Uterine fibroids in women diagnosed with acromegaly: a systematic review.

The review discusses the relationship between acromegaly and uterine fibroids. It highlights variations in research methodologies and inconsistent findings, emphasizing the complex nature of fibroid development and the role of the somatotropic axis. Additionally, it addresses demographic factors and examines the potential impact of therapies on the risk and prevalence of uterine fibroids in individuals with acromegaly. We conducted an analysis of previously published literature that examined the repercussions of acromegaly on gynecological health in female cohorts, with specific attention directed towards elucidating the prevalence of uterine fibroids. We suggest that larger, more focused studies are needed to understand the specific impact of different treatments on the occurrence of gynecological issues in acromegaly patients. Additionally, our study emphasizes the importance of factors such as disease duration and treatment effectiveness. We hypothesize that a relationship between acromegaly and uterine fibroids may occur. However, it remains an area of ongoing research, with the need for larger, multi-center studies to draw more definitive conclusions.

Uterine artery embolization vs myomectomy for the management of women with uterine leiomyomas: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate whether uterine artery embolization offers a better quality of life than myomectomy in premenopausal women diagnosed with leiomyomas of the uterus. DATA SOURCES: A literature search was performed using the electronic databases of PubMed and Cochrane Central Register of Controlled Trials from inception to January 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing uterine artery embolization with myomectomy in women of premenopausal age suffering from uterine leiomyomas were considered. METHODS: The primary outcome was quality of life. The secondary outcomes were reintervention rate and timing, successful pregnancy, stillbirth and miscarriage, cesarean delivery on delivery, and perioperative morbidity. Moreover, time-to-event and standard pairwise meta-analyses were performed, as appropriate. The certainty of the evidence was assessed in line with the Grading of Recommendations, Assessment, Development, and Evaluations methodology. RESULTS: A total of 6 randomized controlled trials met our inclusion criteria. The meta-analysis suggested little to no difference in terms of quality of life between uterine artery embolization and myomectomy (standard mean difference, 0.05; 95% confidence interval, -0.38 to 0.48; I2=92%; very low certainty of evidence). Sensitivity analysis, including randomized controlled trials, which included solely myomectomy procedures in the control arm, demonstrated better quality of life for women treated with myomectomy (standard mean difference, -0.32; 95% confidence interval, -0.49 to -0.15; I2=15%). Concerning reintervention, myomectomy was likely associated with a decreased risk of future reintervention (risk ratio, 0.32; 95% confidence interval, 0.15-0.69; I2=60%; low certainty of evidence) and a more prolonged time interval since a potential reintervention because of recurrence than uterine artery embolization (hazard ratio, 0.41; 95% confidence interval, 0.22-0.77; I2=77%; low certainty of evidence). No difference was found between the 2 interventions concerning severe perioperative adverse events (relative risk, 4.13; 95% confidence interval, 0.44-39.20; I2=0%; low certainty of evidence). CONCLUSION: Uterine artery embolization is likely associated with increased reintervention rates and less time to reintervention compared with myomectomy in premenopausal women diagnosed with uterine leiomyomas. Evidence suggests no difference between the 2 interventions regarding perioperative morbidity. Uterine artery embolization may exert no effect on quality of life and successful pregnancy; however, the evidence is very uncertain.

Altered extracellular matrix-related pathways accelerate the transition from normal to prefibroid myometrium in Black women.

BACKGROUND: Black women experience a disproportionate impact of uterine fibroids compared to White women, including earlier diagnosis, higher frequency, and more severe symptoms. The etiology underlying this racial disparity remains elusive. OBJECTIVE: The aim of this study was to evaluate the molecular differences in normal myometrium (fibroid-free uteri) and at-risk myometrium (fibroid-containing uteri) tissues in Black and White women. STUDY DESIGN: We conducted whole-genome RNA-seq on normal and at-risk myometrium tissues obtained from both self-identified Black and White women (not Hispanic or Latino) to determine global gene expression profiles and to conduct enriched pathway analyses (n=3 per group). We initially assessed the differences within the same type of tissue (normal or at-risk myometrium) between races. Subsequently, we analyzed the transcriptome of normal myometrium compared to at-risk myometrium in each race and determined the differences between them. We validated our findings through real-time PCR (sample size range=5-12), western blot (sample size range=5-6), and immunohistochemistry techniques (sample size range=9-16). RESULTS: The transcriptomic analysis revealed distinct profiles between Black and White women in normal and at-risk myometrium tissues. Interestingly, genes and pathways related to extracellular matrix and mechanosensing were more enriched in normal myometrium from Black than White women. Transcription factor enrichment analysis detected greater activity of the serum response transcription factor positional motif in normal myometrium from Black compared to White women. Furthermore, we observed increased expression levels of myocardin-related transcription factor-serum response factor and the serum response factor in the same comparison. In addition, we noted increased expression of both mRNA and protein levels of vinculin, a target gene of the serum response factor, in normal myometrium tissues from Black women as compared to White women. Importantly, the transcriptomic profile of normal to at-risk myometrium conversion differs between Black and White women. Specifically, we observed that extracellular matrix-related pathways are involved in the transition from normal to at-risk myometrium and that these processes are exacerbated in Black women. We found increased levels of Tenascin C, type I collagen alpha 1 chain, fibronectin, and phospho-p38 MAPK (Thr180/Tyr182, active) protein levels in at-risk over normal myometrium tissues from Black women, whereas such differences were not observed in samples from White women. CONCLUSION: These findings indicate that the racial disparities in uterine fibroids may be attributed to heightened production of extracellular matrix in the myometrium in Black women, even before the tumors appear. Future research is needed to understand early life determinants of the observed racial differences.

