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To investigate the clinical and surgical predictors of urinary tract endometriosis (UTE) relapse.Retrospective single institutional study.Italian multidisciplinary referral center for endometriosis.Consecutive patients affected by UTE and surgically treated between January 2016 and March 2020.Surgical excision for UTE. Uni- and multivariate logistic regression analyses were fitted to evaluate clinical and surgical predictors of recurrence.A total of 105 female age-reproductive patients were enrolled. Median age was 32 years (interquartile range, 24-37). Ureteral involvement was recorded in 53 patients (50.5%), being unilateral and bilateral in 46 patients (43.8%) and 7 patients (6.7%), respectively. Bladder involvement occurred in 52 patients (49.5%). Open surgical approach was performed in 24 cases (22.9%), whereas 30 patients (28.5%) and 51 patients (48.6%) were treated with laparoscopic and robot-assisted approach, respectively. Overall, 53 patients (50.5%) received adjuvant hormonal therapy. At a median follow-up of 39 months (interquartile range, 22-51), 30 patients (28.6%) experienced disease relapse, with 14 recurrences (13.3%) recorded at the level of the urinary tract. At multivariable analysis, age at first surgery25 years (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.10-1.84; p = .02) and the presence of a concomitant autoimmune disease (OR, 1.45; 95% CI, 1.24-2.17; p = .02) were found as predictors of deep infiltrating endometriosis recurrence, whereas adjuvant postsurgical therapy showed a protective role (OR, 0.83; 95% CI, 0.53-0.98; p = .01).Young age (25 years) and the presence of autoimmune diseases were significant predictors for the development of disease recurrence, whereas adjuvant hormonal therapy showed a protective role.

Purpose of the Review The purpose of this review is to provide a synopsis of all the mechanisms involved in the pathogenesis of adenomyosis. It will summarize recent advances in the field, discussing current controversies, and considering potential future directions. Recent Findings Adenomyosis pathogenesis is still a topic under investigation, however advancements in the understanding of disease development and mechanisms have been made. New data coming from new next generation sequencing-based studies and more-in-depth acquisitions on sex hormones imbalance, neuroangiogenesis, inflammation, fibrosis and cell proliferation have been obtained. Summary Adenomyosis is a uterine disorder that affects women of reproductive age, characterized by a benign invasion of the endometrium basalis (glands and stroma) within the myometrium. So far, three theories for the pathophysiology of adenomyosis have been proposed: An invagination of the endometrial basalis into the myometrium by tissue injury and repair. The development from adult stem cells or displaced embryonic müllerian remnants. An “invasion from outside to inside”. In order to invade and develop, endometrial cells require a series of pathogenetic mechanisms which drive to adenomyosis. Altered sex steroids hormones receptors may be the primary event which causes increased endometrial cell proliferations and differentiation from epithelial to mesenchymal cells. Once invaded the myometrium, an inflammatory reaction is displayed, probably driven by local immune changes. The processes of neuroangiogenesis and fibrosis are also involved in the adenomyosis development and may explain some of the associated clinical symptoms (dysmenorrhea, abnormal uterine bleeding, and infertility).

Endometriosis is an estrogen-dependent disease on the background of progesterone resistance. Increased estrogen production, low estrogen metabolization, and altered estrogen receptors (ERs) expression contribute to the hyperestrogenic milieu within endometriotic lesions. Since estrogens play a crucial role in the pathogenesis of the disease, inhibition of estrogen production is one of the main targets of available and emerging drugs.Firstly, we described the molecular alterations responsible for estrogen dependence. Secondly, we reviewed available and emerging treatments that interfere, through central (gonadotropin-releasing hormone analogs (GnRH-a), GnRH antagonists) or local mechanisms (aromatase inhibitors (AIs), inhibitors of steroid sulfatase (STS) and hydroxysteroid dehydrogenase type 1 (17β-HSD1)), with estrogen dependence. Finally, we focused on emerging treatments targeting ERs (selective estrogen receptor modulators (SERMs), estrogen receptors agonists, and antagonists).Available treatments interfering with estrogen pathways exert a contraceptive effect, have hypoestrogenic side effects, and cannot prevent or definitively treat the disease. Preclinical and animal studies are focusing on emerging drugs targeting ERs in order to overcome limitations of available treatments. These treatments may represent a promising option, as they may produce a more specific inhibition of disease activity within endometriotic implants, avoiding prolonged hypoestrogenic status and limiting systemic side effects.

