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Background/Aim: To evaluate p16/Ki-67 dual-staining performance for detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in the management of women with minor cervical abnormalities. Patients and Methods: All 759 enrolled patients were tested for cytology, high-risk human papillomavirus (HR-HPV) and dual p16/Ki-67 staining. Results: Positivity rates for HR-HPV and dual staining increased as dysplasia was worsened from non-CIN (37.6% and 0%) to CIN1 (62.5% and 1.6%) and CIN2+ (98.7% and 97.3%), respectively. HPV18 and HPV16 exhibited the highest odds ratios (53.16 and 11.31) in the CIN2+ group. Both p16/Ki-67 dual staining and HR-HPV presented similar sensitivities (97.3% and 98.7%, respectively) for CIN2+ detection. Dual staining specificity, however, was 99.3%, significantly higher compared to HR-HPV testing (52.2%). The utility of dual staining was evaluated in different screening strategies and appeared to reduce the number of colposcopies required for the detection of CIN2+ cases. Conclusion: p16/Ki-67 dual-staining cytology is a surrogate triage biomarker in cytology-based screening programs, with high performance for efficient risk stratification of women with mild cervical abnormalities. © 2022 International Institute of Anticancer Research. All rights reserved.

Objective: To describe the ultrasound features of different endometrial and other intracavitary pathologies inpre- and postmenopausal women presenting with abnormal uterine bleeding, using the International Endometrial Tumor Analysis (IETA) terminology. Methods: This was a prospective observational multicenter study of consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler and fluid-instillation sonography were performed. Endometrial sampling was performed according to each center’s local protocol. The histological endpoints were cancer, atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (EIN), endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma and other. For fluid-instillation sonography, the histological endpoints were endometrial polyp, intracavitary leiomyoma and cancer. For each histological endpoint, we report typical ultrasound features using the IETA terminology. Results: The database consisted of 2856 consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler was performed in all cases and fluid-instillation sonography in 1857. In 2216 women, endometrial histology was available, and these comprised the study population. Median age was 49 years (range, 19-92 years), median parity was 2 (range, 0-10) and median body mass index was 24.9 kg/m(2) (range, 16.0-72.1 kg/m(2) ). Of the study population, 843 (38.0%) women were postmenopausal. Endometrial polyps were diagnosed in 751 (33.9%) women, intracavitary leiomyomas in 223 (10.1%) and endometrial cancer in 137 (6.2%). None (0% (95% CI, 0.0-5.5%)) of the 66 women with endometrial thickness < 3 mm had endometrial cancer or atypical hyperplasia/EIN. Endometrial cancer or atypical hyperplasia/EIN was found in three of 283 (1.1% (95% CI, 0.4-3.1%)) endometria with a three-layer pattern, in three of 459 (0.7% (95% CI, 0.2-1.9%)) endometria with a linear endometrial midline and in five of 337 (1.5% (95% CI, 0.6-3.4%)) cases with a single vessel without branching on unenhanced ultrasound. Conclusions: The typical ultrasound features of endometrial cancer, polyps, hyperplasia and atrophy and intracavitary leiomyomas, are described using the IETA terminology. The detection of some easy-to-assess IETA features (i.e. endometrial thickness < 3 mm, three-layer pattern, linear midline and single vessel without branching) makes endometrial cancer unlikely. Copyright (C) 2020 ISUOG. Published by John Wiley & Sons Ltd.

Herlyn–Werner–Wunderlich (HWW) syndrome is a rare congenital anomaly of Mullerian duct development characterized by uterus didelphys with blind hemivagina and ipsilateral renal agenesis. We present a case of a 29-year-old nulliparous woman, who was referred to our hospital complaining of chronic pelvic pain, dyspareunia, and a palpable mass in her vagina. At the age of 12, she underwent surgery because of a didelphys uterus diagnosis. Subsequently, she was operated on twice for endometriomas. At our institution, clinical and imaging findings revealed an obstructed hemivagina setting the diagnosis of HWW syndrome. Some of the various syndrome types may go unnoticed for months or even years after the onset of menstruation. Early diagnosis, followed by proper surgical treatment, is the key to avoid potentially severe complications. © 2021 Japan Society of Obstetrics and Gynecology.

Neglected severe obstetric anal sphincter injuries may result in fecal incontinence. It is of paramount importance to identify such injuries at the time of vaginal delivery and have appropriate surgical training for optimal anatomical restoration of the perineal structures. © 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.