MiRNAs related in signaling pathways of women's reproductive diseases: an overview.

BACKGROUND: One of the main health issues that can affect women's health is reproductive diseases, such as polycystic ovary syndrome (PCOS), endometriosis (EMs), uterine leiomyomas (ULs), and ovarian cancer (OC). Although these diseases are very common, we do not have a complete understanding of their underlying cellular and molecular mechanisms. It is important to mention that the majority of patients are diagnosed with these diseases at later stages because of the absence of early diagnostic techniques and dependable molecular indicators. Hence, it is crucial to discover novel and non-invasive biomarkers that have prognostic, diagnostic and therapeutic capabilities. MiRNAs, also known as microRNAs, are small non-coding RNAs that play a crucial role in regulating gene expression at the post-transcriptional level. They are short in length, typically consisting of around 22 nucleotides, and are highly conserved across species. Numerous studies have shown that miRNAs are expressed differently in various diseases and can act as either oncogenes or tumor suppressors. METHODS: The author conducted a comprehensive review of all the pertinent papers available in web of science, PubMed, Google Scholar, and Scopus databases. RESULTS: We achieved three goals: providing readers with better information, enhancing search results, and making peer review easier. CONCLUSIONS: This review focuses on the investigation of miRNAs and their involvement in various reproductive disorders in women, including their molecular targets. Additionally, it explores the role of miRNAs in the development and progression of these disorders.

Spontaneous regression of a giant uterine leiomyoma after delivery: a case report and literature review.

BACKGROUND: Uterine leiomyomas are hormone-dependent benign tumors and often begin to shrink after menopause due to the reduction in ovarian steroids. The influence of pregnancy on uterine leiomyomas size remains unclear. Here, we present a case of spontaneous regression of a giant uterine leiomyoma after delivery. CASE PRESENTATION: A 40-year-old woman presented with multiple uterine leiomyomas, one of which is a giant uterine leiomyomas (approximately 8 cm in diameter) that gradually shrinked after delivery. At over two months postpartum, the large myometrial leiomyoma had transformed into a submucosal leiomyoma, and over 3 years postpartum, both the submucosal leiomyoma and multiple intramural leiomyomas completely regressed. CONCLUSION: Spontaneous regression of a giant uterine leiomyom is rare after delivery. Considering uterine leiomyoma regression until over 3 year postpartum,we need to observe the regression of uterine fibroid for a longer time postpartum in the absence of fibroid related complications. In addition, it will provide new insights for treatment options of uterine leiomyomas in the future.

"In our community, we normalize pain": discussions around menstruation and uterine fibroids with Black women and Latinas.

BACKGROUND: Uterine fibroids are non-cancerous neoplasms that arise from the uterus affecting over 75% of women. However, there is a disparity with Black women having an increased prevalence of nearly 80%. Black women also experience increased symptom burden, including younger age at the time of diagnosis and increased number and volume of fibroids. Less is known about other ethnoracially diverse women such as Latinas and the potential cultural impacts on fibroid burden and treatment. METHODS: Community engagement studios were conducted to facilitate discussions with stakeholders on their uterine fibroid and menstruation experience. We recruited Black women (n = 6) diagnosed with uterine fibroids and Latinas (n = 7) without uterine fibroids. We held two virtual community engagement studios split by uterine fibroid diagnosis. The studios were not audio recorded and notes were taken by four notetakers. The notes were thematically analyzed in Atlas.ti using content analysis. RESULTS: Participants felt there was a lack of discussion around menstruation overall, whether in the home or school settings. This lack of menstruation education was pronounced when participants had their first menstruation experience, with many unaware of what to expect. This silence around menstruation led to a normalization of painful menstruation symptoms. When it came to different treatment options for uterine fibroids, some women wanted to explore alternative treatments but were dismissed by their healthcare providers. Many participants advocated for having discussions with their healthcare provider about life goals to discuss different treatment options for their uterine fibroids. CONCLUSION: Despite uterine fibroid diagnosis, there is silence around menstruation. Menstruation is a normal biological occurrence and needs to be discussed to help prevent delayed diagnosis of uterine fibroids and possibly other gynecological disorders. Along with increased discussions around menstruation, further discussion is needed between healthcare providers and uterine fibroid patients to explore appropriate treatment options.

