Ultrasound-Guided Polypectomy: Evaluation of a Novel Technique to Remove Endometrial Polyps in the Office.

OBJECTIVE: To present a novel technique for office resection of pedunculated endometrial polyps under ultrasound guidance. METHODS: A prospective trial was conducted at an academic center where women with abnormal uterine bleeding (AUB) who were diagnosed an endometrial polyp following saline infusion sonogram (SIS), were offered polyp removal under ultrasound guidance using a universal grasping forceps (2.5 mm × 25 cm). The primary outcome was to evaluate the feasibility of this technique for complete removal of the polyp. The secondary outcomes were to evaluate the patients' pain score, satisfaction score using visual analogue score (VAS), and efficacy of the technique in alleviating symptoms in patients with AUB due to polyps. RESULTS: Thirty patients participated, with a mean age of 54.8 ± 11 years. Average polyp volume was 1.87 cm3 and mean duration for polypectomy was 11 minutes 31 seconds. The median pain score immediately post-procedure was 5 (0-9). We were unable to complete the procedure in two patients due to patient discomfort and poor visualization. Complete removal of polyp was ensured by checking for a thin endometrial echo at the end of the procedure and by performing SIS at 3-months post-procedure. Of the 22 patients who returned for follow-up, 19 (86.36%) showed no evidence of polyp on SIS and all reported resolution of AUB symptoms. The median satisfaction score at the follow-up was 10/10. Adequate pathology samples were obtained from all cases, diagnosing malignancy in one and endometrial hyperplasia in one patient. CONCLUSION: This technique offers safe and effective removal of pedunculated endometrial polyps in an office setting, avoiding the need for general anesthesia. It can be offered as a therapeutic option at the initial point of contact, providing symptom relief and tissue diagnosis while reducing costs and patient visits.

Clinical analysis of uterine parameters evaluated by preoperative magnetic resonance imaging in patients treated by hysteroscopic approach with previous cesarean scar defect-related abnormal uterine bleeding: a retrospective cohort study.

Background: As the cesarean delivery rate continues to rise globally, the treatment of previous cesarean scar defects (PCSD) remains challenging. This study aimed to analyze the variables that may influence the clinical cure rate of patients with PCSD-related abnormal uterine bleeding (AUB) as determined by preoperative magnetic resonance imaging (MRI) following hysteroscopic therapy. Methods: Women who underwent hysteroscopic surgery for PCSD-related AUB at the Gynecology Department of Third Xiangya Hospital of Central South University from 2018 to 2022 were recruited to this retrospective cohort investigation. A total of 147 patients were enrolled in this study and underwent follow-up over 6 months. The significance of clinical characteristics linked to the clinical cure rate of AUB was examined by logistic regression. Results: There were 64 clinically cured (43.5%) and 83 non-clinically cured (56.5%) patients in the study. There were no significant differences in the age, menstrual duration, gravidity, parity, number of cesarean sections, time since the previous cesarean section, uterus position, width, depth, and thickness of the remaining muscle layer of the defect by MRI T2-weighted images (T2WI) before hysteroscopic surgery between the 2 groups. MRI T2WI of the myometrial thickness adjacent to the defect [P=0.038, odds ratio (OR) =2.095, 95% confidence interval (CI): 1.047-4.261] and the distance from the defect to the external cervical os (P=0.021, OR =2.254, 95% CI: 1.136-4.540) before hysteroscopic surgery are risk factors for the clinical cure rate. Conclusions: The myometrial thickness adjacent to the defect and the distance from the defect to the external cervical os in preoperative MRI are risk factors for clinical cure rate in patients with PCSD-related AUB after hysteroscopic treatment, which is helpful for evaluating the prognosis of disease.

Deep Vein Thrombosis as a Rare Post-procedural Complication After Uterine Artery Embolization: A Case Report.

When a patient is undergoing uterine artery embolization (UAE) which is considered a modality that is safer than surgical management for abnormal uterine bleeding (AUB), one must acknowledge as a surgeon the existence of rare but serious complications such as deep vein thrombosis (DVT). We encountered such a case where a 34-year-old female (para-3 living-3) with AUB and severe anemia because of heavy bleeding required multiple blood transfusions and was treated with UAE. The procedure was uneventful and the patient was discharged. However, later she presented with DVT of the right lower limb which was promptly managed with an inferior vena cava filter implant and thrombolysis, which prevented life-threatening sequelae such as pulmonary embolism and, potentially, death. Therefore, one must be vigilant about such complications despite UAE being a safer alternative to surgical management for gynecological complaints.

