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Facts, Views & Vision in ObGyn Sep 2023An isthmocele is a myometrial defect in the site of the caesarean scar. In symptomatic women with abnormal uterine bleeding and secondary infertility, surgical...
BACKGROUND
An isthmocele is a myometrial defect in the site of the caesarean scar. In symptomatic women with abnormal uterine bleeding and secondary infertility, surgical correction can be considered. Most authors advocate that when there's a residual myometrium ≥ 3mm it can be corrected through resectoscopic approach and when < 3mm the treatment should be laparoscopic, eventually guided by diagnostic hysteroscopy. Both these techniques have important limitations; therefore, the authors propose combining both techniques, in the same procedure, in order to overcome them.
OBJECTIVES
To demonstrate the advantages of a surgical technique for correction of an isthmocele using both resectoscopic and laparoscopic resection.
MATERIAL AND METHODS
A stepwise demonstration of the technique with narrated video footage.
MAIN OUTCOME MEASURES
Intraoperative data and outcomes in the patient's follow-up.
RESULTS
One month after the surgery the patient was asymptomatic, reporting a resolution of the uterine abnormal bleeding, and the ultrasound showed a full correction of the isthmocele.
CONCLUSION
A combination of resectoscopic and laparoscopic resection, in correcting bigger isthmoceles, is a good option to fully excise all the fibrotic tissue.
LEARNING OBJECTIVE
This video aims to demonstrate the benefits of using a technique combining resectoscopic and laparoscopic resection for correcting larger isthmoceles.
PubMed: 37742206
DOI: 10.52054/FVVO.15.3.086 -
Gynecologic and Obstetric Investigation 2024Uterine fibroids are benign monoclonal tumors originating from the smooth muscle cells of the myometrium, constituting the most prevalent pathology within the female... (Review)
Review
BACKGROUND
Uterine fibroids are benign monoclonal tumors originating from the smooth muscle cells of the myometrium, constituting the most prevalent pathology within the female genital tract. Uterine sarcomas, although rare, still represent a diagnostic challenge and should be managed in centers with adequate expertise in gynecological oncology.
OBJECTIVES
This article is aimed to summarize and discuss cutting-edge elements about the diagnosis and management of uterine fibroids and sarcomas.
METHODS
This paper is a report of the lectures presented in an expert meeting about uterine fibroids and sarcomas held in Palermo in February 2023.
OUTCOME
Overall, the combination of novel molecular pathways may help combine biomarkers and expert ultrasound for the differential diagnosis of uterine fibroids and sarcomas. On the one hand, molecular and cellular maps of uterine fibroids and matched myometrium may enhance our understanding of tumor development compared to histologic analysis and whole tissue transcriptomics, and support the development of minimally invasive treatment strategies; on the other hand, ultrasound imaging allows in most of the cases a proper mapping the fibroids and to differentiate between benign and malignant lesions, which need appropriate management.
CONCLUSIONS AND OUTLOOK
The choice of uterine fibroid management, including pharmacological approaches, surgical treatment, or other strategies, such as high-intensity focused ultrasound (HIFU), should be carefully considered, taking into account the characteristics of the patient and reproductive prognosis.
Topics: Female; Humans; Treatment Outcome; Leiomyoma; Uterine Neoplasms; Prognosis; Sarcoma; High-Intensity Focused Ultrasound Ablation; Uterine Myomectomy
PubMed: 38382486
DOI: 10.1159/000537730 -
Science Advances Nov 2023The recurrence rate for severe intrauterine adhesions is as high as 60%, and there is still lack of effective prevention and treatment. Inspired by the nature of uterus,...
The recurrence rate for severe intrauterine adhesions is as high as 60%, and there is still lack of effective prevention and treatment. Inspired by the nature of uterus, we have developed a bilayer scaffold (ECM-SPS) with biomimetic heterogeneous features and extracellular matrix (ECM) microenvironment of the uterus. As proved by subtotal uterine reconstruction experiments, the mechanical and antiadhesion properties of the bilayer scaffold could meet the requirement for uterine repair. With the modification with tissue-specific cell-derived ECM, the ECM-SPS had the ECM microenvironment signatures of both the endometrium and myometrium and exhibited the property of inducing stem cell-directed differentiation. Furthermore, the ECM-SPS has recruited more endogenous stem cells to promote endometrial regeneration at the initial stage of repair, which was accompanied by more smooth muscle regeneration and a higher pregnancy rate. The reconstructed uterus could also sustain normal pregnancy and live birth. The ECM-SPS may thereby provide a potential treatment for women with severe intrauterine adhesions.
