Transgender and gender diverse people with endometriosis: A perspective on affirming gynaecological care.

Transgender and gender diverse people presumed female at birth experience gynaecological conditions, such as chronic pelvic pain at elevated rates, estimated to impact between 51% and 72% of this population, compared to rates of up to 26.6% in cisgender women. The negative impact of these conditions is likely amplified due to limited access to safe and affirming healthcare. Despite this high prevalence rate, there is limited research investigating the prevalence, presentation or management options for trans and gender diverse people with endometriosis. Cisgender women with endometriosis report barriers to accessing care, with lengthy times to diagnosis and limited treatment options available. However, barriers for trans and gender diverse individuals are enhanced by physician bias and lack of education in gender-affirming care. This is reflected in stories of discrimination and denial of basic healthcare. A healthcare environment built on the presumption that gynaecological patients are women, others trans and gender diverse patients, which can result in avoidance of needed medical care. A lack of knowledge of gender-affirming care alongside healthcare provider bias highlights a need for gender-affirming care and bias reduction training in undergraduate healthcare provider curricula. Research to date assessing current curriculum in Australia and Aotearoa (New Zealand) shows limited inclusion of lesbian, gay, bisexual, trans, queer, intersex, asexual and other related identities content as a whole with gender-affirming care being among the least-frequently addressed topics. This review will detail barriers to accessing gender-affirming healthcare specific to gynaecology, interweaving the experiences of a non-binary individual seeking access to gender-affirming endometriosis care.

Transgender and gender diverse people with endometriosis: a perspective on affirming gynaecological careTransgender and gender diverse people have limited access to safe and affirming healthcare. Barriers to accessing care are particularly prominent for those presumed female at birth attempting to access gynaecological care for conditions, such as endometriosis or chronic pelvic pain (CPP). A key barrier to safe and affirming healthcare for this population is a lack of inclusion of trans and gender diverse health in healthcare provider curriculum. The dearth of healthcare providers knowledgeable in gender-affirming care results in healthcare discrimination and poorer health outcomes for trans and gender diverse people.

Risk of Iron Deficiency in Women With Endometriosis: A Population-Based Prospective Cohort Study.

BACKGROUND: Endometriosis may be linked to the risk of iron deficiency through chronic systemic inflammation or heavy menstrual bleeding. No longitudinal studies, however, have examined the relationship between endometriosis and the risk of iron deficiency. METHODS: This study included 3,294 participants born from 1973 to 1978 and followed as part of the Australian Longitudinal Study on Women's Health from 2000 to 2018. Participants with endometriosis were identified using self-reported longitudinal surveys linked to administrative health records. During each survey, participants were also asked to report the diagnosis of iron deficiency, and we validated diagnoses using an administrative health database. Generalized estimating equations for binary responses with an autoregressive correlation matrix were used to examine the association between endometriosis and the risk of iron deficiency over the seven time points. FINDINGS: We found that women with endometriosis had a significantly higher risk of iron deficiency than those without endometriosis after adjusting for sociodemographic, lifestyle, reproductive, and nutrition factors (adjusted odds ratio [aOR] = 1.46; 95% confidence interval [CI] [1.29, 1.66]; p < .0001). Women with a surgically confirmed diagnosis and those with clinically suspected endometriosis had a higher risk of iron deficiency (aOR = 1.38; 95% CI [1.17, 1.64] and aOR = 1.53; 95% CI [1.30, 1.81]), respectively. These associations, however, were slightly attenuated (by 8%) when adjusted for the presence of heavy menstrual bleeding. CONCLUSIONS: Women with endometriosis are at a higher risk of developing iron deficiency than those without endometriosis. The findings suggest that iron deficiency should be concomitantly addressed during initial diagnosis and successive management of endometriosis.

Presence of endometriosis and chronic overlapping pain conditions negatively impacts the pain experience in women with chronic pelvic-abdominal pain: A cross-sectional survey.

