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AimTo assess, from a United States (US) payer's perspective, the cost-effectiveness of gels designed to separate the endometrial surfaces (intrauterine spacers) placed following intrauterine surgery.Materials and methodsA decision tree model was developed to estimate the cost-effectiveness of intrauterine spacers used to facilitate endometrial repair and prevent the formation (primary prevention) and reformation (secondary prevention) of intrauterine adhesions (IUAs) and associated pregnancy- and birth-related adverse outcomes. Event rates and costs were extrapolated from data available in the existing literature. Sensitivity analyses were conducted to corroborate the base case results.ResultsIn this model, using intrauterine spacers for adhesion prevention led to net cost savings for US payers of $2,905 per patient over a 3.5-year time horizon. These savings were driven by the direct benefit of preventing procedures associated with IUA formation ($2,162 net savings) and the indirect benefit of preventing pregnancy-related complications often associated with IUA formation ($3,002). These factors offset the incremental cost of intrauterine spacer use of $1,539 based on an assumed price of $1,800 and the related increase in normal deliveries of $931. Model outcomes were sensitive to the probability of preterm and normal deliveries. Budget impact analyses show overall cost savings of $19.96 per initial member within a US healthcare plan, translating to $20 million over a 5-year time horizon for a one-million-member plan.LimitationsThere are no available data on the effects of intrauterine spacers or IUAs on patients' quality of life. Resultingly, the model could not evaluate patients' utility related to treatment with or without intrauterine spacers and instead focused on costs and events avoided.ConclusionThis analysis robustly demonstrated that intrauterine spacers would be cost-saving to healthcare payers, including both per-patient and per-plan member, through a reduction in IUAs and improvements to patients' pregnancy-related outcomes.

Escherichia coli has been attributed to playing a major role in a cascade of events that affect the prevalence and severity of uterine disease in cattle. The objectives of this project were to (i) define the association between the prevalence of specific antimicrobial resistance and virulence factor genes in E. coli with the clinical status related to uterine infection, (ii) identify the genetic relationship between E. coli isolates from cows with diarrhea, with mastitis, and with and without metritis, and (iii) determine the association between the phenotypic and genotypic antimicrobial resistance identified on the E. coli isolated from postpartum cattle. Bacterial isolates (n = 148) were obtained from a larger cross-sectional study. Cows were categorized into one of three clinical groups before enrollment: metritis, cows with purulent discharge, and control cows. For genomic comparison, public genomes (n = 130) from cows with diarrhea, mastitis, and metritis were included in a genome-wide association study, to evaluate differences between the drug classes or the virulence factor category among clinical groups. A distinct E. coli genotype associated with metritis could not be identified. Instead, a high genetic diversity among the isolates from uterine sources was present. A virulence factor previously associated with metritis (fimH) using PCR was not associated with metritis. There was moderate accuracy for whole-genome sequencing to predict phenotypic resistance, which varied depending on the antimicrobial tested. Findings from this study contradict the traditional pathotype classification and the unique intrauterine E. coli genotype associated with metritis in dairy cows.IMPORTANCEMetritis is a common infectious disease in dairy cattle and the second most common reason for treating a cow with antimicrobials. The pathophysiology of the disease is complex and is not completely understood. Specific endometrial pathogenic Escherichia coli have been reported to be adapted to the endometrium and sometimes lead to uterine disease. Unfortunately, the specific genomic details of the endometrial-adapted isolates have not been investigated using enough genomes to represent the genomic diversity of this organism to identify specific virulence genes that are consistently associated with disease development and severity. Results from this study provide key microbial ecological advances by elucidating and challenging accepted concepts for the role of Intrauterine E. coli in metritis in dairy cattle, especially contradicting the existence of a unique intrauterine E. coli genotype associated with metritis in dairy cows, which was not found in our study.

ObjectiveTo evaluate differences based on intrauterine device (IUD) frame geometry in force, and stress, and strain at the stem/arms junction during simulated IUD removal.Study designWe manufactured injection-molded frame models for three Nova-T IUDs (Mirena [model M]; Liletta [model L]; Kyleena [model K]) and a Tatum-T IUD (Paragard [model P]) at two-times scaling. We created a custom fixture to simulate the uterus and used a screw-driven machine to pull models at various displacement rates through the 10 cm fixture cavity to measure force and strain and calculate stress at the IUD stem/arms junction. We tested models at 30 mm/min and higher displacement rates for exploratory analyses. We used Mann-Whitney U test for statistical testing.ResultsWe completed testing at 30 mm/min using five of each Nova-T model and nine model P samples. Resistance against the cavity walls created significantly more force on model P (11.83, interquartile range [IQR] 11.61-12.31) than any Nova-T model samples (p

Embryo-maternal crosstalk is essential to establish pregnancy, with the equine embryo moving throughout the uterus on days 9-15 (ovulation = day 0) as part of this interaction. We hypothesized that the presence of a mobile embryo induces local changes in the gene expression of the endometrium. On Day 12, the endometrial transcripts were compared among three groups: uterine horn with an embryo (P+, n = 7), without an embryo (P-, n = 7) in pregnant mares, and both uterine horns of nonbred mares (NB, n = 6). We identified 1,101 differentially expressed genes (DEGs) between P+ vs. NB and 1,229 DEGs between P- vs. NB. The genes upregulated in both P+ and P- relative to NB were involved in growth factor pathway and fatty acid activation, while downregulated genes were associated with oxytocin signaling pathway and estrogen receptor signaling. Comparing the transcriptome of P+ to that of P-, we found 59 DEGs, of which 30 genes had a higher expression in P+. These genes are associated with regulating vascular growth factors and the immune system, all known to be essential in early pregnancy. Overall, this study suggests that the mobile embryo influences the endometrial gene expression locally.

