Search Results (42)

Background: Women with abnormal uterine bleeding (AUB) is reported in 10–30% of women and is a significant cause of iron deficiency anemia (IDA), with long-term effects on women’s quality of life. This retrospective study looked at the underlying causes of AUB and the contributory factors that required blood transfusions. Objectives: This study aimed to identify the treatable causes of AUB in patients who needed blood transfusion and parenteral iron in the reproductive age group and provide appropriate treatment to these underlying pathologies. Methods: A retrospective study was conducted in reproductive age group women with anemia due to AUB over a period of 10 years from January 2013 to December 2022. All women with significant uterine bleeding, who required blood transfusion were included in this study. Women with pregnancy, and hemolytic anemia, were excluded from the study. Results: During the study period 266 women needed blood transfusion for AUB. The mean age was 37.66 ± 11.4 years, mean parity 3, mean body mass index (BMI): 29.4 ± 8.9 kg/m², and most reported regular cycles. The most common etiology of AUB was uterine fibroids in 37.9% followed by ovulatory dysfunction in 15%. The mean hemoglobin was at 5.7 ± 1.14 gm/L, mean ferritin was 11.01 ± 21.88 ng/mL, mean number of blood transfusion was 2.83 ± 1.2 at first presentation and about 24% needed further transfusions. About 70% of them preferred oral hormonal treatment. Surgical management was required in about 35% of patients. Conclusion: The main cause of AUB was leiomyoma and anovulation. The morbidity of blood transfusion was easily avoidable in these women. Full article

Background/Objectives: Vilaprisan and ulipristal acetate (UPA) have demonstrated efficacy in treating uterine fibroids (UFs). However, a direct comparison of vilaprisan and UPA has been restricted, to date, to a small phase 2 study. Here, we compare the efficacy of vilaprisan and UPA in reducing heavy menstrual bleeding and inducing amenorrhea in women with symptomatic UFs. Methods: ASTEROID 5 (NCT03240523) was planned as a randomized, active-controlled, multicenter phase 3 study comparing three vilaprisan 2 mg/day regimens against the approved regimen of UPA 5 mg/day for the treatment of symptomatic UFs. Participants were initially randomized 1:1:1:1 to one of four treatment arms: VPR-3/1 (vilaprisan for a 3-month treatment period [TP] followed by one menstrual bleeding episode); VPR-6/2 (vilaprisan for a 6-month TP followed by two menstrual bleeding episodes); VPR-3/2 (vilaprisan plus matching UPA placebo for a 3-month TP followed by two menstrual bleeding episodes); and UPA-3/2 (UPA plus matching vilaprisan placebo for a 3-month TP followed by two menstrual bleeding episodes). Results: Treatment was received as planned by 271 (95.4%), 266 (94.0%), 90 (90.0%) and 89 (89.9%) women in the VPR-3/1, VPR-6/2, VPR-3/2, and UPA-3/2 groups, respectively; 109 women in the VPR-3/1 (n = 44, 15.5%) and VPR-6/2 (n = 65, 23.0%) groups and none in the VPR-3/2 and UPA-3/2 groups completed treatment. Vilaprisan (total VPR group) demonstrated non-inferiority but not superiority versus UPA in inducing amenorrhea (82.9% [520/627] vs. 74.2% [66/89]; difference: 8.8% [95% confidence interval: −0.78, 18.34]; p = 0.0553), whereas vilaprisan (VPR-3/1 arm) showed superiority versus UPA in reducing total menstrual blood loss (least squares mean total MBL: 44.2 mL vs. 80.3 mL; difference: −36.1 mL; p = 0.0010). Conclusions: Vilaprisan (VPR-3/1 regimen) was superior to UPA in reducing total MBL, and it was non-inferior (total VPR group) to UPA in inducing amenorrhea. Full article

