PAIN SEVERITY AND DEPRESSIVE SYMPTOMS IN ENDOMETRIOSIS-PATIENTS: MEDIATION OF NEGATIVE BODY AWARENESS AND INTEROCEPTIVE SELF-REGULATION.

Endometriosis-related pain may be associated with depressive symptoms. Although a growing body of evidence supports this association, the underlying mechanisms are still largely unclear. Impaired perceptions of bodily external and internal stimuli may be involved in this process. This study aims to assess the mediating role of two facets of interoception - the awareness of negative body signals and interoceptive self-regulation - in the association between pain severity and depressive symptoms among women with endometriosis. A total of 301 patients who reported a diagnosis of endometriosis were recruited from an endometriosis and chronic pelvic pain outpatient university clinic and through patient associations and completed self-reported instruments. A parallel mediation analysis was conducted. Almost half of women (48.2%) reported depressive symptoms above the self-rating scale cut-off values. Pain severity significantly predicted depressive symptoms (ß =0.39, 95% bootstrap CI [0.719, 1.333]). Negative body awareness (ß =0.121, 95% bootstrap CI [0.174, 0.468]) and interoceptive self-regulation (ß = 0.05, 95% bootstrap CI [0.035, 0.252]) partially mediated this relationship. Our findings indicated that pain may interfere with the perception of the body as a source of calmness and safety, limiting the individual's ability to effectively regulate emotions. Future research should further explore these mechanisms and evaluate the efficacy of interventions focusing on interoceptive sensibility to enhance the psychological well-being of endometriosis patients. PERSPECTIVE: This article investigates for the first time the potential role of two facets of interoceptive sensibility in the relationship between pain severity and depressive symptoms in women with endometriosis. These findings may contribute to advancing knowledge about mechanisms involved in the complex pain-depression cycle.

Diffusion-sensitized magnetic resonance imaging highlights placental microstructural damage in patients with previous SARS-CoV-2 pregnancy infection.

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been a major global health problem since December 2019. This work aimed to investigate whether pregnant women's mild and moderate SARS-CoV-2 infection was associated with microstructural and vascular changes in the placenta observable in vivo by Intravoxel Incoherent Motion (IVIM) at different gestational ages (GA). METHODS: This was a retrospective, nested case-control of pregnant women during the SARS-CoV-2 pandemic (COVID-19 group, n = 14) compared to pre-pandemic healthy controls (n = 19). MRI IVIM protocol at 1.5T was constituted of diffusion-weighted (DW) images with TR/TE = 3100/76 ms and 10 b-values (0,10,30,50,75,100,200,400,700,1000s/mm2). Differences between IVIM parameters D (diffusion), and f (fractional perfusion) quantified in the two groups were evaluated using the ANOVA test with Bonferroni correction and linear correlation between IVIM metrics and GA, COVID-19 duration, the delay time between a positive SARS-CoV-2 test and MRI examination (delay-time exam+) was studied by Pearson-test. RESULTS: D was significantly higher in the COVID-19 placentas compared to that of the age-matched healthy group (p < 0.04 in fetal and p < 0.007 in maternal site). No significant difference between f values was found in the two groups suggesting no-specific microstructural damage with no perfusion alteration (potentially quantified by f) in mild/moderate SARS-Cov-2 placentas. A significant negative correlation was found between D and GA in the COVID-19 placentas whereas no significant correlation was found in the control placentas reflecting a possible accelerated senescence process due to COVID-19. DISCUSSION: We report impaired microstructural placental development during pregnancy and the absence of perfusion-IVIM parameter changes that may indicate no perfusion changing through microvessels and microvilli in the placentas of pregnancies with mild/moderate SARS-Cov-2 after reaching negativity.

Therapeutic Choices for Genitourinary Syndrome of Menopause (GSM) in Breast Cancer Survivors: A Systematic Review and Update.

(1) Background: Genitourinary syndrome of menopause (GSM) is a medical condition that can affect breast cancer survivors (BCS). This is a complication that often can occur as a result of breast cancer treatment, causing symptoms such as vaginal dryness, itching, burning, dyspareunia, dysuria, pain, discomfort, and impairment of sexual function. BCS who experience these symptoms negatively impact multiple aspects of their quality of life to the point that some of them fail to complete adjuvant hormonal treatment; (2) Methods: In this systematic review of the literature, we have analyzed possible pharmacological and non-pharmacological treatments for GSM in BCS. We reviewed systemic hormone therapy, local hormone treatment with estrogens and androgens, the use of vaginal moisturizers and lubricants, ospemifene, and physical therapies such as radiofrequency, electroporation, and vaginal laser; (3) Results: The data available to date demonstrate that the aforementioned treatments are effective for the therapy of GSM and, in particular, vulvovaginal atrophy in BCS. Where possible, combination therapy often appears more useful than using a single line of treatment; (4) Conclusions: We analyzed the efficacy and safety data of each of these options for the treatment of GSM in BCS, emphasizing how often larger clinical trials with longer follow-ups are needed.