The aim of the study is to compare maternal hemodynamic adaptations in gestational diabetes (GDM) versus healthy pregnancies. A prospective case–control study was conducted, comparing 69 singleton pregnancies with GDM and 128 controls, recruited between September 2018 and April 2019 in Maternal–Fetal Medicine Unit, Careggi University Hospital, Florence, Italy. Hemodynamic assessment by UltraSonic Cardiac Output Monitor (USCOM) was performed in both groups in four gestational age intervals: 17–20 weeks (only in early GDM cases), 26–30 weeks, 32–35 weeks and 36–39 weeks. We evaluated six hemodynamic parameters comparing GDM cases versus controls: cardiac output (CO), cardiac index (CI), stroke volume (SV), total vascular resistance (TVR), inotropy index (INO) and potential to kinetic energy ratio (PKR). GDM group had significantly lower values of CO and SV than controls from the early third trimester (26–30 weeks) until term (p

Objective To investigate the role of glycemic control in development of preeclampsia (PE) in women with type 1 diabetes mellitus (T1DM). Methods An observational case-control study comparing 244 women with type 1 diabetes and 488 controls was conducted. Among women with T1DM HbA1c, average daily glucose values, fasting, preprandial, 1-hour and 2-hour postprandial glucose levels, and daily 3 meals postprandial glucose areas were evaluated. Uterine artery pulsatility indices (PI) at 16, 20, 24 weeks‘ gestation were obtained. Data analysis included rates of PE in both groups, and association between glycemic control, uterine artery PI and development of PE among women with T1DM. Results PE developed in 13.1% of diabetic women and in 3.5% of women in the control group (odds ratio 4.2; 95% CI 2.2–8.1). In multivariate logistic regression analysis, HbA1c in the 1st trimester, mean daily glucose level in the 1st and 2nd trimester, daily 3 meal postprandial glucose area in the 1st and 2nd trimester, and the uterine arteries PI at 24 weeks’ gestation were found to be associated with development of PE. The uterine arteries PI showed a significant positive correlation with the 3 meal postprandial glucose area at 16, 20, 24 weeks. Conclusion In women with T1DM, poor glycemic control early in pregnancy is associated with an increased risk of subsequent PE. An association between poor placentation, as indicated by the increased PI of uterine arteries, and a maternal metabolic factor, that is the 3 meal post-prandial glucose area, has been shown, supporting the increased rate of PE among women with T1DM.

Estrogen dependence and progesterone resistance play a crucial role in the origin and development of endometriosis. Therefore, hormonal therapies are currently the most effective treatment. Progestins are considered the first-line approach, especially for a long-term management. Progestins are synthetic compounds that mimic the effects of progesterone by binding progesterone receptors. Continuous use of progestins leads to the suppression of ovarian steroidogenesis with anovulation and low serum levels of ovarian steroids, causing endometrial pseudodecidualisation. Moreover, they act by interfering on several endometriosis pathogenetic pathways, decreasing inflammation, provoking apoptosis in endometriotic cells, stimulating atrophy or regression of endometrial lesions, inhibiting angiogenesis, and decreasing expression of metalloproteinases, thus diminishing the invasiveness of endometriotic implants. Progestins are effective for pain relief and improvement of the quality of life (QoL). The side effects are limited, and the compounds are available in different formulations and routes of administration and represent, in most cases, an inexpensive treatment option. Dienogest, Medroxyprogesterone acetate and Norethisterone acetate are the labeled progestins for endometriosis, but other progestins, such as Dyhidrogesterone, Levonorgestrel and Desogestrel, have been shown to be effective in the treatment of endometriosis-associated pain. The present review aims to describe the available and emerging evidences on progestins used for the treatment of endometriosis.

To evaluate the levels of depression, state and trait anxiety, selfefficacy, and self-esteem among women with high risk pregnancy due to previous adverse pregnancy outcomes (PAPOs) or pre-pregnancy diseases (PPD), before and after delivery, compared to controls.An observational longitudinal study on psychological dimensions was conducted on 86 women attending a university referral centre for high risk pregnancy, by administering the Edinburgh Postnatal Depression Scale, the State and Trait Anxiety Inventory, the General Self-Efficacy Scale, and the Self-esteem Scale. A pre-test (in the third trimester of pregnancy) and a follow-up measurement session (one month after the delivery) were applied. PAPOs group, PPD group and controls were compared.The PAPOs group had higher levels of depression compared to the other groups, with above-threshold levels. However, a more relevant decrease in depression was found in the PAPOs group after delivery. Levels of self-efficacy and self-esteem were unexpectedly high during and after pregnancy in all the groups.A PAPO represents a risk factor for depression development during pregnancy, whereas a PPD seems to be less relevant in influencing affective dimensions. Surprisingly, all pregnant women, independently of the obstetric risk, showed high levels of self-efficacy and self-esteem.

