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1.
Radiology ; 311(1): e232191, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38591980

RESUMEN

Endometriosis is a prevalent and potentially debilitating condition that mostly affects individuals of reproductive age, and often has a substantial diagnostic delay. US is usually the first-line imaging modality used when patients report chronic pelvic pain or have issues of infertility, both common symptoms of endometriosis. Other than the visualization of an endometrioma, sonologists frequently do not appreciate endometriosis on routine transvaginal US images. Given a substantial body of literature describing techniques to depict endometriosis at US, the Society of Radiologists in Ultrasound convened a multidisciplinary panel of experts to make recommendations aimed at improving the screening process for endometriosis. The panel was composed of experts in the imaging and management of endometriosis, including radiologists, sonographers, gynecologists, reproductive endocrinologists, and minimally invasive gynecologic surgeons. A comprehensive literature review combined with a modified Delphi technique achieved a consensus. This statement defines the targeted screening population, describes techniques for augmenting pelvic US, establishes direct and indirect observations for endometriosis at US, creates an observational grading and reporting system, and makes recommendations for additional imaging and patient management. The panel recommends transvaginal US of the posterior compartment, observation of the relative positioning of the uterus and ovaries, and the uterine sliding sign maneuver to improve the detection of endometriosis. These additional techniques can be performed in 5 minutes or less and could ultimately decrease the delay of an endometriosis diagnosis in at-risk patients.


Asunto(s)
Endometriosis , Humanos , Femenino , Endometriosis/diagnóstico por imagen , Consenso , Diagnóstico Tardío , Ultrasonografía , Radiólogos
2.
BMC Pregnancy Childbirth ; 24(1): 230, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38566020

RESUMEN

BACKGROUND: Cumulative live birth rate (CLBR) is considered as the most important endpoint for assessing the probability of having a baby in a complete in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycle. Many previous studies have focused on the association between thyroid autoimmunity (TAI) and live birth rate after first embryo transfer cycle, however, evidence on whether the presence of TAI affects the CLBR is lacking. The purpose of this study is to investigate the impact of TAI on the CLBR in a complete IVF/ICSI cycle. METHODS: This retrospective study included 12,796 women who underwent their first IVF/ICSI treatment between January 2019 and February 2021. Based on the levels of thyroid antibodies, 2,603 women were assigned to the TAI group, and 10,193 women were assigned to the control group. Subgroup analysis was performed according to the different causes of infertility (including male factor only, ovulation disorder, tubal factor, endometriosis and unexplained infertility) and different types and titres of thyroid antibodies. The primary outcome in this study was CLBR, which included live births from the fresh embryo transfer cycle and all subsequent frozen-thawed embryo transfer cycles performed before December 2021. RESULTS: There was no significant difference in the CLBR between the TAI and control groups, even after adjusting for relevant confounders including age, body mass index, cause of infertility, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live birth: 50.6% vs. 52.1%, OR 0.94, 95% CI 0.86-1.02, adjusted OR 0.97, 95%CI 0.89-1.06). Subgroup analysis showed that no significant difference was observed in CLBR between the TAI and control groups for all causes of infertility, except for infertility attributed to endometriosis. Among women with endometriosis, the CLBR was significantly lower in the TAI group than that in the control group; however, this difference was not significant after adjusting for potential confounders including age, body mass index, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live births: 43.1% vs. 51.0%, OR 0.73, 95% CI 0.53-0.99, adjusted OR 0.74, 95% CI 0.53-1.02). Another subgroup analysis demonstrated that the type and titre of thyroid antibody did not affect CLBR in women with TAI. CONCLUSIONS: In our study, there was no significant difference in the CLBR between women with TAI and those without TAI, which suggests that TAI did not affect the chances of having a baby in a complete IVF/ICSI treatment cycle.