How to Manage Endometriosis in Adolescence: The Endometriosis Treatment Italian Club Approach.

The evaluation of endometriosis in an adolescent girl is a challenging topic. The initial stage of the disease and the limited diagnostic instrument appropriate for the youth age and for its typical features can reduce the ability of the gynecologist. At the same time, missing a prompt diagnosis can delay the beginning of specific and punctual management of endometriosis, which could avoid a postponed diagnosis from 6 to 12 years, typical of adolescent girls complaining of dysmenorrhea. This article aimed to answer all the potential questions around the diagnosis and management of endometriosis in adolescents starting from a clinical case looking at the possible solution that is easily reproducible in the clinical practice.

Efficacy of N-Acetylcysteine on Endometriosis-Related Pain, Size Reduction of Ovarian Endometriomas, and Fertility Outcomes.

BACKGROUND: Endometriosis is a chronic, estrogen-dependent, inflammatory disease, whose pivotal symptoms are dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Besides the usual medical treatments, recent evidence suggests there are potential benefits of oral N-acetylcysteine (NAC) on endometriotic lesions and pain. The primary objective of this prospective single-cohort study was to confirm the effectiveness of NAC in reducing endometriosis-related pain and the size of ovarian endometriomas. The secondary objective was to assess if NAC may play a role in improving fertility and reducing the Ca125 serum levels. METHODS: Patients aged between 18-45 years old with a clinical/histological diagnosis of endometriosis and no current hormonal treatment or pregnancy were included in the study. All patients received quarterly oral NAC 600 mg, 3 tablets/day for 3 consecutive days of the week for 3 months. At baseline and after 3 months, dysmenorrhea, dyspareunia and CPP were assessed using the Visual Analog Scale score (VAS), while the size of the endometriomas was estimated through a transvaginal ultrasound. Analgesics (NSAIDs) intake, the serum levels of Ca125 and the desire for pregnancy were also investigated. Finally, the pregnancy rate of patients with reproductive desire was evaluated. RESULTS: One hundred and twenty patients were recruited. The intensity of dysmenorrhea, dyspareunia and CPP significantly improved (p < 0.0001). The use of NSAIDs (p = 0.001), the size of the endometriomas (p < 0.0001) and the serum levels of Ca125 (p < 0.0001) significantly decreased. Among the 52 patients with reproductive desire, 39 successfully achieved pregnancy within 6 months of starting therapy (p = 0.001). CONCLUSIONS: Oral NAC improves endometriosis-related pain and the size of endometriomas. Furthermore, it decreases Ca125 serum levels and may improve fertility in patients with endometriosis.

SARS-CoV-2 Infection in Pregnancy: Clues and Proof of Adverse Outcomes.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represents one of the most threatening viral infections in the last decade. Amongst susceptible individuals, infected pregnant women might be predisposed to severe complications. Despite the extensive interest in SARS-CoV-2 research, the clinical course of maternal infection, the vertical transmission and the neonatal outcomes have not been completely understood yet. The aim of our study was to investigate the association between SARS-CoV-2 infection, obstetric outcomes and vertical transmission. METHODS: A prospective observational study was performed, enrolling unvaccinated pregnant patients positive for SARS-CoV-2 (cases) and matched with uninfected pregnant women (controls). Maternal and neonatal nasopharyngeal swabs, maternal and cord blood, amniotic fluid and placenta tissue samples were collected; blood samples were tested for anti-S and anti-N antibodies, and histologic examination of placental tissues was performed. RESULTS: The cases showed a significant association with the development of some obstetric complications, such as intrauterine growth restriction and pregnancy-associated hypothyroidism and diabetes, as compared to controls; their newborns were more likely to have a low birth weight and an arterial umbilical pH less than 7. The viral genome was detected in maternal and cord blood and placental samples in six cases. CONCLUSIONS: Pregnant women positive for SARS-CoV-2 infection are more likely to develop severe obstetric outcomes; their newborns could have a low birth weight and arterial pH. Vertical transmission seems a rare event, and further investigation is strongly needed.