Background: This study was conducted to assess whether medical treatment with dienogest (DNG) is effective in women with symptomatic adenomyosis. Methods: This single-center, retrospective study included patients with symptomatic adenomyosis treated with oral DNG 2 mg daily. We evaluated the clinical symptoms, uterine volume, and serum CA-125 levels in these patients along with adverse events at baseline and after 3, 6, 12, 18, and 24 months of treatment, respectively. Results: A total of 102 patients were analyzed. Among women with dysmenorrhea, 79.5% reported improvement in dysmenorrhea, and the mean time to improvement in dysmenorrhea was 7.18 months. Improvement in heavy menstrual bleeding was observed in 88.3% of patients, with a mean time to improvement in heavy menstrual bleeding of 5.44 months. We could see that the uterine volume decreased significantly after 18 months of treatment. Serum CA-125 levels declined significantly from 3 months onward and remained reduced through 24 months. More than half of the patients (55.8%) continued DNG without complications, whereas 31.3% discontinued treatment or switched to alternative therapies. Conclusions: DNG effectively improved clinical symptoms and reduced uterine volume and serum CA-125 levels without serious adverse events in patients with symptomatic adenomyosis. Full article

Background and Objectives: Adenomyosis is increasingly being recognized as a heterogeneous uterine disorder with variable clinical expressions. Current ultrasound-based classifications do not consistently align structural severity with symptom burden. Given its role in angiogenesis, inflammation, and endometrial remodeling, vascular endothelial growth factor (VEGF) signaling may influence both morphological features and clinical manifestations. This study evaluated the association between three VEGF polymorphisms (−2578C/A, −634G/C, −936C/T) and adenomyosis presence, ultrasound-based severity, and symptoms in infertile women undergoing in vitro fertilization (IVF). Materials and Methods: In this prospective cohort study, 85 infertile women were assessed for adenomyosis using MUSA criteria and Exacoustos grading. VEGF genotyping was performed by PCR-RFLP. Clinical data included menstrual bleeding status scores and dysmenorrhea intensity. Results: Under a dominant model, the variant genotypes (AA+CA) of the VEGF–2578C/A polymorphism −2578 A showed increased odds of adenomyosis versus CC (adjusted OR = 4.00, 95% CI: 1.48–10.84; p = 0.0037). The A allele frequency was higher in women with adenomyosis (57.14% vs. 33%), which was consistent with increased susceptibility (OR = 2.71, 95% CI: 1.44–5.09; p = 0.003). The AA + CA genotypes were more frequent with higher ultrasound-based severity (p = 0.0029; 50% vs. 72% vs. 100% across increasing severity strata); however, among women with adenomyosis, AA + CA carriers had lower odds of clinically relevant dysmenorrhea (adjusted OR = 0.18, 95% CI: 0.06–0.55; p = 0.0017), which remained significant after correction for multiple testing (adjusted p = 0.0051). No significant associations were identified for −936C/T or −634G/C across adenomyosis presence, ultrasound-based severity, number of sonographic features, dysmenorrhea, or heavy menstrual bleeding (all p > 0.05). Conclusions: These preliminary findings suggest divergent associations of VEGF −2578C/A with structural severity versus symptom expression, supporting a partial dissociation between ultrasound-defined severity and clinical phenotype in adenomyosis. Full article

Background: Transvaginal radiofrequency ablation (TRFA) is a minimally invasive, uterus-preserving technique for symptomatic uterine fibroids. This study evaluates its two-year clinical and volumetric outcomes, safety profile, patient satisfaction, and reintervention rates. Methods: In this single-center, retrospective, single-arm observational cohort study, 121 premenopausal women underwent outpatient TRFA under general anesthesia between 2018 and 2023. Follow-up visits at 1, 6, 12, and 24 months assessed fibroid volume reduction, symptom improvement using the Uterine Fibroid Symptom and Quality of Life Questionnaire (UFS-QoL), vascularity, satisfaction, complications, and the need for reintervention. A total of 169 fibroids were treated. Results: TRFA resulted in progressive fibroid shrinkage, with a mean volume reduction of 57.97% at 6 months and 60.75% at 24 months, accompanied by sustained improvement in UFS-QoL scores (from 30.19 at baseline to 14.97 at 24 months). Patient satisfaction was high (96.61%). Complications were infrequent and predominantly mild, and recovery was rapid, with short postoperative analgesia (mean 2.87 days) and limited sick leave (mean 3.34 days). The two-year reintervention rate was 24.79%, with a substantial proportion corresponding hysteroscopic procedures planned a priori as part of a sequential therapeutic strategy. Among 22 pregnancies recorded after TRFA, 81.82% resulted in term deliveries with favorable neonatal outcomes although fertility was not a predefined study endpoint. Conclusions: TRFA appears to be a safe, effective, and well-tolerated minimally invasive treatment for symptomatic uterine fibroids, offering durable symptom relief and significant volume reduction and rapid recovery, and encouraging reproductive outcomes. Within the limitations of its single-arm observational design, these results support TRFA as a valuable uterus-preserving therapeutic option. Full article

