El tratamiento hormonal es imperativo para todas las pacientes: lo antes posible y siempre / Hormone treatment is imperative for all patients: As soon as possible and always

La endometriosis se considera una enfermedad inflamatoria crónica sistémica benigna y hormonodependiente que afecta aproximadamente a un 10% de las mujeres en edad fértil. Parece que cambios innatos o adquiridos de la capacidad del endometrio para implantar, invadir y crecer en un ambiente inflamatorio con dependencia estrogénica, así como la resistencia a la progesterona son características fundamentales para la aparición y desarrollo de la endometriosis. No existe, por el momento, ningún tratamiento óptimo que consiga alcanzar los cuatro objetivos básicos del tratamiento de la endometriosis: suprimir los síntomas, restaurar la fertilidad, eliminar la endometriosis visible, y evitar la progresión de la enfermedad. Puesto que la enfermedad se considera crónica, el tratamiento médico administrado, hasta la llegada de la menopausia o de una gestación, debe ser de larga duración, efectivo y seguro. Así pues, sus objetivos reales serán la reducción o eliminación de los síntomas y/o mejoría de la fertilidad. Dadas las limitaciones y riesgos de las cirugías, el tratamiento de primera elección en la actualidad es el hormonal. Este debe individualizarse en función de la edad, paridad, deseo genésico, síntomas asociados, antecedentes patológicos y preferencias de la paciente. De forma global, existen dos tipos de tratamientos de primera elección: los estroprogestágenos en regímenes extendidos o continuos y algunos progestágenos en diferentes vías de administración (dienogest, acetato de noretisterona o desogestrel por vía oral, así como el dispositivo intrauterino de levonorgestrel de alta dosis). Los diferentes tratamientos y sus pros y contras se exponen en el artículo.(AU)

Endometriosis is nowadays considered an inflammatory chronic benign disease that responds to hormone manipulation and affects up to 10% of women in fertile age. It seems that innate or acquired changes in the endometrium ability to implant, invade and grow in an inflammatory milieu with estrogenic dependence and progesterone resistance are the responsible for new endometriosis implants and contribute to perpetuate the illness. There is, at the moment, no optimal known treatment that achieves the four basic objectives for the treatment of endometriosis: treat the symptoms, improve fertility, eliminate endometrial implants, and avoid illness progression. As is now considered a chronic condition, the prescribed medical treatment, until the patient arrives to the physiological menopause status or gets pregnant, must be considered in the long term, and must be effective and safe. Therefore, the realistic objectives of the treatment are the reduction or abolishment of symptoms and/or improve fertility. As a consequence of the limitations and risks of endometriosis surgeries, the first-line treatment is hormonal. This must be individualized according to age, parity, pregnancy desire, associated symptoms, other illnesses and patients preferences. Globally, there are two main types of first-line hormonal treatments: estroprogestins in extended or continuous regimens and some progestins in different routes of administration (dienogest, norethisterone acetate or desogestrel orally, and levonorgestrel high-dose intrauterine device). The different hormonal treatments and their pros and cons are explained in the manuscript.(AU)

Endometriosis. Un largo camino / Endometriosis. A life-long journey

La endometriosis es una patología hormonodependiente causada por la presencia de tejido endometrial fuera de la cavidad uterina, que induce una reacción inflamatoria crónica. Tiene una prevalencia del 10% en mujeres en edad reproductiva, pudiendo alcanzar hasta el 50% entre mujeres con infertilidad. Es una enfermedad de interés creciente debido a su prevalencia y a los avances científicos ocurridos que han permitido conocer sus diferentes fenotipos, derivando en un diagnóstico más preciso y un tratamiento con un enfoque multidisciplinar. En los últimos años han cambiado muchos paradigmas en torno a esta patología, tanto en su etiopatogenia como en su diagnóstico y tratamiento. Además, han tomado interés creciente aspectos olvidados anteriormente, como su relación con las complicaciones obstétricas y sus comorbilidades asociadas. Tratamos su impacto a lo largo de la vida de las pacientes, haciendo énfasis en nuevas perspectivas que están revolucionado la manera de entender la endometriosis.(AU)