"Better late than never but never late is better", especially in young women. A multicenter Italian study on diagnostic delay for symptomatic endometriosis.

PURPOSE: The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis. MATERIALS AND METHODS: This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history. RESULTS: The mean diagnostic delay found was of 11.4 years. The mean time (14.8 years) from symptoms onset to diagnosis was significantly longer among patients aged 9-19 vs patients aged 20-30 (mean 6.9 years, p < 0.001) and patients aged 31-45 (mean 2.9, p < 0.001). No significant association were found between a delayed diagnosis and any of the clinically relevant factors such as the number or severity of the reported symptoms, familiarity, hormonal therapy intake or methodology of diagnosis. CONCLUSIONS: The mean diagnostic delay of endometriosis in Italy is about 11 years. The delay can be up to 4 years longer in patients with pain symptoms onset under 20 years. Educating clinicians and patients on pathologic nature of endometriosis related pelvic pain is advisable to reduce waiting time to diagnosis, especially for young women.

In-Silico Functional Metabolic Pathways Associated to Chlamydia trachomatis Genital Infection.

The advent of high-throughput technologies, such as 16s rDNA sequencing, has significantly contributed to expanding our knowledge of the microbiota composition of the genital tract during infections such as Chlamydia trachomatis. The growing body of metagenomic data can be further exploited to provide a functional characterization of microbial communities via several powerful computational approaches. Therefore, in this study, we investigated the predicted metabolic pathways of the cervicovaginal microbiota associated with C. trachomatis genital infection in relation to the different Community State Types (CSTs), via PICRUSt2 analysis. Our results showed a more rich and diverse mix of predicted metabolic pathways in women with a CST-IV microbiota as compared to all the other CSTs, independently from infection status. C. trachomatis genital infection further modified the metabolic profiles in women with a CST-IV microbiota and was characterized by increased prevalence of the pathways for the biosynthesis of precursor metabolites and energy, biogenic amino-acids, nucleotides, and tetrahydrofolate. Overall, predicted metabolic pathways might represent the starting point for more precisely designed future metabolomic studies, aiming to investigate the actual metabolic pathways characterizing C. trachomatis genital infection in the cervicovaginal microenvironment.

SARS-CoV-2 vertical transmission in a twin-pregnant woman: a case report.

SARS-CoV-2 has affected millions of people around the world in recent years. Among susceptible patients, pregnant women seem to be prone to serious complications. The possibility of SARS-CoV-2 vertical transmission represents one of the most debated topics in the literature, providing inconclusive results. We present a case of a confirmed vertical transmission in a monochorial diamniotic twin pregnancy complicated by a selective intrauterine growth restriction and gestational diabetes mellitus. The analysis of different biological specimens identifies the presence of the SARS-CoV-2 genome in the umbilical cord blood of both twins, and the placental histologic examination confirmed indirect signs of viral infection, supporting the hypothesis that a transplacental infection can occur. Despite the devastating impact that SARS-CoV-2 has worldwide, neonatal infections have been infrequently reported, but they can occur under certain biologic conditions. Deep knowledge of the biological mechanisms underlying the risk of SARS-CoV-2 vertical transmission might be useful to understand the pathophysiological bases and the possible long-term implication of a mother-to-child vertical transmission.

MRI and Adenomyosis: What Can Radiologists Evaluate?

Uterine adenomyosis is a common benign condition defined by the presence of heterotopic endometrial glands and stroma within the myometrium. Adenomyosis is often related to infertility and other adverse pregnancy outcomes. Modern imaging techniques allow the non-invasive diagnosis of adenomyosis and, in this framework, Magnetic Resonance Imaging (MRI) has assumed a central role due to its high diagnostic accuracy in the detection of adenomyosis. Currently, there is still a lack of international consensus on adenomyosis diagnostic criteria and classification, despite the fact that an agreed reporting system would promote treatment outcomes and research. This review aims to emphasize the important contribution of MRI to the diagnosis of adenomyosis and to highlight how, thanks to the great tissue differentiation provided by MRI, it is possible to identify the main direct (cystic component) and indirect (junctional zone features) signs of adenomyosis and to distinguish its various subtypes according to different MRI-based classifications. We also explored the main MRI criteria to identify the most common pitfalls and differential diagnoses of adenomyosis, whose features should be considered to avoid misdiagnosis.

