BACKGROUND: Abnormal uterine bleeding (AUB) that occurs in a structurally normal uterus with regular menstrual cycles and without other identifiable etiology is often caused by a primary endometrial disorder (AUB-E). Altered vascular morphological changes and expression of markers of angiogenesis have been implicated as an underlying cause in these cases.
OBJECTIVE:  The study was conducted to investigate the expression of vascular endothelial growth factor (VEGF) and smooth muscle actin-alpha (SMA-α), and to perform microvessel density (MVD), and morphometric evaluation of endometrial vessels in patients with AUB-E.
METHODS: Endometrial biopsies and hysterectomy specimens of 40 patients clinically diagnosed with AUB-E were included in the study with 40 age-matched controls. Immunohistochemistry (IHC) with VEGF and SMA-α was performed, and the expression and staining pattern was recorded as the number of positive vessels per 10 high power fields and intensity scores. Morphometric analysis was performed on CD34 stained sections using Leica Application Suite, version 4.4.0 software (Leica Microsystems, Wetzlar, Germany). MVD was calculated by the vascular hotspot method.
RESULTS: A statistically significant increase in VEGF vessel count (p-value<0.001) and a decline in SMA-α expression (p-value=0.23) was seen in cases as compared to the control group. There was a statistically significant increase in microvessel caliber (p-value=0.01) and MVD (p-value <0.001) in cases as compared to controls.
CONCLUSIONS: These findings support aberrant vascular proliferation and impaired vessel maturation, contributing to the pathology of AUB-E. Alterations in angiogenesis in these patients reveal potential therapeutic targets for AUB.

OBJECTIVE: In the present study, we aimed to compare serum CK-MM levels in patients with and without adenomyosis and to investigate whether CK-MM level can be a non-invasive marker for myometrial damage due to adenomyosis.
METHODS: Our study was a prospective case-control study in a tertiary center and consisted of 40 patients with a clinical/ultrasonographic diagnosis of adenomyosis and 40 patients without a clinical/ultrasonographic diagnosis of adenomyosis as the control group based on recently published morphological uterus sonographic assessment (MUSA) criteria. Individuals of similar age who signed a voluntary consent form were included in our study. Demographic, clinical, and laboratory findings of the patients in both groups were recorded. Blood serum samples were used for the determination of serum CK-MM levels of the participants in our study. The samples were analyzed by using the human CK-MM enzyme-linked immunosorbent assay (ELISA) kit.
RESULTS: In our study, the mean serum CK-MM level was 16.2 ± 21.7 (ng/dL) in patients with adenomyosis and 2.6 ± 2.2 (ng/dL) in patients without adenomyosis. Serum CK-MM level was statistically significantly higher in the patient group with adenomyosis than in the control group (p < 0.001). The CK-MM threshold value of 3.43 ng/mL, with a sensitivity of 82.5% and specificity of 85%, has been found to be a valuable distinguishing level in patients with and without adenomyosis.
CONCLUSIONS: In this study, we demonstrated that serum CK-MM can be used as a non-invasive diagnostic method in patients with adenomyosis. As the number of studies around this subject in the literature is insufficient, larger studies are needed to use CK-MM as a diagnostic marker in adenomyosis.

OBJECTIVE: To investigate the association between caesarean scar defects and abnormal uterine bleeding through systematic literature review.
METHODS: PubMed, Web of Science, Cochrane Library and Embase databases were searched based on PRISMA 2020 to include studies exploring abnormal uterine bleeding in women with caesarean scar defects. The combined relative risk (RR) of uterine bleeding, combined prevalence of abnormal uterine bleeding and combined RR of intermenstrual uterine bleeding were calculated using a fixed- or random-effects model.
RESULTS: Ten studies involving 1,183 women with caesarean scar defects met the inclusion criteria for this study. Compared with women without caesarean scar defects, those with caesarean scar defects had a higher risk of abnormal uterine bleeding (RR: 3.22, 95% CI: 1.83-5.66) and intermenstrual bleeding (RR: 2.93, 95% CI: 1.91-4.50). The prevalence of abnormal uterine bleeding was approximately 0.46 (95% CI: 0.27-0.64), and across populations, women with a previous caesarean section who had undergone imaging specifically for gynaecological disease had a significantly higher prevalence of abnormal uterine bleeding (0.77, 95% CI: 0.65-0.89) than those with at least one caesarean Sect. (0.25, 95% CI: 0.10-0.39).
CONCLUSIONS: A significant association was observed between caesarean scar defects and abnormal uterine bleeding, with the former being a risk factor for the latter. However, previous studies have differed in the definition of caesarean scar defects and abnormal uterine bleeding, and more high-quality studies are needed to further investigate the relevant definitions and study results in the future.