BACKGROUND: Evidence of overlap between endometriosis and chronic pain conditions is emerging; however, little is known about how the pain experience differs based on the presence or absence of endometriosis. OBJECTIVES: In a sample of women reporting chronic pelvic-abdominal pain (CPP), the aim of this study was to characterize differences in pain symptomatology between women with and without endometriosis and to examine the influence of chronic overlapping pain conditions (COPCs) on pain among these two groups. DESIGN: This was a cross-sectional study, based on an online survey. METHODS: Participants (aged 18+ years) completed a survey collecting pain diagnoses and symptoms assessing pelvic pain severity, pain interference, and pain impact. Independent sample t-tests, chi-square, and multiple linear regression models were employed to analyze group differences in pain symptomatology and COPCs. RESULTS: Of the 525 respondents with CPP, 25% (n = 133) reported having endometriosis. Women with endometriosis were younger at the onset of pelvic pain, relative to women without endometriosis (p = 0.04). There were no differences in age, race, ethnicity, or duration of pelvic pain between women with and without endometriosis. Women with endometriosis reported higher pelvic pain severity (+0.8, 95% CI = 0.4-1.1), pain interference (+5.9, 95% CI = 2.4-9.3), and pain impact (+1.9, 95% CI = 0.8-2.9). Endometriosis was associated with a higher number of COPCs (p = 0.003), with 25% (n = 33) of women reporting ⩾3 overlapping pain conditions compared with 12% (n = 45) of those without endometriosis. Women with endometriosis had a higher frequency of fibromyalgia (p < 0.001), chronic fatigue syndrome (p < 0.001), and temporomandibular disorder (p = 0.001). The number of COPCs was associated with higher pain severity, interference, and impact, independently of endometriosis. CONCLUSION: Women with endometriosis experienced higher levels of pain-related burden and COPCs compared with those without endometriosis. Pain intensity, interference, and impact increased with a higher number of pain conditions regardless of endometriosis presence.

Presence of endometriosis and chronic overlapping pain conditions negatively impacts the pain experience in women with chronic pelvic­abdominal pain: A cross-sectional surveyThe presence of endometriosis was associated with a higher number of chronic overlapping pain conditions (COPCs) and greater pain symptomatology, while a greater number of COPCs corresponded to increased pain burden among women with and without endometriosis. These findings underscore the need for a more comprehensive assessment of endometriosis that addresses the full experience of the disease, including its comorbidities. A greater characterization and measurement of COPCs has the potential to facilitate the development of tailored interventions for individuals with pain comorbidities, thereby contributing to improved clinical care strategies for endometriosis-related pain.

Comorbid pathology of the mammary glands and endometriosis: risk factors and prognosis.

OBJECTIVE: Aim: based on a retrospective analysis, the relationship between external genital endometriosis and comorbid breast pathology was established and risk factors were identified, their comparison and the formation of a prognostic risk criterion were determined. PATIENTS AND METHODS: Materials and Methods: to address the objectives of the study, a retrospective analysis of 470 cases of patients treated for external genital endometriosis after surgical treatment and comorbid breast pathology was conducted. The control group included 30 healthy non-pregnant women. Statistical processing was performed on a personal computer using the statistical software package Statistica 10. RESULTS: Results: As a result of the analysis, the age of the patients ranged from 23 to 40 years. The average age of patients in the study group was (32.2}1.18) years, and in the control group (31.1}1.35) (p>0.05). The groups were homogeneous in terms of age (p>0.05), marital status (p>0.05) and level of education (p>0.05). Close relatives in 208 (44.25}2.18) % (OR=8.86; 95 % CI: (0.68-10.53); p<0.002) cases suffered from benign (hormone-dependent) tumours and tumour-like diseases of the uterus and appendages in isolation or in various combinations (fibroids, adenomyosis, endometrial hyperplasia). It was also found that 102 (21.70}1.67) % of patients had endometriosis, which may indicate a genetic predisposition to this disease. In the closest relatives of EM patients: in 118 (25.10}2.01) % of the examined parents, breast problems were noted, in 66 (14.04}1.12) % - diabetes mellitus, and in 98 (20.85}1.22) % thyroid diseases were detected, which in total amounted to (60.00}2.23) % (OR=9.12; 95 % CI: (0.58-11.54); p<0.002). Early menarche almost tripled the risk of EM (OR=2.72; 95% CI: (1.02-5.11); p<0.002), and menstrual irregularities doubled it (OR=2.04; 95% CI: (1.09-3.14); p<0.05), higher education, urban residents - 2.2 times higher (OR= 2.27; 95 % CI: (1.11-3.63); p<0.05), diseases of the gastrointestinal tract and hepatobiliary complex - 5.2 times higher (OR=5.27; 95 % CI: (1.89-12.03); p<0.05), frequently recurrent inflammatory diseases of the appendages - 3 times higher (OR=3.14; 95 % CI: (0.91-5.14); p<0.05), dysmetabolic manifestations (thyroid dysfunction) - 5 times higher (OR=5.11; 95 % CI: (1.61-9.503); p<0.002). CONCLUSION: Conclusions: Thus, in endometriosis and dyshormonal diseases of the mammary glands, menstrual and generative function disorders, along with clinical symptoms of pelvic pain, dysmenorrhoea, autonomic nervous system disorders and sexual dysfunction, are significant components of this problem, initiating comorbidity processes in target organs in the setting of hormonal maladaptation. Therefore, these comorbidities become a trigger for the activation of systemic hormonal imbalance and become an urgent interdisciplinary problem that requires further study.

Association of endometriosis with asthma: a study of the NHANES database in 1999-2006.