What is the Hidden Biological Mechanism Underlying the Possible SARS-CoV-2 Vertical Transmission? A Mini Review.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2) represents an emerging infection that is spreading around the world. Among susceptible patients, pregnant women are more likely to develop serious complications and negative obstetric outcomes. Vertical transmission constitutes a debating issue which has not been completely understood. This review aims at describing the currently available evidence on SARS-CoV2 vertical transmission. We carried out a computerized literature search in the Cochrane Library, PubMed, Scopus and Web of Science, selecting the most relevant studies on vertical transmission from the outbreak onset until February 2022. The analysis of the available literature identifies the presence of SARS-CoV2 genome in different biological specimens, confirming the hypothesis that a transplacental infection can occur. In spite of the high number of infected people around the world, mother-to-child infections have been infrequently reported but it can be observed under certain biologic conditions. A deep knowledge of the underlying mechanisms of SARS-CoV2 vertical transmission is of paramount importance for planning an adequate management for the affected mothers and newborns.

Endometriosis and Sexual Functioning: How Much Do Cognitive and Psycho-Emotional Factors Matter?

Women with endometriosis often suffer from genito-pelvic pain. The objective of the present study was to analyze the relationship between cognitive and psycho-emotional factors and sexual functioning of women with endometriosis, comparing women with and without endometriosis. A total of 87 women with endometriosis (EG) and 100 women without endometriosis (CG) completed a socio-demographic questionnaire; the short-form of McGill Pain Questionnaire (SF-MPQ); the Female Sexual Functioning Index (FSFI); the Sexual Distress Scale (SDS); the Symptoms Checklist (SCL-90-R); the Toronto Alexithymia Scale (TAS-20); the Positive and Negative Affects Scale (PANAS); the Sexual Dysfunctional Belief Questionnaire (SDBQ); the Sexual Modes Questionnaire (SMQ); and the Questionnaire of Cognitive Schema Activation in Sexual Context (QCSASC). EG obtained worse scores than CG in SF-MPQ, Pain subscale of FSFI, and SDS. EG reached higher scores than CG on almost all scales of SCL-90-R and lower scores in the "Identifying Feelings" scale of TAS-20. Furthermore, EG reported more negative emotions toward sexuality than CG (PANAS) higher scores on the "Affection Primacy" scale of SDBQ and the "Helpless" sexual cognitive schema of QCSASC than CG. No significant differences were found in SMQ. Sexual health professionals should address psychological, emotional, and cognitive factors since they seem involved in patients' sexual experiences.

Human placental microperfusion and microstructural assessment by intra-voxel incoherent motion MRI for discriminating intrauterine growth restriction: a pilot study.

OBJECTIVES: To evaluate the potential of Intravoxel Incoherent Motion (IVIM) Imaging in the quantification of placental micro-perfusion and microstructural features to identify and discriminate different forms of intrauterine growth restriction (IUGR) and normal fetuses pregnancies. METHODS: Small for gestational age SGA (n = 8), fetal growth restriction FGR (n = 10), and normal (n = 49) pregnancies were included in the study. Placental Magnetic Resonance Imaging (MRI) was performed at 1.5 T using a diffusion-weighted sequence with 10 b-values. IVIM fractional perfusion (fp), diffusion (D), and pseudodiffusion (D*) were evaluated on the fetal and maternal placental sides. Correlations between IVIM parameters, Gestational Age (GA), Birth Weight (BW), and the presence or absence of prenatal fetoplacental Doppler abnormalities at the US were investigated in SGA, FGR, and normal placentae. RESULTS: fp and D* of the placental fetal side discriminate between SGA and FGR (p = .021; p = .036, respectively), showing lower values in FGR. SGA showed an intermediate perfusion pattern in terms of fp and D* compared to FGR and normal controls. In the intrauterine growth restriction group (SGA + FGR), a significant positive correlation was found between fp and BW (p < .002) in the fetal placenta and a significant negative correlation was found between D and GA in both the fetal (p < .0009) and maternal (p < .006) placentas. CONCLUSIONS: Perfusion IVIM parameters fp and D* may be useful to discriminate different micro-vascularization patterns in IUGR being helpful to detect microvascular subtle impairment even in fetuses without any sign of US Doppler impairment in utero. Moreover, fp may predict fetuses' body weight in intrauterine growth restriction pregnancies. The diffusion IVIM parameter D may reflect more rapid microstructural rearrangement of the placenta due to aging processes in the IUGR group than in normal controls.

Prostatic tissue: an unexpected finding in a mature ovarian teratoma : Case report and systematic literature review.