Vitamin D and its binding protein in patients with leiomyomas.

AIM: This study examined the levels of VitD, VitD binding protein (DBP), and free VitD in leiomyomas patients and their association with the quantity, dimensions, and site of fibroid growths. Additionally, we evaluated the potentiality of employing these factors as a biomarker tool for the diagnosis and assessment of uterine fibroid progression. METHODS: This study involved the participation of 55 women with leiomyomas and 50 healthy women. We utilized commercial ELISA kits to measure the levels of total VitD and DBP in their serum. Additionally, we calculated the levels of free VitD and the ratio of VitD to DBP. Moreover, we determined the number, size, and location of the leiomyomas in the patients. RESULTS: There were no significant differences in the levels of total VitD between the groups. However, patients had significantly lower levels of free VitD and higher levels of DBP compared to the control group. The size of the largest leiomyomas showed a negative relationship with free VitD and a positive relationship with DBP. Receiver operating characteristic analyses, showed that the cut-off value for free VitD was 4.47 pg/mL, with a sensitivity of 75.6% and a specificity of 74.4%. The cut-off value for DBP was 256.2 µg/mL, with a sensitivity of 86% and a specificity of 70.3%. CONCLUSIONS: Free VitD and DBP potentially contribute to the development of leiomyomas and are linked to the size of these tumors. The measurement of serum levels of these factors could serve as additional biomarkers for the diagnosis of leiomyomas.

Diffuse uterine leiomyomatosis: a rare discovery.

PURPOSE: This case report aims to present a rare and challenging clinical scenario involving diffuse uterine leiomyomatosis (DUL), an infrequently encountered benign uterine pathology. The primary objective is to describe this unique case's clinical presentation, diagnostic challenges, and subsequent management. METHODS: A detailed analysis of the patient's medical history, diagnostic evaluations, and treatment approach was conducted. A relevant literature review on DUL was also performed. This case report includes high-resolution images and figures, showcasing MRI scans, surgical procedures, and histopathology slides related to the case. RESULTS: The case report outlines the clinical journey of a patient with DUL, an exceptionally rare uterine condition characterized by the uncontrolled proliferation of smooth muscle cells forming nodules and fascicles. This case illustrates the diagnostic complexities associated with DUL, as it mimics other uterine pathologies such as leiomyomas or adenomyosis. The patient's clinical presentation included abnormal uterine bleeding, heavy menstrual bleeding, fertility issues, and dysmenorrhea, leading to initial misdiagnoses. Surgical intervention eventually addressed the condition with corresponding images illustrating the procedures. CONCLUSION: This case report highlights DUL's rarity and diagnostic challenges. Clinicians must be vigilant when encountering similar clinical presentations, ensuring a comprehensive diagnostic workup to differentiate DUL from other uterine pathologies. Enhanced awareness among healthcare providers and further research into DUL's pathophysiology is essential for accurate diagnosis and timely management. The presented case underscores the need for tailored approaches to managing DUL and expanding the knowledge base surrounding this puzzling uterine disorder.

Periostin's role in uterine leiomyoma development: a mini-review on the potential periostin poses as a pharmacological intervention for uterine leiomyoma.