OBJECTIVE: Asthma is a chronic inflammatory disease of the airways with a gender differences in the prevalence after puberty. Recent studies have reported a relationship between asthma and endometriosis, possibly related to the immune response mechanisms, but the evidences are limited and inconsistent. Herein, this research aimed to investigate the association of endometriosis with asthma based on the representative population in the United States (U.S.) to provide some reference for further exploration on mechanism of gender difference in asthma. METHODS: In this cross-sectional study, data of women aged ≥ 20 years old were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 1999-2006. Weighted univariate and multivariate logistic regression analyses were utilized to explore the association of endometriosis with asthma. The multivariate models adjusted for covariates including age, race, education level, marital status, poverty income ratio (PIR), body mass index (BMI), waist circumference, smoking, estrogen and progesterone hormones use, uterine fibroids, at least one ovary removed, and birth control pills intake. The evaluation indexes were odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses of age, race, BMI, and pregnancy history were also performed. RESULTS: Among 5,556 eligible women, 782 had asthma, and 380 had endometriosis. The average age of participants was 37.19 years old, and more than half of them were non-Hispanic White (68.44%). After adjusting for covariates, endometriosis was associated with higher odds of asthma compared with non-endometriosis [OR = 1.48, 95%CI: (1.10-1.99)]. This relationship was also found in 40-49 years old [OR = 2.26, 95%CI: (1.21-4.23)], BMI of 25-29.9 kg/m2 [OR = 2.87, 95%CI: (1.52-5.44)], and pregnancy history [OR = 1.44, 95%CI: (1.01-2.06)] subgroups. CONCLUSION: Endometriosis had a positive association with asthma in adult women. Females aged 40-49 years old, with BMI of 25-29.9 kg/m2 and had a history of pregnancy should take care about monitoring endometriosis to reduce the potential risk of asthma. Further studies are still needed to clarify the causal association between endometriosis and asthma.

Determinants of Conception and Adverse Pregnancy Outcomes in Women with Endometriosis: A Longitudinal Study.

Endometriosis, affecting approximately 10% of reproductive-aged women globally, poses significant challenges, including chronic pelvic pain, dysmenorrhea, and infertility. In low- and middle-income countries like India, accessibility to affordable infertility care remains a concern. This multicenter prospective cohort study, conducted across six tertiary care hospitals in India from 2017 to 2022, aims to explore the natural progression of conception and pregnancy outcomes in women with endometriosis. Of the 257 participants, 19.1% conceived during the study, revealing significant geographic and income-based variations (p < 0.001, p = 0.01). Dysmenorrhea (p < 0.001) and dyspareunia (p=0.027) were correlated with conception, while no such associations were found with chronic pelvic pain or menstrual factors. Lesion type, number, and severity showed no conclusive link with conception. Natural conception occurred in 70% of cases, with an average post-surgery conception time of 282.1 days. Live birth rate was 85.7%, while complications included placenta previa (16.4%), preeclampsia (4.1%), and preterm births (4.1%). This study, one of the first in India on endometriosis-related fertility progression, emphasizes the need for comprehensive understanding and management of conception and pregnancy outcomes. Considering India's substantial endometriosis burden, the study recommends prioritizing larger multicenter investigations for a better understanding and effective strategies for infertility management.

[Endometriosis, a participatory study in the Serchio Valley (Tuscany Region, Central Italy): state of the art and perspectives]. / Endometriosi, uno studio partecipato nella Valle del Serchio: stato dell'arte e prospettive.

BACKGROUND: endometriosis is a chronic condition with a significant impact on women's health, featured by endometrial tissue outside the uterine cavity. A limited number of studies have been conducted in the general population, and the true prevalence of endometriosis is unknown for many areas of the country. OBJECTIVES: to better estimate the prevalence of endometriosis in three Italian regions (Friuli Venezia Giulia, Tuscany, Apulia) and to assess the relationship between endometriosis and environmental factors in three participating areas (Trieste, Barga, and Taranto), with a focus on Tuscany Region. DESIGN: implementing a specific epidemiological registry for endometriosis, aimed at estimating the incidence and prevalence data. The registry collected information from hospital discharge records and anatomopathological reports of women residing in the three considered regions, aged 15 years or older. Additionally, the analysis includes the assessment of the spatial distribution of endometriosis at both regional and municipal levels in the three study areas. Further research investigations in these areas involve a multilevel screening of a sample of women of childbearing age. Women who test positive in the initial screening (through a self-administered questionnaire) will have the opportunity to undergo a second level of screening, consisting of a gynecological examination, transvaginal ultrasound, a swab for vaginal microbiome analysis, and the collection of blood and urine samples to assess the presence of polychlorinated biphenyls (PCBs) or heavy metals. The adopted scientific approach is based on post-normal science (PNS) concerning the extended peer community. SETTING AND PARTICIPANTS: women aged 15 years or older residing in the three regions. MAIN OUTCOMES MEASURES: estimating the incidence and prevalence of endometriosis based on data collected from the epidemiological registry. The analysis extends to assessing the spatial distribution of endometriosis at municipal levels in the three areas of interest. RESULTS: the preliminary results of the study allowed for the estimation of the spatial distribution of endometriosis incidence in Tuscany. In particular, it was found that there is variability within the region, with some coastal and North-Western areas showing values 20% higher than the regional average. Cities such as Pisa, Lucca, Livorno, Grosseto, Orbetello, and the Serchio Valley with Barga had a probability of excess risk of more than 90% compared to the regional average. CONCLUSIONS: the study is ongoing and requires the active participation of women living in the region to ensure the completeness and accuracy of the collected data. This research effort represents an important contribution to understanding endometriosis in Tuscany and its possible environmental causes.

