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

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

A Systematic Review of Atypical Endometriosis-Associated Biomarkers.

Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed n = 40 studies eligible for inclusion in this systematic review. Of these, n = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.

Fertility Outcome after CO2 Laser Vaporization versus Cystectomy in Women with Ovarian Endometrioma: A Comparative Study.

STUDY OBJECTIVE: To assess the postoperative likelihood of conception in patients with endometriomas managed by either CO2 laser vaporization or cystectomy. DESIGN: A retrospective study with prospective recording of data. SETTING: University hospital. PATIENTS: One hundred and forty-two patients with symptomatic endometriomas. INTERVENTIONS: Patients underwent a standardized laparoscopic stripping technique (Group 1) or cyst vaporization with CO2 fiber laser (Group 2). Patients wishing to become pregnant were allowed to attempt a spontaneous conception after surgery. If spontaneous conception failed, patients were referred for in vitro fertilization (IVF). MEASUREMENTS AND MAIN RESULTS: The primary objective was to compare pregnancy rates between the 2 groups. The secondary objective was the identification of independent predictors of pregnancy. Thirty-nine women in Group 1 (53.4%) and 39 women in Group 2 (56.5%) desired to conceive after surgery. Three patients (7.7%) in Group 1 became pregnant following donor-IVF and were excluded. Pregnancies were recorded in 72.2% of patients treated with cystectomy and in 74.3% of those managed with CO2 fiber laser (p = .83). Twenty patients (55.6%) in Group 1 and 14 patients (35.9%) in Group 2 conceived spontaneously (p = .08). Among patients who failed spontaneous conception, 21 patients (28%) achieved pregnancy through IVF (Group 1: n = 6, 16.7%; Group 2: n = 15, 38.5%; p = .08). Twenty patients (26.7%) never became pregnant. Age at the time of surgery (odds ratio (OR) = 0.86; 95% Confidence intervals (CI): 0.78-0.96, p = .002) and duration of infertility (OR=0.80; 95% CI: 0.69-0.92, p = .006) were identified as independent indicators for pregnancy. CONCLUSION: CO2 laser-treated endometrioma is associated with pregnancy rates equal to those observed after cystectomy and favorable IVF outcomes. The one step CO2 fiber laser technique may represent a viable alternative to cystectomy.

Early-life factors, in-utero exposures and endometriosis risk: a meta-analysis.

This meta-analysis aimed to offer a general picture of the available data on the effects of early-life factors on the risk of developing endometriosis in adult life. An advanced, systematic search of the online medical databases PubMed, EMBASE and CINAHL was limited to full-length manuscripts published in English in peer-reviewed journals up to February 2019. Log of relative risk (RR) was employed to calculate the pooled effect sizes using both fixed and random effects modelling and I-squared tests to assess heterogeneity. Funnel plots were used to investigation publication bias. The meta-analysis was registered in PROSPERO (ID CRD42019138668). Six studies that included a total of 2360 women affected by endometriosis were analysed. The pooled results showed that the risk of developing endometriosis in adult life was significantly increased by being born prematurely (logRR 0.21, 95% CI -0.03 to 0.40), having a low birthweight (logRR 0.35, 95% CI -0.15 to 0.54), being formula-fed (logRR 0.65, 95% CI -0.35 to 0.95) and having been exposed to diethylstilbestrol (DES) in utero (logRR 0.65, 95% CI 0.26 to 1.04. Among intrauterine and early neonatal exposures, prematurity, birthweight, formula feeding and DES were risk factors for the development of endometriosis in adult life.

Recurrence Rate after "One-Step" CO2 Fiber Laser Vaporization versus Cystectomy for Ovarian Endometrioma: A 3-Year Follow-up Study.