Endometriosis is a hormone-dependent disease caused by the presence of endometrial tissue outside the uterine cavity, which induces a chronic inflammatory reaction. It has a prevalence of 10% in women of reproductive age and can reach up to 50% among women with infertility. It is a disease of growing interest due to its prevalence and to the scientific advances regarding its different phenotypes, leading to a more precise diagnosis and treatment with a multidisciplinary approach. In recent years, many paradigms around this pathology have changed, both in its aetiopathogenesis and in its diagnosis and treatment. In addition, previously forgotten aspects such as the relationship with obstetric complications and the associated comorbidities have taken on increasing interest. We discuss its impact throughout the patient's life, emphasizing new perspectives that are revolutionizing the way we understand endometriosis.(AU)

Transvaginal ultrasound for diagnosis of deep endometriosis involving uterosacral ligaments, torus uterinus and posterior vaginal fornix: prospective study.

OBJECTIVE: To evaluate the accuracy of transvaginal ultrasound (TVS) in diagnosing deep endometriosis (DE) involving the uterosacral ligaments (USLs), torus uterinus (TU) or posterior vaginal fornix (PVF) in women with suspected endometriosis scheduled for laparoscopic surgery. METHODS: In this prospective study, consecutive women with clinically suspected pelvic endometriosis who were scheduled for laparoscopic surgery were invited to participate. TVS was performed before surgery. TVS findings were compared with those obtained at laparoscopy and confirmed histologically. The accuracy of TVS for diagnosing DE involving the USLs, TU or PVF was assessed. Additionally, the association of DE involving the USLs, TU or PVF on TVS with symptoms and with DE affecting other pelvic locations was assessed. RESULTS: In total, 172 patients were included. The global sensitivity and specificity of TVS in diagnosing DE affecting the USLs, TU and/or PVF were 92% and 87%, respectively. For DE involving the USLs, the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio and negative likelihood ratio of TVS were 89.5%, 96.6%, 82.1%, 85.0%, 95.8%, 5.41 and 0.04, respectively; the respective values for DE involving the TU were 86.6%, 83.9%, 89.4%, 89.0%, 84.4%, 7.92 and 0.18, and the respective values for DE involving the PVF were 93.6%, 87.0%, 94.6%, 71.4%, 97.9%, 16.20 and 0.14. Logistic regression analysis showed a significant association between DE affecting the USLs, TU and/or PVF and DE affecting the rectosigmoid (odds ratio, 5.43; P < 0.001). Dyschezia was associated strongly with DE involving the USLs, TU and PVF, while dysmenorrhea was associated significantly with DE involving the TU. CONCLUSION: TVS has high accuracy, sensitivity, specificity, PPV and NPV for the detection of DE involving the USLs, TU and PVF in women with suspected endometriosis scheduled for laparoscopic surgery. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Adenomiosis. Una gran desconocida: ¿Qué debemos saber? / Adenomyosis. A great unknown: What should we know?

La adenomiosis es una enfermedad ginecológica benigna que afecta entre el 20-35% de las mujeres en edad fértil. Sus síntomas incluyen sangrado uterino anormal, dolor pélvico e infertilidad, los cuales generan una disminución en la calidad de vida de las pacientes. El objetivo de esta revisión es actualizar «el conocimiento» que existe sobre la enfermedad, hasta ahora poco conocida, haciendo énfasis en la etiopatogenia, el diagnóstico y el manejo. Como conclusión, la adenomiosis está recibiendo más atención en las últimas décadas. Actualmente, gracias a la introducción de técnicas de imagen precisas, se ha convertido en una entidad clínica con la posibilidad de un diagnóstico prequirúrgico. El impacto de la adenomiosis en el dolor, sangrado e infertilidad, y su consecuente disminución en la calidad de vida de estas pacientes hace necesario el desarrollo de pautas de diagnóstico temprano y manejo multidisciplinar.(AU)