Topics: Pregnancy; Female; Humans; Biomimetics; Tissue Scaffolds; Uterus; Extracellular Matrix; Tissue Engineering
PubMed: 37967178
DOI: 10.1126/sciadv.adi6488 -
Best Practice & Research. Clinical... Feb 2024Preeclampsia (PE) is a multiorgan disorder that complicates around 2-8% of pregnancies and is a major cause of perinatal and maternal morbidity and mortality. PE is a... (Review)
Review
Preeclampsia (PE) is a multiorgan disorder that complicates around 2-8% of pregnancies and is a major cause of perinatal and maternal morbidity and mortality. PE is a clinical syndrome characterized by hypertension secondary to systemic inflammation, endothelial dysfunction, and syncytiotrophoblast stress leading to hypertension and multiorgan dysfunction. The uterine arteries are the main blood vessels that supply blood to the uterus. They give off branches and plays an important role in maintaining blood supply during pregnancy. The arcuate artery originates from the uterine artery and runs medially through the myometrium. The arcuate arteries divide almost directly into anterior and posterior branches, from which the radial artery leads directly to the uterine cavity during their course. Near the endometrium-myometrium junction, the radial artery generates spiral arteries within the basal layer and functional endometrium. The walls of radial and spiral arteries are rich in smooth muscle, which is lost when trophoblast cells invade and become large-caliber vessels. This physiological transformation of uteroplacental spiral arteries is critical for successful placental implantation and normal placental function. In normal pregnancy, the luminal diameter of the spiral arteries is greatly increased, and the vascular smooth muscle is replaced by trophoblast cells. This process and changes in the spiral arteries are called spiral artery remodeling. In PE, this genetically and immunologically governed process is deficient and therefore there is decreased vascular capacitance and increased resistance in the uteroplacental circulation. Furthermore, this defect in uteroplacental spiral artery remodeling is not only associated with early onset PE, but also with fetal growth restriction, placental abruption, and spontaneous premature rupture of membranes. Doppler ultrasound allows non-invasive assessment of placentation, while the flow impedance decreases as the pregnancy progresses in normal pregnancies, in those destined to develop preeclampsia the impedance is increased.
Topics: Pregnancy; Female; Humans; Placenta; Uterine Artery; Pre-Eclampsia; Placentation; Ultrasonography, Doppler; Hypertension
PubMed: 38039843
DOI: 10.1016/j.bpobgyn.2023.102426 -
American Journal of Reproductive... Mar 2024Autophagy is a bulk degradation system that maintains cellular homeostasis by producing energy and/or recycling excess proteins. During early placentation, extravillous... (Review)
Review
Autophagy is a bulk degradation system that maintains cellular homeostasis by producing energy and/or recycling excess proteins. During early placentation, extravillous trophoblasts invade the decidua and uterine myometrium, facing maternal immune cells, which participate in the immune suppression of paternal and fetal antigens. Regulatory T cells will likely increase in response to a specific antigen before and during early pregnancy. Insufficient expansion of antigen-specific Treg cells, which possess the same T cell receptor, is associated with the pathophysiology of preeclampsia, suggesting sterile systemic inflammation. Autophagy is involved in reducing inflammation through the degradation of inflammasomes and in the differentiation and function of regulatory T cells. Autophagy dysregulation induces protein aggregation in trophoblasts, resulting in placental dysfunction. In this review, we discuss the role of regulatory T cells in normal pregnancies. In addition, we discuss the association between autophagy and regulatory T cells in the development of preeclampsia based on reports on the role of autophagy in autoimmune diseases.
Topics: Pregnancy; Female; Humans; Placenta; Pre-Eclampsia; Placentation; Trophoblasts; Autophagy; Inflammation; Decidua
PubMed: 38467995
DOI: 10.1111/aji.13835 -
Materials Today. Bio Dec 2023Endometrium is suspectable to severe injury due to recurrent abortion, curettage or intrauterine infection which could lead to pathological conditions and sabotage...