Angioleiomyoma is an uncommon benign neoplasm of mesenchymal origin that arises from perivascular smooth muscle cells. This soft tissue neoplasm usually occurs in the dermal or subcutaneous tissues of the extremities, head and neck, or trunk with fewer than 40 reported angioleiomyomas arising in the uterine corpus. Herein we report a uterine angioleiomyoma in a 44-year-old G5P4 Hispanic woman with a longstanding history of recurrent abdominal pain, pelvic organ prolapse, abnormal uterine bleeding, anemia, and hypertension. The patient underwent surgical treatment with total laparoscopic hysterectomy with bilateral salpingectomy and a uterosacral ligament suspension. Uterine angioleiomyoma was diagnosed post-operatively based on gross and microscopic features. The location of the uterine angioleiomyoma within the myometrium corresponded with contrast enhancement apparent on preoperative imaging. This and other uterine angioleiomyomas have characteristic imaging, macroscopic, and microscopic features which distinguish it from leiomyoma. Enhancing awareness of this underrecognized entity will facilitate precise diagnosis and thereby enable improved understanding of the clinicopathological characteristics of uterine angioleiomyoma.

UNASSIGNED: This study aimed to evaluate characteristics of endometrial surveillance in women treated for breast cancer to build a clinical prediction model.
UNASSIGNED: A multicentric retrospective cohort study was conducted at two tertiary-care university hospitals from January 2020 to June 2023. Perimenopausal and postmenopausal women treated for breast cancer were categorized into two groups: patients with and without diagnosis of endometrial malignancy (endometrial carcinoma) or premalignancy (atypical endometrial hyperplasia). Characteristics of breast cancer and ultrasonographic and hysteroscopic examinations were compared. A prediction model for endometrial malignancy was built using logistic regression. Predictive accuracy was assessed using the receiver operating characteristic (ROC) curve and goodness of fit using the Hosmer-Lemeshow test.
UNASSIGNED: One hundred and thirty-two (28 with premalignancy or malignancy and 104 without malignancy) women were analyzed. A nomogram was produced for prediction model development utilizing the presence and duration in months of abnormal uterine (BL)eeding, ultrasound (US) vascular pattern and echogenicity and (H)ysteroscopic appearance of endometrium (BLUSH) as determined by logistic regression. Sensitivity and specificity were 79.17% and 95.19%, respectively, with an area under ROC curve of 0.965, indicating good accuracy. Good goodness of fit and prediction stability were indicated by the calibration curve and Hosmer-Lemeshow test (χ2 = 26.36; p = 0.999).
UNASSIGNED: Breast cancer survivors undergoing endometrial surveillance might benefit from a potentially useful prediction model based on hysteroscopic appearance, ultrasonographic uniformity of endometrium, Doppler flow and presence of abnormal uterine bleeding.

Osseous metaplasia of the endometrium is a rare and intriguing pathological condition characterized by the presence of bony tissue within the endometrial cavity. This phenomenon can have significant clinical implications, particularly in the context of infertility. The etiology of osseous metaplasia remains unclear, although various hypotheses have been proposed, including chronic inflammation, dystrophic calcification, and residual embryonic tissue. Clinically, patients may present with secondary infertility, abnormal uterine bleeding, or pelvic pain. Diagnosis can be made based on ultrasonography and histopathological analysis of the endometrial tissue. Treatment typically involves the removal of the osseous tissue via hysteroscopy, which can lead to the restoration of normal endometrial function and potentially resolve infertility. Further research is needed to elucidate the etiological factors and optimize treatment protocols.