Physiological hypoxia is a defining feature of early pregnancy, coordinating menstrual repair, implantation, decidualization, placental development, and fetoplacental adaptation. Hypoxia-inducible factors, HIF-1α and HIF-2α, act as master regulators of these processes by sensing oxygen tension and orchestrating cellular responses in metabolism, angiogenesis, immune regulation, and tissue remodeling. Although structurally related, HIF-1α and HIF-2α exhibit distinct spatial and temporal functions across reproductive stages. Embryonic HIF-1α is primarily involved in early embryonic development, whereas embryonic HIF-2α is required for later developmental stages. Furthermore, maternal HIF-1α acts early in pregnancy, coordinating metabolic adaptation, endometrial regeneration, decidualization, angiogenic expansion, placental organization, and maternal immune tolerance. In contrast, maternal HIF-2α regulates epithelial breakdown, trophoblast invasion, implantation mechanics, and vesicle-mediated trafficking. Mouse genetics demonstrate that disruption of either isoform leads to non-redundant defects in reproductive success, from failed implantation to placental insufficiency and fetal lethality. Pathological hypoxia or aberrant HIF signaling drives pregnancy disorders including preeclampsia, fetal growth restriction, recurrent pregnancy loss, and heavy menstrual bleeding. Defining the distinct roles of HIF-1α and HIF-2α supports the development of therapies targeting hypoxia-responsive pathways in infertility and obstetric disease. Full article

Background: Ectopic pregnancy (EP) is a potentially life-threatening condition, often associated with acute abdominal pain and hemoperitoneum. Certain conditions, such as adenomyosis and the use of long-acting reversible contraceptives (LARC), may represent risk factors for the development of ectopic pregnancy. Management is tailored according to hemodynamic stability, reproductive desires, and associated comorbidities. Case Presentation: We report the case of a 39-year-old Caucasian woman with a history of adenomyosis and heavy menstrual bleeding (HMB) treated with a levonorgestrel-releasing intrauterine system (LNG-IUS). She presented to the emergency department with acute abdominal pain, vaginal bleeding, and a rising serum β-human Chorionic Gonadotrophin (β-hCG > 4000 mIU/mL). Transvaginal ultrasound revealed an adnexal mass (24 mm × 19 mm) consistent with a right tubal ectopic pregnancy, associated with hemoperitoneum. The patient, who expressed a desire for definitive sterilization, underwent laparoscopic bilateral salpingectomy. The procedure was uneventful with minimal intraoperative blood loss. Histopathological examination confirmed the diagnosis of right tubal ectopic pregnancy. Literature Review: A case report prompted a focused search of MEDLINE and Scopus (2015–2025) on ectopic pregnancy in users of levonorgestrel-releasing intrauterine systems. Eight eligible case-report studies assessing ectopic pregnancy type and device positioning were ultimately included. Conclusions: This case highlights the importance of early diagnosis of ectopic pregnancy, paying attention to any comorbidities, particularly adenomyosis, the role of minimally invasive surgery, and the possibility of adapting surgical management to the patient’s reproductive wishes. Full article