Endometrium is suspectable to severe injury due to recurrent abortion, curettage or intrauterine infection which could lead to pathological conditions and sabotage women's fertility. Promoting endometrium regeneration is the core of the treatments to uterine related infertility. Patients who received traditional treatments can only expect limited effects, thereby novel therapies are badly in need to promote endometrium regeneration. Here we generated a decellularized extracellular matrix (ECM) from porcine dermis, and composited adipose stem cell derived exosomes (ADSC-exos) on it (ECM@ADSC-exos). In vitro experiments proved that ECM@ADSC-exos exhibited good cytocompatibility and could improve cell proliferation, migration and angiogenesis. We also observed that, when implanted in the uterine cavity of a rat model of endometrium injury, ECM@ADSC-exos improved endometrium regeneration, enhanced local angiogenesis, promoted myometrium repair and finally preserved fertility. Our results proved that ECM@ADSC-exos could be a novel option for endometrium regeneration.
PubMed: 38075259
DOI: 10.1016/j.mtbio.2023.100857 -
MedRxiv : the Preprint Server For... Aug 2023Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the...
Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severity of these complications in maternal-fetal health. Here, we investigated the genetic variation underlying aspects of pregnancy-associated bleeding and identified five loci associated with PPH through a meta-analysis of 21,512 cases and 259,500 controls. Functional annotation analysis indicated candidate genes, , , and / at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors (PGR). Furthermore, there were strong genetic correlations with birth weight, gestational duration, and uterine fibroids. Early bleeding during pregnancy (28,898 cases and 302,894 controls) yielded no genome-wide association signals, but showed strong genetic correlation with a variety of human traits, indicative of polygenic and pleiotropic effects. Our results suggest that postpartum bleeding is related to myometrium dysregulation, whereas early bleeding is a complex trait related to underlying health and possibly socioeconomic status.
PubMed: 37645979
DOI: 10.1101/2023.08.10.23293932 -
BioRxiv : the Preprint Server For... Aug 2023Uterine leiomyoma or fibroids are the most common prevalent noncancerous tumors of the uterine muscle layer. Common symptoms associated with fibroids include pelvic...
Uterine leiomyoma or fibroids are the most common prevalent noncancerous tumors of the uterine muscle layer. Common symptoms associated with fibroids include pelvic pain, heavy menstrual bleeding, anemia, and pelvic pressure. These tumors are a leading cause of gynecological care but lack long-term therapy as the origin and development of fibroids are not well understood. Several next-generation sequencing technologies have been performed to identify the underlying genetic and epigenetic basis of fibroids. However, there remains a systemic gap in our understanding of molecular and biological process that define uterine fibroids. Recent epitranscriptomics studies have unraveled RNA modifications that are associated with all forms of RNA and are thought to influence both normal physiological functions and the progression of diseases. We quantified RNA expression profiles by analyzing publicly available RNA-seq data for 15 known epigenetic mediators to identify their expression profile in uterine fibroids compared to myometrium. To validate our findings, we performed RT-qPCR on a separate cohort of uterine fibroids targeting these modifiers confirming our RNA-seq data. We then examined protein profiles of key mA modifiers in fibroids and their matched myometrium. In concordance with our RNA expression profiles, no significant differences were observed in these proteins in uterine fibroids compared to myometrium. To determine abundance of RNA modifications, mRNA and small RNA from fibroids and matched myometrium were analyzed by UHPLC MS/MS. In addition to the prevalent N6-methyladenosine (mA), we identified 11 other known modifiers but did not identify any aberrant expression in fibroids. We then mined a previously published dataset and identified differential expression of mA modifiers that were specific to fibroid genetic sub-type. Our analysis also identified mA consensus motifs on genes previously identified to be dysregulated in uterine fibroids. Overall, using state-of-the-art mass spectrometry, RNA expression and protein profiles, we characterized and identified differentially expressed mA modifiers in relation to driver mutations. Despite the use of several different approaches, we identified limited differential expression of RNA modifiers and associated modifications in uterine fibroids. However, considering the highly heterogenous genomic and cellular nature of fibroids, and the possible contribution of single molecule mA modifications to fibroid pathology, there is a need for greater in-depth characterization of mA marks and modifiers in a larger and varied patient cohort.
