Unmet needs in abnormal uterine bleeding due to ovulatory dysfunction.

Ovulatory disorders are a common cause of abnormal uterine bleeding in women of reproductive age. The International Federation of Gynecology and Obstetrics currently offers a causal classification system for ovulatory disorders but does not provide clear management recommendations. There remains regional disparity in treatment practices, often influenced by institutional and insurance regulations as well as cultural and religious practices. A panel of experts evaluated current gaps in ovulatory disorder management guidelines and discussed potential strategies for addressing these unmet needs. Key gaps included a lack in consensus about the effectiveness of combined estrogen and progestogen versus progestogen alone, a paucity of evidence regarding the relative effectiveness of distinct hormonal molecules, a lack of data regarding optimal treatment duration, and limited guidance on optimal sequencing of treatment. Recommendations included development of a sequential treatment-line approach and development of a clinical guide addressing treatment scenarios common to all countries, which can then be adapted to local practices. It was also agreed that current guidelines do not address the unique clinical challenges of certain patient groups. The panel discussed how the complexity and variety of patient groups made the development of one single disease management algorithm unlikely; however, a simplified, decision-point hierarchy could potentially help direct therapeutic choices. Overall, the panel highlighted that greater advocacy for a tailored approach to the treatment of ovulatory disorders, including wider consideration of non-estrogen therapies, could help to improve care for people living with abnormal uterine bleeding due to ovarian dysfunction.

Extranodal diffuse large B-cell lymphoma involving the uterine cervix.

This is a case of primary diffuse large B-cell lymphoma involving the uterine cervix which presented with irregular vaginal bleeding. The diagnosis was confirmed following multiple cervical biopsies. Treatment with a combination of immunotherapy, chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP)) and radiotherapy produced a good response.

Endometrial Thickness as a Predictor of Endometrial Malignancy among the Women Presenting with Abnormal Uterine Bleeding.

Abnormal uterine bleeding (AUB) is the most common and frequent presenting complaint in Gynaecology in all age group especially in perimenopausal and postmenopausal women. The spectrum of AUB in women of our country includes a wide varieties of organic pathology. The objective of this study was to assess the role of endometrial thickness as a predictor of endometrial malignancy among the women presenting with AUB. This cross-sectional descriptive type of observational study was conducted among 122 women of perimenopausal (40-50 years) and 87 women of postmenopausal (>50 years) age group presenting with AUB in the Obstetrics and Gynaecology department of Mymensingh Medical College Hospital, Bangladesh from February 2020 to August 2021. These patients were subjected to a detailed history and meticulous general, systemic and local examination. The relevant investigations like Transvaginal Sonography (TVS) followed by endometrial biopsy by dilatation and curettage were done in all study participants. Most of the women were in the age group 41-45 years in perimenopause and 51-55 years in postmenopause. Mean±SD was 45.8±4.1 years in perimenopause and 56.3±6.4 years in postmenopause. There was statistical significance in developing endometrial malignancy regarding risk factors of nulliparity, Hypertention (HTN), Diabetes mellitus (DM) and hormone intake between perimenopause and postmenopause. Endometrial thickness was measured in perimenopause and postmenopause. Mean±SD of Endometrial thickness (ET) in perimenopause and postmenopause was 11.3±4.4mm and 7.2±6.3mm with statistical significance (p<0.001). Sensitivity, specificity, Positive predictive value (PPV), Negative predictive value (NPV) and accuracy of TVS were 85.5%, 67.4%, 81.2%, 73.8% and 78.7% in perimenopause and 85.9%, 20%, 89%, 75% & 83.9% in postmenopause. Cut off limit of ET in detection of endometrial malignancy was 18.5mm with sensitivity 74.8% and specificity 63.6% in perimenopause and 12.2mm with sensitivity 81.0% and specificity 65.8% in postmenopausal women. Women with AUB, endometrial malignancy should be suspected when endometrial thickness on TVS >18.5mm and >12.2mm in perimenopause and postmenopausal age group respectively. TVS has high sensitivity in detection of endometrial malignancy both in perimenopausal and postmenopausal women with AUB and TVS is a reliable, noninvasive method.

