Search Results (106)

Adenomyosis (AM) is a hormonally responsive uterine disorder defined by ectopic endometrial tissue within the myometrium, causing pain, abnormal bleeding, and subfertility. Non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—are post-transcriptional regulators implicated also in uterine remodeling. We systematically reviewed original studies evaluating ncRNAs in AM using human samples, in vitro and animal models, or bioinformatic approaches. Data sources included PubMed and Google Scholar (inception up to 10 August 2025). Forty-one studies were included and synthesized across mechanistic, diagnostic, and translational domains. miRNAs (n = 31) were the most studied subclass, followed by lncRNAs (n = 10) and circRNAs (n = 5). Recurrent miRNAs such as miR-10b and miR-30c-5p (downregulated, inhibitory) and miR-145 (upregulated, promotive) regulate epithelial invasion, epithelial–mesenchymal transition, and cytoskeletal remodeling via PI3K–AKT/MAPK and Talin1 signaling. The let-7a/LIN28B axis governed estrogen-sensitive proliferation in the junctional zone, while miR-21 exhibited compartment-specific roles in decidualization and ectopic cell survival. Extracellular-vesicle (EV)-bornemiRNAs (e.g., miR-92a-3p, miR-25-3p, miR-4669) contributed to immune polarization and show early diagnostic potential. lncRNAs and circRNAs acted via chromatin modifiers and ceRNA networks. Most findings remain at the discovery stage. Convergent dysregulation was observed in key signaling pathways, including JAK–STAT, Wnt/β-catenin, and Hippo–YAP. ncRNAs regulate critical axes of invasion, proliferation, immune modulation, and hormonal response in AM. Targets with preliminary causal support—miR-10b/ZEB1, let-7a/LIN28B, and miR-145/Talin1—warrant further validation. Circulating miRNAs—especially in EVs—offer promise for non-invasive diagnosis. Full article

Polycystic ovary syndrome (PCOS) is a systemic metabolic and endocrine disorder that significantly disrupts reproductive physiology and endometrial function. In this narrative review, we examine the molecular impact of metabolic and hormonal imbalances on the endometrium of women with PCOS. We investigate the specific mechanisms that delineate how hyperinsulinemia and insulin resistance, chronic low-grade inflammation, and estrogen/progesterone/androgen imbalance contribute to altered epigenetic, transcriptomic, metabolomic, and signaling profiles in a wide array of different cell types within endometrial tissues. The synergistic interplay between upregulated inflammatory cytokines (e.g., IL-1,2,6,8,17,18, and TNF-α), along with key changes in critical molecular pathways associated with hyperinsulinemia and insulin resistance (e.g., PI3K/AKT/MAPK, and Wnt/β-catenin), in addition to aberrant sex steroid hormone signaling (e.g., CYP19A1, COX-2, PGE₂, HOXA10, 11βHSD2), promotes deleterious changes within the endometrial microenvironment. These anomalies underpin a spectrum of clinical manifestations observed in women with PCOS at each stage of the life course, including abnormal uterine bleeding in reproductive-age women, impaired decidualization in pregnancy, and altered postmenopausal endometrial physiology. Clinically, these alterations are associated with abnormal uterine bleeding, subfertility, implantation failure, miscarriage, pregnancy complications, and postmenopausal endometrial hyperplasia and cancer. Overall, our review provides novel insights into the molecular mechanisms linking systemic metabolic and endocrine dysfunction with endometrial pathology in PCOS and has broader implications that apply to all women. Full article

