Role of Molecular Biomarkers in Endometriosis-Related Infertility: A Narrative Review of the Literature.

Endometriosis is a chronic benign inflammatory disease that affects women of reproductive age. The clinical presentations of endometriosis include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. There is a well-established association between endometriosis and infertility. Therefore, there is a need for an early diagnosis of endometriosis-related infertility. In this study, we aim to identify the role of biomarkers as predictive factors of the presence of the disease and its severity and their correlation with the pregnancy outcome. We performed an electronic database search of all published studies in PubMed and EMBASE from January 2018 to May 2023. Numerous innovative biomarkers identified in cases of endometriosis and infertility have been studied over the past years, including micro-RNAs, BCL6 endometrial expression, cytotoxic T-lymphocyte antigen 4, human leukocyte antigen G, programmed cell death protein 1, programmed cell death ligand 1 immune checkpoint molecules, plasma fibronectin-fibrin complexes, homeobox A10 gene, systemic inflammatory response markers, uterine natural killer cells, and the eutopic endometrium proteome. Considerable research has been done to identify diagnostic biomarkers for the early detection and prevention of endometriosis-associated infertility. However, none of these biomarkers displayed enough diagnostic accuracy to be used in daily clinical practice. Future research is valuable to establish them as reliable diagnostic tools.

Endometriosis Predictive Models Based on Self-Assessment Questionnaire, Evidence from Clinical Examination or Imaging Findings: A Narrative Review.

OBJECTIVE: The aim of this narrative review is to evaluate existing questionnaires on predictive models for endometriosis. These symptom-based models have the potential to serve as screening tools for adult women to detect endometriosis. DATA SOURCES: A comprehensive search of PubMed and Embase databases was conducted to identify studies on endometriosis screening. SELECTION OF STUDIES: The search targeted predictive models for endometriosis localisation, bowel involvement, need for bowel surgery and fertility. Due to the heterogeneity identified, a systematic review was not possible. A total of 23 studies were identified. DATA EXTRACTION AND SYNTHESIS: Among these studies, twelve included measures for general endometriosis, two targeted specific sites, four focused on deep infiltrating endometriosis (DIE), and three addressed the need for endometriosis-related bowel surgery. Many measures combined clinical, imaging and laboratory tests with patient questionnaires. Validation of these models as screening tools was lacking in all studies, as the focus was on diagnosis rather than screening. CONCLUSION: This review did not identify any fully validated, symptom-based questionnaires for endometriosis screening in adult women. Substantial validation work remains to establish the efficacy of such tools.

Hysteroscopic features suggestive of chronic endometritis: a systematic review.

The purpose of this systematic review is to identify common hysteroscopic findings suggestive of endometritis, chronic or subclinical, based on current scientific evidence. Data sources were MEDLINE, Embase, PubMed and other sources of grey literature. Four (4) authors independently selected studies addressing hysteroscopic detection of CE based on specific and clearly stated hysteroscopic criteria. The diagnosis was confirmed by histologic assessment, as stated in the materials and methods of these studies included. The initial search identified 599 studies, of which 21 met the inclusion criteria. Significant heterogeneity among published studies on Chronic endometritis (CE) remains the main limitation in performing a metanalysis and further analysis of diagnostic accuracy on the subject. Hysteroscopy is an important diagnostic tool in cases of chronic endometritis when accompanied by endometrial biopsies. Clinicians relate hyperaemia and endometrial oedema with chronic endometritis while more than half include micropolyposis as a pathognomonic feature of this subclinical condition. Micropolyps, stromal oedema, haemorrhagic spots, strawberry aspect, and hyperaemia are proposed as adequate indicators of hysteroscopic evidence of CE according to the literature. The impact of CE in long-term reproductive outcomes remain unclear, thus clinicians ought to communicate this to the patients and provide treatment where clinically appropriate. In addition, we present hysteroscopic images of histologically confirmed CE cases that could play the role of a hysteroscopic atlas.

Leydig cell hyperplasia as a cause of virilization in a postmenopausal woman: A case report.

