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Reproductive Biomedicine Online Aug 2023Is there association between the presence of a uterine niche and the presence of symptoms?
RESEARCH QUESTION
Is there association between the presence of a uterine niche and the presence of symptoms?
DESIGN
This cross-sectional study was conducted at a single tertiary medical centre. All women who underwent Caesarean section from January 2017 to June 2020 were invited to the gynaecological clinics, and requested to complete a questionnaire regarding symptoms related to the presence of a niche (heavy menstrual bleeding, intermenstrual spotting, pelvic pain, infertility). Transvaginal two-dimensional ultrasonography was performed to assess the uterus and uterine scar characteristics. The primary outcome was defined as the presence of a uterine niche, evaluated by length, depth, residual myometrial thickness (RMT) and ratio between the residual myometrial thickness (RMT) and adjacent myometrial thickness (AMT).
RESULTS
Of 524 women who were eligible and scheduled for evaluation, 282 (54%) completed the follow-up; 173 (61.3%) were symptomatic and 109 (38.6%) asymptomatic. Niche measurements, including RMT/AMT ratio, were comparable between the groups. In a sub-analysis of each symptom, heavy menstrual bleeding and intermenstrual spotting were associated with reduced RMT (P = 0.02 and P = 0.04, respectively) compared with women with normal menstrual bleeding. An RMT less than 2.5 mm was significantly more prevalent in women reporting heavy menstrual bleeding (11 [25.6%] versus 27 [11.3%]; P = 0.01] and new infertility (7 [16.3%] versus 6 [2.5%]; P = 0.001]. In logistic regression analysis, infertility was the only symptom associated with an RMT less than 2.5 mm (B = 1.9; P = 0.002).
CONCLUSIONS
A reduced RMT was found to be associated with heavy menstrual bleeding and intermenstrual spotting, while values below 2.5 mm were also associated with infertility.
Topics: Female; Pregnancy; Humans; Cesarean Section; Cicatrix; Menorrhagia; Cross-Sectional Studies; Uterus; Metrorrhagia; Infertility; Ultrasonography
PubMed: 37277298
DOI: 10.1016/j.rbmo.2023.04.012 -
Reproductive Biomedicine Online Nov 2023What role, if any, does histone deacetylase 3 (HDAC3) play in adenomyosis-associated heavy menstrual bleeding (HMB)?
RESEARCH QUESTION
What role, if any, does histone deacetylase 3 (HDAC3) play in adenomyosis-associated heavy menstrual bleeding (HMB)?
DESIGN
Seventy-two women with adenomyosis-associated HMB were recruited. Of these, 37 women reported moderate/heavy bleeding (MHB) and the remaining 35 women reported excessive bleeding (EXB). The stiffness of adenomyotic lesions and neighbouring endometrial-myometrial interface (EMI) was measured by transvaginal elastosonography, and full-thickness uterine tissue columns were processed for Masson trichrome staining and immunohistochemistry analyses. The protein expression levels of HDAC3 in endometrial cells cultured on substrates of different stiffnesses, and the protein concentrations of nuclear factor-κB (NF-κB) p65 subunit with HDAC3 suppression were evaluated. Mouse experiments were performed to assess the effect of adenomyosis on Hdac3 expression, endometrial repair and bleeding, and to evaluate the effect of HDAC3 inhibition on endometrial repair.
RESULTS
Compared with controls, the endometrial staining of HDAC3 was significantly lower in women with adenomyosis-associated HMB, concomitant with a greater extent of fibrosis. The stiffness of lesions and neighbouring EMI was significantly higher in the EXB group compared with the MHB group, as was the extent of fibrosis in lesions, their neighboring EMI and endometrium. Expression of HDAC3 was reduced significantly when endometrial epithelial cells were cultured in stiff substrates. Suppression of HDAC3 abrogated the activation and signalling of NF-κB. Mice with induced adenomyosis exhibited reduced Hdac3 staining and elevated fibrosis in endometrium, concomitant with disrupted endometrial repair and more bleeding. Hdac3 inhibition resulted in botched inflammation and increased bleeding.
CONCLUSIONS
Lesional fibrosis results in reduced endometrial HDAC3 expression and subsequent disruption in NF-κB signalling and inflammation, leading to adenomyosis-associated HMB.
