December 2016, 789 women with histologically confirmed endometriosis were enrolled in the study. The mean age at menarche was 12.9 ± 1.6 years of age, (range 9 to 18). The mean age at menarche and the mean time interval between menarche and the 1st surgery for endometriosis were not significantly different between the three phenotypes (SUP, OMA, DIE). When women with early menarche, typical menarche, or late menarche were compared, no differences were observed in terms of the endometriosis phenotype and the anatomical distribution of the endometriotic lesions.ConclusionFor women operated for the first time for endometriosis, age at menarche is not associated with the disease phenotype.

Endometriosis is a condition defined as presence of endometrium outside of the uterine cavity. These endometrial cells are able to attach and invade the peritoneum or ovary, thus forming respectively the deep infiltrating endometriosis (DIE) and the ovarian endometrioma (OMA), the ectopic lesions feature of this pathology. Endometriotic cells display high invasiveness and share some features of malignancy with cancer cells. Indeed, the tissue remodeling underlining lesion formation is achieved by matrix metalloproteinases (MMPs) and their inhibitors. Therefore, these molecules are believed to play a key role in development and pathogenesis of endometriosis. This study investigated the molecular profile of metalloproteinases and their inhibitors in healthy (n = 15) and eutopic endometrium (n = 19) in OMA (n = 10) and DIE (n = 9); moreover, we firstly validated the most reliable housekeeping genes allowing accurate gene expression analysis in these tissues. Gene expression, Western blot, and immunofluorescence analysis of MMP2, MMP3, and MMP10 and their tissue inhibitors TIMP1 and TIMP2 demonstrated that these enzymes are finely tuned in these tissues. In OMA lesions, all the investigated MMPs and their inhibitors were significantly increased, while DIE expressed high levels of MMP3. Finally, in vitro TNFα treatment induced a significant upregulation of MMP3, MMP10, and TIMP2 in both healthy and eutopic endometrial stromal cells. This study, shedding light on MMP and TIMP expression in endometriosis, confirms that these molecules are altered both in eutopic endometrium and endometriotic lesions. Although further studies are needed, these data may help in understanding the molecular mechanisms involved in the extracellular matrix remodeling, a crucial process for the endometrial physiology.

Dysmenorrhea is a common symptom secondary to various gynecological disorders, but it is also represented in most women as a primary form of disease. Pain associated with dysmenorrhea is caused by hypersecretion of prostaglandins and an increased uterine contractility. The primary dysmenorrhea is quite frequent in young women and remains with a good prognosis, even though it is associated with low quality of life. The secondary forms of dysmenorrhea are associated with endometriosis and adenomyosis and may represent the key symptom. The diagnosis is suspected on the basis of the clinical history and the physical examination and can be confirmed by ultrasound, which is very useful to exclude some secondary causes of dysmenorrhea, such as endometriosis and adenomyosis. The treatment options include non-steroidal anti-inflammatory drugs alone or combined with oral contraceptives or progestins.

The study focuses on the perceived nature / technique opposition in pregnancy and delivery emerging from gynaecologist/ midwife/ pregnant woman relationships. We developed a cross-sectional survey to identify, by means of a multidimensional data-driven approach, the main latent concepts structuring the between items correlation correspondent to the different general opinions present in the data set. The obtained results can set the basis to improve patient satisfaction while decreasing healthcare costs.The sample is made of 90 pregnant women within 24-48 hours after natural or operative birth, from three maternity units in Italy. Women filled in a questionnaire about their relationship with gynaecologist and midwife during pregnancy and hospital stay for delivery.Participation rate approached 100%. The emerging factorial structure gave a proof-of-concept of the hypothesis of 'nature vs. technique' as the main dimension shaping women opinions. The results highlighted the role of midwife as the 'link' between the natural and technical dimension of birth. The quality of welcome and the establishing of an empathic relation between mother and healthcare professional was shown to decrease further request of care in the post-partum period.The "fault plane" between nature and technique is a very critical zone for litigation. Women are particularly sensitive to the consideration and attention they receive at their admission in the hospital, as well as to the quality of human relationship with midwife. The perceived quality of welcome scaled with a decreased need of additional care and, more in general, with a more faithful attitude towards health professionals. We hypothesize that increasing the quality of welcome can exert an effect on both welfare costs and litigation. This opens the way (through an extension of this pilot study to wider populations) to relevant ameliorative actions on quality of care at practically null cost.