Adenomyosis and Abnormal Uterine Bleeding: Review of the Evidence.

BACKGROUND: Thomas Cullen described bleeding abnormalities and dysmenorrhea as the "expected" presentations of adenomyomas. Adenomyosis is included within the FIGO classification of structural causes of abnormal uterine bleeding (AUB). Nevertheless, this long-standing association has been questioned by some authors who reported a high incidence of adenomyosis in uteri removed for indications other than AUB or dysmenorrhea. Here, we examine evidence for the link between adenomyosis and AUB. METHODS: A comprehensive Medline literature review of all publications to October 2023. RESULTS: Sixty-three articles were identified and included in the review. Despite a large body of studies, the available literature does not provide conclusive evidence of a link between adenomyosis and AUB. This is because of unsuitable study design, or poor characterization of the study population or of the inclusion or exclusion criteria. Additional challenges arise because of the lack of agreed criteria for diagnosing adenomyosis and the often absence of detailed assessment of menstrual blood loss. Adenomyosis often coexists with other conditions that have also been linked to similar symptoms, and many cases of adenomyosis are asymptomatic. CONCLUSION: Most of the existing literature and studies that addressed treatment outcome of adenomyosis started from the premise that a link between the condition and AUB had been proven. Yet, published information shows that aspects such a relationship is still uncertain. Further research is needed to address the relation between AUB and adenomyosis burden (or subtypes), distribution, and concomitant pathology.

A 42-year-old woman with abnormal uterine bleeding-leiomyoma (AUB-L) reporting a hemoglobin of 1.6 g/dL: a case report.

BACKGROUND: Abnormal uterine bleeding, formerly known as menometrorrhagia, is estimated to occur in up to one-third of women, commonly at menarche or perimenopause. Among many other causes, abnormal uterine bleeding is known to be caused by leiomyomas, and is itself a leading cause of severe iron deficiency and iron deficiency anemia in women. Rarely, abnormal uterine bleeding can lead to critically low hemoglobin values of less than 2 g/dL. We report here a case of a woman with abnormal uterine bleeding caused by leiomyomas presenting with severely low hemoglobin. CASE PRESENTATION: We report the case of a 42-year-old Asian American woman who presented to the emergency department with chronic abnormal uterine bleeding and symptoms of anemia, including multiple syncopal episodes and abnormally pale skin but otherwise alert and oriented. Laboratory tests found a record-low hemoglobin of 1.6 g/dL and hematocrit of 6%. Transabdominal pelvic ultrasound revealed a lower uterine segment/cervical fibroid measuring 7.5 × 5 × 7.8 cm (length × depth × width). Patient was diagnosed with abnormal uterine bleeding-leiomyoma and received five units of packed red blood cells, one unit of fresh frozen plasma, Venofer infusions, tranexamic acid, and medroxyprogesterone. She was discharged from the hospital after 4 days. CONCLUSION: To date, only a handful of cases have been reported of female patient survival following severely low hemoglobin caused by abnormal uterine bleeding. This case adds to this literature, highlighting the remarkable degree of compensation that can lead to an alert, ambulatory, and oriented patient with abnormal uterine bleeding caused by leiomyoma.

Alternative treatments of adenomyosis - an update in procedural management and clinical outcomes.

PURPOSE OF REVIEW: Adenomyosis is a common cause of abnormal uterine bleeding (AUB), dysmenorrhea, and pelvic pain. Definitive diagnosis and treatment have historically been by uterine histopathology at time of hysterectomy; however, advances in imaging have supported earlier diagnosis and subsequent conservative treatment. This review aims to update the evidence supporting the uterine-sparing, procedural management options with a focus on clinical outcomes. RECENT FINDINGS: Uterine artery embolization (UAE), radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), percutaneous microwave ablation (PMWA), and adenomyomectomy are minimally invasive interventions proven to be effective in reducing AUB and dysmenorrhea due to adenomyosis. Symptom improvement is associated with a decrease in uterine volume. Studies support the use of alternative treatment options given the overall low rates of symptom recurrence and reintervention. Combination therapy may be more effective than monotherapy. SUMMARY: This review provides the current evidence for use of alternative treatment options for adenomyosis. Access to ablative therapies in the USA is limited and primarily off label, given lack of FDA approval. High-quality prospective and randomized controlled trials are needed in order to further delineate treatment comparisons, efficacy, safety, and ideal patient selection for these treatments. More data are needed to assess safety and utility in those desiring future fertility.