Topics: Female; Humans; Animals; Mice; Menorrhagia; Adenomyosis; NF-kappa B; Endometrium; Fibrosis; Inflammation
PubMed: 37690341
DOI: 10.1016/j.rbmo.2023.103288 -
Biomolecules May 2024Thomas Cullen described bleeding abnormalities and dysmenorrhea as the "expected" presentations of adenomyomas. Adenomyosis is included within the FIGO classification of... (Review)
Review
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.
Topics: Humans; Adenomyosis; Female; Uterine Hemorrhage; Dysmenorrhea
PubMed: 38927019
DOI: 10.3390/biom14060616 -
Systematic Reviews Jul 2023Abnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and...
BACKGROUND
Abnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and iron deficiency anemia (IDA). Depletion of iron stores has negative implications on physical, social, and emotional health, as well as quality of life. Iron supplements are safe, effective, and readily available, while red blood cell (RBC) transfusions have inherent risks including infectious and immune reactions. Despite high prevalence of IDA among women with AUB, there are limited studies on the impact of iron therapies on patient outcomes. This systematic review and meta-analysis will evaluate the impact of iron supplementation on patient outcomes for women with AUB, when compared to combination therapy, no intervention, placebo, or standard of care.
METHODS
We will conduct a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the impact of iron interventions on patient outcomes for women with AUB. Systematic literature searches will be conducted in major databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science. Studies assessing the impact of iron interventions on patient outcomes in women experiencing AUB, in comparison to combination therapy, no intervention, placebo, or standard of care, will be included in the review. Independent reviewers will screen for eligibility, assess risk of bias, and abstract data. Overall certainty of evidence for each outcome will be assessed using the GRADE approach. We will meta-analyze outcomes which are sufficiently homogeneous to summarize intervention effects and narratively synthesize nonhomogeneous outcomes. The main outcomes of interest are hemoglobin levels immediately prior to surgery and post-operatively, number of RBC transfusions, and adverse effects. Secondary outcomes will include length of hospital stay, intraoperative blood loss, adverse and side effects, quality of life, and iron indices.
DISCUSSION
This review will evaluate the impact of iron interventions on patient outcomes in women with IDA secondary to AUB with focus on changes in hematological and iron indices, red blood cell utilization, quality of life, cost of treatment, and adverse events. The results will inform evidence-based clinical practice for the management of iron deficiency and IDA secondary to AUB.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019137282.
Topics: Female; Humans; Iron; Quality of Life; Systematic Reviews as Topic; Meta-Analysis as Topic; Anemia, Iron-Deficiency; Iron Deficiencies; Uterine Hemorrhage; Dietary Supplements; Review Literature as Topic
PubMed: 37443063
DOI: 10.1186/s13643-023-02222-4 -
Journal of Minimally Invasive Gynecology Nov 2023The purpose of this study was to better elucidate radiofrequency endometrial ablation (REA) durability by assessing the probability of failure as defined by need for...
STUDY OBJECTIVE
The purpose of this study was to better elucidate radiofrequency endometrial ablation (REA) durability by assessing the probability of failure as defined by need for postablation hysterectomy. Age at index REA, duration from REA until hysterectomy, and REA failure (REAF) risk factors were analyzed.
DESIGN
A retrospective cohort study was conducted using patient data between April 1, 2002, and March 31, 2019. REAF cases were identified using operative procedure codes. Cox proportional hazard regression assessed the effect of age at index REA on time to postablation hysterectomy. Kaplan-Meier survival curve evaluated timing of postablation hysterectomy, stratified by age at index REA.
SETTING
This study was conducted at Regina General Hospital in Regina, Saskatchewan, Canada.
PATIENTS
Patient population included those who were 21 years of age or older, were premenopausal, and had a history of heavy menstrual bleeding at the time of REA.
INTERVENTIONS
The intervention under investigation was REA.
MEASUREMENTS AND MAIN RESULTS
The overall probability of postablation hysterectomy was 22.6%. The probabilities of postablation hysterectomy were 36.1% for women younger than 30 years (n = 128), 28% for women 30 to 34.9 years old (n = 528), 29.6% for women 35 to 39.9 years old (n = 1152), and 17.6% for women 40 years and older (n = 2221). Characteristics associated with REAF included tubal occlusion, cesarean section, dysmenorrhea, and chronic pelvic pain (p <.01) among women younger than 40 years. Leiomyomas accounted for higher failure rates in women 40 years and older (p <.01).
CONCLUSION
Postablation hysterectomy is more likely to occur in women younger than 40 years. REA can be considered in women aged 30 to 39.9 years old, who have no known REAF risk factors. Women younger than 40 years with REAF risk factors will experience higher rates of hysterectomy. Thus, the decision to proceed with REA should be individualized with careful consideration for the underlying causes of abnormal uterine bleeding, while respecting patient autonomy.