Menstruation is defined as monthly uterine bleeding, regarded as a sign of reproductive health. When characterized by excessive bleeding (heavy menstrual bleeding [HMB]), it may act as a useful clinical marker for diagnosis of reproductive diseases. Endometrial and myometrial mechanisms underlying abnormal uterine bleeding (AUB), which includes HMB, have hormonal, cellular, and molecular aspects. Structural and nonstructural causes of AUB, presenting with HMB as the major symptom, result in iron depletion and consequent anemia. Heavy menstrual bleeding can be considered as a single entity to identify the possible underlying causes, which may be different to some extent to those of AUB, as a whole. Furthermore, the difficulties in defining HMB through objective methods do not allow the current epidemiological scenario on the prevalence of the symptom among reproductive-age women to be outlined. Moreover, the introduction of new diagnostic methods, including imaging technologies, entails a revision of the available figures on HMB in different age groups from menarche to menopause. In addition, a proper diagnostic algorithm for HMB should be implemented to adapt recommendations for clinical investigation when HMB is present.

Randomized trials reported no difference whether induction or expectant management is performed in non-diabetic women with large for gestational age babies but no tool has been validated for the prediction of high risk cases.Assessing the performance of different growth curves in the prediction of complications.Data from 1066 consecutive non-diabetic women who delivered babies ≥4000 g were collected. Logistic regression analysis was used to analyze the impact of the maternal variables on: instrumental delivery, shoulder dystocia (SD), perineal tears, cesarean section (CS), and postpartum hemorrhage. Intergrowth21 curves and customized Gardosi's curves were compared in terms of prediction of adverse outcomes.Induction of labor was performed in 23.1% cases. The rate of CS was 17%. Hemorrhage, fetal distress, and SD occurred in 2%, 1.3%, and 2.7% of cases, respectively. Induction was significantly associated with instrumental delivery (Gardosi curves showed a better performance in predicting the risk of CS versus Intergrowth curves. Induction is significantly associated with adverse outcome in non-diabetic women with LGA babies.

Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age, frequently associated with pain symptoms and heavy menstrual bleeding (HMB), leading to impaired quality of life. Thus, the aim of the study was to evaluate the global perception of stress and the menstrual distress in patients with UFs. A cross-sectional observational study was conducted on a group (n = 69) of fertile age women with UFs compared to age-matched controls, by administering two questionnaires: the perceived stress scale (PSS) and the Menstrual Distress Questionnaire (MEDI-Q). The PSS, MEDI-Q Total Score and 3 subscales—menstrual symptoms (MS), menstrual symptoms distress (MSD), and menstrual specificity index (MESI)—were evaluated. Patients with UFs showed higher PSS than controls (18.5 ± 5.0 vs. 13.8 ± 5.0, p p p p

To evaluate the different effects of a progestin-only contraceptive with desogestrel (DSG) vs combined oral contraceptives (COCs) for a first line long-term treatment of endometriosis-related pain among patients seeking hormonal contraception.An observational retrospective cohort study was conducted in collaboration with a local outpatient clinic for endometriosis among a group of nulliparous young women (No significant difference was found between the two groups in terms of clinical characteristics and pain scores before treatment. After 6 months both treatments were effective in reducing endometriosis-related pain, and those treated with DSG showed lower levels of dysmenorrhea, dyspareunia and nonmenstrual pelvic pain than COCs group (A progestin-only contraceptive with DSG is a valid option for long term management of endometriosis-related pain in patients seeking hormonal contraception.