Objective: This study aimed to determine the prevalence of isthmocele in patients who had undergone cesarean delivery and to investigate its association with abnormal uterine bleeding (AUB). Additionally, a novel volume-based classification system (Er-Kay Classification) was developed to provide a more precise assessment of cesarean scar defects and their correlation with clinical symptoms. Material and Methods: This retrospective, hospital-based cohort study was conducted at Ankara Etlik Zübeyde Hanım Women’s Health Training and Research Hospital between October 2017 and March 2018. A total of 1098 patients who had undergone cesarean delivery and attended follow-up visits were included. Patients were categorized based on the presence of isthmocele (study group: n = 134) and its absence (control group: n = 964). Isthmocele volume was calculated using the formula (Height × Width × Depth)/3, and patients were classified as Grade 1 (≤50 mm³) or Grade 2 (>50 mm³) based on the novel Er-Kay Classification. Clinical symptoms, including AUB (pre-, inter-, postmenstrual bleeding), dysmenorrhea, dyspareunia, and postcoital bleeding, were compared between groups. Statistical analyses were performed using SPSS 27.0 (NY, USA),with a significance level of p < 0.05. Results: The prevalence of isthmocele was 12.2% (134/1098). Patients with isthmocele had significantly shorter menstrual cycles compared to those without (26.64 ± 5.35 vs. 28.08 ± 4.97 days, p = 0.038). Postmenstrual bleeding (47.0% vs. 4.7%, p < 0.001), dysmenorrhea (38.8% vs. 18.3%, p < 0.001), and dyspareunia (39.6% vs. 14.7%, p < 0.001) were significantly more frequent in the isthmocele group. According to the Er-Kay Classification, intermenstrual bleeding was significantly higher in Grade 2 (23.1%) than in Grade 1 (4.3%) (p = 0.001). Similarly, postmenstrual bleeding was more common in Grade 2 (56.9%) than in Grade 1 (37.7%) (p = 0.026). No significant differences were found for premenstrual bleeding, dysmenorrhea, or dyspareunia between the Er-Kay Classification groups (p > 0.05). Conclusions: The findings indicate that isthmocele is significantly associated with AUB, dysmenorrhea, and dyspareunia. The Er-Kay Classification, based on isthmocele volume, provides a more precise assessment of symptom severity, particularly in intermenstrual and postmenstrual bleeding cases. These results suggest that volume-based evaluations should be incorporated into clinical practice for better patient management and diagnosis of cesarean scar defects. Full article

Background/Objectives: Our study evaluates the performance of the CDO1 and CELF4 methylation assay of cervical scrapings in diagnosing endometrial cancer. Methods: Patients referred for abnormal uterine bleeding, suspected endometrial pathology on imaging, endometrial hyperplasia, or cancer, who were indicated for endometrial sampling +/− hysteroscopy +/− hysterectomy, were recruited prospectively from the gynecology clinic of Prince of Wales Hospital, Hong Kong, from January 2023 to November 2024. Methylation assay was performed on the cervical scrapings of the participants, with the results compared to endometrium histology obtained on the same day. Results: Methylation assay results of 675 patients were compared to 629 outpatient endometrial assessments and 46 hysterectomy histology. The assay yields an accuracy of 97.3%, sensitivity of 84.1%, specificity of 98.8%, PPV of 89.2%, and NPV of 98.2%. The AUC is 0.92 with a Kappa coefficient of 0.85. The false-negative rate was 0.8% among the 629 endometrial assessment cases. Endometrial thickness, abnormal cervical cytology, and endometrial hyperplasia significantly affected the accuracy. Among seven false-positive cases, five had endometrial hyperplasia and two had cervical intraepithelial neoplasia. Eventually, three patients were diagnosed with endometrial cancer and one with cervical cancer 1 to 4 months later. Conclusions: Methylation assay of cervical scrapings is highly accurate in diagnosing endometrial cancer with a high sensitivity, specificity, and low false-negative rate. It can act as a triage to reduce invasive endometrial assessment. All false-positive cases were related to neoplastic processes in the genital tract, indicating that it may be useful for detecting cancer early, before histological change is evident. Full article