BACKGROUND: Mesenchymal neoplasms of the uterus encompass a diverse group of tumors, with varying characteristics and origins, collectively accounting for 8% of uterine malignancies. The most common variants include uterine leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, adenosarcoma, and undifferentiated sarcoma. Clinical presentation is often nonspecific and can lead to delayed diagnosis. Uterine sarcomas are generally aggressive, resulting in poorer prognosis compared to carcinomas. Recent advances in molecular techniques, such as next-generation sequencing (NGS), have led to the identification of new subtypes of uterine sarcomas, including COL1A1::PDGFB fusion-associated fibrosarcoma, which has a specific chromosomal translocation t(17;22)(q22;q13). Imatinib, a tyrosine kinase inhibitor (TKI), is an effective treatment for dermatofibrosarcoma protuberans (DFSP), marked by this translocation. CASE: We present the case of a 42-year-old woman diagnosed with COL1A1::PDGFB fusion-associated uterine fibrosarcoma. The patient underwent total hysterectomy and excision of the tumor, initially misdiagnosed as a low-grade leiomyosarcoma. Subsequent histological examination, immunohistochemistry, and fluorescence in situ hybridization (FISH) confirmed the diagnosis. After 10 months, disease recurrence was detected, and Imatinib therapy was initiated at a dose of 400 mg daily. An allergic reaction led to a temporary discontinuation, but upon resumption with appropriate medication, a positive radiological response was observed. The patient achieved a complete remission after 2 years and is still on Imatinib treatment. CONCLUSIONS: COL1A1::PDGFB fusion-associated uterine fibrosarcoma is an extremely rare mesenchymal neoplasm. In a case we present herein, we treated a patient with imatinib as first-line medical therapy. The patient is currently in complete remission after 37 months from treatment start. To the best of our knowledge, this represents a unique observation. We also provide a detailed literature review of the published cases so far. Prospective case series are needed to further understand the natural history of these tumors and optimize treatment strategies.

Background: Endometrosis (chronic degenerative endometritis) results in morphological changes in the equine endometrium and impairs its secretory function. However, the effect of this condition on the myometrium remains unclear. Lysophosphatidic acid (LPA) may affect female reproductive function and embryo transport by influencing uterine contractility through its receptors (LPARs). The objective of this study was to determine myometrial LPAR1–6 mRNA transcription, and the effects of LPA on myometrial contractions in mares with endometrosis during the mid-luteal and follicular phases of the estrous cycle. Results: A reduction in myometrial LPAR1 mRNA transcription was observed in mares with endometrosis during the mid-luteal phase, in comparison to those with category I endometria (P < 0.05). While, upregulation of myometrial LPAR3 or LPAR6 mRNA transcription was observed in mares with category III or IIB endometria; respectively (P < 0.05). An increase in myometrial LPAR1, LPAR3 and LPAR5 mRNA transcription was observed during the follicular phase in mares with category IIA endometrium in comparison to their expression in category I endometrium (P < 0.05). During endometrosis progression LPA reduced the force of myometrial contractions in both phases of the estrous cycle (P < 0.05). However, in mares with category IIA endometrium during the follicular phase, LPA was found to increase the force of contraction of myometrial strips in comparison to mares with category I endometrium (P < 0.01). Conclusion: In the course of endometrosis in mares, a disruption in the myometrial mRNA transcription of LPARs has been observed. This is the first study to examine the impact of LPA on myometrial contractility at diffrent stage of endometrosis. However, it is essential to consider that multiple factors may contribute to this process. Alternations in contractile activity and changes in myometrial LPARs mRNA transcription may indicate impaired LPA-signaling mechanisms in equine myometrium during endometrosis. [ABSTRACT FROM AUTHOR]

Background: Adenomyosis and endometrial carcinoma present distinct pathological conditions that pose considerable diagnostic hurdles, especially in postmenopausal women, as they share common clinical manifestations. Furthermore, postmenopausal adenomyosis may exhibit radiological features resembling those of endometrial carcinoma, potentially leading to misdiagnosis and inappropriate management. Case presentation: A 64-year-old para four and live four (P4L4) postmenopausal woman, who had been postmenopausal for 15 years, sought evaluation at the Gynecological Outpatient Department due to heavy postmenopausal bleeding lasting 30–45 days. Ultrasonography and MRI findings indicated a loss of the endo-myometrial junctional zone, delayed enhancement of the lesion, and suspected myometrial invasion, suggestive of endometrial malignancy, alongside a polypoidal lesion. Given the strong suspicion of endometrial carcinoma, the patient underwent hysteroscopy-guided endometrial biopsy. However, histopathological analysis revealed disordered proliferative endometrium with no evidence of malignancy. Considering the patient's age, symptoms, and MRI findings, exploratory laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy was planned. Subsequent histopathological examination confirmed adenomyosis of the uterus, with the fallopian tubes and ovaries found to be healthy. Conclusion: The present case report underscores the radiological challenges encountered in distinguishing adenomyosis from endometrial carcinoma in postmenopausal women, emphasizing the importance of a multidisciplinary approach to enhance diagnostic accuracy and improve patient outcomes in this population. [ABSTRACT FROM AUTHOR]