Topics: Pregnancy; Humans; Female; Young Adult; Adult; Endometrial Ablation Techniques; Retrospective Studies; Cesarean Section; Canada; Menorrhagia
PubMed: 37451502
DOI: 10.1016/j.jmig.2023.07.002 -
Hamostaseologie Aug 2023Inherited platelet disorders (IPDs) comprise a heterogeneous group of entities that manifest with variable bleeding tendencies. For successful treatment, the underlying...
Inherited platelet disorders (IPDs) comprise a heterogeneous group of entities that manifest with variable bleeding tendencies. For successful treatment, the underlying platelet disorder, bleeding severity and location, age, and sex must be considered in the broader clinical context. Previous information from the AWMF S2K guideline #086-004 (www.awmf.org) is evaluated for validity and supplemented by information of new available and future treatment options and clinical scenarios that need specific measures. Special attention is given to the treatment of menorrhagia and risk management during pregnancy in women with IPDs. Established treatment options of IPDs include local hemostatic treatment, tranexamic acid, desmopressin, platelet concentrates, and recombinant activated factor VII. Hematopoietic stem cell therapy is a curative approach for selected patients. We also provide an outlook on promising new therapies. These include autologous hematopoietic stem cell gene therapy, artificial platelets and nanoparticles, and various other procoagulant treatments that are currently tested in clinical trials in the context of hemophilia.
Topics: Pregnancy; Humans; Female; Blood Platelet Disorders; Blood Platelets; Hematopoietic Stem Cells; Hemophilia A; Hemostatics
PubMed: 37611608
DOI: 10.1055/a-2080-6602 -
Diagnostics (Basel, Switzerland) Jul 2023Angioleiomyoma, a rare variant of leiomyoma, is a benign tumor of mesenchymal origin. Angioleiomyomas of the female urogenital tract are extremely rare, with only six...
Angioleiomyoma, a rare variant of leiomyoma, is a benign tumor of mesenchymal origin. Angioleiomyomas of the female urogenital tract are extremely rare, with only six cases of uterine cervical angioleiomyoma previously reported in the literature. In this case study, we report on a 49-year-old female patient who presented with menorrhagia whose initial magnetic resonance imaging (MRI) findings suggested cervical squamous cell carcinoma (SCC). However, following the hysterectomy, histological examination confirmed the lesion to be angioleiomyoma. To the best of our knowledge, there have been no previously reported cases of angioleiomyomas presenting with MRI findings that are suggestive of uterine SCC. Recognizing that angioleiomyomas can mimic uterine malignancies on MRI may prove beneficial for future diagnostic and treatment strategies.
PubMed: 37510114
DOI: 10.3390/diagnostics13142370 -
Journal of Thrombosis and Haemostasis :... Jul 2024Bleeding is a well-recognized side effect of anticoagulant therapy, which is used to treat venous thromboembolism (VTE) in individuals of all ages, including those of... (Review)
Review
Bleeding is a well-recognized side effect of anticoagulant therapy, which is used to treat venous thromboembolism (VTE) in individuals of all ages, including those of female sex, who commonly experience VTE as a complication of hormonal therapies and/or pregnancy. Heavy menstrual bleeding (HMB) is also extremely common in reproductive-aged individuals of female sex. Despite these overlapping situations, relatively little attention has been paid to the impact of anticoagulant-associated HMB on treatment strategies and the patient experience. In this review, we summarize incidence and complications of HMB in anticoagulated individuals as well as management strategies for HMB in this population. We also address the patient experience, including the impact of HMB on quality of life and the impact of discontinuing hormonal therapies at the time of VTE diagnosis and anticoagulant initiation. We conclude by highlighting specific gaps related to the patient experience of anticoagulant-associated HMB in both the research and clinical settings.
Topics: Humans; Female; Anticoagulants; Venous Thromboembolism; Menorrhagia; Quality of Life; Risk Factors; Blood Coagulation; Adult; Incidence; Pregnancy; Uterine Hemorrhage
PubMed: 38642705
DOI: 10.1016/j.jtha.2024.04.002 -
American Journal of Obstetrics and... Nov 2023The levonorgestrel intrauterine system and combined oral contraceptives are the 2 most commonly used nonsurgical treatments for heavy menstrual bleeding in the United... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The levonorgestrel intrauterine system and combined oral contraceptives are the 2 most commonly used nonsurgical treatments for heavy menstrual bleeding in the United States. However, there are limited data on their relative effectiveness and on their impact on bleeding-specific quality of life.