PURPOSE: Prostatic tissue in an ovarian teratoma is an unusual finding, whose initiation in a 46, XX karyotype tissue is yet to be clarified. We present a case from our files and review the literature for this intriguing finding. METHODS: Unstained histology sections of the ovarian teratoma containing prostatic tissue were evaluated using immunohistochemistry for PSA and androgen receptor. RESULTS: Both PSA and androgen receptor immunostainings were positive in the prostatic tissue. From the literature review, it appears that most of the patients (74%) with similar findings were either pregnant or experiencing a miscarriage, menopausal or infertile at presentation, showing that an imbalanced hormone status is frequently associated with the presence of male structures in ovarian teratomas.

Can New ENZIAN Score 2020 Represent a Staging System Improving MRI Structured Report?

Structured reporting systems for endometriotic disease are gaining a central role in diagnostic imaging: our aim is to evaluate applicability and the feasibility of the recent ENZIAN score (2020) assessed by MRI. A total of 60 patients with suspected tubo-ovarian/deep endometriosis were retrospectively included in our study according to the following criteria: availability of MR examination; histopathological results from laparoscopic or surgical treatment; patients were not assuming estro-progestin or progestin therapy. Three different readers (radiologists with 2-, 5-, and 20-years of experience in pelvic imaging) have separately assigned a score according to the ENZIAN score (revised 2020) for all lesions detected by magnetic resonance imaging (MRI). Our study showed a high interobserver agreement and feasibility of the recent ENZIAN score applied to MRI; on the other hand, our experience highlighted some limitations mainly due to MRI's inability to assess tubal patency and mobility, as required by the recent score (2020). In view of the limitations which arose from our study, we propose a modified MRI-ENZIAN score that provides a complete structured reporting system, more suitable for MRI. The high interobserver agreement of the recent ENZIAN score applied to MRI confirms its validity as a complete staging system for endometriosis, offering a shared language between radiologists and surgeons.

Effects of Breastfeeding on Endometriosis-Related Pain: A Prospective Observational Study.

Endometriosis is a gynecological estrogen-dependent disease whose commonest pain symptoms are dysmenorrhea, dyspareunia, and acyclic chronic pelvic pain (CPP). Hormonal changes occurring during breastfeeding seem to reduce pain and disease recurrence. The aim of this observational prospective study was to assess the effect of breastfeeding on pain and endometriotic lesions in patients with endometriosis and to evaluate a possible correlation between the duration of breastfeeding, postpartum amenorrhea, and pain. Out of 156 pregnant women with endometriosis enrolled, 123 who breastfed were included in the study and were monitored for 2 years after delivery; 96/123 exclusively breastfed for at least 1 month. Mode of delivery, type and duration of breastfeeding, intensity of pain symptoms, and lesion size before pregnancy and during the 24-month follow-up were analyzed. All patients experienced a significant reduction in dysmenorrhea proportional to the duration of breastfeeding. CPP was significantly reduced only in women who exclusively breastfed. No significant improvement in dyspareunia was observed. Ovarian endometriomas were significantly reduced. Therefore, breastfeeding, particularly if exclusive, may cause improvement in dysmenorrhea and CPP proportional to the duration of breastfeeding, as well as a reduction in the size of ovarian endometriomas.

Does Lung Ultrasound Have a Role in the Clinical Management of Pregnant Women with SARS COV2 Infection?

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection is a major health threat. Pregnancy can lead to an increased susceptibility to viral infections. Although chest computed tomography (CT) represents the gold standard for the diagnosis of SARS-CoV-2 pneumonia, lung ultrasound (LUS) could be a valid alternative in pregnancy. The objectives of this prospective study were to assess the role of LUS in the diagnosis of lung involvement and in helping the physicians in the management of affected patients. Thirty pregnant women with SARS-CoV-2 infection were admitted at the obstetrical ward of our Hospital. Mean age was 31.2 years, mean gestational age 33.8 weeks. Several LUS were performed during hospitalization. The management of the patients was decided according to the LUS score and the clinical conditions. Mean gestational age at delivery was at 37.7 weeks, preterm birth was induced in 20% of cases for a worsening of the clinical conditions. No neonatal complications occurred. In 9 cases with a high LUS score, a chest CT was performed after delivery. CT confirmed the results of LUS, showing a significant positive correlation between the two techniques. LUS seems a safe alternative to CT in pregnancy and may help in the management of these patients.

Dienogest versus continuous oral levonorgestrel/EE in patients with endometriosis: what's the best choice?