Determining the effects of adjuvant radiotherapy in patients with stage IB1-IIB cervical cancer that has invaded the uterine corpus. We retrospectively retrieved and assessed the data of stage IB1 to IIB cervical cancer patients with uterine corpus invasion (UCI) who had undergone radical hysterectomy from 2004 to 2016. The study endpoints were 5-year disease-free survival (DFS) and overall survival (OS). Additionally, independent factors associated with patients' survival were determined through multivariate regression models. A total of 284 patients from 11 institutions across China were eligible for this study. Among them, 90 (31.7%) had endometrial invasion, 105 (37.0%) had myometrial invasion <50%, and 89 (31.3%) had myometrial invasion =50%. The 5-year DFS and OS of patients with myometrial invasion =50% within the uterine corpus who underwent adjuvant radiotherapy were significantly longer than those who did not undergo adjuvant radiotherapy. Furthermore, adjuvant radiotherapy was identified as an independent prognostic factor for improved 5-year DFS (adjusted hazard ratio (aHR), 0.484, 95% confidence interval (CI), 0.249-0.940) and 5-year OS (aHR, 0.435, 95% CI, 0.204-0.925). However, we observed no significant survival benefit for patients with myometrial invasion <50% or endometrial invasion within the uterine corpus following adjuvant radiotherapy. Adjuvant radiotherapy might lead to a better prognosis in patients with stage IB1-IIB cervical cancer that has invaded the myometrium =50% within the uterine corpus but may not improve the survival of those with endometrial invasion or myometrial invasion <50%. [ABSTRACT FROM AUTHOR]

Motile cilia are evolutionarily conserved organelles. In humans, multiciliated cells (MCCs), assembling several hundred motile cilia on their apical surface, are components of the monolayer epithelia lining lower and upper airways, brain ventricles, and parts of the reproductive tracts, the fallopian tube and uterus in females, and efferent ductules in males. The coordinated beating of cilia generates a force that enables a shift of the tubular fluid, particles, or cells along the surface of the ciliated epithelia. Uncoordinated or altered cilia motion or cilia immotility may result in subfertility or even infertility. Here, we summarize the current knowledge regarding the localization and function of MCCs in the human reproductive tracts, discuss how cilia and cilia beating-generated fluid flow directly and indirectly contribute to the processes in these organs, and how lack or improper functioning of cilia influence human fertility. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer is currently the sixth most frequent cancer in women, and scientific research is focusing on the search for particular features of the endometrium that may explain a further predisposition to the onset of endometrial cancer, aimed at improving knowledge of the pathogenetic factors of this disease. The aim of our review is to analyze in detail the results of the literature on the endometrial microbiota in patients with endometrial cancer and to investigate its role. Methods: We performed our research on the Pubmed, Web of Science, and Scopus databases. We searched up to December 2023 and considered manuscripts published from 2000. Only articles in English were included in the search. We excluded studies in which the endometrial microbiota were collected through the vagina or cervical canal. Results: We included in our review a total of five manuscripts at the end of the screening process, and the total number of patients involved was 190. Four studies considered only post-menopausal patients, while one study considered both pre- and post-menopausal patients. In all studies, the microbiota analysis was derived from a post-hysterectomy biopsy. From our review, it emerged that Bacteroidetes, Actinobacteria, Firmicutes, and Proteobacteria are the most represented bacteria in patients with endometrial cancer. These are both Gram-positive and Gram-negative, but predominantly anaerobic bacteria. Conclusions: The reduced microbial diversity and the presence of specific bacteria is often associated with endometrial cancer. Further work on larger population samples, and on healthy women and those affected by endometrial carcinoma, is needed to understand how the endometrial microbiota changes and influences the development of the tumor and whether intervening in the changes in the microbiota will have a therapeutic impact on endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Endometriosis, defined by the growth of endometrial tissues outside of the uterine cavity, is a global health burden for ∼200 million women. Patients with endometriosis usually present with chronic pain and are often diagnosed with infertility. The pathogenesis of endometriosis is still an open question; however, tissue stemness and immunological and genetic factors have been extensively discussed in the establishment of endometriotic lesions. Current treatments for endometriosis can be categorized into pharmacological management of hormone levels and surgical removal of the lesions. Both approaches have limited efficacy, with recurrences often encountered; thus, there is no complete cure for the disease or its symptoms. We review the current knowledge of the etiology of endometriosis and summarize the advancement of pharmacological management of endometriosis. We also discuss our efforts in applying DNA-encoded chemistry technology (DEC-Tec) to identify bioactive molecules for the treatment of endometriosis, offering new avenues for developing non-hormonal treatment options for those patients who seek spontaneous pregnancies. [Display omitted] • Endometriosis is a prevalent yet significantly understudied global health concern. • Current treatment options for endometriosis are limited. • DEC-Tec platforms can rapidly advance drug development programs for endometriosis. [ABSTRACT FROM AUTHOR]

• Total thickness of uterine wall and myometrial thickness are reduced after caesarean section scar. • Proportion of fibrom in myometrial wall is increased after caesarean section scar. • Reduced thickness of uterine wall in scared uterus remains even long after caesarean section scar. In recent years, caesarean section (CS) rate has risen worldwide. Complications associated with CS scars have risen too, such as scar dehiscences and uterine ruptures. Uterine healing is a complex phenomenon still poorly understood. The aim of this study is to carry out a comparative histological analysis of healthy and scarred uterus. Women who underwent hysterectomy for benign pathology were included prospectively and divided into two groups: previous CS (group 1) versus control (group 2). Hysterectomy specimen were analyzed histologically and immunohistochemically. Sixty women were included: 30 women per group. In group 1, only 19 women could be analyzed. Median total thickness at the thinnest site of the scar is significantly thinner (4.34 mm; IQR [2.76–9.45]) than that of adjacent healthy isthmus (12.70 mm; IQR [10.45–14.95]) (p < 0.001). It is also thinner than in group 2 (13.45 mm; IQR [11.03–16.90]) (p < 0.001). Median myometrial thickness within the scar in group 1 was also thinner (1.14 mm; IQR [0.30–2.69]) than that of the adjacent healthy isthmus (8.90 mm; IQR [8.18–10.08]) (p < 0.001) and that in group 2 (10.00 mm; IQR [8.38–13.35]) (p < 0.001). There was a significant increase in fibrosis in the scar (55.01 %; IQR [35.71–63.46]) compared with adjacent tissue (17.41 %; IQR [15.08–24.78]) (p < 0.001) and with healthy uterus (33.91 %; IQR [18.93–46.53]) (p = 0.006). In uterus with previous CS scar, total thickness of the wall and thickness of the myometrium are reduced and proportion of fibrosis is significantly increased. This study shows that the thickness of the wall remains reduced in scarred uterus, even very long after CS. Further studies are currently in progress to understand its pathophysiology within the uterus using animal models. [ABSTRACT FROM AUTHOR]