PubMed: 37609293
DOI: 10.1101/2023.08.07.552278 -
Academic Radiology Sep 2023The purpose of this study was to explore the feasibility of magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) for the treatment of an adenomyosis...
RATIONALE AND OBJECTIVES
The purpose of this study was to explore the feasibility of magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) for the treatment of an adenomyosis model of Bama pigs and the changes in the level of oxytocin receptor (OTR), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) in the myometrium tissues of Bama pigs after MRgFUS.
MATERIALS AND METHODS
Three Bama pig models of adenomyosis were established by autologous endometrial implantation and evaluated by magnetic resonance imaging, computed tomography, and hematoxylin-eosin (H&E) staining. After the successful construction of the model, the pigs underwent MRgFUS. Before the modeling surgery, three months after the modeling, and two months after ablation, the myometrium tissues were clipped, then embedded and H&E stained for immunohistochemical examination. The average optical density of OTR, VEGF, and COX-2 were semi-quantitatively analyzed.
RESULTS
The adenomyosis models were established in all Bama pigs and confirmed by magnetic resonance imaging, computed tomography and H&E staining. Magnetic resonance imaging and computed tomography examination showed that the uterine wall at the modeling site was significantly thickened with uneven enhancement after contrast injection. All Bama pigs with adenomyosis lesions underwent MRgFUS without complications. The expression level of OTR and COX-2 in the myometrium increased three months after modeling surgery and decreased two months after MRgFUS. The expression level of VEGF decreased two months after MRgFUS.
CONCLUSION
Autologous endometrial implantation is effective in establishing the adenomyosis model of Bama pigs. It is feasible to treat adenomyosis in the Bama pig model with MRgFUS. The levels of OTR, COX-2 and VEGF in the local myometrium decreased after MRgFUS, which may be associated with symptom relief after treatment.
Topics: Humans; Female; Animals; Swine; Adenomyosis; Vascular Endothelial Growth Factor A; Cyclooxygenase 2; Magnetic Resonance Imaging; Ultrasonic Surgical Procedures
PubMed: 36624022
DOI: 10.1016/j.acra.2022.11.034 -
Frontiers in Endocrinology 2023Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in...
INTRODUCTION
Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis. Prostaglandin F2α (PGF2α) is one of the myometrial activators and stimulators.
METHODS
Here we investigated the role of PGF2α in pro-inflammatory signalling pathways in human myometrial cells isolated from term non-labouring uterine tissue. Primary myometrial cells were treated with G protein inhibitors, calcium chelators and/or PGF2α. Nuclear extracts were analysed by TranSignal cAMP/Calcium Protein/DNA Array. Whole cell protein lysates were analysed by Western blotting. mRNA levels of target genes were analysed by RT-PCR.
RESULTS
The results show that PGF2α increases inflammation in myometrial cells through increased activation of NF-κB and MAP kinases and increased expression of COX-2. PGF2α was found to activate several calcium/cAMP-dependent transcription factors, such as CREB and C/EBP-β. mRNA levels of NF-κB-regulated cytokines and chemokines were also elevated with PGF2α stimulation. We have shown that the increase in PGF2α-mediated COX-2 expression in myometrial cells requires coupling of the FP receptor to both Gαq and Gαi proteins. Additionally, PGF2α-induced calcium response was also mediated through Gαq and Gαi coupling.
DISCUSSION
In summary, our findings suggest that PGF2α-induced inflammation in myometrial cells involves activation of several transcription factors - NF-κB, MAP kinases, CREB and C/EBP-β. Our results indicate that the FP receptor signals via Gαq and Gαi coupling in myometrium. This work provides insight into PGF2α pro-inflammatory signalling in term myometrium prior to the onset of labour and suggests that PGF2α signalling pathways could be a potential target for management of preterm labour.
Topics: Infant, Newborn; Female; Humans; Dinoprost; NF-kappa B; Calcium; Premature Birth; Cyclooxygenase 2; Myometrium; Inflammation; Obstetric Labor, Premature; Cytokines; RNA, Messenger
PubMed: 37547305
DOI: 10.3389/fendo.2023.1150125