Does Timing of Levonorgestrel Insertion in Women with Abnormal Uterine Bleeding Affect its Expulsion and Bleeding Pattern? A Follow-Up Study.

Background: Levonorgestrel Intra Uterine System insertion for contraception is preferred in the follicular phase. However, the ideal time of insertion for Abnormal Uterine Bleeding is not stated clearly. The aim of our study is to find out the effect of timing of insertion on expulsion and irregular bleeding pattern post insertion. Methods: A follow-up study of patients with LNG-IUS for AUB was conducted. They were grouped into four based on the day of insertion from Last Menstrual Period (LMP). The pattern of irregular bleeding post insertion was compared with odds ratio and the expulsion rate was compared with log rank test. Results: The most common indication for the 76 patients was ovulatory dysfunction (39.4%) followed by Adenomyosis (36.84%). Those who had LNG-IUS insertion from day 22-30 had quicker expulsions of 25% of patients by 3 months. By 6 months and later expulsion rate was much higher in the luteal phase than the follicular phase (p < 0.03). The least risk of moderate or heavy bleeding was for the 8-15 day group when compared to the 22-30 day group, the odds ratio being 0.03 [95% CI: (0.01-0.2)]. Conclusion: Based on expulsion rate alone, insertion of LNG-IUS at any time in the follicular phase is ideal. Considering both expulsion rate and pattern of bleeding the ideal time would be late follicular phase, that is 8-15th day.

Pre-clinical models to study abnormal uterine bleeding (AUB).

Abnormal Uterine Bleeding (AUB) is a common debilitating condition that significantly reduces quality of life of women across the reproductive age span. AUB creates significant morbidity, medical, social, and economic problems for women, their families, workplace, and health services. Despite the profoundly negative effects of AUB on public health, advancement in understanding the pathophysiology of AUB and the discovery of novel effective therapies is slow due to lack of reliable pre-clinical models. This review discusses currently available laboratory-based pre-clinical scientific models and how they are used to study AUB. Human and animal in vitro, ex vivo, and in vivo models will be described along with advantages and limitations of each method.

Should body mass index replace age to drive the decision for endometrial sampling in premenopausal women with abnormal uterine bleeding?

OBJECTIVE: This study aimed to evaluate risk factors for endometrial intraepithelial neoplasia/malignancy in premenopausal women with abnormal uterine bleeding or oligomenorrhea. Specifically, we aimed to elucidate whether body mass index (BMI) or age confers a higher risk. STUDY DESIGN: A retrospective cohort study was performed at a large academic center examining risk factors for endometrial hyperplasia/malignancy in premenopausal women undergoing endometrial sampling. RESULTS: Of the 4170 women ages 18-51 who underwent endometrial sampling from 1987 to 2019, 77 (1.85%) were found to have endometrial intraepithelial neoplasia or malignancy. Clinical predictors of EIN/malignancy in this population included obesity (OR: 3.84, 95%, p < .001), Body mass index [(OR30 vs. 25:2.11, p < .001) and OR35 vs. 30: 1.65, p < .001], Diabetes (OR: 3.6, p-value <.001), hormonal therapy use (OR: 2.93, p < .001), personal history of colon cancer (OR: 9.90, p = .003), family history of breast cancer (OR: 2.65, p < .001), family history of colon cancer (OR: 3.81, p < .001), and family history of endometrial cancer (OR: 4.92, p = .033). Age was not significantly associated with an increased risk of disease. Adjusting for other factors, a model using BMI to predict the risk of EIN/malignancy was more discriminative than a model based on age. CONCLUSIONS: Increased BMI, may be more predictive of endometrial hyperplasia/malignancy than age in premenopausal women with abnormal uterine bleeding. Modification of evaluation guidelines in a contemporary demographic setting could be considered.

Ferric carboxymaltose for treatment of iron deficiency and iron deficiency anemia caused by abnormal uterine bleeding.