This study aimed to evaluate the presence of superficial peritoneal endometriosis (SUP) in women referred to emergency surgery for right iliac fossa (RIF) pain and undergoing an appendectomy, considering which factors may be useful to suspect and identify endometriosis.An observational case-control study was conducted on a group (n = 149) of fertile age women. After surgery, Group A was selected upon the diagnosis of endometriosis (n = 34); Group B (n = 115) represented the controls. Demographics, comorbidities and clinical findings were registered and analysed.Appendicitis of various grades of severity was diagnosed in all patients, but SUP was also identified in 23%, of which 14.7% also presented with endometriosis of the appendix. Women in Group A reported chronic pelvic pain, dysmenorrhoea, dyspareunia and oral contraceptive use more frequently. At multivariate analysis, factors associated with endometriosis were: age40 years, autoimmune disorders, multiple allergies, abdominal chronic pain, associated gynaecological pain symptoms, Alvarado score ≤6, and inconclusive ultrasound findings.The incidental finding of SUP in fertile age women presenting with an acute RIF pain and undergoing emergency surgery is a relevant observation. Clinical history and symptoms should guide surgeons in performing a correct diagnosis and in referring the patient to the gynaecology specialist.

BACKGROUNDDespite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis.OBJECTIVE AND RATIONALEWe review here the action mechanisms of progesterone receptor ligands in endometriosis, identify critical differences between the effects of progestins on normal endometrium and endometriosis and envisage pathways to escape drug resistance and improve the therapeutic response of endometriotic lesions to such treatments.SEARCH METHODSWe performed a systematic Pubmed search covering articles published since 1958 about the use of progestins, estro-progestins and selective progesterone receptor modulators, to treat endometriosis and its related symptoms. Two reviewers screened the titles and abstracts to select articles for full-text assessment.OUTCOMESProgesterone receptor signalling leads to down-regulation of estrogen receptors and restrains local estradiol production through interference with aromatase and 17 beta-hydroxysteroid dehydrogenase type 1. Progestins inhibit cell proliferation, inflammation, neovascularisation and neurogenesis in endometriosis. However, progesterone receptor expression is reduced and disrupted in endometriotic lesions, with predominance of the less active isoform (PRA) over the full-length, active isoform (PRB), due to epigenetic abnormalities affecting the PGR gene transcription. Oxidative stress is another mechanism involved in progesterone resistance in endometriosis. Among the molecular targets of progesterone in the normal endometrium that resist progestin action in endometriotic cells are the nuclear transcription factor FOXO1, matrix metalloproteinases, the transmembrane gap junction protein connexin 43 and paracrine regulators of estradiol metabolism. Compared to other phenotypes, deep endometriosis appears to be more resistant to size regression upon medical treatments. Individual genetic characteristics can affect the bioavailability and pharmacodynamics of hormonal drugs used to treat endometriosis and, hence, explain part of the variability in the therapeutic response.WIDER IMPLICATIONSMedical treatment of endometriosis needs urgent innovation, which should start by deeper understanding of the disease core features and diverse phenotypes and idiosyncrasies, while moving from pure hormonal treatments to drug combinations or novel molecules capable of restoring the various homeostatic mechanisms disrupted by endometriotic lesions.

Endometriosis is a gynecological disease characterized by pain and infertility. The diagnosis is very often made during the infertility work-up, together with other reproductive diseases and uterine disorders. A retrospective cohort study was conducted on infertile women with clinical or ultrasound suspect of endometriosis, undergoing an ultrasound (US) evaluation by a team of expert sonographers (

Clinical studies clearly indicate that endometriosis is a condition associated with high levels of chronic stress. The stress intensity correlates with pain severity and disease extension. However, it is unknown whether chronic stress represents a primary cause of endometriosis and, therefore, if avoiding or treating chronic stress may reduce the risk of developing endometriosis. Repeated, uncontrolled stress either before or after experimental endometriosis induction promotes disease mechanisms and accelerates lesion growth in rodents. Furthermore, patients with endometriosis have a heightened risk of other inflammatory and immune-related diseases, many of which have also been associated with stress. Here, we review the latest evidences regarding the relationship between chronic stress and endometriosis and discuss the potential bidirectional aspect of such association. Further research may clarify if endometriosis is a cause and/or a consequence of stress and whether stress-reducing therapies are effective to mitigate symptoms and slow down the development of endometriotic lesions.