Asunto(s)
Endometriosis , Infertilidad , Embarazo , Masculino , Femenino , Humanos , Inyecciones de Esperma Intracitoplasmáticas/métodos , Tasa de Natalidad , Estudios Retrospectivos , Autoinmunidad , Glándula Tiroides , Semen , Fertilización In Vitro/métodos , Nacimiento Vivo/epidemiología , Índice de Embarazo
3.
Front Endocrinol (Lausanne) ; 15: 1359649, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562412

RESUMEN

Background: The objective of our study was to investigate the risk factors for a decrease in ovarian reserve in patients with endometriomas after standardized laparoscopic procedures and evaluation to provide corresponding clinical guidance for patients with fertility requirements. Methods: Anti-Müllerian hormone (AMH) levels and other clinical data from 233 patients with endometriomas and 57 patients with non-endometrioma ovarian cysts admitted to the Peking Union Medical College Hospital between January 2018 and September 2023 were prospectively analysed. The pretreatment AMH levels of the study groups were compared to assess the impact of endometrioma on ovarian reserve, and the decrease in AMH after treatment was analysed to determine potential risk factors contributing to this change. Results: Pretreatment AMH levels did not significantly differ between patients with endometriomas and those with non-endometrioma ovarian cysts. Within the endometrioma group, older age, higher body mass index (BMI), and shorter menstrual cycles were found to be associated with decreased AMH levels prior to treatment (p<0.05). Participants presenting with bilateral cysts, advanced surgical staging, or a completely enclosed Douglas pouch demonstrated significantly lower levels of AMH prior to treatment compared to those without these conditions (p<0.05). Furthermore, their AMH levels further declined within one year after undergoing laparoscopic cystectomy (p<0.05). However, there was no difference in AMH levels after surgery between patients who successfully became pregnant and those who did not (p>0.05). Conclusion: Laparoscopic removal of endometriomas can adversely affect ovarian reserve, especially during bilateral cysts removal and when patients are diagnosed as having a higher stage of endometriosis, further impacting ovarian function. It should be noted that a decrease in AMH levels may not necessarily indicate an absolute decline in fertility. Therefore, it is crucial to conduct thorough patient evaluations and provide comprehensive patient education to offer appropriate guidance for fertility preservation.


Asunto(s)
Endometriosis , Laparoscopía , Quistes Ováricos , Embarazo , Femenino , Humanos , Endometriosis/cirugía , Endometriosis/etiología , Hormona Antimülleriana , Cistectomía , Quistes Ováricos/cirugía , Factores de Riesgo , Laparoscopía/efectos adversos , Laparoscopía/métodos
4.
Front Endocrinol (Lausanne) ; 15: 1336496, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38559689

RESUMEN

Immune dysfunction is one of the central components in the development and progression of endometriosis by establishing a chronic inflammatory environment. Western-style high-fat diets (HFD) have been linked to greater systemic inflammation to cause metabolic and chronic inflammatory diseases, and are also considered an environmental risk factor for gynecologic diseases. Here, we aimed to examine how HFD cause an inflammatory environment in endometriosis and discern their contribution to endometriotic-associated hyperalgesia. Our results showed that HFD-induced obesity enhanced abdominal hyperalgesia that was induced by endometriotic lesions. Peritoneal inflammatory macrophages and cytokine levels increased by lesion induction were elevated by chronic exposure to HFD. Increased expression of pain-related mediators in the dorsal root ganglia was observed after lesion induction under the HFD condition. Although HFD did not affect inflammatory macrophages in the peritoneal cavity without lesion induction, the diversity and composition of the gut microbiota were clearly altered by HFD as a sign of low-grade systemic inflammation. Thus, HFD alone might not establish a local inflammatory environment in the pelvic cavity, but it can contribute to further enhancing chronic inflammation, leading to the exacerbation of endometriosis-associated abdominal hyperalgesia following the establishment and progression of the disease.


Asunto(s)
Endometriosis , Femenino , Humanos , Endometriosis/complicaciones , Endometriosis/metabolismo , Hiperalgesia/etiología , Dieta Alta en Grasa/efectos adversos , Inflamación/metabolismo , Abdomen
6.
BMC Pregnancy Childbirth ; 24(1): 237, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575880