The modern management of uterine fibroids-related abnormal uterine bleeding.

Uterine fibroids (UFs) are the most common female benign pelvic tumors, affecting >60% of patients aged 30-44 years. Uterine fibroids are asymptomatic in a large percentage of cases and may be identified incidentally using a transvaginal ultrasound or a magnetic resonance imaging scan. However, in approximately 30% of cases, UFs affect the quality of life and women's health, with abnormal uterine bleeding and heavy menstrual bleeding being the most common complaints, along with iron deficiency (ID) and ID anemia. Medical treatments used for UFs-related abnormal uterine bleeding include symptomatic agents, such as nonsteroidal antiinflammatory drugs and tranexamic acid, and hormonal therapies, including combined oral contraceptives, gonadotropin-releasing hormone agonists or antagonists, levonorgestrel intrauterine systems, selective progesterone receptor modulators, and aromatase inhibitors. Nevertheless, few drugs are approved specifically for UF treatment, and most of them manage the symptoms. Surgical options include fertility-sparing treatments, such as myomectomy, or nonconservative options, such as hysterectomy, especially in perimenopausal women who are not responding to any treatment. Radiologic interventions are also available: uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound, and radiofrequency ablation. Furthermore, the management of ID and ID anemia, as a consequence of acute and chronic bleeding, should be taken into account with the use of iron replacement therapy both during medical treatment and before and after a surgical procedure. In the case of symptomatic UFs, the location, size, multiple UFs, or coexistent adenomyosis should guide the choice with a shared decision-making process, considering long- and short-term treatment goals expected by the patient, including pregnancy desire or wish to preserve the uterus independently of reproductive goals.

Solving the mysteries surrounding uterine fibroids: are we almost there?

A better understanding of uterine fibroid-related pathogenesis and symptoms like uterine bleeding and infertility is mandatory.

Is Neonatal Uterine Bleeding Involved in Early-Onset Endometriosis?

BACKGROUND: There has been considerable progress in our understanding of endometriosis, but its pathophysiology remains uncertain. Uncovering the underlying mechanism of the rare instances of endometriosis reported in early postmenarcheal years and in girls before menarche can have wide implications. METHODS: We conducted a literature review of all relevant articles on Medline. RESULTS: In the review, we explore the pathogenetic theories of premenarcheal endometriosis, the role of retrograde menstruation in the adult and its potential role in early-onset disease, as well as the factors that argue against the existence of a link between early-onset endometriosis (EOE) and neonatal uterine bleeding (NUB). CONCLUSIONS: As with endometriosis in adult women, the pathogenesis of early-onset disease remains unclear. A link between NUB and EOE is plausible, but there are considerable challenges to collating supporting evidence. The state of our understanding of early uterine development and of the pathophysiology of NUB leaves many unknowns that need exploration. These include proof of the existence of viable endometrial cells or endometrial mesenchymal stem cells in NUB, their passage to the pelvic cavity, their possible response to steroids, and whether they can reside within the pelvic cavity and remain dormant till menarche.

Recurrent postmenopausal bleeding: Pathological findings and predictive factors. A multicenter, prospective, observational study.