Background and Clinical Significance: Uterine arteriovenous malformation (AVM) is a rare but potentially life-threatening condition due to the risk of severe acute hemorrhage. Unlike AVMs in other anatomical locations, which are predominantly congenital, uterine AVMs are often acquired, typically developing after uterine procedures such as dilatation and curettage (D&C), cesarean section, or pregnancy-related events. Women commonly present with abnormal bleeding disorders. Case Presentation: We are presenting the case of a 41-year-old Caucasian woman with secondary amenorrhea three months after vacuum curettage in the 7th week of pregnancy. Based on her clinical history and the findings on transvaginal sonography (TVS), uterine AVM was highly suspected. Contrast-enhanced magnetic resonance imaging (MRI) confirmed the diagnosis. The patient underwent successful embolization of the left uterine artery. Follow-up examinations demonstrated complete resolution of the vascular malformation, and regular menstrual cycles resumed during her recovery. With the increasing frequency of uterine surgical interventions, the incidence of uterine AVMs is also expected to rise. The clinical impact is significant when fertility preservation and family planning are still ongoing. To the best of our knowledge, this is the first reported case in which amenorrhea is the primary presenting symptom of a uterine AVM. Conclusions: Given the high risk of life-threatening hemorrhage associated with undetected or incorrectly treated AVMs, their presence must always be carefully ruled out in case of bleeding disorders after pregnancy or uterine surgery. Accurate diagnosis prior to any further intrauterine interventions, such as curettage, is crucial to prevent severe complications and ensure appropriate management. In order to avoid life-threatening complications, the possibility of uterine AVM should be considered in the differential diagnosis even in the presence of amenorrhea. The proposed diagnosis and treatment algorithm for uterine AVMs can help avoid misdiagnosis. Full article

Background and Clinical Significance: Left ventricular hypoplasia is often repaired surgically in sequence to a Fontan circulation, which is a physiologic state that presents unique challenges during pregnancy. Although women with Fontan physiology can achieve successful pregnancy outcomes, they remain at elevated risk for cardiac, thrombotic, and obstetric complications. Case Presentation: We describe a 38-year-old woman with Fontan physiology and acquired von Willebrand syndrome (AVWS) who was admitted at 23 weeks gestation for preterm premature rupture of membranes. The patient had history of prior classical cesarean delivery and two previous miscarriages. Her pregnancy was further complicated by abnormal placental vasculature and uterine arteriovenous malformation. Given her bleeding diathesis, hematology advised against anticoagulation or antiplatelet therapy, and she ultimately underwent a successful low transverse cesarean delivery under general anesthesia at 24 weeks. Postpartum hemorrhage was managed with clotting factor replacement and supportive care. Conclusions: This case illustrates how AVWS may mitigate thrombotic risk in Fontan physiology and how early activation of a cardio-obstetrics team can enable tailored planning. As more patients with complex congenital heart disease reach reproductive age, multidisciplinary coordination, shared infrastructure, and individualized birth plans will be essential to achieving optimal maternal–fetal outcomes. Full article

Retained products of conception (RPOC) represent a significant cause of morbidity in the post-abortive and postpartum periods, potentially leading to abnormal uterine bleeding, pelvic pain, infections, and intrauterine adhesions. Accurate diagnosis is crucial to avoid unnecessary surgical interventions and to preserve future fertility. Transvaginal ultrasound constitutes the primary imaging modality for identifying RPOC, but the lack of standardized diagnostic criteria complicates clinical decision-making. This narrative review explores the current literature on sonographic findings associated with RPOC, focusing on the diagnostic value of endometrial thickness (ET), the presence of intrauterine echogenic masses, and the use of Color Doppler imaging. Although an ET ≥15 mm is frequently used to suspect RPOC, the variability in cut-off thresholds and limited specificity reduce its diagnostic reliability. The detection of an echogenic intrauterine mass appears to be the most sensitive and specific sonographic feature. Color Doppler assessment, particularly the presence of enhanced myometrial vascularity (EMV) and classification systems like the Gutenberg score, offers further insight by stratifying hemorrhagic risk and guiding therapeutic choices. However, vascular parameters such as peak systolic velocity (PSV) and resistive index (RI) demonstrate a substantial overlap between benign and pathological conditions, limiting their stand-alone utility. The review also addresses the differential diagnosis of RPOC, including blood clots, arteriovenous malformations, placental polyps, gestational trophoblastic disease, and endometrial osseous metaplasia. The role of three-dimensional ultrasound remains limited in clinical practice, offering no significant advantage over two-dimensional imaging. Finally, the timing of follow-up ultrasound after medical treatment with misoprostol is critical: delayed assessment reduces overtreatment by allowing time for spontaneous resolution. In conclusion, despite advances in ultrasound technology, the diagnosis of RPOC remains challenging due to heterogeneity in imaging findings and inter-observer variability. A multimodal approach integrating grayscale and Doppler ultrasound with clinical evaluation is essential for optimal management. Full article