STUDY OBJECTIVE: To assess postoperative recurrence rates in patients with endometriomas managed by either "one-step" CO2 fiber laser vaporization or cystectomy. DESIGN: Retrospective study with prospective recording of data. SETTING: University hospital. PATIENTS: One hundred twenty-five patients with symptomatic endometriomas. INTERVENTIONS: Patients underwent a standardized laparoscopic stripping technique (group 1) or cyst vaporization with CO2 fiber laser (group 2). After surgery, patients were incorporated in a prolonged surveillance program with periodic clinical follow-up to check for recurrence of the cyst and/or recurrence of symptoms. Endometrioma recurrence was defined as an ovarian cyst (>10 mm) with a typical aspect arising on the operated ovary identified by transvaginal ultrasound. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the comparison of recurrence rates between the 2 groups. The secondary endpoint was the evaluation of endometriosis-related pain recurrence in the 2 groups. Other endpoints selected for analysis included the identification of risk factors for the recurrence of endometrioma and of endometriosis-related symptoms. The mean follow-up was 29 ± 13 months (range, 13-49). Recurrence of ovarian endometriosis was recorded in 6.3% of patients (n = 4) treated with cystectomy and in 4.9% of patients (n = 3) managed with CO2 fiber laser (p = .74). Recurrence of endometriosis-related pain was observed in 5 patients (7.8%) in group 1 and in 6 patients (9.8%) in group 2 (p = .67). Mean endometrioma diameter > 5 cm at the time of surgery was identified as the only independent poor prognostic indicator for cyst recurrence (p = .008; odds ratio [OR], 2.21; 95% confidence interval [CI], 1.19-3.32). Moreover, the presence of deep endometriosis at surgery (p = .032; OR, 4.60; 95% CI, 1.14-18.57) and discontinuation of hormonal treatment (p = .015; OR, 3.18; 95% CI, 1.25-8.06) were independent poor prognostic indicators for pain recurrence. CONCLUSION: This study suggests that one-step CO2 fiber laser vaporization may be effective for endometrioma treatment because it is associated with recurrence rates comparable with those occurring after cystectomy, with the advantage of being an ovarian tissue-sparing technique.

Cellular Components Contributing to Fibrosis in Endometriosis: A Literature Review.

Endometriosis-related fibrosis represents a complex phenomenon with underlying mechanisms yet to be clarified. Fibrosis is consistently present in all disease forms and contributes to classic endometriosis-related symptoms of pain and infertility. The purpose of this literature review was to examine the role of various cellular populations and biologic mechanisms and signaling pathways in inducing fibrogenesis of endometriotic lesions. A search was performed through PubMed and MEDLINE for animal and human studies published in English in the last 23 years that examined fibrosis in superficial, ovarian, and deep infiltrating endometriosis. The main cell types found to be involved in the development of fibrosis were platelets, macrophages, ectopic endometrial cells, and sensory nerve fibers. Interactions among each of the cell types contribute to the production of fibrosis through the production of soluble factors, mostly transforming growth factor-ß but also other cytokines and neuropeptides. Cell types known to be critical to the pathophysiology of endometriosis also contribute to fibrogenesis, thus supporting the theory that fibrosis is an inherent part of endometriosis.

Inside the Endometrial Cell Signaling Subway: Mind the Gap(s).

Endometrial cells perceive and respond to their microenvironment forming the basis of endometrial homeostasis. Errors in endometrial cell signaling are responsible for a wide spectrum of endometrial pathologies ranging from infertility to cancer. Intensive research over the years has been decoding the sophisticated molecular means by which endometrial cells communicate to each other and with the embryo. The objective of this review is to provide the scientific community with the first overview of key endometrial cell signaling pathways operating throughout the menstrual cycle. On this basis, a comprehensive and critical assessment of the literature was performed to provide the tools for the authorship of this narrative review summarizing the pivotal components and signaling cascades operating during seven endometrial cell fate "routes": proliferation, decidualization, implantation, migration, breakdown, regeneration, and angiogenesis. Albeit schematically presented as separate transit routes in a subway network and narrated in a distinct fashion, the majority of the time these routes overlap or occur simultaneously within endometrial cells. This review facilitates identification of novel trajectories of research in endometrial cellular communication and signaling. The meticulous study of endometrial signaling pathways potentiates both the discovery of novel therapeutic targets to tackle disease and vanguard fertility approaches.

Thoracic Endometriosis Syndrome: Association With Pelvic Endometriosis and Fertility Status.