Introduction: Heavy menstrual bleeding leads to depletion of iron stores, with subsequent iron deficiency (ID) and iron deficiency anemia (IDA). To evaluate the efficacy and safety of ferric carboxymaltose (FCM) in treatment of ID/IDA caused by abnormal uterine bleeding (AUB). Material and methods: One hundred and twenty women ≥ 40 years old with chronic AUB and ID/IDA were included in this study for correction of ID/IDA. Participants received FCM infusion for correction of ID/IDA. The pre-treatment ferritin, hemoglobin (Hb), red blood cell (RBC) mean corpuscular volume (MCV), and RBC mean corpuscular hemoglobin (MCH) values were compared with the 6- and 12-week post-treatment values. Results: The pre-treatment ferritin and Hb levels significantly increased from 13.2 ±7.4 µg/l and 8.8 ±0.8 g/dl, respectively, to 111.5 ±5.6 µg/l and 13.9 ±0.6 g/dl, respectively, 6 weeks after FCM (p = 0.001 and 0.0009; respectively), and to 98.7 ±6.1 µg/l and 12.9 ±0.65 g/dl, respectively, 12 weeks after FCM (p = 0.01 and 0.01; respectively). In addition, the pre-treatment RBC MCV and RBC MCH values significantly increased from 74.3 ±2.3 fl and 26.6 ±5.3 pg, respectively, to 88.7 ±1.9 fl and 29.6 ±4.5 pg, respectively, 6 weeks after FCM (p = 0.01 and 0.03, respectively), and to 93.3 ±1.75 fl and 30.3 ±3.8 pg, respectively, 12 weeks after FCM (p = 0.001 and 0.0001, respectively). Conclusions: FCM was safe and effective for correction of ID/IDA caused by chronic AUB within 6 weeks. The serum ferritin, Hb, and RBC indices remained significantly high compared to the pre-treatment values 12 weeks after FCM infusion.

Symptoms and Quality of Life Changes after Hysteroscopic Treatment in Patients with Symptomatic Isthmocele-Preliminary Results.

Due to an increasing number of cesarean section deliveries, the common consequences of that surgery are observed more often in the population. One of them is the uterine cesarean scar defect known as niche or isthmocele. Most patients with that aliment are asymptomatic, but some of them can report abnormal uterine bleeding, pelvic pain, subfertility which can be the reason for reduced quality of life (QoL) of the patients. In our study, we analyzed the subjective feelings of changes in the severity of symptoms and quality of life of women with niche after diagnostic and operative hysteroscopy. The patients n = 85 included in the study group completed a follow up questionnaire six months after the procedure. Patients after operative hysteroscopy in comparison to patients after diagnostic procedure reported statistically significant reduction in post-menstruation bleeding/spotting and improvement in the quality of sexual activity. We have also noticed a higher pregnancy rate in the operative group, however, the difference was not statistically significant. According to our study, most women reported a positive effect of hysteroscopy on their QoL in social, psychological, environmental, and health domains.

Low dose dexamethasone as treatment for women with heavy menstrual bleeding: A response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM).

BACKGROUND: The symptom of heavy menstrual bleeding (HMB) diminishes quality-of-life for many mid-age women and imposes substantial societal burden. We investigated our hypothesis that HMB reflects impaired endometrial vasoconstriction due to endometrial glucocorticoid deficiency. Does reversing this deficiency, by short-term luteal-phase treatment with exogenous glucocorticoid (dexamethasone), ameliorate HMB? METHODS: In our Bayesian response-adaptive parallel-group placebo-controlled randomised trial, five pre-planned interim analyses used primary outcome data to adjust randomisation probabilities to favour doses providing most dose-response information. Participants with HMB, recruited from Lothian (Scotland) NHS clinics and via community invitations/advertisements, were aged over 18 years; reported regular 21-42 day menstrual cycles; and had measured menstrual blood loss (MBL) averaging ≥ 50 mL over two screening periods. Identically encapsulated placebo, or one of six Dexamethasone doses (0·2 mg, 0·4 mg, 0·5 mg, 0·6 mg, 0·75 mg, 0·9 mg), were taken orally twice-daily over five days in the mid-luteal phase of three menstrual cycles. Participants, investigators, and those measuring outcomes were masked to group assignment. Primary outcome, change in average MBL from screening to 'treatment', was analysed by allocated treatment, for all with data. TRIAL REGISTRATION: ClinicalTrials.gov NCT01769820; EudractCT 2012-003,405-98 FINDINGS: Recruitment lasted 29/01/2014 to 25/09/2017; 176 were screened, 107 randomised and 97 provided primary outcome data (n = 24,5,9,21,8,14,16 in the seven arms, placebo to 1·8 mg total daily active dose). In Bayesian normal dynamic linear modelling, 1·8 mg dexamethasone daily showed a 25 mL greater reduction in MBL from screening, than placebo (95% credible interval 1 to 49 mL), and probability 0·98 of benefit over placebo. Adverse events were reported by 75% (58/77) receiving dexamethasone, 58% (15/26) taking placebo. Three serious adverse events occurred, two during screening, one in a placebo participant. No woman withdrew due to adverse effects. INTERPRETATION: Our adaptive trial in HMB showed that dexamethasone 1·8 mg daily reduced menstrual blood loss. The role of dexamethasone in HMB management deserves further investigation. FUNDING: UK MRC DCS/DPFS grant MR/J003611/1.