Objective: Congenital uterine anomalies during pregnancy increase the risk of pregnancy complications such as miscarriage, preterm delivery, fetal malpresentation, cesarean delivery, and fetal growth restriction. However, few studies have examined uterine anomalies in relation to perinatal complications other than those mentioned above. We investigated the association between pregnancies complicated by congenital uterine anomalies and various perinatal outcomes at our institution. Methods: This retrospective cohort study was conducted from January 2009 to May 2021. We included cases of uterine anomalies, such as septate, bicornuate, unicornuate, and didelphic uterus. First, the perinatal complications and neonatal outcomes were compared between pregnancies complicated by uterine anomalies and those with normal uteri. Second, we conducted an analysis based on the type of uterine anomalies classified into two groups: the minor anomaly group consisted of anomalies limited to the uterine cavity, such as the septate uterus, whereas the major anomaly group included anomalies affecting the uterine shape, such as bicornuate, unicornuate, and didelphic uterus. We compared the incidence of perinatal complications among the major anomaly, minor anomaly, and normal uterus groups. Results: During the study period, 45 pregnancies were complicated with uterine anomalies. The minor anomaly group included 11 patients and the major anomaly group included 34 patients. The incidence of fetal malpresentation was significantly higher in the uterine anomaly group than in the normal uterus group (18% vs. 3.7%, p =.04). Furthermore, the frequency of abnormal placental cord insertion was significantly higher in the uterine anomaly group (16% vs. 3.7%, p =.01). Examination based on the type of uterine anomaly revealed significant differences in cervical incompetence, malpresentation, cesarean section, and abnormal placental cord insertion. Cervical incompetence was more likely in patients with minor anomalies. In contrast, fetal malpresentation, cesarean section, and abnormal placental cord insertion were more likely in the major anomaly group. Conclusions: In addition to the findings reported in previous studies, abnormal placental cord insertion was more frequent in pregnancies complicated by uterine anomalies. [ABSTRACT FROM AUTHOR]

Objective: To report the outcome of cesarean scar pregnancy (CSP) undergoing treatment. Methods: MEDLINE, Embase and CINAHL databases were searched. Inclusion criteria were women with CSP undergoing treatment. The primary outcome was successful treatment for CSP, defined as no need for additional medical or surgical strategies. Secondary outcomes were the type of additional treatment (surgical or medical), need for blood transfusion, emergency laparotomy, hysterectomy, post-treatment complications. All these outcomes were explored in women undergoing single and compound treatments for CSP. Furthermore, we performed a separate sub-group analysis only including studies which reported on the outcomes of elective treatments. Random effects meta-analyses were used to analyze the data and results reported as pooled proportions or odd ratio (OR). Results: 176 studies (13431 women with CSP undergoing treatment) were included. Successful treatment after primary intervention was achieved in 86.2% (95% CI 82.3–89.7) of women with CSP undergoing treatment with ultrasound guided suction curettage, 72.4% (95% CI 64.8-79.3) with systemic MTX, 81.6% (95% CI 72.3–89.3) with local MTX, 83.9% (95% CI 66.7–95.6) with interventional radiology, 90.42% (95% CI 82.9–96.0) with hysteroscopy, 96.1% (95% CI (92.3–98.6) with laparoscopy and 92.6 with high intensity focused ultrasound (95% CI 78.2–99.6). Post-treatments complications were reported in 3.5% (95% CI 1.7–6.0) of women treated with systemic MTX, 5.9% (95% CI 0.8–15.1) with local MTX or KCl, 1.2% (95% CI 0.1–3.5) with interventional radiology, 1.4% (95% CI 0.4–2.9) with hysteroscopy, 5.5% (95% CI 0.4–25.7) with high intensity focused ultrasound and in none of the cases treated with ultrasound guided suction curettage. When considering compound treatments, successful resolution of CSP was achieved in 91.9% (95% CI 88.0–95.10) of women treated with interventional radiology followed by curettage, 83.3% (95% CI 68.8–93.8) with systemic MTX and curettage, 79.4% (95% CI 56.3–95.2) with local MTX and curettage, 96.2% (95% CI 92.3–98.7) with curettage followed by single or double balloon insertion in the uterine cavity, 98.3% (95% CI 95.9–99.7) with high intensity focused ultrasound followed by curettage, 91.1% (95% CI 3.4–97.0) with interventional radiology followed by removal of CSP with hysteroscopy, 64.3% (95% CI 13.8–99.2) with interventional radiology and systemic MTX and in 95.5% (95% CI 92.9–97.5) with curettage and hysteroscopy. When considering studies reporting a comparison between different treatments, there was no difference between systemic vs local MTX in the primary outcome. Curettage was associated with a higher chance of achieving a successful treatment. Conclusions: A multitude of treatments for CSP have been reported in the published literature. All treatments described for CSP are apparently equally effective in treating this condition. The findings from this systematic review highlight the need for adopting a common definition and outcome reporting of CSP to better elucidate its natural history, estimate the magnitude of maternal complication after treatment and design appropriately powered RCT to elucidate the optimal treatment of CSP according to its ultrasound phenotype and gestational age at treatment, in terms of effective resolution of the condition and risk of post-intervention complications. [ABSTRACT FROM AUTHOR]