Platelet-rich plasma (PRP) therapy is a non-invasive, autologous treatment with regenerative potential in gynaecology beyond fertility applications. This review evaluates PRP in non-fertility-related gynaecological conditions affecting women’s quality of life (QoL). Methods: Following PRISMA-ScR guidelines, we searched Embase, CINAHL, Web of Science, Scopus, CENTRAL, and MEDLINE for studies on PRP in conditions such as vulvar lichen sclerosus (VLS), vulvovaginal atrophy (VVA), sexual dysfunction (SD), stress urinary incontinence (SUI), and interstitial cystitis/bladder pain syndrome (IC/BPS). Of 3660 records screened, 43 studies (randomised controlled trials, quasi-experimental, cohort, and case series) were included. Results: PRP improved symptoms and QoL in several conditions, particularly VLS and SD, and was generally well tolerated with minor adverse effects (e.g., injection-site pain, transient discomfort). Evidence for abnormal uterine bleeding (AUB) and pelvic organ prolapse (POP) was inconclusive. Considerable heterogeneity in preparation protocols and outcome measures limited cross-study comparison. Conclusions: PRP shows promise as a minimally invasive therapy for certain gynaecological conditions. Standardisation of preparation and administration, along with large-scale RCTs, is needed to determine long-term efficacy and safety. Full article

Objective: This retrospective study aims to evaluate the effect of copper intrauterine device (Cu-IUD) use on the adequacy and diagnostic quality of endometrial biopsy specimens in women with abnormal uterine bleeding (AUB). Patients with levonorgestrel-releasing intrauterine systems (LNG-IUS, e.g., Mirena) were excluded from the study. The study compares the histopathological adequacy of endometrial samples between Cu-IUD users and non-users, highlighting potential interpretation challenges in routine pathological assessment. Methods: The study was conducted on 409 women aged 25–55 who presented with abnormal uterine bleeding (AUB) to the Gynecology and Obstetrics Outpatient Clinic at Kayseri City Hospital between 1 April 2021 and 1 April 2023. The patients were divided into two groups: copper IUD (Cu-IUD) users (n = 215) and non-IUD users (n = 194). Patients using levonorgestrel-releasing intrauterine systems (LNG-IUS, e.g., Mirena) were excluded from the study. Endometrial biopsies were obtained using the Pipelle curette technique without anesthesia, preserved in 10% formalin, and assessed for pathological classification and diagnostic adequacy. Results: The proportion of unclassifiable pathological categories was significantly higher in copper IUD users (63.93%) compared to non-IUD users (36.05%) (p = 0.013). Additionally, a negative correlation was observed between pathological category and endometrial thickness (r = −0.3147, p < 0.001), suggesting that thinner endometrial lining may reflect atrophic or diagnostically ambiguous tissue patterns. However, no significant association was found between IUD use and endometrial thickness (p = 0.073). Conclusions: The findings indicate that copper IUD use may affect the diagnostic adequacy of endometrial biopsy specimens, likely due to inflammatory or structural changes in the endometrium. These results underline the importance of considering IUD-related alterations when interpreting biopsy findings. Further research is needed to refine diagnostic approaches and better understand the clinical implications of these effects. Full article

Endometriosis is a chronic inflammatory disease characterized by the presence of ectopic endometrial tissue, mainly in the pelvic cavity. It primarily affects women of reproductive age and is associated with significant morbidity, particularly chronic pelvic pain and infertility. Despite its high prevalence, diagnosis is often delayed, contributing to prolonged suffering and increased healthcare burden. This review examines the management of endometriosis in Primary Care, focusing on clinical presentation, risk factors, diagnostic approaches, and therapeutic options. A comprehensive bibliographic search was conducted using PubMed, Scopus, and Uptodate, including evidence-based clinical guidelines and literature up to January 2025. Women diagnosed with endometriosis in Primary Care are typically of reproductive age, with symptoms including dysmenorrhea, dyspareunia, and abnormal uterine bleeding. Risk factors include early menarche, low birth weight, short menstrual cycles, and family history. Transvaginal ultrasound is the recommended first-line imaging tool. Treatment includes analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and hormonal therapies such as combined oral contraceptives or progestins. Non-pharmacological interventions, including dietary modifications and psychological support, are also relevant. Early identification in Primary Care is key to improving out-comes. Enhancing awareness among healthcare providers and promoting multidisciplinary management are essential to optimize care and reduce diagnostic delays. Full article