Adenomyosis is a benign gynaecological disease that affects between 20-35% of women of reproductive age. Its symptoms include abnormal uterine bleeding, pelvic pain, and infertility, and can lead to a decrease in the quality of life of these patients. The objective of this review is to update «the knowledge» that exists about the disease, until now little known, with emphasis on its etiopathogenesis, diagnosis, and management. In conclusion, adenomyosis is receiving more attention in recent decades. Nowadays, thanks to the introduction of precise imaging techniques, it has become a clinical entity with the possibility of a pre-surgical diagnosis. The impact of adenomyosis on pain, bleeding and infertility, and its consequent decrease in quality of life of these patients makes it necessary to develop guidelines for early diagnosis and multidisciplinary management.(AU)

Bowel preparation prior to transvaginal ultrasound improves detection of rectosigmoid deep infiltrating endometriosis and is well tolerated: prospective study of women with suspected endometriosis without surgical criteria.

OBJECTIVES: To analyze the effect of bowel preparation prior to transvaginal ultrasound (TVS) examination on the detection of bowel involvement and the description of rectosigmoid nodules of deep infiltrating endometriosis (DIE), and to evaluate patient tolerance of bowel preparation. METHODS: This was a prospective study of paired data obtained between September 2015 and March 2016 from a cohort of women referred, on suspicion of DIE but without surgical criteria, to the endometriosis unit of a tertiary university hospital. In all patients, the wall of the rectum and lower sigmoid colon was evaluated by two TVS examinations: the first was performed without bowel preparation and the second was done after the patient had followed a 3-day low-residue diet and received two 250-mL enemas, one the night before TVS and the second 1-3 h before the examination. The presence of adhesions, number and size of rectosigmoid nodules, deepest layer of the rectum affected, percentage of the circumference of the bowel affected and distance from the most caudal part of the bowel nodule to the anal verge were determined. Patient tolerance to bowel preparation was assessed using a 5-point Likert scale, in which 1 represented 'very well tolerated' and 5 represented 'very poorly tolerated'. RESULTS: The mean ± SD age of the 110 patients included in the study was 36.8 ± 5.07 years. As many as 55% of those identified during the first examination (TVS alone) as having adhesions were identified at the second examination (TVS with prior bowel preparation) as having rectosigmoid nodules, and 22 additional nodules were observed on TVS following bowel preparation. These newly detected rectosigmoid nodules, initially assessed mainly as adhesions, were smaller and more superficial compared with the nodules detected on TVS alone, or located in the anterior sigmoid wall. Patient tolerance overall to bowel preparation scored a mean of 1.81 on the 5-point Likert scale. CONCLUSIONS: Bowel preparation is well tolerated by patients. When bowel preparation is performed before TVS, the detection of small and superficial nodules and those in the anterior sigmoid wall is improved, allowing more detailed description of these nodules in patients with suspected endometriosis. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Total circulating microparticle levels are increased in patients with deep infiltrating endometriosis.

STUDY QUESTION: Are the levels of total circulating cell-derived microparticles (cMPs) and circulating tissue factor-containing microparticles (cMP-TF) increased in patients with endometriosis? SUMMARY ANSWER: The levels of total cMP, but not cMP-TF, were higher in patients with endometriosis, and these were attributed to higher levels in patients with deep infiltrating endometriosis (DIE). WHAT IS KNOWN ALREADY: Previous studies have reported elevated levels of total cMP in inflammatory conditions as well as higher levels of other inflammatory biomarkers in endometriosis. Increased expression of tissue factor (a transmembrane receptor for Factor VII/VIIa) in eutopic and ectopic endometrium from patients with endometriosis has been described. There is no previous data regarding total cMP and cMP-TF levels in patients with endometriosis. STUDY DESIGN, SIZE, DURATION: A prospective case-control study including two groups of patients was carried out. The E group included 65 patients with surgically confirmed endometriosis (37 with DIE lesions) and the C group comprises 33 women without surgical findings of any form of endometriosis. Patients and controls were recruited during the same 10-month period. Controls were the next patient without endometriosis undergoing surgery, after including two patients with endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Venous blood samples for total cMP and cMP-TF determinations were obtained at the time of surgery, before anesthesia at a tertiary care center. To assess total cMP, an ELISA functional assay was used and cMP-TF activity in plasma was measured using an ELISA kit. MAIN RESULTS AND THE ROLE OF CHANCE: Total cMP levels in plasma were higher in the E group compared with the C group (P < 0.0001). The subanalysis of endometriosis patients with DIE or with ovarian endometriomas without DIE showed that total cMP levels were higher in the DIE group (P = 0.001). There were no statistically significant differences in cMP-TF levels among the groups analyzed. LIMITATIONS, REASONS FOR CAUTION: This is a preliminary study in which the sample size was arbitrarily decided, albeit in keeping with previous studies analyzing cMP in other inflammatory diseases and other biomarkers in endometriosis. The control group included patients with other pathologies as well as healthy controls, and blood samples were taken at different phases of the cycle. WIDER IMPLICATIONS OF THE FINDINGS: Elevated total cMP levels in DIE patients may reflect an inflammatory and/or procoagulant systemic status in these patients. Further studies are warranted to confirm our findings and to assess the role of cMP levels in the pathophysiology of DIE. STUDY FUNDING/COMPETING INTERESTS: This study was supported in part by a grant from FIS-PI11/01560 and FIS-PI11/00977 within the 'Plan Nacional de I + D + I' and co-funded by the 'ISCIII-Subdirección General de Evaluación' and 'Fondo Europeo de Desarrollo Regional (FEDER)' and by the grant 'Premi Fi de Residència Emili Letang 2015' from the Hospital Clínic of Barcelona. The authors have no competing interests to disclose.