Factors associated with chronic pelvic pain in women with endometriosis: A national study on clinical and sociodemographic characteristics, lifestyles, quality of life, and perceptions of quality of care, during the COVID-19 pandemic.

BACKGROUND: Endometriosis is a persistent inflammatory condition that affects women of reproductive age and causes pelvic pain. Chronic pelvic pain is a chronic regional pain syndrome involving the pelvic area. OBJECTIVES: This survey aimed to characterize the clinical and sociodemographic characteristics, lifestyles, quality of life, and perceptions of quality of care in women with endometriosis who reported chronic pelvic pain during the Covid pandemic. DESIGN: We conducted a cross-sectional survey among the Italian population from July to September 2021. METHODS: Snowball sampling was used to interview a large sample of adult women who reported a diagnosis of endometriosis, through a self-reported questionnaire. Univariate and multivariable logistic regression analyses were performed to identify the factors associated with chronic pelvic pain. The primary outcome was describing women who reported chronic pelvic pain. RESULTS: A total of 661 out of 1045 (63%) women who responded to the survey reported chronic pelvic pain. The multivariable analysis evidenced that chronic pelvic pain was related to physical and mental quality perception, pelvic floor disorders (adjusted odds ratio = 1.58; 95% CI = 1.10-2.27; p = 0.012), dyspareunia (adjusted odds ratio = 1.87; 95% CI = 1.31-2.65; p < 0.001), adhesions syndrome (adjusted odds ratio = 1.49; 95% CI = 1.05-2.11; p = 0.026), and the delay in diagnosing endometriosis (adjusted odds ratio = 1.04; 95% CI = 1.00-1.09; p = 0.034). The only social factor associated with chronic pelvic pain was marital status (adjusted odds ratio = 0.66; 95% CI = 0.46-0.93; p = 0.019). CONCLUSION: In the pandemic period, there was a very high prevalence of chronic pelvic pain in women with endometriosis in Italy. The pandemic highlighted the need for careful attention to diagnose endometriosis and the need for psychological and partner support, which would allow better pain management and prevent chronicity.

Correlation between endometriosis and migraine features: Results from a prospective case-control study.

BACKGROUND: Endometriosis and migraine frequently coexist, but only a limited number of studies have focused on their mutual association. The aim of our study was to investigate, in untreated women with comorbid endometriosis/adenomyosis and migraine, the correlation between headache features and endometriotic subtypes and their possible relationship with pain severity and disease disability. METHODS: Fifty women affected by endometriosis/adenomyosis and migraine matched (1:2) with 100 patients with endometriosis alone and 100 patients with only migraine were recruited and underwent pelvic ultrasound imaging and neurological examination. RESULTS: Severe adenomyosis, posterior and anterior deep infiltrating endometriosis (p = 0.027, p = 0.0031 and p = 0.029, respectively) occurred more frequently in women with migraine. Dysmenorrhea was the most commonly reported symptom in women with endometriosis and migraine and the mean VAS scores of all typical endometriotic symptoms were significantly higher in the presence of comorbidity. Women with both migraine and endometriosis reported significant higher pain intensity (p = 0.004), higher monthly migraine days (p = 0.042) and increased HIT 6-scores (p = 0.01), compared with those without endometriosis. CONCLUSIONS: Our results demonstrated that the co-occurrence of migraine in untreated women with endometriosis is associated with more severe gynecological infiltrations and correlated with increased pain intensity and disease disability.Trial Registration: Protocol number 119/21.

Causal effects of endometriosis on cancer risk: A Mendelian randomization study.