Uterine leiomyomas, also known as fibroids or myomas, occur in an estimated 70-80% of reproductive aged women. Many experience debilitating symptoms including pelvic pain, abnormal uterine bleeding (AUB), dyspareunia, dysmenorrhea, and infertility. Current treatment options are limited in preserving fertility, with many opting for sterilizing hysterectomy as a form of treatment. Currently, surgical interventions include hysterectomy, myomectomy, and uterine artery embolization in addition to endometrial ablation to control AUB. Non-surgical hormonal interventions, including GnRH agonists, are connotated with negative side effects and are unacceptable for women desiring fertility. Periostin, a regulatory extra cellular matrix (ECM) protein, has been found to be expressed in various gynecological diseases including leiomyomas. We previously determined that periostin over-expression in immortalized myometrial cells led to the development of a leiomyoma-like cellular phenotype. Periostin is induced by TGF-ß, signals through the PI3K/AKT pathway, induces collagen production, and mediates wound repair and fibrosis, all of which are implicated in leiomyoma pathology. Periostin has been linked to other gynecological diseases including ovarian cancer and endometriosis and is being investigated as pharmacological target for treating ovarian cancer, post-surgical scarring, and numerous other fibrotic conditions. In this review, we provide discussion linking pathological inflammation and wound repair, with a TGF-ß-periostin-collagen signaling in the pathogenesis of leiomyomas, and ultimately the potential of periostin as a druggable target to treat leiomyomas.

Insulin-Like Growth Factor-1 Promotes Human Uterine Leiomyoma Cell Proliferation via PI3K/AKT/mTOR Pathway.

The present research aimed to evaluate the expression of insulin-like growth factor-1 (IGF-1) in uterine leiomyoma, and explore its relationship with the occurrence and development of uterine leiomyoma and potential signal pathways. qRT-PCR and enzyme-linked immunosorbent assay were used for estimating the levels of IGF-1 in human uterine leiomyoma compared to myometrium. The expression of cell proliferation and PI3K/AKT/mTOR signaling pathway-related proteins in uterine leiomyoma cells was evaluated by western blot. Cell viability analysis was performed by CCK-8 assay. Lentivirus infection was used for IGF-1 overexpression and knockdown in uterine leiomyoma cells. The IGF-1 expression level was elevated in human uterine leiomyomas compared to myometrium. IGF-1 promoted the cell viability of human uterine leiomyoma cells. Overexpression of IGF-1 induced the expression of pro-proliferation markers including c-Myc, PCNA, and cyclin D1 in uterine leiomyoma cells. IGF-1 elevated the phosphorylation levels of PI3K, AKT, and mTOR, thus modifying PI3K/AKT/mTOR signaling in uterine leiomyoma cells. IGF-1 promotes proliferation of human uterine leiomyoma cells via PI3K/AKT/mTOR pathway.

Quality of life with relugolix combination therapy for uterine fibroids: LIBERTY randomized trials.

BACKGROUND: Symptomatic uterine fibroids are burdensome to live with; they are associated with symptom-related distress, affect daily activities, and reduce health-related quality of life. The LIBERTY randomized clinical trials showed that oral relugolix combination therapy (40 mg relugolix, 1 mg estradiol, and 0.5 mg norethindrone acetate once daily) markedly improved fibroid-associated symptoms and conditions, including heavy menstrual bleeding, pain, and anemia, and was well-tolerated. OBJECTIVE: This study aimed to evaluate the effect of relugolix combination therapy on the symptom burden and health-related quality of life among women with uterine fibroids. STUDY DESIGN: Two replicate, multinational, double-blind, 24-week, randomized, placebo-controlled, phase 3 studies, LIBERTY 1 and LIBERTY 2, were conducted in premenopausal women with uterine fibroid-associated heavy menstrual bleeding (≥80 mL per cycle for 2 cycles or ≥160 mL during 1 cycle). The symptom burden and health-related quality of life were secondary endpoints and were assessed using the validated Uterine Fibroid Symptom and Quality of Life questionnaire, which the participants completed at baseline and at week 12 and 24 of treatment. For this secondary analysis, the pooled LIBERTY 1 and LIBERTY 2 data set was used. The Uterine Fibroid Symptom and Quality of Life questionnaire is made up of a Symptom Severity scale and a Health-Related Quality of Life scale, the latter of which includes 6 subscales focusing on the following aspects of daily life: concern, activities, energy or mood, control, self-consciousness, and sexual function. The Revised Activities subscale of the Health-Related Quality of Life scale addresses the impact of uterine fibroids on physical and social activities. Symptom burden was also assessed via the Bleeding and Pelvic Discomfort subscale, a patient-reported outcome measure derived from the Uterine Fibroid Symptom Severity scale that focuses on distress from key uterine fibroid symptoms, which was a key secondary endpoint. Least squares mean changes from baseline to week 24 in the Symptom Severity scale, Bleeding and Pelvic Discomfort subscale, overall Health-Related Quality of Life scale, and the respective subscales were compared between the relugolix combination therapy and placebo groups. Responder analyses of the proportion of women who experienced a clinically meaningful change from baseline to week 24 were conducted for the Bleeding and Pelvic Discomfort and the activity subscales. A stratified Cochran-Mantel-Haenszel test, adjusted for stratification factors (region [North America vs rest of world] and baseline menstrual blood loss volume), was used for treatment comparisons. RESULTS: Across both trials, 509 women were randomized to the relugolix combination therapy or placebo groups (April 2017-December 2018). Participants on relugolix combination therapy showed a statistically significant reduction in symptom severity (-33.5 vs -12.1; nominal P<.0001) and the Bleeding and Pelvic Discomfort subscale from baseline to week 24 when compared with those on placebo treatment (-48.4 vs -17.4; nominal P<.0001). Overall, the total Health-Related Quality of Life scores improved significantly from baseline to week 24 in the relugolix combination therapy group when compared with the placebo (+37.6 vs +13.1; nominal P<.0001). Responder analyses demonstrated that more women treated with relugolix combination therapy reported a clinically meaningful reduction in the Bleeding and Pelvic Discomfort subscale and an improvement in physical and social activities when compared with those treated with the placebo (nominal P<.0001). CONCLUSION: After 24 weeks of treatment with relugolix combination therapy, women with symptomatic uterine fibroids experienced substantial improvements in health-related quality of life with all subscales showing improvement, including emotional well-being, physical and social activities, and sexual function. In addition, women reported substantial reductions in the overall symptom burden and distress caused by key fibroid-associated symptoms.