INTRODUCTION: Recurrent postmenopausal bleeding (PMB) occurs in 6%-25% of postmenopausal women who have experienced a previous episode of PMB. The question of whether recurrent PMB leads to a higher risk of endometrial cancer (EC) in comparison to a single episode of PMB is, however, controversial. Furthermore, little is known about predictive factors for recurrent PMB. MATERIAL AND METHODS: A multicenter prospective cohort study was conducted over a 5-year period in four hospitals in the Netherlands. Women with PMB undergoing endometrial sampling and aged 40 years and older were included. Occurrence of recurrent PMB was retrospectively determined. Primary outcomes included (1) the incidence of recurrent PMB and (2) differences in pathological findings between patients with a single episode vs recurrent PMB. Secondary outcomes included (1) the association between diagnosis of benign polyps at first PMB and pathological findings at recurrent PMB and (2) factors predictive for recurrent PMB. RESULTS: A total of 437 women with PMB were included, of whom 360 were at risk of recurrent PMB. With a median follow-up of 61 months (IQR (Interquartile range) 44-73), 26.4% experienced recurrent PMB. Patients with recurrent PMB were more often diagnosed with benign polyps (34.7% vs. 25.1%, p-value 0.015) and less frequently with a malignancy (5.3% vs. 17.8%, p-value 0.015), compared to patients with a single episode of PMB. Benign polyps at initial PMB were not associated with a (pre)malignancy at recurrence (OR 4.16, 95% CI 0.75-23.03). Predictive factors for recurrent PMB included use of hormone replacement therapy (HRT) (OR 3.32, 95% CI 1.64-6.72), and benign polyps at initial PMB (OR 1.80, 95% CI 1.07-3.04). CONCLUSIONS: Recurrent PMB is common in women with a previous episode of PMB. Compared to patients with a single episode of PMB, patients with recurrent PMB and benign histological outcomes at accurate workup during their first episode were less often diagnosed with malignancies and more frequently with benign polyps. Benign polyps at first PMB are predictive for recurrent PMB, but not for a higher risk of (pre)malignancy.

Contributing factors related to abnormal uterine bleeding in perimenopausal women: a case-control study.

Abnormal uterine bleeding (AUB) during the menopausal transition results in reproductive endocrine disorders and both physiological and pathological changes, substantially impacting women's health. This study aimed to investigate the factors influencing AUB in perimenopausal women. Between April 2021 and June 2022, 120 perimenopausal women with AUB in the menopausal transition, diagnosed and treated at the Gynaecology Department of Kunming Tongren Hospital, were included in the case group. Concurrently, women undergoing routine health examinations at the same hospital were randomly selected as the control group. Univariate and multivariate logistic regression analyses identified factors related to AUB. The univariate analysis revealed significant associations (P < 0.05) between AUB and several factors, including age, body mass index (BMI), age at menarche, gravidity, and intrauterine device (IUD) placement in perimenopausal women. The multivariate regression analysis indicated that the independent risk factors for AUB include benign endometrial lesions (odds ratio [OR] 5.243, 95% confidence interval [CI] 3.082-9.458, P < 0.001), endometrial thickness ≥ 10 mm (OR 1.573, 95% CI 0.984-3.287, P < 0.001), age ≥ 50 years (OR 2.045, 95% CI 1.035-4.762, P = 0.001), BMI ≥ 25 kg/m2 (OR 2.436, 95% CI 1.43-4.86, P = 0.002), and IUD placement (OR 2.458, 95% CI 1.253-4.406, P < 0.001). Abnormal uterine bleeding during the menopausal transition is associated with several factors, including age, BMI, and IUD placement, highlighting the importance of early screening for these risk factors in the diagnosis and treatment of AUB.

Isolated Vaginal Bleeding Before the Onset of Puberty.

Isolated vaginal bleeding before the onset of puberty is a rare presentation of isosexual precocity. In most cases, isolated vaginal bleeding without an abnormal genital examination is self-limited with resolution usually within 1 to 3 episodes. Watchful waiting is appropriate in most patients who do not have persistent bleeding, other signs of puberty, or signs/symptoms of an underlying etiology. Workup for patients with concerning features may include puberty hormone levels and/or transabdominal and transperineal ultrasound.

Clinicopathological Pattern of Endometrial Specimens in Women with Abnormal Uterine Bleeding and Ultrasonography Correlation.