Endometriosis has been reported in epidemiological studies to be associated with certain types of cancer. However, the presence of reverse causality and residual confounding due to common risk factors introduces uncertainty regarding the extent to which endometriosis itself contributes to the development of cancer. We performed the Mendelian randomization (MR) to investigate the causal associations between endometriosis and 34 different types of cancers. The results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for ovarian cancer (OR = 3.2913; p-value = .0320). The genetic liabilities to endometriosis had causal associations with the decreased risk for skin cancer (OR = 0.9973; p-value = .0219), hematological cancer (OR = 0.9953; p-value = .0175) and ER- breast cancer (OR = 0.6960; p-value = .0381). The causal association of the above combinations were robust by test of heterogeneity and pleiotropy. Together, our study suggests that endometriosis had causal effect on cancer risk.

Dysmenorrhea pattern in adolescences informing adult endometriosis.

BACKGROUND: Endometriosis (EMs) is a chronic and progressive disease that, if diagnosed late, can lead to infertility and deep infiltrating endometriosis (DIE). Dysmenorrhea is the most prominent symptom of EMs. However, limited research exists on the specific correlation between dysmenorrhea patterns and EMs. Early prevention of EMs is essential to effectively manage the progression of the disease, and is best detected during adolescence. Our objective was to associate the development of EMs with dysmenorrhea patterns during adolescence and quantify the risk of adult EMs for adolescent girls, with the aim of supporting primary intervention strategy planning. METHODS: This case-control study examined predictors for adult EMs based on dysmenorrhea patterns in adolescents. We collected 1,287 cases of 641 EMs and 646 healthy females regarding their basic demographic information, adolescent menstrual characteristics, adolescent dysmenorrheal patterns, and adolescent lifestyles. Age-matching (1-to-1) was employed to control for the confounding effect of age between the groups. Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression models were utilized to identify predictors for adult EMs. The predictive value of the model was evaluated using the area under the receiver operating characteristic curve (AUC) and the C-index, while Hosmer-Lemeshow Test assessed the goodness of fit of the model. Data from one additional cohort in Shenzhen hospitalized with EMs were used to external validation were analyzed. RESULTS: Individuals who always experienced dysmenorrhea had a risk of adult endometriosis 18.874 (OR = 18.874; 95%CI = 10.309-34.555) times higher than those occasional dysmenorrhea, The risk of developing EMs was 5.257 times higher in those who experienced dysmenorrhea more than 12 months after menarche than in those who experienced dysmenorrhea less than 6 months after menarche (OR = 5.257, 95% CI = 3.343-8.266), AUC in the external validation cohort was 0.794(95%CI: 0.741-0.847). We further found that high-intensity physical activity and sun-sensitive skin of burning were influential factors in high-frequency dysmenorrhea. The AUC value for the internal evaluation of the model was 0.812 and the AUC value for the external validation was 0.794. CONCLUSION: Our findings revealed that the frequency of dysmenorrhea during adolescence contributed to the development of adult endometriosis. The frequency and onset of dysmenorrhea in adolescence were promising predictors for adult EMs. Both internal and external validation proved the model's good predictive ability. TRIAL REGISTRATION: http://www.chictr.org.cn/ , TRN: ChicTR2200060429, date of registration: 2022/06/01, retrospectively registered.

Causal effects of endometriosis on SLE, RA and SS risk: evidence from meta-analysis and Mendelian randomization.

BACKGROUND: Endometriosis is an underdiagnosed disorder that affects an estimated 6-10% of women of reproductive age. Endometriosis has been reported in epidemiological studies to be associated with autoimmune diseases. However, the relationship remains controversial. METHODS: A meta-analysis of observational studies was undertaken to evaluate the risk of autoimmune diseases in patients with endometriosis. The relevant studies were retrieved via the databases Medline, Embase and Web of Science until July 20, 2023. Mendelian randomization (MR) was subsequently utilized to scrutinize the causal influence of genetic predisposition toward endometriosis on three autoimmune diseases. RESULTS: The meta-analysis findings revealed a relationship between endometriosis and the onset of SLE (cohort studies: RR = 1.77, 95% confidence interval (CI): 1.47-2.13, I2 = 0%; Case-control and cross-sectional studies: OR = 5.23, 95% CI: 0.74-36.98, I2 = 98%), RA (cohort studies: RR = 2.18, 95% CI: 1.85-2.55, I2 = 92%; Case-control and cross-sectional studies: OR = 1.40, 95% CI: 1.19-1.64, I2 = 0%) and SS (cohort studies: RR = 1.49, 95% CI: 1.34-1.66, I2 = 0%). Similarly, in our MR study, the results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for SLE (OR = 1.915, 95% CI: 1.204-3.045, p = 0.006) and RA (OR = 1.005, 95% CI: 1.001-1.009, p = 0.014). CONCLUSIONS: Both our meta-analysis and MR study indicate that endometriosis increases the risk of autoimmune diseases. These findings not only broaden our understanding of the genetic mechanisms underlying the comorbidity of endometriosis and autoimmune diseases, but also offer a new strategy for autoimmune disease prevention.