RESUMEN

BACKGROUND: Endometriosis frequently results in pain and infertility. While conservative surgery offers some relief, it often falls short of ensuring satisfactory pregnancy outcomes. Adjuvant GnRH-a is administered post-surgery to mitigate recurrence; however, its impact on pregnancy outcomes remains debated. This study endeavors to assess the efficacy of adjuvant GnRH-a in enhancing pregnancy outcomes post-conservative surgery in endometriosis patients. METHODS: Databases including PubMed, Embase, the Cochrane Library, Medline (Ovid), Web of Science, and Scopus were rigorously searched up to 02 August 2023, without linguistic constraints. Identified articles were screened using strict inclusion and exclusion criteria. Evaluated outcomes encompassed pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, multiple pregnancy rate, mean postoperative pregnancy interval, recurrence rate, and adverse reaction rate. The Cochrane risk of bias tool and the Jadad score evaluated the included studies' quality. Subgroup and sensitivity analysis were implemented to analyze the pooled results. A meta-analysis model expressed results as standardized mean difference (SMD) and Risk ratio (RR). RESULTS: A total of 17 studies about 2485 patients were assimilated. Meta-analysis revealed that post-surgery, the GnRH-a cohort experienced a marginally elevated pregnancy rate (RR = 1.20, 95% CI = 1.02-1.41; P = 0.03) and a reduced mean time to conceive (RR = -1.17, 95% CI = -1.70- -0.64; P < 0.0001). Contrarily, other evaluated outcomes did not exhibit notable statistical differences. CONCLUSIONS: Incorporating adjuvant GnRH-a following conservative surgery may be deemed beneficial for women with endometriosis, especially before Assisted Reproductive Technology (ART). Nonetheless, owing to pronounced heterogeneity, subsequent research is warranted to substantiate these potential advantages conclusively. REGISTRATION NUMBER: CRD42023448280.


Asunto(s)
Endometriosis , Resultado del Embarazo , Embarazo , Humanos , Femenino , Endometriosis/cirugía , Índice de Embarazo , Embarazo Múltiple , Hormona Liberadora de Gonadotropina
7.
Gynecol Endocrinol ; 40(1): 2336121, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38579790

RESUMEN

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


Asunto(s)
Endometriosis , Nandrolona , Nandrolona/análogos & derivados , Femenino , Humanos , Endometriosis/complicaciones , Endometriosis/tratamiento farmacológico , Endometriosis/inducido químicamente , Resultado del Tratamiento , Estudios de Cohortes , Calidad de Vida , Dolor Pélvico/tratamiento farmacológico , Dolor Pélvico/etiología , Nandrolona/efectos adversos
8.
Wiad Lek ; 77(2): 247-253, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38592985

RESUMEN

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.


Asunto(s)
Endometriosis , Glándulas Mamarias Humanas , Femenino , Humanos , Lactante , Adulto Joven , Adulto , Endometriosis/epidemiología , Glándulas Mamarias Humanas/patología , Estudios Retrospectivos , Factores de Riesgo , Comorbilidad , Pronóstico
9.
J Health Popul Nutr ; 43(1): 50, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594768

RESUMEN

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.


Asunto(s)
Asma , Endometriosis , Adulto , Embarazo , Humanos , Estados Unidos/epidemiología , Femenino , Adulto Joven , Persona de Mediana Edad , Encuestas Nutricionales , Endometriosis/complicaciones , Endometriosis/epidemiología , Estudios Transversales , Índice de Masa Corporal , Asma/complicaciones , Asma/epidemiología
10.
Am J Case Rep ; 25: e942581, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38581119

RESUMEN

BACKGROUND Endometriosis is a common cause of chronic pelvic pain among women globally. Pharmacological therapy for endometriosis includes non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal contraceptives, while surgical therapy often involves either laparoscopic excision and ablation of endometriosis implants or open surgery. Surgical therapy is one of the mainstays of treatment especially for extrapelvic endometriomas. However, little guidance exists for the treatment of non-palpable or intermittently palpable lesions of this nature. CASE REPORT A 33-year-old woman with a previous cesarean section presented with complaints of intermittent discomfort in the area between her umbilicus and the surgical incision, for the previous 7 years, that worsened during her menstrual cycle. A 3×3-cm area of fullness was only intermittently palpable during various clinic visits, but was visualizable on computed tomography and magnetic resonance imaging. Given the lesion's varying palpability, a Savi Scout radar localization device was placed into the lesion pre-operatively to aid with surgical resection. The mass was excised, pathologic examination revealed endometrial tissue, and the patient had an uncomplicated postoperative course with resolution of her symptoms. CONCLUSIONS Surgical removal of extrapelvic endometrioma lesions can be made difficult by varying levels of palpability or localizability due to a patient's menstrual cycle. The Savi Scout, most commonly used in breast mass localization, is a useful tool in guiding surgical excision of non-palpable or intermittently palpable extrapelvic endometrioma lesions.