The COVID-19 global pandemic has led to the death of millions around the world and impacted the overall health of many people. In this article we aim to compare reproductive health indicators in the first 6 months of 2020 to the prior year, as well as explore stress and quality of life during this time.This retrospective observational study examined the menstrual cycles of 1159 women who were using a fertility tracking device to record their menstrual cycle and BBT data. We utilised a supplemental mobile application to administer a supplemental survey to collect data on stress and quality of life. Descriptive analyses were conducted withStudy participants from 15 countries contributed to a total of 13,194 cycles. 23.1% (268/1159) responded to the survey focussed on assessing psychosocial distress. 44.4% (119/268) of the study participants reported that they had noticed a change in their menstrual cycle, temperature curve, or menstruation in the past 12 months. Cycle analysis found the average cycle length and pre-ovulation phase length was longer in the first 6 months of 2019, while the average days of menstruation was slightly longer in 2020.Our findings indicate that menstrual cycle indicators changed only slightly in the first 6 months of 2020 but were still statistically significant. We were also able to understand that these study participants had some level of awareness of changes to their menstrual health.

Heavy menstrual bleeding (HMB) has an estimated prevalence of 18–32% but is known to be under-reported due to poor recognition and estimation of menstrual blood loss (MBL). HMB can negatively impact quality of life, affecting social interactions, work productivity and sexual life. Abnormal menstrual bleeding may have an underlying structural or systemic cause, such as endometrial and myometrial disorders; however, for some, there is no identified pathological cause. Several methods are available for assessing MBL, including the alkaline hematin (AH) method and the menstrual pictogram (MP). The AH method is considered to be the most accurate way to monitor MBL; however, it is associated with inconvenience and expense, therefore limiting its value outside of research. The MP requires the user to select an icon from a chart that reflects the appearance of a used sanitary product; the icon is associated with a blood volume that can be used to determine MBL. Validation studies have demonstrated that the results of the MP and AH method are well correlated, showing that the MP can measure MBL with sufficient accuracy. Additionally, the MP is more convenient for users, less expensive than the AH method, may be used in regions where the AH method is unavailable and may also be used as part of a digital application. Overall, the MP offers a convenient approach to monitor MBL both in research and clinical practice settings.

Introduction Compared to spontaneous conception (SC), pregnancies conceived through assisted reproductive technologies (ART) carry worse pregnancy and neonatal outcomes. Evidences focused on preterm births are limited. Early preterm delivery is a critical situation for medical management and parental counselling. The aim of this study was to analyze if ART procedures influenced pregnancy and neonatal outcomes in singleton pregnancies with early preterm delivery. Material and methods This was a retrospective case control study. The population consisted of all consecutive early preterm deliveries occurred at Careggi University Hospital in Florence (Italy) between 2010 and 2017. Cases were considered patients who conceived though ART, including intra cytoplasmic sperm injection (ICSI), in vitro fertilization and embryo transfer (IVF-ET), intra uterine insemination (IUI) and ovarian stimulation. Controls were patients who conceived in the natural way. Main outcomes of the study were: birth weight, umbilical artery pH, Apgar score at 1 and 5 min, gestational age at delivery and mode of delivery. Secondary outcomes were: spontaneous preterm labor initiation, gestational diabetes mellitus, intrauterine growth restriction (IUGR), cholestasis of pregnancy, intra uterine fetal demise (IUFD), placenta previa, fetal malformations, pregnancy induced hypertensive (PIH) disorders (gestational hypertension, preeclampsia and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome) and postpartum hysterectomy. Shapiro-Wilk test was used to check the normality of the data; Mann-Whitney test was used to compare two continuous variables not-normally distributed. Multiple and binomial logistic regression analyses were used to adjust the results of the statistical analysis for potential confounding factors. The analysis for the main outcomes was performed for all deliveries and then repeated for spontaneous deliveries, separately. Results Seventy-one patients had ART and 640 SC. We found no differences in birthweight, umbilical artery pH, Apgar at 1 and 5 min and gestational age at delivery between ART and SC groups. C-section rate, placenta previa and PIH disorders were higher in the ART group. The higher prevalence of C-sections in the ART group was not statistically significant after adjusting for age and parity in the whole population but resulted significantly different when analyzing the subgroup of patients with spontaneous initiation of labor. Conclusions Fetal outcomes seem to be equal between ART and SC in early preterm neonates ; C-section rate and pregnancy complications such as placenta previa and PIH disorders seem to be higher in the ART group. These information should be part of the family counselling in these cases. We suggest that clinicians, after management of preterm delivery had been properly addressed, should not apply different management in ART compared to SC pregnancies.