Uterine-preserving treatments or hysterectomy reintervention after myomectomy or uterine artery embolisation: A retrospective cohort study of long-term outcomes.

OBJECTIVE: To assess comparative rates of further uterine-preserving procedures (UPP) or hysterectomy reintervention, after myomectomy or uterine artery embolisation (UAE). DESIGN: Population-based, retrospective cohort study. SETTING: England. POPULATION: Women who underwent myomectomy or UAE between 2010 and 2015 under the NHS. METHODS: Data was abstracted from NHS Health Episode Statistics datasets. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional-hazards regression. MAIN OUTCOMES MEASURES: 30-day readmission, UPP and hysterectomy reintervention rates. RESULTS: 9443 and 6224 women underwent elective myomectomy or UAE, respectively. After 118 136 total person-years of follow-up, the rate of hysterectomy was 8.34 and 20.98 per 1000 patient years for myomectomy or UAE, respectively. There was a 2.4-fold increased risk of undergoing hysterectomy after UAE when compared with myomectomy in adjusted models (HR 2.38 [95% CI 2.10-2.66]) [adjusted for age, ethnicity, multiple deprivation index, geographical region and comorbidities]. The HR for undergoing a UPP reintervention was 1.44 (95% CI 1.29-1.60) in favour of myomectomy. The rate of hysterectomy was increased 22% following UAE compared with laparoscopic myomectomy (0.97-1.52). Age may influence reintervention rates, and there was variation in hysterectomy risk when stratified by geographical region. CONCLUSIONS: After a median of 7 years of follow-up, there is a 2.4-fold increased rate of hysterectomy and 44% increased risk of UPPs as reintervention after UAE, relative to myomectomy. These findings will aid pre-procedure counselling for women with fibroids. Future work should investigate the effect of other outcome modifiers, such as fertility intentions and fibroid anatomical characteristics.

Pregnancy outcomes following ultrasound-guided high-intensity focused ultrasound in submucous leiomyomas: a retrospective study.

OBJECTIVE: To investigate the impact of ultrasound-guided high-intensity focused ultrasound (USgHIFU) on pregnancy in submucous leiomyomas. MATERIALS AND METHODS: Between October 2015 and October 2021, a retrospective observational study was conducted at the Affiliated Hospital of North Sichuan Medical College, China, for 32 women with submucous leiomyomas who became pregnant after USgHIFU. Pregnancy outcomes, submucous leiomyomas characteristics, and USgHIFU parameters were analyzed. RESULTS: A total of 17 (53.1%) deliveries were successfully achieved, with full-term delivery in 16 (94.1%) patients and preterm delivery in 1 (5.9%). After USgHIFU, the effective volume in the uterus cavity and the volume of submucous leiomyomas shrank in all 32 patients. The median time to achieve pregnancy after USgHIFU was 11.0 months. Before pregnancy, myoma type was downgraded in 13 (40.6%) patients, stable in 10 (31.3%) and upgraded in 9 (28.1%). The vaginal expulsion rate of submucous leiomyomas was 28.1%, with complete expulsion in 3 (9.4%) patients and partial expulsion in 6 (18.8%). After USgHIFU, the size of submucous leiomyomas did not increase in each trimester (all p > 0.05). The high complications rate during pregnancy (7/17, 41.2%) was associated with advanced maternal age, with only one (5.9%) premature rupture of membranes possibly associated with submucous leiomyomas. There were 6 (35.5%) vaginal delivery and 11 (64.7%) cesarean sections. All 17 newborns developed well, with a mean birth weight of 3482 g. CONCLUSIONS: In patients with submucous leiomyomas, pregnancies and full-term deliveries can be successfully achieved following USgHIFU, with few related complications.