OBJECTIVE: Combined oral contraceptives (COC) and progestogens are widely used for the treatment of endometriosis. The objective of the study is to compare the efficacy of dienogest 2 mg vs continuous oral levonorgestrel/EE (levonorgestrel 0.1 mg/ethinyl estradiol 0.02 mg) on ovarian endometriomas, deep infiltrating endometriosis (DIE), chronic pelvic pain (CPP), dyspareunia, analgesic use, quality of life (QoL), compliance and side effects. METHODS: Prospective cohort study. Two cohorts of patients with endometriosis, 50 taking dienogest (group A) and 50 taking continuous levonorgestrel/EE (group B), were evaluated at the beginning of therapy (t0), after 3 (t3) and 6 months (t6). Size of endometriomas, DIE, QoL, pain symptoms, and side effects were assessed. RESULTS: Dienogest was significantly effective on CPP (p = .002), dyspareunia (p = .021) ovarian endometriomas (p = .015) and DIE lesions reduction (p = .014). Levonorgestrel/EE was significantly effective on dyspareunia (p = .023). Analgesics consumption significantly decreased in both groups (p < .001). Both treatments significantly improved the QoL. Over 6 months a significant improvement was found, more frequently in patients taking dienogest. The only side effect that both groups complained about was vaginal bleeding, present in the first 3 months of treatment (p < .001). CONCLUSIONS: Both treatments are effective and safe for patients with endometriosis. Patients compliance and side effects are similar in both groups, however, there was a significantly higher reduction in endometriotic lesions, pain symptoms, and improvement of the QoL in women taking dienogest than in women taking continuous COC.

TLR4 T399I Polymorphism and Endometriosis in a Cohort of Italian Women.

BACKGROUND: Endometriosis is a widespread multifactorial disease in which environmental, genetic, and epigenetic factors contribute to the phenotype. Single Nucleotide Polymorphisms (SNPs) in genes implicated in pivotal molecular mechanisms have been investigated as susceptible risk factors in distinct populations. Among these, Toll-like receptor 4 (TLR4) represents a good candidate due to its role in the immune/inflammatory response and endometriosis pathogenesis. METHODS: The TRL4 gene T399I SNP (C/T transition, rs4986791) was investigated in 236 Italian endometriosis patients and 150 controls by using the PCR-RFLP method. One-tailed Fisher's exact test was used to compare differences between categorical variables. T399I genotype distribution was evaluated for Hardy-Weinberg equilibrium in both groups using the Chi-squared test for given probabilities. RESULTS: Fisher's exact test comparing C and T allele frequencies showed a difference in the frequency of T alleles between patients and controls (OR = 1.96, 95% confidence interval 0.91-4.23; p-value = 0.0552). Genotype frequencies did not show any significant difference between patients and controls. The homozygous TT genotype was observed in 2% of endometriosis women and not in controls. CONCLUSIONS: Our results show that the TLR4 rs4986791 T variant may be considered a genetic risk factor for endometriosis in Italian women. More extensive studies in other populations are needed to confirm this result.

Irritable Bowel Syndrome-Like Disorders in Endometriosis: Prevalence of Nickel Sensitivity and Effects of a Low-Nickel Diet. An Open-Label Pilot Study.

Alimentary nickel (Ni) may result in allergic contact mucositis (ACM), whose prevalence is >30% and may present with IBS-like and extra-intestinal symptoms. These symptoms are also frequent in endometriosis, and Ni allergic contact dermatitis has already been observed in endometriosis. Therefore, intestinal and extra-intestinal symptoms in endometriosis may depend on a Ni ACM, and a low-Ni diet could improve symptoms. We studied the prevalence of Ni ACM in endometriosis and focused on the effects of a low-Ni diet on gastrointestinal, extra-intestinal, and gynecological symptoms. We recruited 84 women with endometriosis, symptomatic for gastrointestinal disorders. Thirty-one out of 84 patients completed the study. They underwent Ni oral mucosa patch test (omPT), questionnaire for intestinal/extra-intestinal/gynecological symptoms, and a low-Ni diet. Clinical evaluation was performed at baseline (T0) and after three months (T1). Twenty-eight out 31 (90.3%) patients showed Ni omPT positive results, with Ni ACM diagnosis, whereas three out of 31 (9.7%) patients showed negative Ni omPT. After three months of low-Ni diet, all gastrointestinal, extra-intestinal and gynecological symptoms showed a statistically significant reduction. Ni ACM has a high prevalence in endometriosis and a low-Ni diet may be recommended in this condition to reduce gastrointestinal, extra-intestinal and gynecological symptoms.