OBJECTIVE
This study aimed to compare the effectiveness of the 52-mg levonorgestrel intrauterine system with that of combined oral contraceptives for improving quality of life among individuals who self-report heavy menstrual bleeding. We hypothesized that the levonorgestrel intrauterine system would be more effective than combined oral contraceptives at 6 and 12 months after treatment.
STUDY DESIGN
We conducted a pragmatic randomized trial of individuals who self-reported heavy menstrual bleeding. Individuals were eligible if they did not have contraindications to either the levonorgestrel intrauterine system or combined oral contraceptives and were determined to have a nonstructural cause of heavy menstrual bleeding. Eligible and consenting participants were randomly assigned in a 1:1 ratio to receive a 52-mg levonorgestrel intrauterine system or a monophasic 30- or 35-μg ethinyl estradiol-containing combined oral contraceptive. The main outcome was mean change in bleeding-related quality of life, measured by the 20-question Menstrual Bleeding Questionnaire (score range, 0-75) at 6 and 12 months. Differences in group means and confidence intervals for the Menstrual Bleeding Questionnaire score were computed by multivariable linear mixed-effects regression; 24 participants per group were needed to detect a 10-point difference in change in mean Menstrual Bleeding Questionnaire score between individuals treated with the levonorgestrel intrauterine system and those treated with combined oral contraceptives at each follow-up time point.
RESULTS
A total of 62 individuals were randomly assigned to treatment (n=29 allocated to levonorgestrel intrauterine system and n=33 allocated to combined oral contraceptives) and included in the intention-to-treat analyses; 19 of 29 received the levonorgestrel intrauterine system and 31 of 33 received combined oral contraceptives. Eleven percent identified as Black or African American and 44% identified as Hispanic or Latina. Participant characteristics were similar among study groups. Bleeding-related quality of life increased in both study arms, as reflected by a significant decrease in Menstrual Bleeding Questionnaire scores beginning at 6-week follow-up. In the main intention-to-treat analyses (n=62), there were no differences in mean change in Menstrual Bleeding Questionnaire scores at 6 months (difference=-2.5; 95% confidence interval, -10.0 to +5.0) or 12 months (difference=-1.1; 95% confidence interval, -8.7 to +6.5). Findings were similar in the subsets of participants with any follow-up visits (n=52) and who completed all follow-up visits (n=42). In the per-protocol analyses (n=47), a significantly greater decrease in Menstrual Bleeding Questionnaire score was observed in the levonorgestrel intrauterine system arm at 6 months after treatment (difference=-7.0; 95% confidence interval, -13.8 to -0.2) but not at 12 months (difference=-4.8; 95% confidence interval, -11.8 to 2.3) compared with the combined oral contraceptive arm.
CONCLUSION
No differences in change of bleeding-related quality of life were observed between the levonorgestrel intrauterine system and combined oral contraceptives at 6 or 12 months. Patients should be counseled that the levonorgestrel intrauterine system and combined oral contraceptives are both effective options for improving bleeding-related quality of life.
Topics: Female; Humans; Levonorgestrel; Menorrhagia; Contraceptives, Oral, Combined; Quality of Life; Intrauterine Devices, Medicated
PubMed: 37536486
DOI: 10.1016/j.ajog.2023.07.049 -
Pediatric Annals Mar 2024Heavy menstrual bleeding has a high prevalence and is well documented in adult patients with hypermobile-type Ehlers-Danlos syndrome, but there is limited research... (Review)
Review
Heavy menstrual bleeding has a high prevalence and is well documented in adult patients with hypermobile-type Ehlers-Danlos syndrome, but there is limited research surrounding work-up and treatment for the adolescent population. Excessive menstrual blood loss can significantly interfere with emotional and physical quality of life. A provider should acquire a comprehensive medical and menstrual history and focused physical examination, as well as baseline laboratory studies, to determine the presence of anemia or underlying bleeding disorder. Use of a pictorial blood assessment chart may be considered to help quantify the amount of bleeding. Treatment to reduce heavy menstrual flow and referral to specialty care should be initiated swiftly to improve quality of life for this population. .
Topics: Adolescent; Female; Humans; Ehlers-Danlos Syndrome; Joint Instability; Menorrhagia; Quality of Life
PubMed: 38466333
DOI: 10.3928/19382359-20240109-05