Informational Preferences of Women Seeking Treatment for Symptomatic Uterine Fibroids: A Qualitative Study.

STUDY OBJECTIVE: To establish the informational needs and preferences of women navigating treatment options for symptomatic uterine fibroids. DESIGN: Qualitative study using semistructured interviews. SETTING: Academic institution. PATIENTS: Participants had a diagnosis of symptomatic uterine fibroids with an active treatment plan. INTERVENTIONS: Semistructured video interviews were conducted with female patients undergoing treatment for symptomatic uterine fibroids (n = 20). Women were recruited from the outpatient Center for Complex Gynecology in Chicago, IL. Interviews were recorded and transcribed verbatim. A codebook was developed based on the interview transcripts, and the finalized coding was used to conduct a thematic analysis. MEASUREMENTS AND MAIN RESULTS: Four distinct themes emerged from the interviews: (1) Social supports-including social media-play an important role in informing patients' treatment choices; (2) Patients spend significant energy seeking additional information beyond their obstetrician-gynecologist; (3) Patients prioritize receiving full and complete information from their provider; and (4) Patients experience information-related delays in receiving care. CONCLUSION: Patients seeking care for symptomatic uterine fibroids have strong preferences about both the quality and extent of information they receive from their gynecologists. Physicians treating these conditions must adapt to changing informational desires and consider expanding physician engagement with patients' social media needs.

E. faecalis Sepsis and Asherman's Syndrome as Complications of Sonata System Transcervical Fibroid Ablation.

The Sonata System is a minimally invasive, ultrasound-guided transcervical fibroid ablation procedure for the management of symptomatic uterine fibroids. Since its approval by the US Food and Drug Administration in 2018, this procedure has demonstrated an excellent safety profile and postprocedure satisfaction rate. We present the case of a patient treated with Sonata, who subsequently developed bacterial sepsis and Asherman's syndrome-serious complications with long-term sequelae and implications for fertility. A nulligravid woman in her 40s presented in the outpatient setting with dysmenorrhea and bulk symptoms, with imaging showing an enlarged myomatous uterus compressing the urinary bladder. She desired minimally invasive, fertility-preserving management and underwent the Sonata procedure at an outside hospital. On postoperative day 3, she was admitted to our institution with abdominal pain, fever, tachycardia, and Enterococcus faecalis bacteremia. Despite 6 days of culture-directed antibiotic therapy, the patient remained septic with worsening symptoms and imaging findings and with persistent bacteremia. On hospital day 7, the patient underwent laparoscopic myomectomy and excision of hemorrhagic, infected myometrium. She recovered appropriately after surgery and was discharged home on hospital day 11 to continue 2 weeks of intravenous antibiotics. Nine months after myomectomy, the patient was diagnosed as having Asherman's syndrome. She subsequently had an early pregnancy loss with retained products of conception, requiring hysteroscopic lysis of adhesions and dilation and curettage. Ultimately, careful patient selection is critical for the optimal application of the Sonata procedure. Limiting the extent of fibroid necrosis after treatment is a reasonable goal to minimize the risk of secondary bacterial infection and adhesiogenesis as procedural sequelae.

Torsion of uterus in twin pregnancy.

Uterine torsion is defined as a rotation of uterus around its axis by more than 45° in its longitudinal length. Uterine torsion is very rare, it is reported that a physician encounters it only 1 time in a lifetime. Our case describes uterine torsion in a twin pregnancy, in a completely asymptomatic patient, where the dia-gnosis was made only peroperatively.

Halofuginone inhibits cell proliferation and AKT/mTORC1 signaling in uterine leiomyoma cells.

The present study aimed to explore the effects of antifibrotic agent halofuginone on uterine leiomyomas (ULs) cells. The survival of the uterine smooth muscle (UtSMC) cells and UL ELT3 cells were measured. Flow cytometry was used to assess the cell cycle distribution and apoptosis. Effects of halofuginone on the state of AKT/mTOR pathway were evaluated. Xenograft animal model was applied to explore the effects of halofuginone in vivo. Halofuginone inhibited the proliferation of ELT3 cells dose-dependently without obvious influence on UtSMC cells. Halofuginone suppressed cell cycle progression and promoted apoptosis of ELT3 cells dose-dependently. Also, p-AKT/AKT and p-p70S6/p70S6 were significantly lowered after treatment with 20 nM halofuginone. Additionally, halofuginone reduced ELT3 tumor growth in xenograft tumor animal model. The present study illustrates that halofuginone inhibits cell proliferation of ULs with low side effects on normal smooth muscle cells, and AKT/mTOR signaling pathway was inactivated meanwhile.