Gynecologic perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms characterized by the co-expression of melanocytic markers (HMB-45 and Melan-A) and smooth muscle markers (SMA, desmin, and caldesmon). The uterus is the most common organ affected, with approximately 110 cases reported worldwide, while occurrences in the cervix, vagina, ovary, and other gynecologic locations are exceptionally rare. These tumors typically present with nonspecific symptoms such as abnormal uterine bleeding and pelvic pain, often mimicking other uterine neoplasms. Histopathologically, PEComas exhibit epithelioid and spindle cell morphology with variable nuclear atypia, mitotic activity, and characteristic immunohistochemical profiles. Although most PEComas behave benignly, a subset demonstrates malignant potential, associated with larger tumor sizes, an increased mitotic index, necrosis, and vascular invasion; however, standardized diagnostic criteria remain scarce. Molecular alterations frequently involve the mTOR signaling pathway through tuberous sclerosis complex (TSC) 1 and TSC2 gene mutations, offering potential targets for therapy. Surgical resection with clear margins remains the cornerstone of treatment. For advanced or metastatic cases, mTOR inhibitors have shown promising efficacy, whereas the role of radiotherapy remains uncertain. This review aims to synthesize current knowledge regarding the epidemiology, clinical presentation, histologic features, malignant potential, and treatment of uterine PEComas, emphasizing the importance of accurate histopathological classification and molecular profiling to guide individualized therapeutic strategies. Full article

Background/Objectives: Adenomyosis is a benign gynecological disorder associated with abnormal uterine bleeding, dysmenorrhea, and subfertility. Its pathogenesis has not yet been elucidated. The most widely accepted theory points to repeated mechanical or hormonal stress at the endometrial–myometrial interface, leading to activation of the tissue injury and repair (TIAR) mechanism. Studies suggest that the immune system may play a role in disease pathogenesis, but inconsistencies persist due to differences in studied samples and evaluated menstrual cycle phases. The goal of our study was to apply a novel technique (multiplex) to investigate different immune cell phenotypes in uteri from adenomyosis patients according to the cycle phase. Methods: This study analyzed immune cell populations in adenomyotic uteri using immunohistochemistry and multiplex immunofluorescence on 30 adenomyotic and 15 healthy hysterectomy samples. Results: Compared to eutopic endometrium, transitional and adenomyotic lesions displayed reduced immune infiltrates, particularly T cells, NK cells, B cells, macrophages, and dendritic cells. Conversely, mast cells were significantly elevated in transitional lesions. Conclusions: The present study suggests mast cell implication in adenomyosis development and pain, through their implication in tissue remodeling, angiogenesis, and neurogenic inflammation. Transitional lesions highlighted the progressive nature of adenomyosis, supporting the TIAR hypothesis. These findings emphasize the importance of mast cells in disease progression and underscore the need for further studies to explore immune-targeted therapies. Full article

Adenomyosis is a benign gynecologic disease that mainly affects women aged 30–50 years old. Background: This pathology is characterized by glands and stroma of the endometrium that enter the myometrium and is confirmed through histopathological examination after hysterectomy. Transvaginal ultrasound is the most accepted imaging approach for the diagnosis and classification of adenomyosis. Existing medical treatments are not curative and are associated with several side effects. Uterine artery embolization is an alternative treatment for controlling the symptoms of adenomyosis with less trauma while preserving the uterus. Methods: The aim of our study was to observe the utility of uterine artery embolization (UAE) compared to hysterectomy in specific cases of adenomyosis. A retrospective cohort study was carried out between February 2024 and April 2025. We included 52 patients in our study: 27 opted for hysterectomy, while the other 25 chose to receive uterine artery embolization between January 2017 and December 2018. Clinical follow-up was assessed using a questionnaire regarding symptomatic changes in menorrhagia, pelvic pain, and quality of life before and after the surgical procedure. Statistical analyses were performed. Results: Patients opted for hysterectomy in cases of severe abnormal uterine bleeding before surgery that severely affected quality of life (p < 0.03 and p < 0.001). After surgery, pelvic pain improved for women who underwent UAE, but patients also reported no pelvic pain after hysterectomy. Furthermore, mild to moderate abnormal uterine bleeding was reported in cases of UAE, and bleeding stopped completely for women who had their uterus removed (p < 0.001). Quality of life improved for both groups and was reported as being good after the interventions. Conclusions: Embolization remains an alternative therapeutic option in adenomyosis but not a substitute for hysterectomy. This was concluded based on a case-by-case evaluation, depending on the desire for pregnancy, with a focus on improved clinical outcomes. Full article