Is sphingosine 1-phosphate (S1P) pathway involved in the process of fibrosis in adenomyosis?RNA was extracted from paraffin-embedded slices collected from the ectopic endometrium of patients with nodular adenomyosis (n = 27) and eutopic endometrium of healthy controls women (n = 29). Expression of genes involved in the metabolism and signalling of S1P, and actin-alpha-2 smooth muscle, encoded by ACTA2 gene, a gene involved in fibrogenesis, was evaluated by real-time polymerase chain reaction analysis.In adenomyotic samples, the expression of sphingosine kinase 1 (SPHK1), the enzyme responsible for the synthesis of S1P, and of S1P phosphatase 2 (SGPP2), the enzyme responsible for the conversion of S1P back to sphingosine, was lower (P = 0.0006; P = 0.0015), whereas that of calcium and integrin-binding protein 1, responsible for membrane translocation of SPHK1, was higher (P = 0.0001) compared with healthy controls. In S1P signalling, a higher expression of S1P receptor S1PPresent data show a profound dysregulation of the S1P signalling axis in adenomyosis. This study also highlights that the bioactive sphingolipid might be involved in the fibrotic tract of the disease, correlated with the expression of ACTA2, suggesting its role as novel potential biomarker of adenomyosis.

Endometriosis is a benign uterine disorder characterized by menstrual pain and infertility, deeply affecting women’s health. It is a chronic disease and requires a long term management. Hormonal drugs are currently the most used for the medical treatment and are based on the endocrine pathogenetic aspects. Estrogen-dependency and progesterone-resistance are the key events which cause the ectopic implantation of endometrial cells, decreasing apoptosis and increasing oxidative stress, inflammation and neuroangiogenesis. Endometriotic cells express AMH, TGF-related growth factors (inhibin, activin, follistatin) CRH and stress related peptides. Endocrine and inflammatory changes explain pain and infertility, and the systemic comorbidities described in these patients, such as autoimmune (thyroiditis, arthritis, allergies), inflammatory (gastrointestinal/urinary diseases) and mental health disorders.The hormonal treatment of endometriosis aims to block of menstruation through an inhibition of hypothalamus-pituitary-ovary axis or by causing a pseudodecidualization with consequent amenorrhea, impairing the progression of endometriotic implants. GnRH agonists and antagonists are effective on endometriosis by acting on pituitary-ovarian function. Progestins are mostly used for long term treatments (dienogest, NETA, MPA) and act on multiple sites of action. Combined oral contraceptives are also used for reducing endometriosis symptoms by inhibiting ovarian function. Clinical trials are currently going on selective progesterone receptor modulators, selective estrogen receptor modulators and aromatase inhibitors. Nowadays, all these hormonal drugs are considered the first-line treatment for women with endometriosis to improve their symptoms, to postpone surgery or to prevent post-surgical disease recurrence. This review aims to provide a comprehensive state-of-the-art on the current and future hormonal treatments for endometriosis, exploring the endocrine background of the disease.

Research question Menstruation is a physiological event often associated with subjective distress. Is there a tool that assesses and objectively evaluates the global distress experienced by women during their period? Design An observational cross-sectional study conducted between June 2019 and May 2020 at Careggi University Hospital, Florence, Italy. A new questionnaire, The Menstrual Distress Questionnaire (MEDI-Q), was developed and administered to a group of healthy women (n = 418) of fertile age (18–50 years), without known uterine, psychiatric disorders, or both. The MEDI-Q investigated 25 items, covering the following areas: pain, discomfort, psychic or cognitive changes, gastrointestinal symptoms and changes in physiological functions. MEDI-Q Total Score and the three sub-scales, Menstrual Symptoms (MS), Menstrual Symptoms Distress (MSD) and Menstrual Specificity Index (MESI) were evaluated. The validation of MEDI-Q was achieved by testing test–retest reliability and internal consistency, convergent and concurrent validity. Results The MEDI-Q produced reliable results with good internal consistency, convergent and concurrent validity. MEDI-Q Total Score, MS and MSD all positively correlated with general psychopathology and premenstrual symptoms. A receiver operating characteristic analysis was used to determine the cut-off value of 20 (inclusive) and to identify the women with clinically relevant menstrual distress (area under the curve 0.90, 95% CI 0.86 to 0.93; P Conclusion MEDI-Q is a new tool for evaluating menstruation-related distress, and provides a representative score of stress perception. MEDI-Q may be added to routine women's healthcare to help identify and adequately monitor menstruation-related disorders, and their effect on wellbeing, promptly.