Single-cell sequencing reveals novel cellular heterogeneity in uterine leiomyomas.

STUDY QUESTION: What are the cellular composition and single-cell transcriptomic differences between myometrium and leiomyomas as defined by single-cell RNA sequencing? SUMMARY ANSWER: We discovered cellular heterogeneity in smooth muscle cells (SMCs), fibroblast and endothelial cell populations in both myometrium and leiomyoma tissues. WHAT IS KNOWN ALREADY: Previous studies have shown the presence of SMCs, fibroblasts, endothelial cells and immune cells in myometrium and leiomyomas. However, there is no information on the cellular heterogeneity in these tissues and the transcriptomic differences at the single-cell level between these tissues. STUDY DESIGN, SIZE, DURATION: We collected five leiomyoma and five myometrium samples from a total of eight patients undergoing hysterectomy. We then performed single-cell RNA sequencing to generate a cell atlas for both tissues. We utilized our single-cell sequencing data to define cell types, compare cell types by tissue type (leiomyoma versus myometrium) and determine the transcriptional changes at a single-cell resolution between leiomyomas and myometrium. Additionally, we performed MED12-variant analysis at the single-cell level to determine the genotype heterogeneity within leiomyomas. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected five MED12-variant positive leiomyomas and five myometrium samples from a total of eight patients. We then performed single-cell RNA sequencing on freshly isolated single-cell preparations. Histopathological assessment confirmed the identity of the samples. Sanger sequencing was performed to confirm the presence of the MED12 variant in leiomyomas. MAIN RESULTS AND ROLE OF CHANCE: Our data revealed previously unknown heterogeneity in the SMC, fibroblast cell and endothelial cell populations of myometrium and leiomyomas. We discovered the presence of two different lymphatic endothelial cell populations specific to uterine leiomyomas. We showed that both myometrium and MED12-variant leiomyomas are relatively similar in cellular composition but differ in cellular transcriptomic profiles. We found that fibroblasts influence the leiomyoma microenvironment through their interactions with endothelial cells, immune cells and SMCs. Variant analysis at the single-cell level revealed the presence of both MED12 variants as well as the wild-type MED12 allele in SMCs of leiomyomatous tissue. These results indicate genotype heterogeneity of cellular composition within leiomyomas. LARGE SCALE DATA: The datasets are available in the NCBI Gene Expression Omnibus (GEO) using GSE162122. LIMITATIONS, REASONS FOR CAUTION: Our study focused on MED12-variant positive leiomyomas for single-cell RNA sequencing analyses. Leiomyomas carrying other genetic rearrangements may differ in their cellular composition and transcriptomic profiles. WIDER IMPLICATIONS FOR THE FINDINGS: Our study provides a cellular atlas for myometrium and MED12-variant positive leiomyomas as defined by single-cell RNA sequencing. Our analysis provides significant insight into the differences between myometrium and leiomyomas at the single-cell level and reveals hitherto unknown genetic heterogeneity in multiple cell types within human leiomyomas. Our results will be important for future studies into the origin and growth of human leiomyomas. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by funding from the National Institute of Child Health and Human Development (HD098580 and HD088629). The authors declare no competing interests.

Minimally invasive myomectomy: practice trends and differences between Black and non-Black women within a large integrated healthcare system.