Embryo implantation and processes of early pregnancy occur in a low-oxygen tissue environment controlled by hypoxia-inducible transcription factors of the hypoxia inducible factor (Hif) family. Hif2α has emerged as a pivotal factor in mediating uterine adaptation to hypoxia during early pregnancy. In mice, endometrial stromal Hif2α regulates the expression of the vesicular trafficking protein Rab27b, which in turn controls the release of both secretory granules and extracellular vesicles (EVs). These EVs harbor a variety of cargoes that control essential functional steps during pregnancy. In both mice and humans, EVs secreted by decidualizing stromal cells are taken up by stromal, endothelial, and trophoblast cells to support decidualization, blood vessel formation, and trophoblast development in the uterine milieu during early pregnancy. In mice, embryonic Hifs are essential for placental development. In humans, Hifs intrinsic to the trophoblast precursor cells are critical for their differentiation to the extravillous trophoblast (EVT) lineage. During the process of implantation, the embryo first attaches to the uterine epithelium and then invades the underlying stroma, resulting in the transformation of the stroma into a secretory tissue that surrounds the embryo. An intricate dialogue allows the developing embryo and the maternal tissue to be in constant communication with each other. In many mammals, including humans, embryo implantation and early pregnancy events take place in a low-oxygen environment regulated by hypoxia-inducible transcription factors. The mechanisms by which maternal and embryonic tissue compartments adapt to hypoxia are essential for the success of pregnancy outcomes. In this review we highlight recent work describing signaling pathways that operate in the hypoxic uterus to facilitate embryo implantation and promote the successful establishment of pregnancy. [ABSTRACT FROM AUTHOR]

Cyclic ADP‐ribose (cADPR) has emerged as a calcium‐regulating second messenger in smooth muscle cells. CD38 protein possesses ADP‐ribosyl cyclase and cADPR hydrolase activities and mediates cADPR synthesis and degradation. We have previously shown that CD38 expression is regulated by estrogen and progesterone in the myometrium. Considering hormonal regulation in gestation, the objective of the present study was to determine the role of CD38/cADPR signaling in the regulation of intracellular calcium upon contractile agonist stimulation using immortalized pregnant human myometrial (PHM1) cells. Western blot, immunofluorescence, and biochemical studies confirmed CD38 expression and the presence of ADP‐ribosyl cyclase (2.6 ± 0.1 pmol/mg) and cADPR hydrolase (26.8 ± 6.8 nmoles/mg/h) activities on the PHM1 cell membrane. Oxytocin, PGF2α, and ET‐1 elicited [Ca2+]i responses, and 8‐Br‐cADPR, a cADPR antagonist significantly attenuated agonist‐induced [Ca2+]i responses between 20% and 46% in average. The findings suggest that uterine contractile agonists mediate their effects in part through CD38/cADPR signaling to increase [Ca2+]i and presumably uterine contraction. As studies in humans are limited by the availability of myometrium from healthy donors, PHM1 cells form an in vitro model to study human myometrium. [ABSTRACT FROM AUTHOR]

Background: Congenital uterine anomalies include a wide diversity of uterine malformations that can compromise reproductive potential. Uterus transplantation (UTx) proposes an innovative treatment for absolute uterine factor infertility; however, there is a lack of standardized protocols to guide clinical management among this population. Objectives: To describe recipient and donor characteristics and obstetric outcomes in patients undergoing UTx. Search Strategy: We performed a literature search using the PubMed database to retrieve available scientific articles. We analyzed the references of included articles to assess additional articles that could be eligible to be included in the review. Likewise, we identified further studies using other methods, including Google Scholar. Selection Criteria: Titles and abstracts were screened in duplicate to select original reports with information available for the outcomes of interest. Data Collection and Analysis: This review assessed the advantages and disadvantages of the techniques used, patient characteristics, obstetric and non‐obstetric complications, functional duration of the organ, and neonatal outcomes. Main Results: Among the 36 reports included in this review we found 55 pregnancies and 38 live births following UTx and a higher success rate for in vivo uterine donations. The most common obstetric complications reported included miscarriage, pre‐eclampsia, and gestational hypertension. The most common non‐obstetric complications reported include episodes of rejection, acute kidney injury, anemia, and cholestasis. Living donors required a comprehensive preoperative workup, decreasing organ rejection, infection, and vascular complications. Conclusions: More studies are needed to standardize the UTx procedure and improve obstetric, fetal, and neonatal outcomes. Further understanding of which recipient and donor characteristics minimize complications will significantly decrease the risk of adverse outcomes. Synopsis: Thirty‐eight live births resulting from uterus transplantation were identified. More studies are needed to standardize the procedure and improve obstetric, fetal, and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Endometriosis is a disorder that commonly affects females of reproductive age and is defined as the presence of endometrial glands or stroma outside the uterine cavity. Patients typically present with cyclical pain during menses. Endometriosis can be characterized as endopelvic or extrapelvic depending on the sites involved. We report a case of a 40-year-old, right-hand-dominant, female who presented with a painful mass in her right proximal forearm. She was ultimately diagnosed with intramuscular endometriosis and underwent surgical excision. [ABSTRACT FROM AUTHOR]

Uterine intussusception is defined as the uterus telescoping onto itself. This condition has been rarely described in animals, and when it occurs, is often associated with post‐partum or pregnant animals. This case report describes the diagnosis and treatment of a uterine horn intussusception in a 1‐year 7‐month‐old, female, entire nulliparous pet rat (Rattus norvegicus). The rat presented for a 1‐day history of sanguineous vaginal discharge. An exploratory laparotomy was performed, and the rat was diagnosed with a firm, off‐white approximately 1 cm cervical mass and a left uterine horn intussusception. An ovariohysterectomy was performed for therapeutic and diagnostic purposes, and the mass was diagnosed as a benign endometrial stromal polyp on histopathology. Ten days post‐operative, the surgical incision developed a bacterial infection, which resolved with a course of amoxicillin/clavulanic acid. No further post‐operative complications occurred. The rat continues to do well 10 months after surgery. [ABSTRACT FROM AUTHOR]