Asunto(s)
Endometriosis , Laparoscopía , Embarazo , Femenino , Humanos , Adulto , Endometriosis/cirugía , Endometriosis/complicaciones , Cesárea , Mama/patología , Laparoscopía/métodos , Dolor Pélvico/complicaciones , Dolor Pélvico/cirugía
11.
Front Endocrinol (Lausanne) ; 15: 1359182, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38567305

RESUMEN

Background: The aim of this study was to analyze the concentration of leptin in peritoneal fluid and plasma and to assess their role as potential biomarkers in the diagnosis of endometriosis. Materials & methods: Leptin adjusted for BMI (leptin/BMI ratio) was measured using surface plasmon resonance imaging (SPRI) biosensors. Patients with suspected endometriosis were included in the study. Plasma was collected from 70 cases, and peritoneal fluid from 67 cases. Based on the presence of endometriosis lesions detected during laparoscopy, patients were divided into a study group and a control group (patients without endometriosis). Results: Leptin/BMI ratio in plasma did not differ between women with endometriosis and the control group (0.7159 ± 0.259 vs 0.6992 ± 0.273, p= 0,7988). No significant differences were observed in peritoneal leptin/BMI ratio levels in patients with and without endometriosis (0.6206 ± 0.258 vs 0.6215 ± 0.264, p= 0,9896). Plasma and peritoneal leptin/BMI ratios were significantly lower in women with endometriosis - related primary infertility compared to women with endometriosis without primary infertility (0.640 ± 0.502 vs 0.878 ± 0.623, p < 0.05). The difference was observed in case of primary infertility, but not in terms of the secondary one. No significant differences were noted between leptin/BMI ratio in the proliferative phase and the secretory phase (0.716 ± 0.252 vs 0.697 ± 0.288, p= 0,7785). Conclusion: The results of present study do not support the relevance of leptin concentration determination as a biomarker of the endometriosis. Due to the limited number of samples in the tested group, further studies are needed to confirm its role.


Asunto(s)
Endometriosis , Infertilidad Femenina , Humanos , Femenino , Endometriosis/patología , Leptina , Índice de Masa Corporal , Biomarcadores
12.
JSLS ; 28(1)2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562950

RESUMEN

A Comparison of Ovarian Loss Following Laparoscopic versus Robotic Cystectomy As Analyzed by Artificial Intelligence-Powered Pathology Software. Background and Objective: To compare the area of ovarian tissue and follicular loss in the excised cystectomy specimen of endometrioma performed by laparoscopic or robotic technique. Methods: Prospective observational study performed between April 2023 to August 2023. There were 14 patients each in Laparoscopic group (LC) and Robotic group (RC). Excised cyst wall sent was for to the pathologist who was blinded to the technique used for cystectomy. The pathological assessment was done by artificial intelligence-Whole Slide Imaging (WSI) software. Results: The age was significantly lower in LC group; the rest of demographic results were comparable. The mean of the median ovarian area loss [Mean Rank, LC group (9.1 ± 15.1); RC (8.1 ± 12.4)] was higher in LC group. The mean of the median total follicular loss was higher in LC group (8.9 ± 9.2) when compared to RC group (6.3 ± 8.9) and was not significant. The area of ovarian loss in bilateral endometrioma was significantly higher in LC group (mean rank 7.5) as compared to RC group (mean rank 3) - (P = .016) despite more cases of bilateral disease in RC group. With increasing cyst size the LC group showed increased median loss of follicles when compared to RC group (strong correlation coefficient 0.347) but not statistically significant (P = .225). AAGL (American Association of Gynecologic Laparoscopists) score did not have any impact on the two techniques. Conclusion: Robotic assistance reduces the area of ovarian and follicular loss during cystectomy of endometrioma especially in bilateral disease and increasing cyst size. It should be considered over the laparoscopic approach if available.