BACKGROUND: Neonatal death in full-term infants who suffer from perinatal asphyxia (PA) is a major subject of investigation, since few tools exist to predict patients at risk of ominous outcome. We studied the possibility that urine S100B measurement may identify which PA-affected infants are at risk of early postnatal death. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study between January 1, 2001 and December 1, 2006 we measured S100B protein in urine collected from term infants (n = 132), 60 of whom suffered PA. According to their outcome at 7 days, infants with PA were subsequently classified either as asphyxiated infants complicated by hypoxic ischemic encephalopathy with no ominous outcome (HIE Group; n = 48), or as newborns who died within the first post-natal week (Ominous Outcome Group; n = 12). Routine laboratory variables, cerebral ultrasound, neurological patterns and urine concentrations of S100B protein were determined at first urination and after 24, 48 and 96 hours. The severity of illness in the first 24 hours after birth was measured using the Score for Neonatal Acute Physiology-Perinatal Extension (SNAP-PE). Urine S100B levels were higher from the first urination in the ominous outcome group than in healthy or HIE Groups (p1.0 microg/L S100B had a sensitivity/specificity of 100% for predicting neonatal death. CONCLUSIONS/SIGNIFICANCE: Increased S100B protein urine levels in term newborns suffering PA seem to suggest a higher risk of neonatal death for these infants.

Following myomectomy the rate of fertility is restored and pregnancy may be attempted with a good outcome. In the present study a 3 month treatment with OCs in a group of women after a myomectomy was evaluated. The drug compliance and side effects, the benefits of OC in order to reduce symptoms, to increase post-surgical hemoglobin levels and to avoid an early pregnancy after myomectomy were analyzed. A group of women (𝑛=55) each with myoma ≥5 cm was recruited: they presented menorrhagia, pelvic pain, dyspareunia and dysmenorrhae. After laparotomic myomectomy the women were divided into 3 groups. Group 1: women (𝑛=16) treated with pill A (15 mcg of ethynilestradiol + 60 mcg of gestodene); group 2: women (𝑛=23) treated with pill B (20 mcg of ethynilestradiol + 100 mcg of levonorgestrel); group 3: women (𝑛=16) treated with a placebo (oral calcium). After three months from myomectomy and treatment patients in each group reported a reduced menorrhagia, dismenorrhea and pelvic pain. Serum haemoglobin levels increased in all women (𝑃

Background Sexual health is a major concern in women with endometriosis, however only a few controlled studies have examined this with validated instruments. The effect of hormonal treatments on sexual function in endometriosis is also an underrated topic. The aim of this study was to investigate sexual function of patients with endometriosis by a specific tool to better evaluate their sexual function (including different domains), and the influence of hormonal treatment or surgery on these parameters. Methods An observational, cross-sectional, multicentre study was conducted in a group (n=194) of sexually active, women aged 25–45 years old, with surgical or ultrasonographic diagnosis of endometriosis, referred to the Endometriosis Center of Careggi University Hospital or Negrar di Valpolicella. Sexual function was assessed by administering the Female Sexual Function Index (FSFI), which assesses the domains of desire, arousal, lubrication, orgasm, satisfaction and pain. FSFI scores were compared to those of a control group (n=58) and according to the treatment received by patients with endometriosis. Results Ovarian endometriosis was present in 50 patients (25.8%), deep infiltrating endometriosis in 65 patients (33.5%) and both in 79 patients (40.7%). Adenomyosis coexisted in 102 patients (52.6%). Women with endometriosis reported a mean total FSFI score of 18.3 [4.2-25.8] (< 26.55), indicating female sexual dysfunction (FSD) in all patients. At multivariate analysis, after adjusting for confounders (BMI and hormonal therapy), women with endometriosis presented significantly lower scores than controls in all the FSFI (p Conclusions Patients with endometriosis are at risk for FSD, encompassing not only dyspareunia, but all domains of sexual function. Hormonal treatments do not result in improvement in sexual symptoms.

Adenomyosis is a benign uterine disorder in which endometrial glands and stroma are pathologically demonstrated in the uterine myometrium and it is considered a specific entity in the PALM-COEIN FIGO (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified – International Federation of Gynecology and Obstetrics) classification of causes of abnormal uterine bleeding (AUB). Although it has always been considered the classic condition of multiparous women over 40 years old who have pain and heavy menstrual bleeding, diagnosed at hysterectomy, the epidemiological scenario has completely changed. Adenomyosis is increasingly identified in young women with pain, AUB, infertility, or no symptoms by using imaging techniques such as transvaginal ultrasound and magnetic resonance. However, there is no agreement on the definition and classification of adenomyotic lesions from both the histopathology and the imaging point of view, and the diagnosis remains difficult and unclear. A uniform and shared reporting system needs to be implemented in order to improve our understanding on imaging features, their relationship with pathogenic theories, and their importance in terms of clinical symptoms and response to treatment. In fact, adenomyosis pathogenesis remains elusive and not a single theory can explain all of the different phenotypes of the disease. Furthermore, adenomyosis often coexists with other gynecological conditions, such as endometriosis and uterine fibroids, increasing the heterogeneity of available data. Treatment requires a lifelong management plan as the disease has a negative impact on quality of life in terms of menstrual symptoms, fertility, and pregnancy outcome and has a high risk of miscarriage and obstetric complications.