Primary dysmenorrhea (PD) is the most common gynecologic disorder during adolescence and it is characterized by crampy lower abdominal pain that occurs during menstruation. Secondary dysmenorrhea, in contrast, has the same clinical features but occurs in women with a disease that could account for their symptoms (endometriosis, adenomyosis, uterine fibroids, pelvic inflammatory disease). Endometriosis is the most common cause of secondary dysmenorrhea and it should be considered in patients with persistent and clinically significant dysmenorrhea despite treatment. It is often diagnosed after a long delay, increasing the likelihood of pain chronicity and fertility problems at a later age. Women who suffer from dysmenorrhea in adolescence have higher risk of endometriosis in future. The open question is if endometriosis was already present at the onset of dysmenorrhea but undiagnosed or if PD favors subsequent development of endometriosis-associated pain. Since PD is associated with higher risk for developing chronic pain state and shares some of the same pain pathways of endometriosis (prostaglandins overproduction, inflammation, peripheral sensitization, central sensitization and abnormal stress responses), a correlation between PD and endometriosis is suggested. To know whether it is a risk factor for the development of endometriosis-associated pain may provide an opportunity for early intervention and prevention. The present review aims to investigate the clinical and pathogenetic features of PD and endometriosis in order to identify a possible association between the two conditions.

The aim of the study is to compare maternal hemodynamic adaptations in gestational diabetes (GDM) versus healthy pregnancies.A prospective case-control study was conducted, comparing 69 singleton pregnancies with GDM and 128 controls, recruited between September 2018 and April 2019 in Maternal-Fetal Medicine Unit, Careggi University Hospital, Florence, Italy. Hemodynamic assessment by UltraSonic Cardiac Output Monitor (USCOM) was performed in both groups in four gestational age intervals: 17-20 weeks (only in early GDM cases), 26-30 weeks, 32-35 weeks and 36-39 weeks. We evaluated six hemodynamic parameters comparing GDM cases versus controls: cardiac output (CO), cardiac index (CI), stroke volume (SV), total vascular resistance (TVR), inotropy index (INO) and potential to kinetic energy ratio (PKR).GDM group had significantly lower values of CO and SV than controls from the early third trimester (26-30 weeks) until term (p 0.001). CI is significantly lower in GDM women already at the first evaluation (p = 0.002), whereas TVR and PKR were significantly higher in GDM (p 0.001). GDM women showed also lower INO values than controls in all assessments.A hemodynamic maternal maladaptation to pregnancy can be detected in GDM women. The effect of hyperglycemia on vascular system or a poor pre-pregnancy cardiovascular (CV) reserve could explain this hemodynamic maladaptation. The abnormal CV response to pregnancy in GDM women may reveal a predisposition to develop CV disease later in life and might help in identifying patients who need a CV follow-up.

Endometriosis is a benign reproductive tract disease, characterized by ectopic implantation of endometrial cells with elevated proliferation and migration capacity outside the uterus, mainly in the pelvis. Despite its benign nature, a number of studies support the notion that endometriosis may represent the initial stage of a neoplastic process, especially in the ovary. In fact, endometriosis shares several common features with cancer, including the ability to evade apoptosis, cell migration and proliferation, implantation at distant sites, neovascularization, creating a microenvironment eluding the immune system. A possible genetic link has been suggested in recent studies, highlighting driver mutations in PIK3CA, KRAS, ARID1A, and other genes. However, the underlying molecular and cellular mechanisms are still not fully understood.

Objective To explore the link between sphingosine 1-phosphate (S1P) signaling and leiomyoma and the possible S1P cross-talk with the fibrotic effect of activin A. Design Case-control laboratory study. Setting University institute and university hospital. Patient(s) Patients with uterine fibroids (n = 26). Interventions(s) Tissue specimens of leiomyoma and normal myometrium were obtained from patients undergoing myomectomy or total hysterectomy. Main Outcome Measure(s) Expression of mRNA levels of the enzyme involved in S1P metabolism, S1P receptors, and S1P transporter Spns2 was evaluated in matched leiomyoma/myometrium specimens and cell populations. The effects of inhibition of S1P metabolism and signaling was evaluated on activin A–induced fibrotic action in leiomyoma cell lines. Result(s) The expression of the enzymes responsible for S1P formation, sphingosine kinase (SK) 1 and 2, and S1P2, S1P3, and S1P5 receptors was significantly augmented in leiomyomas compared with adjacent myometrium. In leiomyoma cells, but not in myometrial cells, activin A increased mRNA expression levels of SK1, SK2, and S1P2. The profibrotic action of activin A was abolished when SK1/2 were inhibited or S1P2/3 were blocked. Finally, S1P augmented by itself mRNA levels of fibrotic markers (fibronectin, collagen 1A1) and activin A in leiomyomas but not in myometrial cells. Conclusion(s) This study shows that S1P signaling is dysregulated in uterine fibroids and involved in activin A–induced fibrosis, opening new perspectives for uterine fibroid treatment.