This study is aimed at describing a noninvasive conservative strategy to the treatment of cervical pregnancy and highlighting the success of ultrasound-guided therapeutic techniques. A 43-year-old woman with a history of one previous cesarean section presented in our unit with vaginal spotting and a positive urine pregnancy test. She was diagnosed with a cervical pregnancy, and she was successfully treated conservatively with the administration of intragestational sac methotrexate under ultrasound guidance. Cervical pregnancy is a rare form of ectopic pregnancy that results from conceptus implantation in the cervical canal. The main concern is the associated life-threatening hemorrhage and subsequent need for urgent hysterectomy. The evolution of ultrasound over the past decades has enabled early diagnosis and has shifted the management from a radical surgical approach towards a stepwise conservative therapeutic approach, when possible. © 2021 Angeliki Rouvali et al.

Background: Molecular biology tools, such as the detection of Single Nucleotide Polymor-phisms (SNPs), have been considered to assist in the management of ovarian stimulation protocols. Purpose: The aim of this study was to evaluate the impact of two polymorphisms, the Asn680Ser pol-ymorphism of the FSHR gene, and the FSH β subunit (FSHβ) gene polymorphism-211 G>T, in a Greek population of women undergoing IVF/ICSI program in our center. In addition, a control group of fertile women was studied to verify whether there are differences in the genotype distribution between fertile and infertile population for both polymorphisms, as the FSHβ gene polymorphism-211 G>T is studied for the first time in the Greek population. Results: The FSH β-211 G>T polymorphism, studied for the first time in the infertile Greek popula-tion, appears to be quite rare. When studying the two polymorphisms separately, statistically signifi-cant differences were obtained that concerned the LH levels. Discussion: According to the combination analysis of the two polymorphisms by the number of al-leles, women with 2-3 polymorphic alleles needed more days of stimulation, but there were no differences in pregnancy rates. Conclusion: This molecular genetic study helps to elucidate whether the polygenic combination of the Asn680Ser and FSH β subunit-211 G>T gene polymorphisms is of additive value in the prediction of ovarian response to exogenous gonadotropins. © 2021 Bentham Science Publishers.

Objective: To present the case of a young patient with an Altman type IV sacrococcygeal teratoma (Fig 1) managed exclusively with laparoscopy. Design: A step-by-step demonstration of the technique. Setting: A 24-year-old patient complaining of dysmenorrhea, deep dyspareunia, chronic constipation, dyschezia, and bladder atony was diagnosed with a 5-cm cystic tumor compressing the low rectum and overlying the left levator ani muscle. Interventions: Laparoscopic excision of the tumor. At laparoscopy, significant bilateral pelvic venous congestion was found. The left medial and lateral pararectal fossa and the rectovaginal space were developed to the level of the pelvic floor. Several branches of the left internal artery and vein were dissected. The left hypogastric nerve and deep hypogastric plexus were dissected in an effort to preserve ipsilateral autonomic nerve supply to the rectum. Owing to the tumor's soft consistency and dense adherence to the surrounding structures, transrectal sonography facilitated dissection, which was performed medially to the mesorectal fascia and anteriorly to the presacral fascia. The middle sacral artery and peripheral branches of the internal iliac vasculature supplying the tumor were ligated. Part of the left levator ani had to be excised. The rectum was injured during the effort to detach the tumor from its lateral wall. The injury was repaired laparoscopically. The cut edge of the levator ani was used as a flap to reinforce the repair. Conclusion: Sacrococcygeal teratomas lying entirely in the pelvis (Altman type IV) are extremely rare [1,2]. Complete laparoscopic excision is challenging and potentially dangerous [3–5], but it is feasible with careful dissection. © 2020 AAGL

OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.

Purpose: To investigate DNA methylation changes in peripheral blood from patients with gestational diabetes mellitus (GDM) and preeclampsia (PE) due to poorly treated GDM. Methods: Eighteen pregnant women participated in the study: 6 with GDM, 6 with PE, and 6 healthy controls. The promoter methylation status of genes was profiled using the Human Inflammatory Response and Autoimmunity EpiTect Methyl II Signature PCR Array profiles. The results were validated with quantitative real-time polymerase chain reaction (qRT-PCR). Results: Fewer inflammation-related genes were significantly hypomethylated in PE cases compared to healthy subjects than in GDM cases. Some of the examined genes show different methylation patterns between GDM and PE. Conclusions: The epigenetic changes observed in this study indicate that GDM and PE exhibit specific DNA methylation profiles, with possible clinical applications. © 2019, Hellenic Endocrine Society.