Asunto(s)
Quistes , Endometriosis , Laparoscopía , Quistes Ováricos , Enfermedades del Ovario , Procedimientos Quirúrgicos Robotizados , Humanos , Femenino , Quistes Ováricos/cirugía , Endometriosis/cirugía , Inteligencia Artificial , Cistectomía/métodos , Quistes/cirugía , Laparoscopía/métodos , Enfermedades del Ovario/cirugía
13.
FASEB J ; 38(5): e23515, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38470367

RESUMEN

Endometriosis is a benign gynecological disease that shares some common features of malignancy. Autophagy plays vital roles in endometriosis and influences endometrial cell metastasis, and hypoxia was identified as the initiator of this pathological process through hypoxia inducible factor 1 alpha (HIF-1α). A newly discovered circular RNA FOXO3 (circFOXO3) is critical in cell autophagy, migration, and invasion of various diseases and is reported to be related to hypoxia, although its role in endometriosis remains to be elucidated up to now. In this study, a lower circFOXO3 expression in ectopic endometrium was investigated. Furthermore, we verified that circFOXO3 could regulate autophagy by downregulating the level of p53 protein to mediate the migration and invasion of human endometrial stromal cells (T HESCs). Additionally, the effects of HIF-1α on circFOXO3 and autophagy were examined in T HESCs. Notably, overexpression of HIF-1α could induce autophagy and inhibit circFOXO3 expression, whereas overexpressing of circFOXO3 under hypoxia significantly inhibited hypoxia-induced autophagy. Mechanistically, the direct combination between HIF-1α and HIF-1α-binding site on adenosine deaminase 1 acting on RNA (ADAR1) promoter increased the level of ADAR1 protein, which bind directly with circFOXO3 pre-mRNA to block the cyclization of circFOXO3. All these results support that hypoxia-mediated ADAR1 elevation inhibited the expression of circFOXO3, and then autophagy was induced upon loss of circFOXO3 via inhibition of p53 degradation, participating in the development of endometriosis.


Asunto(s)
Endometriosis , Femenino , Humanos , Endometriosis/genética , Proteína p53 Supresora de Tumor , ARN , ARN Circular/genética , Autofagia , Hipoxia
14.
J Obstet Gynaecol ; 44(1): 2321651, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38466134

RESUMEN

BACKGROUND: Abnormal stromal-epithelial cell communication is a pathogenic mechanism in endometriosis, and metformin can modulate it. Insulin-like growth factor binding protein-1 (IGFBP1) plays a role in endometriosis, but the exact mechanism is unknown. IGFBP1 is reportedly a downstream target of metformin in some diseases. We aimed to investigate the role of IGFBP1 in endometriosis development, whether it is associated with abnormal communication, and whether metformin affects IGFBP1 expression. METHODS: Patients who underwent surgical treatment for endometriosis or other diseases were enrolled. Ten patients with ovarian-type endometriosis and eight patients each who underwent surgical treatment for other lesions with or without endometriosis were selected, and their tissues taken for cell proliferation, western blotting, polymerase chain reaction, and knockdown experiments. RESULTS: Ectopic and eutopic stromal cells (EcSCs and EuSCs) lost their ability to inhibit epithelial cell proliferation, and IGFBP1 expression was downregulated in both groups of stromal cells compared to that in normal stromal cells (NSCs; 1.09 vs. 0.25, p = .0002 1.09 vs. 0.57, p = .0029). In an EcSC IGFBP1 overexpression model, the ability of EcSCs to inhibit epithelial cell proliferation was enhanced (EdU positivity decreased from 38% to 25%, p = .0001). Furthermore, adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation was downregulated in EcSCs and EuSCs compared to that in NSCs (0.99 vs. 0.42, p = .0006/0.99 vs. 0.57, p = 0.0032). Treatment of EcSCs with metformin increased AMPK phosphorylation (0.47 vs. 1.04, p = .0107) while upregulating IGFBP1 expression (0.69 vs. 1.01, p = .0164), whereas pre-treatment with an AMPK phosphorylation inhibitor abrogated metformin-induced IGFBP1 upregulation. CONCLUSIONS: IGFBP1 mediates aberrant stromal-epithelial communication in endometriosis. Metformin can upregulate IGFBP1 expression in EcSCs by activating AMPK, and upregulated IGFBP1 enhances the inhibition of epithelial cell proliferation. IGFBP1 is expected to be a therapeutic target for endometriosis.


Insulin-like growth factor binding protein 1 (IGFBP1) is a protein that regulates cell growth and proliferation and is expressed at abnormal levels in patients with endometriosis. In some cases, metformin has been shown to modulate the expression of this protein. Here, we investigated the role of IGFBP1 in endometriosis development, whether it is associated with abnormal communication, and whether metformin affects IGFBP1 expression in endometrial cells. We found that downregulation of IGFBP1 in endometriosis diminished the ability of stromal cells to inhibit the proliferation of epithelial cells through inhibition of the protein kinase B and extracellular regulated protein kinase pathways. In addition, metformin upregulated IGFBP1 expression by activating adenosine 5'-monophosphate-activated protein kinase, suggesting that IGFBP1 may be one of the potential targets for drug therapy for endometriosis.