Menopause is associated with significant hormonal and reproductive changes in women. Evidence documents interindividual differences in the signs and symptoms associated with menopause, including cognitive decline. Hypothesized reasons for the cognitive decline include changes in hormone levels, especially estrogen, but study findings have been inconsistent. Hormone replacement therapies (HRTs) are often recommended to alleviate menopause-related symptoms in both peri- and postmenopausal women. However, the North American Menopause Society does not recommend the use of HRT for the management of cognitive complaints in perimenopausal women due to lack of evidence. Additionally, there are many women for which the use of HRT is contraindicated. As such, it would be helpful to have an alternative method for alleviating symptoms, including declines in cognition, during the menopause transition. Iron supplementation may be a promising candidate as it has been associated with improved cognitive performance in premenopausal women with iron deficiency and iron deficiency anemia. Because many women will experience heavy blood losses during perimenopause, they are at risk of becoming iron deficient and/or anemic. The use of iron supplementation in women with iron deficiency may serve to not only improve iron status but also to alleviate many of the signs and symptoms associated with perimenopause (lethargy, depressed affect, etc.), including cognitive decline. However, evidence to inform treatment protocols is lacking. Well-designed studies of iron supplementation in perimenopausal women are needed in order to understand the potential of such supplementation to alleviate the cognitive decline associated with perimenopause. Full article

Background: In recent decades, there has been a notable rise in the prevalence of caesarean sections, which has been accompanied by a concomitant increase in the incidence of long-term complications, including the occurrence of isthmocele. This anatomical alteration has been associated with symptoms such as abnormal uterine bleeding (AUB), chronic pelvic pain, and secondary infertility. On the other hand, chronic endometritis (CE), characterised by the infiltration of plasma cells into the endometrium, is also associated with infertility and repeated implantation failures. Given the coincidence of symptoms between these two conditions, the question arises as to whether there is an association between isthmocele and CE. Objective: This systematic review and meta-analysis aim to examine the association between isthmocele and CE and to assess its potential clinical implications. Methods: A systematic literature search was conducted in Medline, Embase, and Cochrane CENTRAL up to February 2025. The inclusion criteria were studies involving histopathological findings in isthmocele. The results of the meta-analysis incorporated observational studies and trials to evaluate the prevalence of CE in women with isthmocele, as well as the odds ratios (OR) for CE in isthmocele compared to women without isthmocele, and for CE in isthmocele with AUB compared to women without AUB. Results: A total of seven studies were included in the systematic review, comprising 976 women in the systematic review and 876 women in the meta-analysis. The pooled prevalence of CE in women with an isthmocele was 40% (95% CI: 24–58%). Here, the risk of CE was threefold higher in the presence of an isthmocele as compared to its absence (OR = 3.01; 95% CI: 1.02–9.03). Furthermore, the risk of CE was further increased in women with AUB and isthmocele compared to those without AUB (OR = 6.33, 95% CI: 1.94–20.67). Conclusions: CE and isthmocele are both under-diagnosed and poorly understood conditions. The high prevalence of CE in isthmocele indicates a substantial clinical burden. Specifically, women with AUB and isthmocele exhibit a six-fold higher risk of developing CE. These results underscore the importance of recognising isthmocele as a significant risk factor for CE, particularly in women presenting with isthmocele-associated AUB. Further research is warranted to elucidate the underlying mechanisms and to develop targeted interventions for the prevention and management of CE in this population. Full article