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.
CONCLUSIONS: 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.

BACKGROUND: Adolescent heavy menstrual bleeding(HMB), menorrhagia or abnormal uterine bleeding commonly occur in adolescent women. The differential diagnosis can be challenging. The pneumonic: PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified), is commonly used but it does not stratify as to the likelihood of a disorder. We have sought to develop a probability-based differential diagnosis for Adolescent HMB, menorrhagia or abnormal uterine bleeding.
METHODS: A comprehensive literature search was conducted using PubMed, EMBASE, and SCOPUS databases. Case series describing adolescents from 10-19 years of age with HMB, menorrhagia or abnormal uterine bleeding was acceptable if: more than 10 patients were included; editorials, case reports, and secondary sources such as review articles, or book chapters were excluded. No language filter was used, but an English abstract was required. The etiology of HMB, menorrhagia or abnormal uterine bleeding, and the country of origin was extracted from articles that met inclusion criteria. Cumulative rate estimates were determined by Bayesian probability modeling.
RESULTS: Seventeen full text articles were reviewed in detail; 2,770 patients were included. The most frequent causes of HMB were Ovarian Uterine Disorders (23.7%; 95% CredI 22-25.5%), Coagulation Disorders (19.4%; 95% CredI 17.8-21.1%), and Platelet Disorders (6.23%; 95% CredI 5.27-7.27%) with 45.9% (95% CredI 43.8-47.%9) of the cases of indeterminate origin.
CONCLUSIONS: The leading causes of HMB in healthy adolescent females were varied. The sub-analysis identified distinct etiologies, suggesting that multiple factors must be considered in the evaluation of HMB. While PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified) provides us with a comprehensive picture of the possible causes of HMB in females, this systematic review assigns probabilities to the etiologies of HMB in adolescent females, providing physicians with a more focused and efficient pathway to diagnosis.

Background: Vaginal bleeding during pregnancy has been recognised as a significant risk factor for adverse pregnancy outcomes. This study aimed to investigate the association between vaginal bleeding during the first trimester of pregnancy and clinical adverse effects using a systematic review and meta-analysis.Methods: Databases of Scopus, Web of Science, PubMed (including Medline), Cochrane Library and Science Direct were searched until June of 2023. Data analysis using statistical test fixed- and random-effects models in the meta-analysis, Cochran and meta-regression. The quality of the eligible studies was assessed by using the Newcastle-Ottawa Scale checklist (NOS).Results: A total of 46 relevant studies, with a sample size of 1,554,141 were entered into the meta-analysis. Vaginal bleeding during the first trimester of pregnancy increases the risk of preterm birth (OR: 1.8, CI 95%: 1.6-2.0), low birth weight (LBW; OR: 2.0, CI 95%: 1.5-2.6), premature rupture of membranes (PROMs; OR: 2.3, CI 95%: 1.8-3.0), abortion (OR: 4.3, CI 95%: 2.0-9.0), stillbirth (OR: 2.5, CI 95%: 1.2-5.0), placental abruption (OR: 2.2, CI 95%: 1.4-3.3) and placenta previa (OR: 1.9, CI 95%: 1.5-2.4).Conclusions: Vaginal bleeding in the first trimester of pregnancy is associated with preterm birth, LBW, PROMs, miscarriage, stillbirth, placental abruption and placenta previa. Therefore, physicians or midwives need to be aware of the possibility of these consequences and manage them when they occur.
Vaginal bleeding in the first trimester of pregnancy increases the relative risk of preterm birth, low birth weight, premature rupture of membranes, abortion, stillbirth, placental abruption and placenta previa.