BACKGROUND: Although multiple professional organizations encourage minimally invasive surgical approaches whenever feasible, nationally, fewer than half of myomectomies are performed via minimally invasive routes. Black women are less likely than their non-Black counterparts to have minimally invasive surgery. OBJECTIVE: This study aimed to assess the trends in surgical approach among women who underwent minimally invasive myomectomies for uterine leiomyomas within a large integrated healthcare system as initiatives were implemented to encourage minimally invasive surgery, particularly evaluating differences in the proportion of minimally invasive surgery performed in Black vs non-Black women. STUDY DESIGN: We conducted a retrospective cohort study of women, aged ≥18 years, who underwent a myomectomy for a uterine leiomyoma within Kaiser Permanente Northern California between 2009 and 2019. Generalized estimating equations and Cochran-Armitage testing were used to assess myomectomy incidence and linear trend in the proportions of myomectomy by surgical route-abdominal myomectomy and minimally invasive myomectomy. Multivariable logistic regression analyses were used to assess the associations between surgical route and (1) race and ethnicity and (2) complications, controlling for patient demographic, clinical, and surgical characteristics. RESULTS: A total of 4033 adult women underwent a myomectomy during the study period. Myomectomy incidence doubled from 0.12 (95% confidence interval, 0.12-0.13) per 1000 women in 2009 to 0.25 (95% confidence interval, 0.24-0.25) per 1000 women in 2019 (P<.001). During the 11-year study period, the proportion of minimally invasive myomectomy increased from 6.0% to 89.5% (a 15-fold increase). The proportion of minimally invasive myomectomy in Black women remained lower than in non-Black women (54.5% vs 64.7%; P<.001). Black women undergoing myomectomy were younger (36.4±5.6 vs 37.4±5.8 years; P<.001), had a higher mean fibroid weight (436.0±505.0 vs 324.7±346.1 g; P<.001), and had a higher mean body mass index (30.8±7.3 vs 26.6±5.9 kg/m2; P<.001) than their non-Black counterparts. In addition to patient race, surgery performed between 2016 and 2019 compared with surgery performed between 2009 and 2012 and higher surgeon volume compared with low surgeon volume were associated with an increased proportion of minimally invasive myomectomy (adjusted relative risks, 12.58 [95% confidence interval, 9.96-15.90] and 6.63 [95% confidence interval, 5.35-8.21], respectively). Black race and fibroid weight of >500 g each independently conferred lower rates of minimally invasive myomectomy. In addition, there was an interaction between race and fibroid weight such that Black women with a fibroid weight of ≤500 g or >500 g were both less likely to have minimally invasive myomectomy than non-Black women with a fibroid weight of ≤500 g (adjusted relative risks, 0.74 [95% confidence interval, 0.58-0.95] and 0.26 [95% confidence interval, 0.18-0.36], respectively). Operative, perioperative, and medical complications were low during the 11-year study period. In regression analyses, after controlling for race, age, fibroid weight, parity, low-income residence, body mass index, surgeon volume, and year of myomectomy, the risk of complications was not markedly different comparing abdominal myomectomy with minimally invasive myomectomy. Similar results were found comparing laparoscopic minimally invasive myomectomy with robotic-assisted minimally invasive myomectomy except for women who underwent laparoscopic minimally invasive myomectomy had a lower risk of experiencing any medical complications than those who underwent robotic-assisted minimally invasive myomectomy (adjusted relative risk, 0.27; 95% confidence interval, 0.09-0.83; P=.02). CONCLUSION: Within an integrated healthcare delivery system, although initiatives to encourage minimally invasive surgery were associated with a marked increase in the proportion of minimally invasive myomectomy, Black women continued to be less likely to undergo minimally invasive myomectomy than their non-Black counterparts. Race and fibroid weight alone did not explain the disparities in minimally invasive myomectomy.

Appraisal of national and international uterine fibroid management guidelines: a systematic review.

BACKGROUND: Guidelines standardise high-quality evidence-based management strategies for clinicians. Uterine fibroids are a highly prevalent condition and may exert significant morbidity. OBJECTIVES: To appraise national and international uterine fibroid guidelines using the validated AGREE-II instrument. SELECTION STRATEGY: Database search of PubMed and EMBASE from inception to October 2020 for all published English-language uterine fibroid clinical practice guidelines. DATA COLLECTION AND ANALYSIS: In all, 939 abstracts were screened for eligibility by two reviewers independently. Three reviewers used the AGREE-II instrument to assess guideline quality in six domains. Recommendations were mapped to allow a narrative synthesis regarding areas of consensus and disagreement. MAIN RESULTS: Eight national guidelines (AAGL, SOGC 2014, ACOG, ACR, SOGC 2019, CNGOF, ASRM and SOGC 2015) and one international guideline (RANZOG) were appraised. The highest scoring guideline was RANZOG 2001(score 56.5%). None of the guidelines met the a priori criteria for being high-quality overall (score ≥66%). There were 166 recommendations across guidelines. There were several areas of disagreement and uncertainty. There were only three areas of consensus. Supporting evidence was not evident for many recommendations; 27.7% of recommendations were based on expert opinion only. CONCLUSIONS: There is a need for high-quality guidelines on fibroids given their heterogeneity across individuals and the large range of treatment modalities available. There are also areas of controversy in the management of fibroids (e.g. Ulipristal acetate, power morcellation), which should also be addressed in any guidelines. Future guidelines should be methodologically robust to allow high-quality decision-making regarding fibroid treatments. TWEETABLE ABSTRACT: Current national fibroid guidelines have deficiencies in quality when appraised using the validated AGREE instrument.