Virilization is a rare condition in postmenopausal women, usually attributed to androgen excess of ovarian or adrenal origin. A 62-year-old woman presented with excessive hair loss of 3 months' duration and was investigated for an endocrine cause of alopecia. The hormonal evaluation revealed increased testosterone but normal levels of androstenedione and dehydroepiandrosterone sulfate, while the results of transvaginal ultrasonography and abdominal computed tomography were unremarkable. Based on these findings, the possibility of an adrenal androgen-secreting tumor was ruled out and suspicion of Leydig cell hyperplasia was raised. A bilateral laparoscopic salpingo-oophorectomy was performed due to the age of the patient and the diagnosis of Leydig cell hyperplasia was confirmed by histopathological examination. The postoperative course of the patient was uneventful and a repeat hormonal evaluation after the operation showed a normalization of androgen levels. In conclusion, Leydig cell hyperplasia should be considered as a likely cause of hyperandrogenism of ovarian origin in women who develop virilization. In postmenopausal women, bilateral oophorectomy will treat the disorder and provide a conclusive diagnosis via histopathological examination.

Ovarian Masses in Children and Adolescents: A Review of the Literature with Emphasis on the Diagnostic Approach.

Most abdominal masses in the pediatric population derive from the ovaries. Ovarian masses can occur in all ages, although their incidence, clinical presentation and histological distribution vary among different age groups. Children and adolescents may develop non-neoplastic ovarian lesions, such as functional cysts, endometrioma, torsion, abscess and lymphangioma as well as neoplasms, which are divided into germ cell, epithelial, sex-cord stromal and miscellaneous tumors. Germ cell tumors account for the majority of ovarian neoplasms in the pediatric population, while adults most frequently present with epithelial tumors. Mature teratoma is the most common ovarian neoplasm in children and adolescents, whereas dysgerminoma constitutes the most frequent ovarian malignancy. Clinical manifestations generally include abdominal pain, palpable mass, nausea/vomiting and endocrine alterations, such as menstrual abnormalities, precocious puberty and virilization. During the investigation of pediatric ovarian masses, the most important objective is to evaluate the likelihood of malignancy since the management of benign and malignant lesions is fundamentally different. The presence of solid components, large size and heterogenous appearance on transabdominal ultrasonography, magnetic resonance imaging and computed tomography indicate an increased risk of malignancy. Useful tumor markers that raise concern for ovarian cancer in children and adolescents include alpha-fetoprotein, lactate dehydrogenase, beta subunit of human chorionic gonadotropin, cancer antigen 125 and inhibin. However, their serum levels can neither confirm nor exclude malignancy. Management of pediatric ovarian masses needs to be curative and, when feasible, function-preserving and minimally invasive. Children and adolescents with an ovarian mass should be treated in specialized centers to avoid unnecessary oophorectomies and ensure the best possible outcome.

Diagnosis and Treatment of Adenomyosis with Office Hysteroscopy-A Narrative Review of Literature.

INTRODUCTION: Adenomyosis is a common chronic disease in women of reproductive age, characterised by the presence of ectopic endometrial tissue within myometrium. Even though adenomyosis presents with chronic pelvic pain, menorrhagia or abnormal uterine bleeding, dysmenorrhoea, and dyspareunia and is often recognised after hysterectomies. However, the development of ultrasonography and magnetic resonance imaging has improved the pre-operative diagnosis of the disease. Hysteroscopy provides information in real time from the uterine cavity and the offers the possibility of obtaining direct biopsies. MATERIAL AND METHODS: The literature was searched via Pubmed and Embase with the following headings: diagnosis of adenomyosis or adenomyoma and office hysteroscopy, hysteroscopy findings of adenomyosis or adenomyoma, treatment of adenomyosis or adenomyoma with office hysteroscopy. RESULTS: The literature showed that hysteroscopy can identify superficial adenomyosis. There are a variety of hysteroscopic images that can be connected with the disease. New equipment like the spirotome has been used to access deeper layers of myometrium and obtain biopsies under direct vision from the adenomyotic areas. Different methods of treatment have been also described, like enucleation of focal superficial adenomyoma, coagulation, evacuation of cystic adenomyosis when the lesion is smaller than 1.5 cm, and resection of adenomyotic nodules in case of bigger lesions (>1.5 cm). Diffuse superficial adenomyosis is also managed by resection. CONCLUSIONS: Hysteroscopy has revolutionised the approach to adenomyosis. It is a useful tool in assessing mainly superficial adenomyosis. The role of hysteroscopy in surgical management of adenomyosis need to be confirmed with further studies.