Background/Objectives: Adenomyosis is characterized by aberrant endometrial invasion and heavy menstrual bleeding, with angiogenesis being implicated as a key mechanism of this condition. We compared vascular endothelial growth factor (VEGF), angiopoietin-1 (ANGPT-1), and angiopoietin-2 (ANGPT-2) expression in eutopic and ectopic endometria from patients with adenomyosis and evaluated whether the levonorgestrel intrauterine system (LNG-IUS) modulates these angiogenic markers. Methods: In a case–control analysis, specimens from patients with adenomyosis without an LNG-IUS (n = 20), those with adenomyosis with prior LNG-IUS insertion (n = 18), and controls (n = 12) were analyzed. Immunohistochemistry with H-scores was used to assess protein expression in eutopic and ectopic tissues. ANGPT1, ANGPT2, and VEGFA mRNA in eutopic endometrial tissue were quantified by qRT-PCR. Results: In untreated adenomyosis patients, ectopic endometria showed higher protein expression than eutopic tissue for ANGPT-1, ANGPT-2, and VEGF (all p ≤ 0.05). The LNG-IUS was associated with significantly lower expression of all three markers in both eutopic and ectopic tissue (all p < 0.01), with eutopic levels approaching those of controls. qRT-PCR findings corroborated the decrease in ANGPT1, ANGPT2, and VEGFA transcript levels after LNG-IUS insertion (all p < 0.05). Conclusions: Adenomyosis is characterized by upregulated angiogenic signaling in both eutopic and ectopic endometria. The LNG-IUS attenuates ANGPT-1, ANGPT-2, and VEGF expression at both the protein and transcript levels, suggesting that modulation of angiogenic pathways may contribute to its therapeutic benefit in abnormal uterine bleeding associated with adenomyosis. Full article

Background: Adenomyosis is a benign uterine disorder defined by the invagination of ectopic endometrial-like tissue into the myometrium, causing heavy menstrual bleeding and pain. While its pathogenesis remains unclear, shared-symptomology with endometriosis suggests a common mechanism. Adenomyosis is often diagnosed after age 40 due to its complex presentation and the need for histopathological confirmation, underscoring the need for non-invasive markers. Methods: Ten unrelated women with histopathological diagnosis of adenomyosis were recruited. All recruits completed the WERF-EPHect questionnaire and were additionally questioned about any comorbidities. Genomic DNA isolated from peripheral blood was subjected to whole exome sequencing (WES) on Illumina NovaSeq 6000 and was analyzed using the Pairend NGS Cloud platform. Variants were filtered for MAF < 1% and were prioritized based on functional relevance and impact determined by in silico prediction tools. Variant selection adhered to stringent quality metrics to identify candidate variants associated with adenomyosis. Results: WES analysis did not reveal any variant common to the cohort. A total of eight pathogenic and two likely pathogenic novel variants were identified. Moreover, novel variants of p.(Val331Ile) in EFHB and p.(Phe14Val) in MEIS1 were the most frequently shared genetic variants in the cohort. Conclusions: Our findings suggest novel candidate genes for adenomyosis that warrant validation and functional investigation in larger, independent cohorts. Full article

Objectives: To evaluate the impact of hormonal therapy on the evolution of painful symptoms in premenopausal women with adenomyosis, with or without concomitant endometriosis, over an 18-month follow-up period. This study aimed to compare the symptomatic progression between treated and untreated patients, highlighting the potential role of medical therapy in symptom control and disease stabilization. Secondary, an objective was to explore sonographic changes within our study population, in parallel with clinical outcomes. Methods: This retrospective observational study, conducted at the Endometriosis Referral Center of the University Hospital of Siena, included 40 women with ultrasound evidence of adenomyosis with and without endometriosis. The population was divided into two groups: 20 patients receiving hormone treatment and 20 not receiving hormone treatment. All patients underwent clinical and ultrasound examinations throughout an 18-month follow-up period, during which types, locations, degrees of disease, and associated symptoms were evaluated. Results: Forty patients enrolled in the study presenting with symptoms such as dysmenorrhea, dyspareunia, and heavy menstrual bleeding were included. A total of 22 patients showed isolated adenomyosis, while 18 adenomyosis and endometriosis both. The mean age was 38.5 years (±4.2 SD), with 57.5% being nulliparous. The types of adenomyosis detected were focal in 25%, diffuse in 50%, and mixed (both focal and diffuse) in 25%. Disease severity was classified as mild in 15%, moderate in 45%, and severe in 40%. After 18 months of continuous hormonal therapy, a reduction in focal adenomyosis was observed in 10%, and an improvement of dysmenorrhea and Heavy Menstrual Bleeding (HMB) was noted, while a slight ameliorating of dyspareunia was detected. In contrast, untreated patients showed either unchanged or worsened symptoms. Conclusions: The findings underscore the value of medical therapy in the management of adenomyosis, supporting current recommendations. Given the heterogeneity of clinical presentations and frequent overlap with endometriosis, a personalized treatment approach remains essential. Further larger-scale, long-term studies are needed to confirm these preliminary results and explore the potential impact on fertility preservation. Full article