An observational cross-sectional study was conducted in a group (n = 371) of fertile age women with endometriosis, by administering a structured questionnaire, in order to evaluate the incidence of gynecological and systemic comorbidities and the impact on quality of life (QoL) in two different groups of Italian and Chinese patients affected by endometriosis. Chinese (n = 175) and Italian (n = 196) women were compared regarding systemic (inflammatory, autoimmune, and mental) and gynecological comorbidities, pain symptoms, and QoL, by using the Short Form 12 (SF-12). Italian patients resulted younger at the diagnosis and suffered more frequently from severe pain than Chinese ones. Deep infiltrating endometriosis (DIE) and mixed phenotypes were more frequent in Italian patients, whereas ovarian (OMA) and superficial endometriosis (SUP) were more common in the Chinese. The Italian group showed more systemic comorbidities, and those disorder were already present before the diagnosis of endometriosis. Furthermore, the Italian group showed lower SF-12 physical and mental scores, suggesting a worse health-related QoL in Italian endometriotic patients. A number of differences has been observed between Italian and Chinese women with endometriosis in terms of comorbidities and QoL, which may be related to the ethnicity, the different health system organization and the social and cultural background.

Research question How effective is medical hormonal treatment in preventing endometriosis recurrence and in improving women's clinical symptoms and quality of life? Design This observational cross-sectional study evaluated the effects of hormonal medical treatment (progestins, gonadotrophin-releasing hormone analogues or continuous oral contraceptives) on endometriosis recurrence, current clinical symptoms and quality of life in three groups of patients: Group A (n = 34), no hormonal treatment either before or after the first endometriosis surgery; Group B (n = 76), on hormonal treatment after the first endometriosis surgery; and Group C (n = 75), on hormonal treatment both before and after the first endometriosis surgery. Results Group C patients were characterized by a lower rate of endometriosis reoperation (P = 0.011) and a lower rate of dysmenorrhoea (P = 0.006). Women who experienced repetitive endometriosis surgery showed worse physical (P = 0.004) and mental (P = 0.012) status than those who received a single surgery, independent of the treatment. Conclusion Hormonal treatments represent a valid cornerstone of endometriosis management and may be useful as an alternative to surgery, but also before surgery, to plan better, and after surgery in order to reduce the risk of recurrence. Medical counselling is very helpful in choosing the correct and individualized endometriosis treatment. In fact, the gold standard for modern endometriosis management is the individualized approach and surgery should be considered, depending on the clinical situation and a patient's symptoms.

In recent years, a growing interest has arisen regarding the possible relationship between adverse pregnancy outcomes (APOs) and inadequate maternal hemodynamic adaptations to the pregnancy. A possible association between “placental syndromes,” such as preeclampsia (PE) and fetal growth restriction (FGR), and subsequent maternal cardiovascular diseases (CVD) later in life has been reported. The two subtypes of FGR show different pathogenetic and clinical features. Defective placentation, due to a poor trophoblastic invasion of the maternal spiral arteries, is believed to play a central role in the pathogenesis of early-onset PE and FGR. Since placental functioning is dependent on the maternal cardiovascular system, a pre-existent or subsequent cardiovascular impairment may play a key role in the pathogenesis of early-onset FGR. Late FGR does not seem to be determined by a primary abnormal placentation in the first trimester. The pathological pathway of late-onset FGR may be due to a primary maternal cardiovascular maladaptation: CV system shows a flat profile and remains similar to those of non-pregnant women. Since the second trimester, when the placenta is already developed and increases its functional request, a hypovolemic state could lead to placental hypoperfusion and to an altered maturation of the placental villous tree and therefore to an altered fetal growth. Thus, this review focalizes on the possible relationship between maternal cardiac function and placentation in the development of both early and late-onset FGR. A better understanding of maternal hemodynamics in pregnancies complicated by FGR could bring various benefits in clinical practice, improving screening and therapeutic tools.