BACKGROUND: Menopause causes a variety of symptoms such as hot flashes and night sweats. While menopausal hormonal therapy has been used for managing postmenopausal vasomotor symptoms (VMS) for quite a while, it has a considerably poor safety profile.
OBJECTIVE: To review and analyze existing data to evaluate the efficacy of the neurokinin-3 antagonist, fezolinetant, in treating postmenopausal VMS and to assess its safety profile.
METHODS: A thorough literature search was performed on PubMed, Cochrane Library, and Google Scholar in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020, to find publications on the efficacy of fezolinetant for postmenopausal VMS. Changes in the frequency and severity scores of moderate/severe VMS and changes in the Hot Flash-Related Daily Interference Scale (HFRDIS), Greene Climacteric Scale (GCS), and Menopause-Specific Quality of Life (MENQoL) were the efficacy outcomes. Adverse events, drug-related treatment-emergent adverse effects (TEAEs), drug-related dropouts, hepatotoxicity, endometrial hyperplasia or tumor, and uterine bleeding were all safety outcomes. We used Review Manager 5.4 for pooling risk ratios (RRs) and mean differences (MDs) for dichotomous and continuous outcomes, respectively. A P value of < .05 was considered significant.
RESULTS: There was a significant reduction in mean daily VMS frequency at weeks 4 and 12 (MD, -2.36; 95% confidence interval [CI], -2.85 to -1.87; P < .00001, for week 12) and also a significant decrease in VMS severity scores in the treatment group. Furthermore, improvements in MENQoL, HFRDIS, and GCS scores were observed. There was no significant difference in adverse events while drug-related TEAEs (RR, 1.21; 95% CI, 0.90-1.63; P = .21) showed a slight increase with fezolinetant. Drug-related dropouts were again similar across the 2 groups. Uterine bleeding had a lower incidence while endometrial events and hepatotoxicity showed a statistically insignificant, increasing trend in the fezolinetant group.
CONCLUSIONS: Fezolinetant can be a treatment option for postmenopausal VMS but warns of a risk increase in endometrial hyperplasia or tumors. The heterogeneity in the data being analyzed, short follow-up period, and small sample size in most of the included randomized controlled trials were the greatest limitations, which must be considered in further research and safety profile exploration.

BACKGROUND: Pulmonary embolism (PE) is a common cause of cardiovascular death whose major acquired risk factors include postoperative states, pregnancy, malignancy, and age. We report a case of PE that occurred after diagnostic curettage for abnormal uterine bleeding, with a medical history of adenomyosis and hysteromyoma.
METHODS: A 31-year-old Han Chinese female was referred to our hospital with menstrual disorders, increased menstrual flow, and severe anemia. After admission, the patient was treated with a blood transfusion, iron supplementation, and erythropoietin, and diagnostic curettage was performed the following day. On the first postoperative day, the patient developed pulmonary embolism with dyspnea and fever diagnosed by CT pulmonary angiography and significantly elevated D-dimer.
RESULTS: Molecular weight heparin was administered for PE for 2 weeks, dyspnea was relieved significantly after 2 days of treatment and the uterine bleeding did not increase; and gonadotropin-releasing hormone agonists were administered for adenomyosis after 1 week of anticoagulant therapy to reduce bleeding. We followed up for 6 months, and the patient had no recurrence of thrombosis and uterine bleeding had improved.
CONCLUSIONS: We speculate that the occurrence of pulmonary embolism was closely related to adenomyosis, hysteromyoma, and curettage in this patient. Treating the presence of both menstrual bleeding and thromboembolism is challenging, and careful management is necessary to avoid therapeutic contradictions.

BACKGROUND: Adenomyosis, a gynecological condition characterized by endometrial tissue within the uterine myometrium, often leads to menstrual pain and heavy bleeding, significantly affecting the quality of life. The primary treatment for adenomyosis and leiomyomas is hysterectomy. However, in rare instances, these conditions can recur in the cervical stump following a hysterectomy.Here, we present a case of cervical adenomyoma development after a prior laparoscopic supracervical hysterectomy.
METHODS: A 47-year-old woman sought medical attention due to increased vaginal bleeding.
METHODS: She had undergone a laparoscopic supracervical hysterectomy 7 years earlier to address uterine myoma and adenomyosis. Just 1 month posthysterectomy, a pelvic ultrasound revealed the presence of a cervical stump measuring approximately 4.0 × 4.0 cm. Subsequent follow-up ultrasounds documented the gradual growth of the cervical mass. Two years ago, a recurrent myoma was identified, and the patient experienced intermittent vaginal bleeding. Over 7 years, the cervical mass increased from 4 to 7 cm. Preadmission pelvic ultrasonography confirmed the existence of cervical adenomyoma measuring 7 × 6 cm.
METHODS: Consequently, the patient underwent a laparoscopic trachelectomy. Intraoperatively, an enlarged cervix, approximately 7 × 6 cm in size, containing adenomyoma was observed. A gross examination of the specimen indicated hypertrophic muscle tissue and hemorrhagic foci. Subsequent histopathological examination confirmed the presence of adenomyoma.
RESULTS: Remarkably, the patient exhibited no recurrence over the subsequent 8 months.
CONCLUSIONS: The case presented here highlights the potential occurrence of cervical adenomyoma following a supracervical hysterectomy. Management options include hormone therapy and surgical excision. Furthermore, annual follow-up comprising ultrasound and pap smear evaluations is recommended for patients with supracervical hysterectomies to detect and address possible recurrences.