Genetic Disorders Underlying Polyhydramnios and Congenital Hypotonia: Three Case Reports and a Review of the Literature.

An abnormal rise in the amount of amniotic fluid is a frequent prenatal observation called polyhydramnios, which can indicate a number of underlying problems. Even while it frequently goes undiagnosed during pregnancy, it may be linked to dangerous fetal illnesses. In three cases of newborns with congenital hypotonia, polyhydramnios was the sole prenatal symptom reported in this study. This fact highlights the significance of understanding the possible connection between genetic abnormalities or neurological problems and polyhydramnios, underscoring the responsibility obstetricians have in educating expectant mothers who are at potential risk for these uncommon but serious illnesses. Whole-genome sequencing (WES), an advanced kind of prenatal testing, is essential for determining genetic reasons and assisting families in making decisions. Working together with specialists in fetal medicine is crucial in guaranteeing the best possible treatment and results for the mother and child.

Ovarian Teratomas in Children and Adolescents: Our Own Experience and Review of Literature.

Background: Ovarian teratomas are the most common type of ovarian mass during childhood and adolescence. There is no clear guidance for the management of the ovarian teratomas in children and adolescents. It is necessary, however, to understand the feature of these tumours and the indications for operating on them, and to put subjective criteria for the management in elective or emergency presentations. Methods: Medical records of patients between the age of 12 and 20 years old that underwent surgery for ovarian teratomas at the Department of Obstetrics and Gynaecology in University Hospital of Ioannina, between January 2000 and August 2022, were reviewed. A medical database was searched between January 2000 and August 2022 with the following keywords: ovarian teratoma, paediatrics and adolescents. Results: We present the results of forty patients, with a mean age of 11.8 years of age. All patients had surgery, where three out of four underwent oophorectomy and only one out of four underwent ovary-sparing operation; similar results were found in the literature. Conclusion: Ovary-sparing treatment is more common recently compared with the past, such as MIS compared with laparotomy. Better-organised and -planned prospective multi-centre studies are necessary to gain a deeper knowledge of the physiology and prognostic factors of teratomas in children.

Axillary lymph node dissection vs. sentinel node biopsy for early-stage clinically node-negative breast cancer: a systematic review and meta-analysis.

ΟBJECTIVE: This study aimed at comparing survival outcomes between systematic axillary lymph node dissection (ALND) vs sentinel lymph node and axillary lymph node dissection only if sentinel positive (SLN ± ALND) in early-stage, clinically node-negative breast cancer patients. ΜETHODS: A systematic review and meta-analysis adhered to PRISMA guidelines was performed. Included studies were prospective randomized controlled trials (RCTs) comparing survival outcomes of ALND vs. SLN ± ALND in early-stage, node-negative breast cancer patients. Patients enrolled were only those with tumor size lower than 4 cm, clinically negative nodes and treated with breast-conservative surgery. Primary endpoints were locoregional recurrence, overall death and cancer-related death. RESULTS: There were four studies included in the analysis, enrolling overall 2982 patients, of which 1494 in ALND arm and 1488 in the SLN ± ALND arm. No statistically significant difference was observed in locoregional recurrence, breast cancer-related death and overall death. Locoregional recurrence was observed in 2.8% (ALND) vs. 4.1% (SLND ± ALND), (RR 0.69, 95% CI 0.20-2.30). Overall death rate was 7.0% vs. 6.8% respectively, (RR 1.00, 95% CI 0.73-1.39, I2 = 28.7%). Breast cancer-related death was 3.6% vs. 3.5%, respectively (SLN ± ALND), (RR 1.11, 95% CI 0.70-1.78, I2 = 0%). No statistically significant difference was observed in any of secondary study outcomes. CONCLUSIONS: Systematic axillary axillary lymph node dissection provides no survival benefit compared with sentinel lymph node dissection for early-stage clinically node-negative breast cancer patients.