STUDY OBJECTIVE: To evaluate associations among catamenial pneumothorax, pelvic endometriosis, and fertility status. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Departments of Thoracic Surgery and Obstetrics and Gynecology, San Raffaele Hospital, Milan, Italy. PATIENTS: Sixteen females referred to the Department of Thoracic Surgery for treatment of spontaneous pneumothorax between January 2001 and January 2014 and referred to the outpatient clinic for gynecologic follow-up. INTERVENTIONS: Thoracoscopy for catamenial pneumothorax and laparoscopy for pelvic endometriosis. MEASUREMENTS AND MAIN RESULTS: Characteristics of the patients, the presence of endometriosis, and their fertility status were statistically analyzed. Pelvic endometriosis was diagnosed in 9 patients (56.3%), but 6 patients did not undergo a laparoscopic procedure to confirm or exclude the disease. Seven of the affected patients (77.8%) had stage III-IV endometriosis. Two-thirds of the patients with pelvic endometriosis who attempted conception conceived spontaneously, as did all of the patients without histopathological confirmation of endometriosis. CONCLUSION: Thoracic endometriosis syndrome, characterized mainly by catamenial pneumothorax, is a relevant condition in patients affected by endometriosis. However, few previous studies have analyzed this condition from a gynecologic standpoint, in terms of characteristics of endometriosis and fertility status of affected women. Our findings support the presence of a strong association between catamenial pneumothorax and pelvic endometriosis, as well as a minimal effect of catamenial pneumothorax on fertility status, even in the presence of pelvic endometriosis.

Is the endometrial evaluation routinely required in patients with adult granulosa cell tumors of the ovary?

OBJECTIVE: Granulosa cell tumors (GCTs) are the most common estrogen-secreting ovarian tumors; perhaps due to the persistent hyperestrogenism, a wide spectrum of associated endometrial pathologies ranging from endometrial hyperplasia to carcinoma has been documented in patients with GCTs. The aim of this study is to evaluate the incidence of endometrial pathologies in a large series of GCT patients treated in MITO centers. METHODS: A retrospective multi-institutional review of patients with granulosa cell tumors of the ovary treated or referred to MITO centers was conducted. Descriptive statistics were used to characterize the patient population and to assess the association of GCT and endometrial abnormalities at the time of diagnosis; multivariate regression analysis was also performed to identify independent predictors of endometrial abnormalities. RESULTS: A total of 150 patients with primary adult GCT was identified. During the preoperative assessment, endometrial pathology was found in 35.9% of symptomatic patients and in 90.9% of asymptomatic women with endometrial thickening at transvaginal ultrasound. At the time of surgery, hyperplasia was documented in 29.2% of patients, whereas endometrial cancer occurred in 7.5% of patients. Almost all of the patients (97.6%) with endometrial hyperplasia were older than 40years. All patients with endometrial cancer were older than 40years and postmenopausal. CONCLUSIONS: Endometrial carcinoma/atypical hyperplasia were commonly observed in GCT patients >40years; based on these data, endometrial sampling should be performed in symptomatic women at least 40years of age. In asymptomatic women <40years, endometrial sampling is of low yield.

Fertility preservation in female cancer patients: a single center experience.

Advances in cancer treatment allow women to be cured and live longer. However, the necessary chemotherapy and radiotherapy regimens have a negative impact on future fertility. Oncofertility has emerged as a new interdisciplinary field to address the issue of gonadotoxicity associated with cancer treatment and to facilitate fertility preservation, including oocyte and ovarian tissue cryopreservation. These fertility issues are often inadequately addressed, and referral rates to oncofertility centers are low. The aim of this study was to report the 3-year experience of the San Raffaele Oncofertility Unit. A total of 96 patients were referred to the Oncofertility Unit for evaluation after the diagnosis of cancer and before gonadotoxic treatment between April 2011 and June 2014. Of the 96 patients, 30 (31.2%) were affected by breast cancers, 20 (20.8%) by sarcomas, 28 (29.2%) by hematologic malignancies, 13 (13.5%) by central nervous system cancers, 3 (3.1%) by bowel tumors, 1 (1.0%) by Wilms' tumor, and 1 (1.0%) by a thyroid tumor; 47 (49.0%) were referred for oocyte cryopreservation before starting chemotherapy, 20 (20.8%) were referred for ovarian tissue cryopreservation, and 29 (30.2%) were not recruited. The mean time between the patients' counseling and oocyte retrieval was 15 days (range, 2-37 days). The mean time between the laparoscopic surgery and the beginning of treatment was 4 days (range, 2-10 days). The number of patients who were referred increased over time, whereas the rate of patients who were not recruited decreased, showing an improvement in referrals to the Oncofertility Unit and in the patients' counseling and understanding. Our results indicate that an effective multidisciplinary oncofertility team is necessary for prompt referrals and treatment.