Time to diagnosis (TTD) of childhood soft tissue sarcoma (STS) is significantly associated with survival. This review aims to identify pre-diagnostic symptoms/signs to inform earlier diagnosis interventions.
Medline, Embase, Cochrane and Web-of-Science were searched between January 2010 and February 2021 for studies including children (<18 years) diagnosed with STS, with no language restrictions. Pooled proportions of symptoms/signs were calculated and subanalysed by tumour location and age.
Fifty-nine eligible studies were identified, totalling 2462 cases. The most frequent symptoms were lump/swelling (38%, 95% CI 27% to 51%), pain (6%, 95% CI 3% to 10%), cutaneous changes (4%, 95% CI 0 to 9%), localised eye swelling (3%, 95% CI 0 to 7%), cranial nerve deficits (2%, 95% CI 0 to 5%) and constitutional symptoms (2%, 95% CI 0 to 5%).Symptoms varied by location and age. Localised eye swelling (20%, 95% CI 3% to 45%), cranial nerve deficits (14%, 95% CI 4% to 28%) and impaired visual function (6%, 95% CI 0 to 17%) were frequent in head and neck tumours. For abdomen/pelvic tumours, urinary symptoms (24%, 95% CI 5% to 15%), abdominal distension/discomfort (22%, 95% CI 4% to 47%), genital lump/swelling (16%, 95% CI 1% to 42%), constitutional symptoms (9%, 95% CI 0%] to 23%), vaginal bleeding (7%, 95%C I 0 to 21%) and bowel habit changes (6%, 95% CI 0 to 17%) were frequent.In <5 years, consumptive coagulopathy (16%, 95% CI 0 to 48%), cutaneous changes (5%, 95% CI 0 to 40%), genital lump/swelling (4%, 95% CI 0 to 14%), reduced mobility (3%, 95% CI 0 to 11%), vaginal bleeding (2%, 95% CI 0 to 11%) and bleeding/bruising/petechiae (2%, 95% CI 0 to 20%) were frequent compared with lump/swelling, constitutional symptoms, pain and headaches which were frequent among >11 years.
For STS, pre-diagnostic symptoms differ by age and location, highlighting the need to tailor early diagnosis interventions.

Von Willebrand disease (VWD) is a bleeding disorder caused by a congenital quantitative reduction, deficiency, or qualitative abnormality of the von Willebrand factor (VWF). Here, we report a case of delayed postoperative bleeding in an infertile woman with endometrial polyps complicated by VWD. The patient was a 39-year-old infertile woman with type 2A VWD. At 38 years of age, she was referred to our hospital for infertility and heavy menstrual bleeding. Hysteroscopy revealed a 15-mm polyp lesion in the uterus. The patient was scheduled for transcervical resection (TCR) of the endometrial polyp. Gonadotropin-releasing hormone agonists were preoperatively administered to prevent menstruation. The VWF-containing concentrate was administered for 3 days according to guidelines. The patient was discharged on postoperative day 3 after confirming the absence of uterine bleeding. Uterine bleeding began on postoperative day 6. The patient was readmitted on postoperative day 7 and treated with VWF-containing concentrate for 5 days, after which hemostasis was confirmed. TCR surgery for endometrial lesions is classified as a minor surgery, and guidelines recommend short-term VWF-containing concentrate replacement. However, it should be kept in mind that only short-term VWF-containing concentrate replacement may cause rebleeding postoperatively.

Adenomyosis is associated with pelvic pain, abnormal uterine bleeding, and infertility. Several ultrasound-based classifications have been reported, but it is not clear which criteria reflect the severity of symptoms. The aim of this review is to summarize the ultrasound features that correlate with clinical manifestations of adenomyosis and to discuss diagnostic methods for predicting disease severity. A literature search of PubMed and Google Scholar published up to March 2022 was performed. A consensus-based classification was determined primarily by defining the mapping or topography of the lesion. Ultrasound features can be classified into direct (i.e., the presence of ectopic endometrial tissue within the myometrium) and indirect findings (i.e., changes in the myometrial structure and translesional vascularity secondary to myometrial invasion). There are some reports that symptoms are positively correlated with the location and spread of the disease. Indeed, the lesion thickness, diffuse or internal adenomyosis, and focal adenomyosis may be associated with increased risks of dysmenorrhea, abnormal uterine bleeding, and infertility, respectively. Two ultrasound markers (i.e., the presence of heterogeneous myometrium and myometrial cysts) appear to be the criteria most clinicians focus on. However, decision-making on treatment necessity is determined by symptom severity rather than the topography of the lesions. There is currently no consensus that symptom severity can be predicted based on ultrasound features, but the ultrasound-based criteria may be helpful in diagnosing adenomyosis.

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.
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.
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.
PROSPERO CRD42019137282.