Inguinal endometriosis: A systematic review.

Inguinal endometriosis is a very rare entity with uncertain pathophysiology, that poses several diagnostic and therapeutic challenges. This study aimed to summarize published literature on the diagnosis and treatment of this condition. Thus, a systematic literature search was conducted in PubMed/MEDLINE, Scopus and the Cochrane Library. An effort was made to numerically analyze all parameters included in case reports and retrospective analyses, as well. The typical and atypical features of this condition, investigations used, type of treatment and histopathology were recorded. More specifications about the surgical treatment, such as operations previously performed, type of surgery and treatment after surgery have been acknowledged. Other sites of endometriosis, the presence of pelvic endometriosis and the follow-up and recurrence have been also documented. Overall, the search yielded 61 eligible studies including 133 cases of inguinal endometriosis. The typical clinical presentation includes a unilateral inguinal mass, with or without catamenial pain. Transabdominal or transvaginal ultrasound was typically used as the first line method of diagnosis. Groin incision and exploratory surgery was the treatment indicated by the majority of the authors, while excision of part of the round ligament was reported in about half of the cases. Chemotherapy and radiotherapy were initiated in cases of coexisting endometriosis-related neoplasia. Inguinal recurrence or malignant transformation was rarely reported. The treatment of inguinal endometriosis is surgical and a long-term follow-up is needed. More research is needed on the effectiveness of suppressive hormonal therapy, recurrence rate and its relationship with endometriosis-associated malignancies.

Dilatation and curettage in endometrial cancer. What is the correlation with hysterectomy histology? A 14 years retrospective cohort study.

PURPOSE: The aim of the present study is to evaluate the concordance between preoperative endometrial sampling histopathology performed by conventional dilatation and curettage (D&C) and final histopathological diagnosis after total hysterectomy concerning tumor grade and subtype in patients with endometrial cancer (EC). METHODS: In this comparative retrospective study, 203 women with endometrial cancer were included who underwent at first dilatation and curettage and then total hysterectomy. The preoperative histopathological report obtained by dilatation and curettage was compared with the final histopathology after total hysterectomy to assess the accuracy of endometrial sampling. RESULTS: Comparison of preoperative with postoperative histopathological results showed an overall 5.9% and 10.9% discordance regarding endometrial cancer histological subtype and grade, respectively. Six (4.9%) of the patients with preoperative grade 1 were grade 2 and 1 (0.8%) was found to be grade 3. Three (8.3%) of the patients with preoperative grade 2 were found to be grade 3 after hysterectomy. Discordance is higher for endometrioid endometrial cancer grade 2 (25%) compared with grade 1 (5.7%) and 3 (18.8%). CONCLUSION: Patients should be informed and consent for the potential discrepancy between the pre and postoperative histopathological features of malignancy. This discrepancy may result in either under or overtreatment. Thus, it should be accounted for when counseling for a major operation.

Breast Disorders in Adolescence: A Review of the Literature.

BACKGROUND: Adolescence is accompanied by a variety of changes in young breast development, which greatly affects the adolescent's psychology and socialization. SUMMARY: PubMed, EMBASE, and the Cochrane Library were searched for studies relative to epidemiology, clinical characteristics, diagnosis, and management of all breast disorders in adolescence and their consequences. Development disorders are breast asymmetry, breast atrophy, breast hypoplasia, hypomastia, juvenile breast hypertrophy, and tuberous breast. Breast congenital abnormalities include athelia, amastia, accessory breast tissue, polymastia, polythelia, and congenital disorders of nipples. Breast infections are commonly caused from Gram-positive coccus rather than Gram-negative bacteria. Breast abscess occurs when breast infections are not promptly treated. Nipple discharge is caused by a variety of conditions and should be managed carefully. Fibrocystic changes, cysts, and fibroadenomas are the most common benign masses in adolescence. Primary, secondary, or metastatic breast cancer is extremely rare in adolescence. However, clinicians should include breast cancer in the differential diagnosis of a breast mass in adolescence. KEY MESSAGES: Clinicians should be aware of all breast disorders that may occur in adolescence. Early diagnosis and treatment will result in the reassurance of adolescents and their families without any detrimental effect on their psychology, sexual behavior, and socialization. Adolescents with breast disorders may require a multidisciplinary approach by a pediatrician, a gynecologist specializing in pediatric-adolescent gynecology, a plastic surgeon, and a psychologist for the best management of breast disorders.