Background: Ovarian tumours are usually surgically removed because of the presumed risk of complications. Few large prospective studies on long-term follow-up of adnexal masses exist. We aimed to estimate the cumulative incidence of cyst complications and malignancy during the first 2 years of follow-up after adnexal masses have been classified as benign by use of ultrasonography. Methods: In the international, prospective, cohort International Ovarian Tumor Analysis Phase 5 (IOTA5) study, patients aged 18 years or older with at least one adnexal mass who had been selected for surgery or conservative management after ultrasound assessment were recruited consecutively from 36 cancer and non-cancer centres in 14 countries. Follow-up of patients managed conservatively is ongoing at present. In this 2-year interim analysis, we analysed patients who were selected for conservative management of an adnexal mass judged to be benign on ultrasound on the basis of subjective assessment of ultrasound images. Conservative management included ultrasound and clinical follow-up at intervals of 3 months and 6 months, and then every 12 months thereafter. The main outcomes of this 2-year interim analysis were cumulative incidence of spontaneous resolution of the mass, torsion or cyst rupture, or borderline or invasive malignancy confirmed surgically in patients with a newly diagnosed adnexal mass. IOTA5 is registered with ClinicalTrials.gov, number NCT01698632, and the central Ethics Committee and the Belgian Federal Agency for Medicines and Health Products, number S51375/B32220095331, and is ongoing. Findings: Between Jan 1, 2012, and March 1, 2015, 8519 patients were recruited to IOTA5. 3144 (37%) patients selected for conservative management were eligible for inclusion in our analysis, of whom 221 (7%) had no follow-up data and 336 (11%) were operated on before a planned follow-up scan was done. Of 2587 (82%) patients with follow-up data, 668 (26%) had a mass that was already in follow-up at recruitment, and 1919 (74%) presented with a new mass at recruitment (ie, not already in follow-up in the centre before recruitment). Median follow-up of patients with new masses was 27 months (IQR 14–38). The cumulative incidence of spontaneous resolution within 2 years of follow-up among those with a new mass at recruitment (n=1919) was 20·2% (95% CI 18·4–22·1), and of finding invasive malignancy at surgery was 0·4% (95% CI 0·1–0·6), 0·3% (

Abnormal placentation often requires the involvement of a multidisciplinary team of medical caregivers. Practicing Obstetrics is a challenging and skillful duty. This is more obvious in cases of abnormal placentation, which represents one of the most dangerous and complex clinical conditions in materno-fetal medicine. Pathological placentation involves position and invasion abnormalities and represents a serious and potentially life-threatening condition for both the pregnant woman and the fetus. The dramatic increase in cesarean section rates is an important factor which could explain the rapid raise in abnormal placentation cases, which were considered rare a few years ago. Nevertheless, the scientific armamentarium sometimes seems to be poor and this could be explained by the fact that treatment options are offered too late, since this condition is often detected late, entailing higher patients’ risks. In fact, the later the diagnosis is made the poorer the prognosis is for cases of abnormal placentation. Given that abnormal placentation is constantly increasing, the scientific community should aim at early diagnosis and appropriate management of such cases based on the best evidence available. Future improvement of knowledge and practice lies in perspective, preferably randomized studies so that we obtain high quality of evidence which is still needed. The purpose of this study is to review the current literature and to update the available scientific knowledge on the topic of abnormal placentation which is an emerging issue which clinicians should learn to deal with, considering its continuous increase in the last years. © 2018 Elsevier B.V.

Objectives During the last 2 decades, ultrasonography has been proposed for the morphologic evaluation of the urethral rhabdosphincter. The aims of this study were to evaluate the feasibility of a simple sonographic technique for the assessment of the urethral rhabdosphincter morphology by using a 2-dimensional (2D) transvaginal transducer and to evaluate any associations between the sonographic parameters of rhabdosphincter morphology with the presence of urodynamic stress incontinence (USI). Methods This was a prospective study of women who underwent urodynamic studies and an introital 2D ultrasonography and divided in 2 groups based on the presence or absence of USI. Measurements included rhabdosphincter thickness at the 3-o'clock (right) and 9-o'clock (left) positions and the rhabdosphincter outer (Π) and inner circumference (π). Based on these values, the mean thickness of the rhabdosphincter (R + L / 2), the rhabdosphincter differential perimeter (Π - π), and area (A - α) were also calculated. Results Statistical analysis showed that women with a rhabdosphincter area of less than 0.65 cm 2, mean thickness of less than 0.24 cm, and differential perimeter of less than 1.08 cm had 3.98, 5.67, and 5.41 times greater odds for USI, respectively. Receiver operating characteristic curve analysis results showed that the optimal cutoff values for the prediction of USI from rhabdosphincter thickness, differential perimeter. and surface area were 0.24 cm (79.6% sensitivity, 63.4% specificity), 1.08 cm (70.8% sensitivity and 69.1% specificity), and 0.65 cm 2 (71.9% sensitivity, 57.1% specificity), respectively. Conclusions Introital ultrasonography with a 2D transvaginal probe allowed the visualization of the urethral rhabdosphincter morphology in greater than 90% of the cases. Sonographic measurements showed that patients with USI had a thinner urethral rhabdosphincter than did women with a normal sphincteric mechanism. © 2017 Wolters Kluwer Health, Inc. All rights reserved.