Background: The decline in women's fertility becomes clinically relevant between 35–40 years old, when there is insufficient ovarian activity, and it becomes more difficult to achieve pregnancy naturally and through artificial reproductive technologies. A competent endometrium is required for establishing and maintaining a pregnancy to term, however, experts in the field underestimate the contribution of endometrial age and its impact on reproductive outcomes remains unclear. Study design: A systematic search of full-text articles available in PubMed was conducted to retrieve relevant studies published until March 2023. Search terms included: endometrium, uterus, age, aging, pregnancy, and oocyte donation. Terms related to reproductive pathologies were excluded. Eligibility criteria included original, rigorous, and accessible peer-reviewed work, published in English on the effect of age on the uterus and endometrium. Results: From 11,354 records identified, 142 studies were included for systematic review, and 59 were eligible for meta-analysis of endometrial thickness (n = 7), pregnancy rate (n = 22), implantation rate (n = 10), live birth rate (n = 10) and pregnancy loss rate (n = 11). Studies for the meta-analysis of reproductive outcomes only included transfers of embryos from ovum donation (ovum donors < 36 years old). Age shrinks the uterus; depletes endometrial blood supply through narrow uterine veins and a progressive loss of uterine spiral arteries; disrupts endometrial architecture and cellular composition; alters hormone production, shortening menstrual cycle length and impeding endometrial progression to the secretory stage; and dysregulates key endometrial functions such as adhesion, proliferation, apoptosis, and receptivity, among others. Women over 35–40 years old had significantly thinner endometrium (MD 0.52 mm). Advanced maternal age is associated with lower odds of achieving implantation (27%) and clinical pregnancy (20%), or higher odds of experiencing pregnancy loss (44%). Conclusion: Due to the effect of age on endometrium reported in this review, managing patients with advanced maternal age may require considering the endometrial factor as a potential tissue to treat with anti-aging strategies. This review provides researchers and clinicians with an updated and in-depth summary of this topic, encouraging the development of new tailored anti-aging and preventive strategies for precision medicine in endometrial factor in infertility. Trial registration: PROSPERO 2023 (CRD42023416947). [ABSTRACT FROM AUTHOR]

Breast cancer patients have high serum reactive oxygen species (ROS) levels, which exert toxicity on the ovary. However, it is still unclear whether tumor‐derived ROS play a role in endometrial development and function in breast cancer. Breast cancer patients and healthy controls were recruited and endometrial thickness was measured by transvaginal ultrasound (TVUS). Xenograft tumors of the breast cancer cell line MDA–MB–231 in a female BALB/c nude mice model were established, and the therapeutic mechanism of vitamin C (VC) was investigated on uterine pathology in vivo and the contribution of co‐culture of breast cancer cell and endometrial epithelial cell on this process was examined in vitro. Median thickness in endometria was lower in breast cancer patients and tumor‐bearing mice compared to controls. A gene signature of uteri in tumor‐bearing mice demonstrated differential expression of genes (DEGs) regulating extracellular matrix (ECM) and epithelial–mesenchymal transition (EMT), and activation of TGF‐β and MAPK signaling pathways. In addition, ROS, EMT‐ and ECM‐related protein levels were enhanced in uteri in tumor‐bearing mice, as well as in Ishikawa cells which were co‐cultured with MDA‐MB‐231 cells compared to controls. Supplementation with VC reduced endometrial damage, inhibited the EMT process and collagen deposition, and maintained better histologic architecture of uteri in tumor‐bearing mice via inactivation of the TGF‐β1/p38MAPK pathway. In women with breast cancer oxidative stress in the endometrium results in a fibrotic response as a consequence of EMT. VC could alleviate endometrial fibrosis via TGF‐β1/p38MAPK pathway and provide new predictive and therapeutic targets for fertility preservation in younger breast cancer patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions Adhesions between the uterus, bladder and anterior abdominal wall are associated with clinical sequelae, including chronic pelvic pain and dyspareunia, and can also yield complications during surgery. The transvaginal sonographic (TVS) sliding bladder sign is a minimally invasive diagnostic tool to evaluate the presence of vesicouterine adhesions. This study aimed to determine the predictive value and intra‐ and interobserver variation of the TVS sliding bladder sign in the assessment of vesicouterine adhesions.This was a prospective observational double‐blind diagnostic accuracy study conducted at the Amsterdam University Medical Center. Patients scheduled for gynecological laparoscopic surgery for a benign disorder between January 2020 and December 2022 were included consecutively. All patients underwent preoperative TVS, including a dynamic sliding bladder sign examination in our outpatient clinic. Videoclips of the TVS scans were stored for offline assessment and used as an index test. The recordings of both TVS and laparoscopy were evaluated for diagnostic characteristics of vesicouterine adhesions by independent assessors, who were blinded to the clinical situation in addition to the laparoscopic findings when assessing recordings of TVS and vice versa. The presence of adhesions on laparoscopy was used as the reference standard. The positive predictive value (PPV), negative predictive value (NPV), specificity and sensitivity of the sliding bladder sign were calculated. In addition, inter‐ and intraobserver variability of the sliding bladder sign on TVS were assessed.Of 116 included women, 57 had a negative sliding bladder sign on TVS, while on laparoscopy, 51 women had mild and 28 had severe vesicouterine adhesions. A negative sliding bladder sign had a PPV of 94.7% (95% CI, 88.9–100%) for the presence of any vesicouterine adhesions, and a positive sliding bladder sign had a specificity of 91.9% (95% CI, 83.1–100%). For severe adhesions, the negative sliding bladder sign had a sensitivity of 89.3% (95% CI, 77.8–100%) and a positive sliding bladder sign had a NPV of 94.9% (95% CI, 89.3–100%). When using Cohen's kappa coefficient, inter‐ and intraobserver agreement between assessors was good.Sliding bladder sign evaluation using TVS is a reliable diagnostic tool for the prediction of vesicouterine adhesions on laparoscopy. A negative sliding bladder sign indicates the presence of vesicouterine adhesions, while a positive sliding bladder sign makes the presence of severe adhesions unlikely. Establishing vesicouterine adhesions by TVS may optimize preoperative planning, and can be used for future studies to evaluate the relationship between symptomatology and vesicouterine adhesions and, subsequently, the effect of adhesion‐prevention interventions. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