Endometriosis diagnosed by ultrasound is associated with lower live birth rates in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection treatment.

OBJECTIVE: To study the cumulative live birth rate (CLBR) after the first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment in women with or without deep-infiltrating endometriosis (DIE) and/or endometrioma diagnosed by transvaginal ultrasonography (TVUS), using the International Deep Endometriosis Analysis (IDEA) group definitions. DESIGN: Prospective observational cohort study at a university hospital. PATIENTS(S): In total, 1,040 women with subfertility aged 25 to ≤39 years were undergoing their first IVF/ICSI treatment between January 2019 and October 2022. Of these, 234 (22.5%; 95% confidence interval [CI], 20.0-25.0) women were diagnosed with DIE and/or endometrioma at systematic TVUS before starting their treatment. INTERVENTION(S): All women underwent their first IVF or ICSI treatment. Fresh and/or frozen embryos from the first cycle were used until pregnancy was achieved or no embryos remained. MAIN OUTCOME MEASURE(S): Cumulative live birth rate after the first IVF/ICSI cycle in women with or without DIE and/or endometrioma. RESULT(S): The CLBR after the first IVF/ICSI treatment in the total cohort of women was 426/1,040 (41.0%; 95% CI, 38.0-44.0). Women with DIE and/or endometrioma had a lower CLBR (78/234, 33.3%; 95% CI, 27.3-39.4) than women without the disease (348/806, 43.2%; 95% CI, 39.8-46.6). The crude relative risk (RR) for cumulative live birth for women with DIE and/or endometrioma was 0.77; 95% CI, 0.63-0.94, and after adjustments were made for age, body mass index, s-antimüllerian hormone, stimulation protocol, and day for embryo transfer, the adjusted RR was 0.63; 95% CI, 0.48-0.82. There was no difference in the number of retrieved mature oocytes, fertilization rate, or good quality embryos between the 2 groups. CONCLUSION: The presence of DIE and/or endometrioma diagnosed by TVUS lowers the chance of live birth in women undergoing their first IVF/ICSI treatment.

Association of Fibroids, Endometriosis, and Gynecologic Surgeries with Breast Cancer Incidence and Hormone Receptor Subtypes.

BACKGROUND: Fibroids and endometriosis are sex hormone-mediated and exhibit cancer-like behavior. Breast cancer may be more common in women who have had these conditions, but the literature is conflicting and does not always address factors like hysterectomy/oophorectomy status, race/ethnicity, menopause, and hormone receptor subtypes. METHODS: Data are from the Sister Study, a cohort of 50,884 U.S. women enrolled in 2003 to 2009 and followed through 2020. Cox proportional hazards models with time-varying exposures and covariates assessed the relationship of fibroids or endometriosis with breast cancer. Logistic regression examined the association with estrogen receptor (ER) status among cases. RESULTS: Fibroids (19,932 cases) were positively associated with breast cancer [fully adjusted HR: 1.07; 95% confidence interval (CI): 1.01-1.14], notably among Black participants (HR: 1.34; 95% CI: 1.07-1.69) and women who had a hysterectomy (HR: 1.18; 95% CI: 1.05-1.31). Endometriosis (3,970 cases) was not associated with breast cancer (HR: 0.99; 95% CI: 0.91-1.08). Among 4,419 breast cancer cases, fibroids were positively associated with ER+ subtypes (OR: 1.34; 95% CI: 1.10-1.65), while endometriosis was negatively associated with ER+ subtypes (OR: 0.78; 95% CI: 0.61-1.01). CONCLUSIONS: We observed a modest positive association between fibroids and breast cancer, particularly ER+ breast cancer. No relationship with endometriosis and breast cancer incidence was found. IMPACT: Fibroids, even in those with a family history of breast cancer, might modify breast cancer risk stratification tools. Future studies should further assess this link and interrogate shared risk factors.

Epidemiology of infertility in women with endometriosis.

Endometriosis is a benign, chronic, inflammatory condition affecting up to 10 % of women and characterised by the presence of glands and stroma tissue outside the uterus. Epidemiological and clinical studies demonstrate a consistent association between endometriosis and infertility. However, this relationship is far to be clearly understood and several mechanisms are involved. Available data show that patients with endometriosis have an increased estimated risk of infertility between two and four times compared with the general population. On the other hand, the probability of patients with infertility to have endometriosis is reported up to about 50 % of the cases. Future studies should aim to better elucidate the mechanisms behind endometriosis-associated infertility in order to offer the more appropriate and tailored management for the patients.

Neonatal uterine bleeding: Risk factors and its association with endometriosis-related symptoms later in life.