BACKGROUND: Abnormal uterine bleeding (AUB) refers to any symptomatic deviation from normal menstruation. AUB is a common gynecological disorder in non-pregnant women of reproductive age, accounting for approximately 33% of gynecological outpatient visits. The early diagnosis and management cause of AUB is important because of increased incidence of endometrial carcinoma with rapid growth. Transvaginal ultrasound is non-invasive imaging technique used to find endometrial carcinoma before referring patients for invasive techniques. Dilatation and curettage (D&C) and endometrial biopsy are surgical procedures that scrape the endometrial lining of the uterus for diagnosis and treatment. The aim of this study is to describe the clinicopathologic pattern of endometrial specimens in women with AUB and ultrasonographic correlation. METHODS: Tissues from endometrial biopsy and curettage of 411 patients with AUB who referred to Shahid Mohammadi hospital were prospectively selected from 2021 to 2023. Patients were divided into three groups based on age and menstrual status including: premenopausal (18-39 years), perimenopausal (40-49 years) and postmenopausal (≥50 years). The results were correlated to patient's age and other data and evaluated with statistical analysis. RESULTS: During the two-year study period, a total of 411 endometrial specimens with clinical diagnosis of AUB were submitted and the results were analyzed. The youngest patient presenting with AUB was 21 years old, while the oldest was 77 years old. The most common complaint was menorrhagia in 201 (48.0%) out of 411 patients. The most common pathology finding in three groups was polyp in 100 (24.3%) cases. Hormonal effect was the next commonly observed pattern seen in 70 (17.0%) cases. P value was calculated as 0.003 which was significant using chi-square for the trend seen in age. CONCLUSION: Endometrial sampling is a useful tool for evaluation of women with AUB and referring patients for treatment. Histopathological evaluation of the endometrium is very useful in detecting the etiology of AUB. Transvaginal sonography has high sensitivity in detecting polyps.

Rate and risk factors of inadequate endometrial tissues after endometrial sampling among Bhutanese women at the national referral hospital of Bhutan: a cross-sectional study.

INTRODUCTION: Women presenting with abnormal uterine bleeding needs careful and thorough assessment including ultrasound examination of endometrium and histopathological assessment of the endometrial tissues. The objective of this cross-sectional study was to determine the rate and the factors associated with inadequate endometrial tissues after endometrial sampling using MedGyn® pipette among Bhutanese women at the colposcopy clinic, Jigme Dorji Wangchuck National Referral Hospital (JDWNRH), Bhutan. METHODS: This cross-sectional study was conducted at the colposcopy clinic, JDWNRH, Thimphu between October, 2021 and March, 2022. Women included in this study underwent endometrial sampling using MedGyn® pipette without anesthesia as an office procedure. Data were collected using an interviewer-administered questionnaire and results extracted into a structured pro forma. The histopathology reports were extracted from the Department of Pathology and Laboratory Medicine, JDWNRH using the unique Bhutanese citizenship identity card number of the study participants. RESULTS: Inadequate endometrial tissues were noted in 27% (33 out of 122 cases). Among 89 patients with an adequate endometrial tissue, histologic results were normal in 30 (33.7%), benign pathology in 22 (24.7%), atrophy in 10 (8.2%), and hyperplasia in 27 (30.3%). In a univariate analysis, menopausal state (OR 1.6, 95% CI 0.708-3.765), overweight and obese (OR 1.6 95% CI 0.640-3.945), unemployed (OR 1.7, 95% CI 0.674-1.140), nulliparous (OR 1.7, 95% CI 0.183-15.816), primipara (OR 5.1, 95% CI 0.635-40.905) and use of hormonal contraception (OR 2.1, 95% CI 0.449-10.049) were associated with increased risk of inadequate endometrial tissues. On multivariate regression analysis, nulliparity (OR 1.1, 95% CI 0.101-12.061), overweight and obesity (OR 1.4, 95% CI 0.490-3.917), use of hormonal contraceptives (OR 2.2, 95% CI 0.347-13.889), and junior surgeons (OR 1.1, 95%CI 0.463-2.443) were found to be associated with inadequate endometrial tissues. However, the above associations were not statistically significant (p > 0.05). CONCLUSION: The rate of inadequate endometrial tissue following endometrial sampling using MedGyn® pipette was 27.0%. Factors associated with an increased risk of inadequate endometrial tissue after endometrial sampling were menopausal state, overweight and obese, unemployed, nulliparous, primipara and use of hormonal contraception.