Asunto(s)
Endometriosis , Metformina , Femenino , Humanos , Proteínas Quinasas Activadas por AMP , Proliferación Celular , Células Epiteliales , Metformina/farmacología
15.
Womens Health (Lond) ; 20: 17455057241227361, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38449294

RESUMEN

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.


Asunto(s)
COVID-19 , Endometriosis , Adulto , Femenino , Humanos , Masculino , Calidad de Vida , Pandemias , Estudios Transversales , Endometriosis/complicaciones , Endometriosis/epidemiología , COVID-19/epidemiología , Estilo de Vida , Dolor Pélvico/epidemiología
16.
Artículo en Inglés | MEDLINE | ID: mdl-38478380

RESUMEN

Endometriosis is a debilitating gynecological disease defined as the presence of endometrium-like epithelium and/or stroma outside the uterine cavity. The most commonly affected sites are the pelvic peritoneum, ovaries, uterosacral ligaments, and the rectovaginal septum. The aberrant tissue responds to hormonal stimulation, undergoing cyclical growth and shedding similar to appropriately located endometrial tissue in the uterus. Common symptoms of endometriosis are painful periods and ovulation, severe pelvic cramping, heavy bleeding, pain during sex, urination and bowel pain, bleeding, and pain between periods. Numerous theories have been proposed to explain the pathogenesis of endometriosis. Sampson's theory of retrograde menstruation is considered to be the most accepted. This theory assumes that endometriosis occurs due to the retrograde flow of endometrial cells through the fallopian tubes during menstruation. However, it has been shown that this process takes place in 90% of women, while endometriosis is diagnosed in only 10% of them. This means that there must be a mechanism that blocks the immune system from removing endometrial cells and interferes with its function, leading to implantation of the ectopic endometrium and the formation of lesions. In this review, we consider the contribution of components of the Major Histocompatibility Complex (MHC)-I-mediated antigen-processing pathway, such as the ERAP, TAP, LMP, LNPEP, and tapasin, to the susceptibility, onset, and severity of endometriosis. These elements can induce significant changes in MHC-I-bound peptidomes that may influence the response of immune cells to ectopic endometrial cells.


Asunto(s)
Endometriosis , Humanos , Femenino , Endometriosis/diagnóstico , Endometriosis/etiología , Endometriosis/patología , Endometrio/metabolismo , Endometrio/patología , Trastornos de la Menstruación/complicaciones , Trastornos de la Menstruación/patología , Sistema Inmunológico/patología , Dolor/complicaciones , Dolor/metabolismo
17.
Epidemiol Prev ; 48(1): 60-65, 2024.
Artículo en Italiano | MEDLINE | ID: mdl-38482786

RESUMEN

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.


Asunto(s)
Endometriosis , Bifenilos Policlorados , Humanos , Femenino , Endometriosis/epidemiología , Italia/epidemiología , Ambiente , Encuestas y Cuestionarios
18.
Sci Rep ; 14(1): 5984, 2024 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-38472314

RESUMEN

Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships between depression and different types of female reproductive disorders remain unclear in terms of direction and magnitude. We conducted a comprehensive investigation using a two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish a causal relationship between genetically predicted depression and the risk of various female reproductive pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), ovarian cysts, abnormal uterine and vaginal bleeding(AUB), endometriosis, leiomyoma of the uterus, female infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting in pregnancy, cervical cancer, and uterine/endometrial cancer. We analyzed a substantial sample size, ranging from 111,831 to 210,870 individuals, and employed robust statistical methods, including inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO, to estimate causal effects. Sensitivity analyses, such as Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots, were also conducted to ensure the validity of our results. Furthermore, risk factor analyses were performed to investigate potential mediators associated with these observed relationships. Our results demonstrated that genetic predisposition to depression or dysthymia was associated with an increased risk of developing PCOS (OR = 1.43, 95% CI 1.28-1.59; P = 6.66 × 10-11), ovarian cysts (OR = 1.36, 95% CI 1.20-1.55; P = 1.57 × 10-6), AUB (OR = 1.41, 95% CI 1.20-1.66; P = 3.01 × 10-5), and endometriosis (OR = 1.43, 95% CI 1.27-1.70; P = 2.21 × 10-7) after Bonferroni correction, but no evidence for reverse causality. Our study did not find any evidence supporting a causal or reverse causal relationship between depression/dysthymia and other types of female reproductive disorders. In summary, our study provides evidence for a causal relationship between genetically predicted depression and specific types of female reproductive disorders. Our findings emphasize the importance of depression management in the prevention and treatment of female reproductive disorders, notably including PCOS, ovarian cysts, AUB, and endometriosis.