Background/Objectives: An endometrial sampling is recommended for patients experiencing abnormal uterine bleeding above the age of 40 or 45. Valid risk prediction models are needed to accurately assess the risk of endometrial cancer and avoid an unnecessary endometrial biopsy in premenopausal women. We aimed to assess the necessity and usefulness of preoperative endometrial sampling by evaluating premenopausal women who underwent hysterectomy for abnormal uterine bleeding after preoperative endometrial sampling at our clinic. Methods: A retrospective analysis was conducted on 339 patients who underwent preoperative endometrial sampling and subsequently underwent hysterectomy due to abnormal uterine bleeding. Detailed gynecologic examinations, patient histories, and reports of endometrial sampling and hysterectomy were recorded. Cohen\'s Kappa (κ) statistic was utilized to evaluate the concordance between histopathological results from an endometrial biopsy and hysterectomy. Results: The mean age of the cohort was 47 ± 4 years. Endometrial biopsies predominantly revealed benign findings, with 137 (40.4%) cases showing proliferative endometrium and 2 (0.6%) cases showing endometrial cancer. Following hysterectomy, final pathology indicated proliferative endometrium in 208 (61.4%) cases, with 7 (2.1%) cases showing endometrioid cancer. There was a statistically significant but low level of concordance between histopathological reports of endometrial biopsy and hysterectomy results (Kappa = 0.108; p < 0.001). Significant differences were observed only in the body mass index of patients based on hysterectomy results (p = 0.004). When demographic characteristics were compared with cancer incidence, smoking status and preoperative endometrial biopsy findings showed statistically significant differences (p = 0.042 and p = 0.010, respectively). Conclusions: The concordance between the pathological findings of a preoperative endometrial biopsy and hysterectomy is low. Body mass index is an important differentiating factor between benign histopathologic findings of endometrium and endometrial neoplasia. Moreover, adenomyosis was found to be associated with endometrial cancer cases. The current approach to premenopausal women with abnormal uterine bleeding, which includes a routine endometrial biopsy, warrants re-evaluation by international societies and experts.

BACKGROUND: Chronic pelvic pain (CPP) is a multifactorial syndrome that can substantially affect a patient\'s quality of life. Endometriosis is one cause of CPP, and alterations of the immune and microbiome profiles have been observed in patients with endometriosis. The objective of this pilot study was to investigate differences in the vaginal and gastrointestinal microbiomes and cervicovaginal immune microenvironment in patients with CPP and endometriosis diagnosis compared to those with CPP without endometriosis and no CPP.
METHODS: Vaginal swabs, rectal swabs, and cervicovaginal lavages (CVL) were collected among individuals undergoing gynecologic laparoscopy. Participants were grouped based on patients seeking care for chronic pain and/or pathology results: CPP and endometriosis (CPP-Endo) (n = 35), CPP without endometriosis (n = 23), or patients without CPP or endometriosis (controls) (n = 15). Sensitivity analyses were performed on CPP with endometriosis location, stage, and co-occurring gynecologic conditions (abnormal uterine bleeding, fibroids). 16S rRNA sequencing was performed to profile the microbiome, and a panel of soluble immune mediators was quantified using a multiplex assay. Statistical analysis was conducted with SAS, R, MicrobiomeAnalyst, MetaboAnalyst, and QIIME 2.
RESULTS: Significant differences were observed between participants with CPP alone, CPP-Endo, and surgical controls for body mass index, ethnicity, diagnosis of ovarian cysts, and diagnosis of fibroids. In rectal microbiome analysis, both CPP alone and CPP-Endo exhibited lower alpha diversity than controls, and both CPP groups revealed enrichment of irritable bowel syndrome-associated bacteria. CPP-Endo exhibited an increased abundance of vaginal Streptococcus anginosus and rectal Ruminococcus. Patients with CPP and endometrioma (s) demonstrated increased vaginal Streptococcus, Lactobacillus, and Prevotella compared to other endometriosis sites. Further, abnormal uterine bleeding was associated with an increased abundance of bacterial vaginosis-associated bacteria. Immunoproteomic profiles were distinctly clustered by CPP alone and CPP-Endo compared to controls. CPP-Endo was enriched in TNF⍺, MDC, and IL-1⍺.
CONCLUSIONS: Vaginal and rectal microbiomes were observed to differ between patients with CPP alone and CPP with endometriosis, which may be useful in personalized treatment for individuals with CPP and endometriosis from those with other causes of CPP. Further investigation is warranted in patients with additional co-occurring conditions, such as AUB/fibroids, which add additional complexity to these conditions and reveal the enrichment of distinct pathogenic bacteria in both mucosal sites. This study provides foundational microbiome-immunoproteomic knowledge related to chronic pelvic pain, endometriosis, and co-occurring gynecologic conditions that can help improve the treatment of patients seeking care for pain.

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.

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.