Enhanced Diagnostic Efficiency of Endometrial Carcinogenesis and Progression in Women with Abnormal Uterine Bleeding through Peripheral Blood Cytokine Testing: A Multicenter Retrospective Cohort Study.

Objective: This study aimed to evaluate the role of plasma cytokine detection in endometrial cancer screening and tumor progression assessment in patients with abnormal uterine bleeding. Methods: In this multicenter retrospective cohort study of 287 patients with abnormal uterine bleeding, comprehensive clinical information and laboratory assessments, including cytokines, routine blood tests, and tumor markers, were performed. Associations between the clinical indicators and endometrial carcinogenesis/progression were evaluated. The independent risk factors for endometrial cancer and endometrial cancer with deep myometrial invasion were analyzed using multivariate binary logistic regression. Additionally, a diagnostic model was used to evaluate the predictive efficacy of these identified risk factors. Results: In patients with abnormal uterine bleeding, low IL-4 and high IL-8 levels were independent risk factors for endometrial cancer (p < 0.05). Combining IL-4, IL-8, CA125, and menopausal status improved the accuracy of assessing endometrial cancer risk. The area under curve of the model is 0.816. High IL-6 and IL-8 levels were independent risk factors for deep myometrial invasion in patients with endometrial cancer (p < 0.05). Similarly, combining IL-6, IL-8, and Monocyte counts enhanced the accuracy of assessing endometrial cancer risk with deep myometrial invasion. The area under curve of the model is 0.753. Conclusions: Cytokines such as IL-4, IL-8, and IL-6 can serve as markers for monitoring endometrial cancer and its progression in women with abnormal uterine bleeding.

The impact of embedment of the side arms of 52 mg levonorgestrel-intrauterine device on bleeding and pain: A prospective cohort study.

PURPOSE: The purpose of this study was to analyse the impact of embedment of side arms of the levonorgestrel 52 mg intrauterine device (LNG-IUD) in the myometrium (assessed by three-dimensional transvaginal ultrasound (3D-TVUS)) on uterine bleeding and pain. MATERIALS AND METHODS: We performed a prospective cohort study in a large Dutch teaching hospital between February 2015 and December 2016. Participants over 18 years of age who selected a LNG-IUD for contraception or because of heavy menstrual bleeding were eligible for inclusion. Six weeks after insertion, a 3D-TVUS was performed to diagnose embedment of the side arms. At that moment participants filled in questionnaires about their bleeding pattern and pelvic pain. Menstruation patterns 'no bleeding', 'regular menstruation', 'sometimes a day of spotting (maximum once a week)' were classified as favourable bleeding pattern. Menstruation patterns 'heavy menstrual bleeding', 'several days a week bleeding days', 'several days a week spotting days', 'continuously spotting', and 'completely irregular cycle' were classified as unfavourable bleeding pattern. Univariate and multivariate logistic regression analysis was used to calculate odds ratios (OR) and 95 %-confidence intervals (CI). The multivariate analysis included endometrial thickness, reason for insertion and parity. The analysis of pelvic pain additionally included previous insertion. RESULTS: A total of 220 participants were evaluated for the study of whom 176 returned the questionnaires. Embedment of the side arms was observed in 43 of the 176 responding participants (24.4 %). Favourable bleeding pattern was reported by 25/43 (58.1 %) participants with embedment and 53/133 (39.8 %) participants without embedment (ORadj 1.8, 95 % CI 0.9-3.9). Pelvic pain was reported by 4/43 (9.3 %) participants with embedment and 24/133 (18.1 %) participants without embedment (ORadj 0.3; CI 0.1-1.2). CONCLUSIONS: The present study suggests that embedment of the side arms of the LNG-IUD in the myometrium assessed by 3D-TVUS is not associated with a unfavourable bleeding pattern nor pelvic pain six weeks after insertion. From this point of view, we do not recommend to perform standard 3D-TVUS for the purpose of excluding or demonstrating embedment.