Higher levels of procoagulant microparticles in women with recurrent miscarriage are not associated with antiphospholipid antibodies.

STUDY QUESTION: Are the levels of circulating cell-derived microparticles (cMPs) in patients with recurrent miscarriage (RM) associated with the antiphospholipid syndrome (APS)? SUMMARY ANSWER: cMPs in women with RM are not associated with antiphospholipid antibodies (aPLs). WHAT IS KNOWN ALREADY: Previous studies have focused on cMP levels in RM patients. Most studies have shown higher levels of cMPs in RM patients whereas others have reported lower levels. Data regarding cMPs in patients with the APS are scanty in the literature. STUDY DESIGN, SIZE, DURATION: A case-control study including three groups of patients. A total of 154 women were prospectively recruited from September 2009 to October 2013. Four patients refused to participate. The APS group consisted of 50 women that had been previously diagnosed with primary APS and had had ≥3 consecutive first trimester miscarriages. The uRM group included 52 couples with ≥3 consecutive first trimester miscarriages of unknown etiology. The fertile control (FER) group was composed of 52 healthy fertile women with no history of pregnancy losses. Miscarriage was defined as intrauterine pregnancy loss at <10 weeks' size on ultrasound. PARTICIPANTS/MATERIALS, SETTING, METHODS: Venous blood samples for coagulation studies and cMP determinations were obtained. All patients underwent a thrombophilia study. MAIN RESULTS AND THE ROLE OF CHANCE: cMP levels were significantly higher in the APS and uRM groups versus the FER group (P < 0.0001 and P = 0.009, respectively) (cMP number × 10(3)/ml plasma [mean ± SD]: APS: 18.5 ± 13.6; uRM: 16.3 ± 13.8; FER: 9.7 ± 4.6). There were no statistically significant differences in cMP levels between the APS and uRM groups. LIMITATIONS, REASONS FOR CAUTION: The sample size was arbitrarily decided according to previous studies analyzing cMPs in RM patients. Different cMP subtypes were not investigated. WIDER IMPLICATIONS OF THE FINDINGS: The present study adds further data on the subject showing that patients with RM, irrespective of testing positive for aPLs, have increased levels of cMPs compared with healthy fertile controls. The presence of elevated cMPs in RM women may reflect an ongoing systemic pathological, albeit asymptomatic, status that can become deleterious in the setting of pregnancy. STUDY FUNDING/COMPETING INTERESTS: This study was supported in part by grant from FIS-PI11/01560 within the 'Plan Nacional de I+D+I' and co-funded by the 'ISCIII-Subdirección General de Evaluación' and the 'Fondo Europeo de Desarrollo Regional (FEDER)'. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: Not applicable.

Increased levels of dioxin-like substances in adipose tissue in patients with deep infiltrating endometriosis.