In most murine species, spermatozoa exhibit a falciform apical hook at the head end. The function of the sperm hook is not yet clearly understood. In this study, we investigate the role of the sperm hook in the migration of spermatozoa through the female reproductive tract in Mus musculus (C57BL/6), using a deep tissue imaging custom-built two-photon microscope. Through live reproductive tract imaging, we found evidence indicating that the sperm hook aids in the attachment of spermatozoa to the epithelium and facilitates interactions between spermatozoa and the epithelium during migration in the uterus and oviduct. We also observed synchronized sperm beating, which resulted from the spontaneous unidirectional rearrangement of spermatozoa in the uterus. Based on live imaging of spermatozoa-epithelium interaction dynamics, we propose that the sperm hook plays a crucial role in successful migration through the female reproductive tract by providing anchor-like mechanical support and facilitating interactions between spermatozoa and the female reproductive tract in the house mouse. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions Uterus transplantation (UTx) is a treatment for absolute uterine factor infertility. The results of pregnancies of this complex infertility treatment should be established. The aim of the study was to systematically review maternal and neonatal outcomes in the pregnancies of women who have undergone UTx.The population of this review were women that have undergone UTx and delivered child(ren). Cesarean delivery after UTx were planned to be compared with studies reporting maternal mortality/morbidity and perinatal mortality/morbidity after delivery by elective cesarean section without UTx. Systematic literature searches were performed utilizing Medline, Embase, the Cochrane Library, Cinahl, PsycInfo, Web of Science, and clinicaltrials.gov for studies written in English language and published between January 1, 2010, and November 08, 2023. No study design limitation was applied. If no comparative studies were identified, we planned to report the outcomes from the case reports and case series. Included studies were assessed for risk of bias using a checklist for case series. The study protocol was registered with the International Platform of Registered Systematic Review and Meta‐analysis Protocols (registration number: INPLASY202310052).Twenty‐four articles were identified, containing data on 40 unique live births. Multiple publications including same cases were identified and clearly indicated. No comparative studies were identified. The certainty of evidence was very low, as all studies were either case reports (n = 15) or case series (n = 9). All deliveries were by cesarean section and 47.5% of them resulted in emergency cesarean sections. Out of the 21 elective cesarean sections, 52.4% were performed before 37 weeks' gestation. Historical comparison to population data on pregnancies delivered by cesarean section found a markedly increased risk for both the mother and child following cesarean section for UTx. Risks for placenta previa and preterm birth were notably high after UTx; however, some of the later may reflect the results of provider‐initiated births.The maternal and perinatal outcomes of 40 live births post‐UTx indicate that these pregnancies may be at high risk of maternal and perinatal complications. Aiming to delay elective cesarean section beyond 37 weeks' gestation could potentially reduce some of these risks. Registration of maternal and perinatal outcomes after UTx through quality registries are essential and obstetrical care guidelines for these women should be established. [ABSTRACT FROM AUTHOR]

Background: Uterus transplantation (UTx) is currently the only available treatment for absolute uterine factor infertility. Deceased donors have recently emerged as a valid alternative to living donors for uterus transplantation, with similar results. Methods: We report the first experience in Italy of uterus transplantation from deceased donors. Three uterus transplantations from deceased donors were performed at the Organ Transplant Unit of the University Hospital of Catania, Italy, between August 2020 and January 2022. Results: Two patients underwent UTx due to Mayer–Rokitansky–Küster–Hauser syndrome, while one patient had a previous hysterectomy due to benign disease. The donors' ages were between 25 and 43 years and the mean cold ischemia time was 18.3 h. The mean age of the recipients was 31.6 years, and the mean recipient surgery duration was 5.3 h, with a mean blood loss of 766.66 mL. Two recipients developed a post-transplant hematoma, which was treated conservatively. No uterus recipient needed a re-operation during the first 30 days after transplantation. No histological signs of acute rejection were detected at the cervical biopsies performed at 1, 3, and 6 months after transplantation. First menstruation occurred in all recipients after 39 ± 12 days after transplantation. One live birth was reported 15 months after UTx. One graft was lost three months after UTx due to graft thrombosis. Conclusions: Uterus transplantation from deceased donors is emerging as a valid alternative to living donors in order to increase the donor pool. [ABSTRACT FROM AUTHOR]

The growing demand for uterus transplantation (UTx) invites continued philosophical evaluation of the function of UTx (and what constitutes its ‘success’), as well as the recipient eligibility for UTx. Currently, UTx caters to partnered, cisgender women of childbearing age looking to get pregnant and give birth to a biogenetically related child. The medical justification for this—the treatment of uterine infertility—explains the primacy of this practice. However, this dominant conceptualization of UTx does not necessarily capture the diverse needs for which both cis‐ and transgender women might take interest in UTx that are not strictly procreative, such as bodily integrity and gender identity reasons. In this paper, I argue that non‐procreative motivations for uterus acquisition ought to be taken seriously as a matter of non‐discrimination and consistency. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a type of specific molecules that control the activities of the uterus, such as the process of cellular maturing and evolution. A lot of substances like growth factors, cytokines, and transcription factors play a role in embryo-endometrial interaction. MiRNAs could regulate various these factors by attaching to the 3' UTR of their mRNAs. Moreover, current research show that miRNAs participate in formation of blood vessels in endometrium (miR-206, miR-17-5p, miR-16-5p...), decidualization (miR-154, miR-181, miR-9...), epithelial-mesenchymal transition (miR-30a-3p), immune response (miR-888, miR-376a, miR-300...) embryo attachment (miR-145, miR-27a,451...) and pinopod formation (mir-223-3p, mir-449a, mir-200c). In this study, the focus is on the role of miRNAs in managing the uterus' receptivity to an embryo and its ability to facilitate attachment. More specifically, we are exploring the mechanisms by which miRNAs regulate the presence of specific molecules involved in this crucial physiological process. [ABSTRACT FROM AUTHOR]