Asunto(s)
Endometriosis , Quistes Ováricos , Síndrome del Ovario Poliquístico , Embarazo , Femenino , Humanos , Depresión , Trastorno Distímico , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo
19.
Am J Reprod Immunol ; 91(3): e13830, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38454570

RESUMEN

PROBLEM: Endometriosis exhibits several immune dysfunctions, including deficient natural killer (NK) cell cytotoxicity. MICA (MHC class I chain-related molecule A) is induced by biological stress and soluble MICA (sMICA) negatively modulates the expression of the activating receptor, NKG2D, reducing NK cells activities. We investigated the involvement of soluble MICA in NK cell-deficient activity in endometriosis. METHODS OF STUDY: sMICA levels (serum and peritoneal fluid-PF) were evaluated by ELISA. Circulating NK cell subsets quantification and its NKG2D receptor expression, NK cell cytotoxicity and CD107a, IFN-γ and IL-10 expressions by NK cells stimulated with K562 cells were determined by flow cytometry. RESULTS: We found higher sMICA levels (serum and PF) in endometriosis, especially in advanced and deep endometriosis. Endometriosis presented lower percentages of CD56dim CD16+ cytotoxic cells and impaired NK cell responses upon stimulation, resulting in lower CD107a and IFN-γ expressions, and deficient NK cell cytotoxicity. NK cell stimulation in the MICA-blocked condition (mimicking the effect of sMICA) showed decreased cytotoxicity in initial endometriosis stages and the emergence of a negative correlation between CD107a expression and sMICA levels. CONCLUSIONS: We suggest that soluble MICA is a potential player in endometriosis pathophysiology with involvement in disease progression and severity, contributing to NK cell impaired IFN-γ response and degranulation. NK cell compartment exhibits multiple perturbations, including quantitative deficiency and impaired cytotoxicity, contributing to inadequate elimination of ectopic endometrial tissue.


Asunto(s)
Endometriosis , Femenino , Humanos , Degranulación de la Célula , Células Asesinas Naturales , Expresión Génica , Progresión de la Enfermedad , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Antígenos de Histocompatibilidad Clase I/metabolismo
20.
Mol Biol Rep ; 51(1): 414, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38472662

RESUMEN

BACKGROUND: One of the main health issues that can affect women's health is reproductive diseases, such as polycystic ovary syndrome (PCOS), endometriosis (EMs), uterine leiomyomas (ULs), and ovarian cancer (OC). Although these diseases are very common, we do not have a complete understanding of their underlying cellular and molecular mechanisms. It is important to mention that the majority of patients are diagnosed with these diseases at later stages because of the absence of early diagnostic techniques and dependable molecular indicators. Hence, it is crucial to discover novel and non-invasive biomarkers that have prognostic, diagnostic and therapeutic capabilities. MiRNAs, also known as microRNAs, are small non-coding RNAs that play a crucial role in regulating gene expression at the post-transcriptional level. They are short in length, typically consisting of around 22 nucleotides, and are highly conserved across species. Numerous studies have shown that miRNAs are expressed differently in various diseases and can act as either oncogenes or tumor suppressors. METHODS: The author conducted a comprehensive review of all the pertinent papers available in web of science, PubMed, Google Scholar, and Scopus databases. RESULTS: We achieved three goals: providing readers with better information, enhancing search results, and making peer review easier. CONCLUSIONS: This review focuses on the investigation of miRNAs and their involvement in various reproductive disorders in women, including their molecular targets. Additionally, it explores the role of miRNAs in the development and progression of these disorders.


Asunto(s)
Endometriosis , MicroARNs , Síndrome del Ovario Poliquístico , Humanos , Femenino , MicroARNs/genética , Síndrome del Ovario Poliquístico/metabolismo , Biomarcadores , Transducción de Señal
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