OBJECTIVE: We examined the prevalence and risk factors in association with neonatal uterine bleeding (NUB) by retrospective search of contemporary and historical medical records and investigated the possible association between the history of NUB at birth and endometriosis-related symptoms later in life who are now young women. STUDY DESIGN: This was a retrospective case-controlled cohort study and prospective evaluation of web-based questionnaire survey on symptoms related to endometriosis among young women born with and without NUB. Multiple regression analysis was performed incorporating various confounding variables that may influence the occurrence of NUB or the reporting of endometriosis symptoms later in life. RESULTS: Among the 1093 female neonates born between 1996 and 2000, 105 of them had NUB, yielding with a prevalence of 9.6 %. Of the 807 female babies born between 2013 and 2017, 25 (3.1 %) had NUB. Multiple Logistic regression analysis indicated that younger age of the mother [odds ratio (OR) = 0.92, 95 % confidence interval (CI) = 0.85-1.00, P = 0.048] and longer gestational age of 39 weeks (OR = 3.04, 95 % CI = 1.43-6.45, P = 0.004) and of ≥ 40 weeks (OR = 4.54, 95 % CI = 2.20-9.39, P < 0.0001) of gestation were significantly associated with the occurrence of NUB. While the possibility of recall bias cannot be ruled out, newborn females who had a history of NUB appeared to complain of various endometriosis-related symptoms later in life during adulthood. CONCLUSIONS: We confirmed the validity of the reported prevalence and risk factors of NUB. NUB indeed occurs with a prevalence of 3-10% during the historical and contemporary period. Longer gestational age and younger maternal age may be considered as high-risk factors for the occurrence of NUB. The clinical relevance of our findings remains to be elucidated. Future prospective studies, preferably with larger sample sizes and the inclusion of NUB cases after discharge from the hospital, may further illuminate some unresolved issues. We also need to confirm the endometriosis-related symptoms in women with and without history of NUB via more definitive diagnosis such as imaging and histology.

Diaphragm endometriosis: Random localization or extended form of pelvis endometriosis. A large comparative analysis of 202 cases.

OBJECTIVE: The aim of this study was to investigate and present the clinical characteristics of diaphragm endometriosis, to approach the pathogenetic mechanisms, and to answer the question of whether this disease can be considered an extended form of pelvic endometriosis. STUDY DESIGN: It was a retrospective comparative one-to-one analysis of 202 cases. Two groups of patients were compared: Group 1 patients with diaphragm endometriosis vs Group 2 (control group) with pelvis endometriosis, each with 101 patients. RESULTS: Patients with diaphragm endometriosis had extreme significantly higher prevalence of severe pelvis endometriosis included deep infiltrated endometriosis and severe adhesions in term of complete Douglas obliteration (p value = 0.0001). There was neither age nor BMI difference in two groups. Besides of cyclic shoulder or upper abdomen pain there was no difference of symptoms. CONCLUSION: Diaphragm endometriosis is a rare condition with an approximate prevalence of 1.1% of all endometriosis cases. Since the symptoms are very specific and patients do not associate the pain with diaphragmatic endometriosis, the symptoms should be asked about explicitly. If patients with diaphragmatic endometriosis have no symptoms, the lesions do not necessarily need to be removed. The pathogenesis is still unclear. The authors of this study consider this disease to be an extended form of severe pelvic and deep infiltrated endometriosis. However, the right-side dominance still cannot be explained. Further research is needed to fully understand the origin of diaphragmatic endometriosis.

Clinical course of multiple sclerosis with comorbid endometriosis: A matched cohort study.

BACKGROUND: Endometriosis (EMS) is pain syndrome in which endometrial tissue grows outside the uterus. EMS is associated with an increased risk of multiple sclerosis (MS), a demyelinating disease of the central nervous system. OBJECTIVE: To characterize clinical phenotypes of a cohort of patients with both EMS and MS compared to a cohort of matched controls with only MS. METHODS: We retrospectively identified patients with EMS and MS at Beth Israel Deaconess Medical Center (BIDMC). We collected data on EMS treatments and analyzed differences in histories of gynecological cancer, smoking, fatigue, anxiety, depression, headache, and neuropathic pain compared to matched controls. We used Wilcoxon signed rank tests for paired samples to compare Expanded Disability Status Scores (EDSS) and timed 25-foot walk values (T25FW). RESULTS: Using a case-control methodology, we found significantly increased EDSS (p < 0.001) and T25FW (p = 0.01) in the EMS-MS group compared to the MS group. More patients in the EMS-MS group had histories of smoking, anxiety, depression, and headaches, while more patients in the MS group had histories of fatigue and neuropathic pain. CONCLUSION: When controlling for age, race, and MS therapy, those with EMS-MS experience more MS disability than controls, suggesting this population requires more monitoring and efficacious treatment.

Elevated levels of Zn, Cu and Co are associated with an increased risk of endometriosis: Results from a casecontrol study.