Nutritional factors play a crucial role in many gynecological disorders, particularly those influenced by estrogen. Uterine fibroids are benign tumors that affect a large proportion of women of reproductive age, especially between 30 and 40 years. These lesions may cause significant symptoms, including pelvic pain, heavy menstrual bleeding, and infertility. In younger women, the onset of fibroids is often associated with familial and genetic predisposition, whereas in adulthood, hormonal influences linked to environmental factors and states of exogenous or endogenous hyperestrogenism are more frequently observed. In both contexts, supportive management through an appropriate diet may provide clinical benefit. Although the precise pathogenesis remains incompletely understood, hormonal, genetic, and environmental components—particularly hyperestrogenism—are considered key contributors to fibroid development. Current evidence suggests that consumption of saturated fats, particularly from red meat and full-fat dairy, may raise circulating estrogen concentrations and contribute to the development of fibroids. In contrast, diets abundant in fiber, fruits, and vegetables appear to exert a protective effect, potentially lowering fibroid risk. Obesity, through increased aromatization and consequent estrogen production, also represents an established risk factor. This narrative review aims to explore the role of nutritional determinants in the onset and progression of uterine fibroids, with a specific focus on the impact of individual nutrients, foods, and dietary patterns on clinical outcomes. Particular emphasis is placed on obesity and macronutrient composition (e.g., high-fat versus high-fiber dietary regimens) as potential modulators of circulating estrogen levels and, consequently, fibroid growth dynamics. Furthermore, the potential of nutritional strategies as complementary therapeutic approaches, capable of integrating established clinical practices, is examined. Full article

Endometriosis is a complex and multifaceted gynecological disorder characterized by the abnormal growth and presence of endometrial-like tissue outside the confines of the uterine cavity. It can lead to a wide range of distressing symptoms, including chronic pelvic pain, heavy and/or irregular menstrual bleeding, and significant challenges with fertility. While the association between endometriosis and infertility is well recognized, the precise mechanisms through which the disease affects oocyte and embryo quality remain controversial. Studies that utilized transcriptomic, metabolomic, and ultrastructural analyses indicated dysregulated energy metabolism, oxidative stress, mitochondrial dysfunction, and inflammatory alterations in the ovarian microenvironment. The impact of endometriosis on fertilization, embryo development, and implantation remains debated, with conflicting findings across different study designs. Some investigations reported impaired oocyte morphology, reduced fertilization rates, and poorer embryo quality, while others suggested that endometriosis does not significantly affect ART outcomes when confounding factors are controlled. Recent studies highlight the importance of distinguishing the disease severity, lesion location, and prior surgical interventions when assessing reproductive outcomes. The need for standardized methodologies in evaluating oocyte and embryo quality, alongside personalized treatment approaches, is emphasized. Further research is warranted to elucidate the precise molecular mechanisms underlying these effects and to develop targeted therapeutic strategies aimed at improving ART success in women with endometriosis. This narrative review provides a thorough examination of the previous research on the impact of endometriosis on oocyte and embryo quality, highlighting both the known mechanisms and the areas that require further investigation. This will help to guide future research and clinical management strategies to improve reproductive outcomes for women with endometriosis. Full article