Menstruation Dysregulation and Endometriosis Development.

Endometriosis is a common gynecological condition characterized by the growth of endometrial-like tissue outside of the uterus which may cause symptoms such as chronic pelvic pain or subfertility. Several surgical and medical therapies are available to manage symptoms, but a cure has yet to be determined which can be attributed to the incomplete understanding of disease pathogenesis. Sampson's theory of retrograde menstruation is a widely accepted theory describing how shed endometrial tissue can enter the peritoneal cavity, but other factors are likely at play to facilitate the establishment of endometriosis lesions. This review summarizes literature that has explored how dysregulation of menstruation can contribute to the pathogenesis of endometriosis such as dysregulation of inflammatory mediators, aberrant endometrial matrix metalloproteinase expression, hypoxic stress, and reduced apoptosis. Overall, many of these factors have overlapping pathways which can prolong the survival of shed endometrial debris, increase tissue migration, and facilitate implantation of endometrial tissue at ectopic sites. Moreover, some of these changes are also implicated in abnormal uterine bleeding and endometrial diseases. More research is needed to better understand the underlying mechanisms driving dysregulation of menstruation in endometriosis specifically and identifying specific pathways could introduce new treatment targets. Analyzing menstrual fluid from women with endometriosis for inflammatory markers and other biomarkers may also be beneficial for earlier diagnosis and disease staging.

90 YEARS OF PROGESTERONE: Selective progesterone receptor modulators in gynaecological therapies.

Abnormal uterine bleeding (AUB) is a chronic, debilitating and common condition affecting one in four women of reproductive age. Current treatments (conservative, medical and surgical) may be unsuitable, poorly tolerated or may result in loss of fertility. Selective progesterone receptor modulators (SPRMs) influence progesterone-regulated pathways, a hormone critical to female reproductive health and disease; therefore, SPRMs hold great potential in fulfilling an unmet need in managing gynaecological disorders. SPRMs in current clinical use include RU486 (mifepristone), which is licensed for pregnancy interruption, and CDB-2914 (ulipristal acetate), licensed for managing AUB in women with leiomyomas and in a higher dose as an emergency contraceptive. In this article, we explore the clinical journey of SPRMs and the need for further interrogation of this class of drugs with the ultimate goal of improving women's quality of life.

Study of causes behind abnormal uterine bleeding according to PALM- COEIN classification at a tertiary care hospital.

This descriptive observational study was carried out to determine the frequency of causes behind Abnormal Uterine Bleeding (AUB) amongst patients of reproductive age presenting to gynaecology OPD from January to June 2018 at the Combined Military Hospital Kharian, a tertiary care hospital. All women presenting with complaints of AUB were enrolled for the study, except for those who were pregnant, adolescent and postmenopausal. Detailed history, physical examination and relevant investigations were done and patients were categorised according to FIGO PALM-COEIN classification system and placed in nine main categories. A total of 238 patients were enrolled and the incidence of AUB among them was found to be 11% according to PALM-COEIN classification system. The frequency and percentage of all etiologies was calculated. Frequency of structural causes was Polyp 10 (6.7%), Adenomyosis 35 (23.5%), Leiomyomata 80 (53.7) and Malignancy 24 (16.1%). Nonstructural causes were Coagulation Disorders 5 (5.6%), Ovulatory 56 (37.6%), Endometrial Dysfunction 3 (3.4%), Iatrogenic 14 (15.7%) and Not-yet-classified 11 (12.4%). Development of a universally accepted classification system is a step towards facilitating clinicians, patients and researchers to communicate with each other and make objective management plans.