STUDY QUESTION: Are the levels of biologically active and the most toxic dioxin-like substances in adipose tissue of patients with deep infiltrating endometriosis (DIE) higher than in a control group without endometriosis? SUMMARY ANSWER: DIE patients have higher levels of dioxins and polychlorinated biphenyls (PCBs) in adipose tissue compared with controls without endometriosis. WHAT IS KNOWN ALREADY: Some studies have investigated the levels of dioxin-like substances, in serum samples, in patients with endometriosis, with inconsistent results. STUDY DESIGN, SIZE, DURATION: Case-control study including two groups of patients. The study group (DIE group) consisted of 30 patients undergoing laparoscopic surgery because of DIE. In all patients, an extensive preoperative work-up was performed including clinical exploration, magnetic resonance imaging (MRI) and transvaginal sonography. All patients with DIE underwent a confirmatory histological study for DIE after surgery. The non-endometriosis control group (control group), included the next consecutive patient undergoing laparoscopic surgery in our center due to adnexal benign gynecological disease (ovarian or tubal procedures other than endometriosis) after each DIE patient, and who did not present any type of endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: During the surgical procedure 1-2 g of adipose tissue from the omentum were obtained. Dioxin-like substances were analyzed in adipose tissue in DIE patients and controls without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: The total toxic equivalence and concentrations of both dioxins and PCBs were significantly higher in patients with DIE in comparison with the control group (P < 0.05), mainly due to the significantly higher values of the two most toxic dioxins (2,3,7,8-tetrachlorodibenzo-p-dioxin [2,3,7,8-TCDD] and 1,2,3,7,8-pentachlorodibenzo-p-dioxin [1,2,3,7,8-PeCDD]) (P < 0.01 for each compound). The levels of furan 2,3,4,7,8-PeCDF were statistically higher in the DIE group compared with controls. Only four congeners of PCBs had toxic equivalence values and concentrations that were statistically higher in patients with DIE, but these included the most toxic and carcinogenic PCB-126 (PCB-114 P < 0.05; PCB-156 P < 0.05; PCB-189 P = 0.04; PCB-126 P < 0.01). LIMITATIONS, REASONS FOR CAUTION: Since few patients were recruited, the study is only exploratory. Our results need to be confirmed in larger and more heterogeneous population studies since environmental and even genetic factors involved in determining dioxins and PCBs widely vary in different countries. Furthermore, the strict eligibility criteria used may preclude generalization of the results to other populations and the surgery-based sampling frame may induce a selection bias. Finally, adipose tissue was obtained only from the omentum, and not from other adipose tissue of the body. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest a potential role of dioxin-like substances in the pathogenesis of DIE. Further studies are warranted to confirm our findings. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: Not applicable.

Laparoscopic ovarian transposition in patients with early cervical cancer.

The aim of this study was to evaluate the feasibility, efficacy, and morbidity of laparoscopic ovarian transposition on the preservation of hormonal function in patients younger than 45 years operated for early cervical cancer. According to risk factors on pathologic evaluation of the specimen, some of them will receive postoperative pelvic radiotherapy. This subset of patients could benefit from taking the ovaries away from the irradiation field in an effort to preserve their functionality. This prospective study included 28 FIGO stage IB1 cervical cancer patients, 45 years old or younger, maintaining menstrual cycles, who were considered suitable for conservation of the ovaries. The ovarian transposition was performed by laparoscopy as a part of the same celio-Schauta operation. Twelve patients underwent adjuvant pelvic radiotherapy. No intraoperative or postoperative morbidity related to the ovarian transposition was observed, and the procedure only entailed a minimum delay of the operative time. There were no cases of ovarian metastasis. At a mean follow-up of 44 months, 63.6% of patients receiving radiotherapy and 93% of those who nonirradiated maintained normal ovarian function. Two patients developed benign ovarian cysts, requiring oophorectomy, but no other long-term adverse effects of the transposition were identified. To the best of our knowledge, this is the largest series of the laparoscopic procedure reported to date in this setting. According to our results, laparoscopic ovarian transposition is a safe and effective procedure for the preservation of ovarian function in young patients with early cervical cancer undergoing adjuvant radiotherapy after surgery.