Background and Clinical Significance: Paratubal Leydig cell nodules are rare incidental findings that present diagnostic challenges. Case Presentation: A 45-year-old female with a history of hypertension and diabetes mellitus presented with fever and chills following an episode of severe dysmenorrhea and menorrhagia. The patient reported heavy menstrual bleeding, persisting for 2–3 years. Physical examination revealed erythema of the perineum and whitish vaginal discharge, with no cervical lesions. Imaging revealed a 15 cm right ovarian cyst. Laboratory investigations showed elevated C-reactive protein (6.37 mg/L) and CA125 (88.82 U/mL) levels, whereas other tumor markers were within normal limits. A pelvic ultrasound revealed a retroverted uterus and a large ovarian mass suggestive of malignancy. The patient underwent a right salpingo-oophorectomy, during which a 15 cm ovarian tumor adherent to the right pelvic sidewall was excised. Histopathological examination revealed an endometriotic cyst with endometrial glandular epithelium positive for estrogen receptor and focal mucinous metaplasia. CD10-positive endometrial stromal cells and paratubal cysts were also observed. Additionally, a small Leydig cell tumor originated from the ovarian hilum was identified and confirmed by positive staining for inhibin, calretinin, and androgen receptors, as well as negative estrogen receptor staining. The postoperative recovery was uneventful, and at the five-week follow-up, the patient’s hormonal levels were normal, and there were no complications. Conclusions: This case highlights the importance of thorough histopathological evaluation in managing ovarian masses and the potential coexistence of benign and rare pathological entities, such as Leydig cell tumors. Full article

Background/Objectives: Iron deficiency has been suggested as a potential mechanism for attention-deficit hyperactivity disorder (ADHD) development due to involvement in neurotransmitter synthesis and transporter expression. As iron deficiency is particularly common in women of reproductive age, often due to heavy menstrual bleeding (HMB), we aimed to explore the relationship between iron deficiency, HMB and ADHD in women. Methods: We screened women (18–49 years) at university and local sporting events in Western Australia. To screen for ADHD, section A of the Adult ADHD Self-Report Scale-V1.1 (ASRS-V1.1) and the Adult Concentration Inventory were used to assess cognitive disengagement syndrome (CDS) symptoms. Risk factors for iron deficiency, such as HMB, commonly reported symptoms and a fingerpick haemoglobin concentration (Hb) (Hemocue Hb801) were recorded. Results: Of the 405 completed questionnaires, the mean age was 24.8 ± 10.1 years, the mean Hb was 136.8 ± 12.4 g/L and 6.4% of women were anaemic. Symptoms suggestive of ADHD were reported by 174/405 (43%) women, and 128/405 (32%) women reported HMB. There was a greater prevalence of HMB reported in those experiencing symptoms suggestive of ADHD (39% vs. 26%, p = 0.01). Symptoms of fatigue, dizziness, brain fog, anxiety, heart palpitations, headaches, restless legs and depression were more common in patients with symptoms suggestive of ADHD (p ≤ 0.01) and HMB (p < 0.05). Anaemia status did not influence ADHD status (p = 0.87) nor CDS scores (15.7 ± 7.0 vs. 13.8 ± 6.1, p = 0.17). Conclusions: There is an apparent relationship between those with symptoms reported in ADHD, HMB and iron deficiency. Further exploration is required to determine whether there is a causative relationship. Full article

Background and Objectives: The International Federation of Gynecology and Obstetrics (FIGO) and the American College of Obstetricians and Gynecologists (ACOG) define abnormal uterine bleeding (AUB) as “bleeding from the uterus that is abnormal in regularity, volume, frequency, or duration and occurs in the absence of pregnancy”. The impact of AUB on the physical and psychosocial well-being of adolescent girls can be significant. In this study, we aim to investigate the menstrual cycle characteristics in adolescent Sudanese schoolgirls and the prevalence of abnormal uterine bleeding (AUB) and its associated factors. Materials and Methods: A school-based cross-sectional study was conducted in Almatamah locality, Sudan. A questionnaire was used to collect sociodemographic data and menstrual cycle parameters. Weight and height were measured, body mass index (BMI) was calculated, and hemoglobin levels were determined. Logistic regression was also performed. Results: Of the 162 girls in the study, 27.2% had frequent cycles, 3.7% had infrequent cycles, 2.5% had prolonged menses duration, 44.4% had irregular cycles, and 21.0% had heavy menstrual bleeding. The overall prevalence of AUB in the study was 64.8%. None of the investigated factors (chronological age, maternal education or occupation, gynecological age, BMI, and hemoglobin level) were associated with AUB. Conclusions: In conclusion, the prevalence of AUB was high among the study participants, with irregular cycles, frequent cycles, and heavy menstrual bleeding being the most common types. Full article