Cardiometabolic Risk Factors in Adolescents with Polycystic Ovary Syndrome.

It is well-established that adults with polycystic ovary syndrome (PCOS) have an increased prevalence of several cardiometabolic risk factors, including obesity, insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Accumulating data suggest that these risk factors are already present in adolescence in patients with PCOS. This has major implications for the management of this population since the timely identification of these risk factors is essential for preventing cardiovascular disease in adulthood. The present review summarizes the existing evidence regarding the prevalence of traditional and non-traditional cardiometabolic risk factors in adolescents with PCOS.

Long-term effects of treatment of central precocious puberty with gonadotropin-releasing hormone analogs every three months.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) analogs represent the treatment of choice in patients with central precocious puberty (CPP). Recently, GnRH analogs that can be administered every 3 months have been developed and appear to be as safe and effective as one-monthly formulations. However, there are limited data regarding its long term safety and efficacy profile. We aimed to evaluate the long-term safety and efficacy treatment of CPP with GnRH analogs every 3 months. METHODS: We prospectively studied all patients who were diagnosed with CPP in our center between January 2015 and December 2019. All patients were treated with intramuscular leuprolide acetate 11.25 mg every 3 months. RESULTS: Twenty-four patients with CPP were included in the study. Mean follow-up was 3.1 years. Height gain ranged between 4 and 6 cm. Bone mineral density (BMD) was not affected. Body mass index (BMI) increased in all subjects but none was obese at the end of follow-up. CONCLUSIONS: Treatment of patients with CPP with GnRH analogs every 3 months induces substantial increases in height and does not affect BMI or BMD. Therefore, it represents an attractive option for these young patients.

Cervical Pathology Following HPV Vaccination in Greece: A 10-year HeCPA Observational Cohort Study.

BACKGROUND: In Greece the population-level impact of HPV vaccination is unknown due to lack of official registries. This study presents in a pragmatic frame the comparison of cervical pathology data between HPV-vaccinated and unvaccinated women referred for colposcopy. PATIENTS AND METHODS: This is an observational prospective cohort study performed in 7 academic Obstetrics and Gynaecology Departments across Greece between 2009-2019. Cases were women that had completed HPV vaccination before coitarche and were referred for colposcopy due to abnormal cytology. For each vaccinated woman an unvaccinated matched control was selected. RESULTS: A total of 849 women who had been vaccinated before coitarche and 849 unvaccinated controls were recruited. The combination of cytological, colposcopic and molecular findings necessitated treatment in only a single case among vaccinated (0.1%) and in 8.4% among unvaccinated. CONCLUSION: HPV vaccination at a proper age can markedly reduce development of severe cervical precancers and consequently the need for treatment, as well as their long-term related obstetrical morbidity.

Management of obesity in adolescents with polycystic ovary syndrome.

Introduction: Approximately 1% of adolescents have polycystic ovary syndrome (PCOS) and almost 40-70% of these patients are overweight or obese. Obese adolescents with PCOS have more severe insulin resistance and hyperandrogenemia, a more adverse lipid profile and a worse quality of life than normal-weight adolescents with PCOS. Accordingly, weight loss is an important component of the management of these patients.Areas covered: The authors discuss the different options for weight loss in obese adolescents with PCOS. Lifestyle changes appear to be effective but adherence to this intervention is suboptimal. There are also limited data regarding the optimal diet in this population. Few small studies have evaluated the effects of pharmacotherapy in these patients. Conflicting data have been reported regarding the effects of metformin on body weight. Notably, agents that have been approved for weight loss in adults have not been evaluated in adolescents with PCOS.Expert opinion: More studies are needed to identify the most appropriate diet for obese adolescents with PCOS. Well-designed randomized controlled studies are also needed to define the safety and efficacy of pharmacotherapy in this population.