BACKGROUND: Endometriosis is a common gynecological disease that affects approximately 5 %∼10 % of reproductive-aged women. Zinc (Zn), selenium (Se), copper (Cu), cobalt (Co) and molybdenum (Mo) are essential trace elements and are very important for human health. However, studies on the relationship between mixtures of essential trace elements and the risk of endometriosis are limited and inconsistent. In particular, studies confirming the association via different sample types are limited. OBJECTIVE: This study aimed to investigate the associations between Zn, Se, Cu, Co and Mo concentrations in blood and follicular fluid (FF) and endometriosis risk in a Chinese population. METHODS: A total of 609 subjects undergoing in vitro fertilization (IVF) were recruited; 836 samples were analyzed, including 451 blood samples (234 controls and 217 cases) and 385 FF samples (203 controls and 182 cases). In addition, 227 subjects provided both blood and FF samples. Zn, Se, Cu, Co and Mo concentrations in blood and FF were quantified via inductively coupled plasma-mass spectrometry (ICP-MS). The associations between the levels of Zn, Se, Cu, Co and Mo and the risk of endometriosis were assessed using single-element models (logistic regression models), and the combined effect of the trace elements on endometriosis risk was assessed using multielement models (Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression). RESULTS: Based on the single-element models, significant associations of Zn concentrations in blood (high-level vs. low-level group: aOR = 14.17, 95 % CI: 7.31, 27.50) and FF (first tertile vs. second tertile group: aOR = 0.34, 95 % CI: 0.16, 0.71; third tertile vs. second tertile group: aOR = 2.32, 95 % CI: 1.38, 3.91, respectively) and Co concentrations in blood (first tertile vs. second tertile group, aOR = 0.24, 95 % CI: 0.12, 0.48) and FF (third tertile vs. second tertile group: aOR = 3.87, 95 % CI: 2.19, 6.84) with endometriosis risk were found after adjustment for all confounders. In FF, Cu and Mo levels were significantly greater among the cases than among the controls, with a positive association with endometriosis risk (Cu (first tertile vs. second tertile group: aOR = 0.39, 95 % CI: 0.19, 0.81; third tertile vs. second tertile group: aOR = 2.73, 95 % CI: 1.61, 4.66, respectively) and Mo (high-level vs. low-level group: aOR = 14.93, 95 % CI: 7.16, 31.12)). However, similar associations between blood Cu and Mo levels and endometriosis risk were not found. In addition, the levels of these five essential trace element mixtures in blood and in FF were significantly and positively associated with endometriosis risk according to the BKMR analyses; the levels of Zn and Cu in blood and the levels of Mo in FF were significantly related to the risk of endometriosis, and the posterior inclusion probabilities (PIPs) were 1.00, 0.99 and 1.00 for Zn and Cu levels in blood and Mo levels in FF, respectively. Furthermore, Zn and Mo were the highest weighted elements in blood and FF, respectively, according to WQS analyses. CONCLUSION: The risk of endometriosis was associated with elevated levels of several essential trace elements (Zn, Cu and Co). Elevated levels of these elements may be involved in the pathomechanism of endometriosis. However, further studies with larger sample sizes will be necessary to confirm these associations.

The association of endosalpingiosis with chronic pelvic pain.

BACKGROUND: Endosalpingiosis is a pathologic diagnosis of ectopic epithelium resembling the fallopian tubes. It has been described with clinical characteristics that are similar to endometriosis. The primary objective is to determine if endosalpingiosis (ES) has a similar association with chronic pelvic pain when compared to endometriosis (EM). METHODS: This is a retrospective case-control analysis of patients with a histologic diagnosis of endosalpingiosis or endometriosis at three affiliated academic hospitals between 2000 and 2020. All ES patients were included, and 1:1 matching was attempted to obtain a comparable EM cohort. Demographic and clinical data were obtained, and statistical analysis was performed. RESULTS: A total of 967 patients (515 ES and 452 EM) were included. ES patients were significantly older than EM patients (median age 52 vs. 48 years, P<0.001), but other demographic variables were similar. Fewer ES patients had baseline chronic pelvic pain than EM patients (25.3% vs. 47%, P<0.001), and patients with ES were less likely to undergo surgery for the primary indication of pelvic pain (16.1% vs. 35.4%, P<0.001). Pelvic pain as the surgical indication remained lower in the ES group in multivariable analysis (OR=0.49, P<0.001). There were similar rates of persistent postoperative pain between ES and EM groups (10.1% vs. 13.5%, P=0.109). CONCLUSIONS: Although endosalpingiosis can be associated with chronic pelvic pain, the incidence of pain is significantly lower than in patients who have endometriosis. These findings suggest that ES is a unique condition that differs from EM. Further research including long-term follow-up and patient-reported outcomes is imperative.