Deciphering the intervention mechanism of Taohong Siwu Decoction following the abnormal uterine bleeding rats based on serum metabolic profiles.

Abnormal uterine bleeding (AUB), one of the most significant characters of incomplete abortion, is a widespread phenomenon in gynecological that put a woman into a terrible physiological and psychological state. Taohong Siwu Decoction (TSD) is a traditional Chinese medicine (TCM) prescriptions which have treated AUB in China for decades. Our previous study elucidated that TSD reduced the volume of uterine bleedings as well as repaired the endometrium. The present study aims to investigate the mechanisms of TSD on AUB based on serum metabolomics. In this study, serum metabolic profile data was collected using ultra high-performance liquid chromatography with ion trap/time-of-flight mass spectrometry and gas chromatography-mass spectrometry. 23 potential biomarkers (urea, serine, L-proline, L-glutamic acid, palmitic acid, l-acetylcarnitine, LysoPC(16:0), LysoPC(20:4), l-proline, linoleic acid, stearic acid, l-isoleucine, phenylalanine, l-tyrosine, Oleic acid, et al) were eventually identified using multivariate statistical analysis (PCA and OPLS-DA) with VIP > 1, P < 0.05. Correlation analysis, fold-change (FC), area under receiver characteristic (ROC), false discovery rate (FDR) were used for data confirmation to ensure the authenticity of the data. The related-metabolic pathway mainly included amino acid metabolism (Phenylalanine, tyrosine, and tryptophan metabolism; Valine, leucine and isoleucine biosynthesis; Arginine and proline metabolism; Glycine, serine and threonine metabolism) and lipid metabolism (linoleic acid metabolism, glycerophospholipid metabolism). The results show that TSD has a favorable therapeutic effect on AUB by adjusting the metabolic disorders, which could provide dietary guidance for the clinic.

Use of ultrasound imaging for the diagnosis of abnormal uterine bleeding in the bonnet macaque ( Macaca radiata).

Ultrasound is a powerful, low-cost, non-invasive medical tool used by laboratory animal veterinarians for diagnostic imaging. Sonohysterography and transvaginal ultrasound are frequently used to assess uterine anomalies in women presenting with abnormal uterine bleeding (AUB). In the present study, we have evaluated the abdominal ultrasound of bonnet monkeys ( n = 8) showing spontaneous ovulatory ( n = 5) and anovulatory ( n = 3) AUB. The ovulatory ( n = 5) macaques showed cyclic AUB for 7-8 days. The anovulatory ( n = 3) macaques had irregular AUB with menstrual cycles of 40-45 days. The B-mode abdominal, colour Doppler and 3D ultrasound scans were performed during the proliferative phase of the menstrual cycle. Ultrasound examination revealed endometrial polyps in five macaques and endometrial hyperplasia in three animals. The width and length of endometrial polyps was around 0.5-1 cm (average 0.51 ± 0.23 cm × 0.96 ± 0.16 cm) with significant increase in endometrial thickness ( P < 0.0002). 3D ultrasound also showed a homogeneous mass in the uterine cavity and colour Doppler ultrasound showed increased vascularity in the endometrial polyps. Endometrial hyperplasia characteristically appeared as a thickened echogenic endometrium ( P < 0.0002). This study demonstrates the use of non-invasive ultrasound techniques in the diagnosis of AUB in macaques.

Abnormal uterine bleeding.

Abnormal uterine bleeding (AUB) is a common and debilitating condition with high direct and indirect costs. AUB frequently co-exists with fibroids, but the relationship between the two remains incompletely understood and in many women the identification of fibroids may be incidental to a menstrual bleeding complaint. A structured approach for establishing the cause using the Fédération International de Gynécologie et d'Obstétrique (FIGO) PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system will facilitate accurate diagnosis and inform treatment options. Office hysteroscopy and increasing sophisticated imaging will assist provision of robust evidence for the underlying cause. Increased availability of medical options has expanded the choice for women and many will no longer need to recourse to potentially complicated surgery. Treatment must remain individualised and encompass the impact of pressure symptoms, desire for retention of fertility and contraceptive needs, as well as address the management of AUB in order to achieve improved quality of life.