Background Objective Design and setting Results/outcomes Conclusion While uterus transplantation offers a promising treatment option for women with uterine factor infertility (UFI), the potential for graft failure and lack of organ availability could have subsequent psychological repercussions for women. Exploring baseline psychological well‐being for women with UFI who could become uterine transplant recipients is essential to identify specific psychological challenges to be considered prior to transplantation. UFI can be congenital uterine absence, namely Mayer‐Rokitansky‐Küster‐Hauser syndrome (MRKH), or acquired uterine absence (hysterectomy).To analyse baseline psychological well‐being among women with UFI.A survey including demographic data and two internationally validated psychological questionnaires, Depression, Anxiety and Stress Scale (DASS‐21),13 and Fertility Quality of Life (FertiQoL), was disseminated to women with UFI. Data from these instruments was compared between groups and then to data that uses these tools in the general infertility population.The study included 39 women (mean age 29.54 years). Higher scores for moderate symptoms of depression, anxiety, and stress were reported for the entire UFI cohort. More women with congenital UFI showed ‘severe’ symptoms for depression/anxiety, compared to women with acquired UFI. Women with acquired UFI showed poorer FertiQoL scores compared to both women with congenital UFI and to the general infertility population scores in previously published data.Clinicians should consider accessing increased psychological support for women with UFI when discussing fertility options including uterine transplant, and they may need to tailor this support depending on whether the patient has congenital or acquired UFI. [ABSTRACT FROM AUTHOR]

Objective To analyze the pregnancy outcomes of combined B-Lynch suture and intrauterine packing with gauze versus combined B-Lynch suture and intrauterine balloon tamponade in the treatment of central placenta previa with abnormally adherent placenta. Methods A retrospective analysis was conducted on 48 patients with central type placenta previa combined with adhesive placental implantation at Nanfang Hospital of Southern Medical University from July 2021 to October 2023. Among them, 23 patients were treated with B-Lynch suture combined with uterine gauze tamponade (study group), and 25 patients were treated with B-Lynch suture combined with uterine balloon tamponade (control group ). The intraoperative bleeding volume, postpartum 24-hour bleeding volume, postoperative intervention surgery rate, postoperative ICU transfer rate, and hospitalization costs were compared between the two groups. Results There was no statistically significant difference in intraoperative bleeding between the two groups (P > 0.05 ). Compared with the control group, the study group showed a decrease in 24-hour postpartum hemorrhage, red blood cell infusion, surgical time, and hospitalization costs; The postoperative hospitalization days are shorter (P < 0.05). Three patients in the control group underwent uterine artery embolization intervention surgery, and one patient was transferred to the ICU. There was no statistically significant difference in the ICU transfer rate and postoperative intervention surgery rate between the two groups (P > 0.05 ). There was no difference in Apgar scores between the two groups of newborns. After discharge, patients were followed up until 42 days postpartum, and the results showed that all patients had no late postpartum hemorrhage, no poor healing of uterine incisions, no complications such as bladder ureteral iniury and intestinal obstruction. Conclusion Combined B-Lynch suture and intrauterine gauze packing is a simple, feasible, safe, and reliable hemostatic method. It is suitable for primary healthcare institutions and worthy of promotion. [ABSTRACT FROM AUTHOR]

Background: Endometrial polyps are common benign lesions characterized by localized overgrowths of endometrial tissue within the uterine cavity. The etiology and pathogenesis of these polyps remain unclear. Human papillomavirus (HPV) infection, known for its association with various genital tract conditions, has been investigated concerning endometrial polyps, although research in this area is limited. Methods: A case-control study involving 62 premenopausal women was conducted, with endometrial polyp cases and control groups matched for age and BMI. Biopsy samples were collected for HPV testing using polymerase chain reaction (PCR). Clinical and demographic data were collected and analyzed for associations between HPV presence and endometrial polyps. Results: Results showed a higher prevalence of HPV (all types) in cases (4, 12.9%) compared to controls (1, 3.2%), with low-risk HPV being the most prevalent genotype detected and HPV 16 tested positive in one case diagnosed with polyp. While no significant association was found between HPV infection and the presence of endometrial polyps, the study suggests a potential role for HPV in their development. Interestingly, HPV presence in endometrial polyps was unrelated to histopathological features, patients' age, or BMI. Conclusion: This study provides insights into the potential involvement of HPV infection in the development of endometrial polyps. Despite no significant association found, the prevalence of HPV in these polyps suggests a possible contributory role. Further research with larger sample sizes and more robust methodologies is warranted to clarify this association and its clinical implications. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions This study investigates the impact of intracavitary pressure levels on pain, visualization quality, and procedure duration in office hysteroscopy, comparing standard pressures (60–100 mmHg) with high pressures (110–150 mmHg).We conducted a retrospective cohort study involving non‐menopausal women undergoing diagnostic hysteroscopy at a tertiary clinic. Patients were categorized into two groups based on intracavitary pressure: the standard pressure group (60–100 mmHg; n = 72) and the high‐pressure group (110–150 mmHg; n = 37). Outcomes measured included pain scores, procedure duration, and fluid volume used. Logistic regression was employed to identify risk factors for severe pain.The high‐pressure group demonstrated significantly shorter procedure durations compared to the standard pressure group (96.56 ± 34.36 vs. 163.00 ± 61.78 s, p < 0.001). Pain scores were lower in the high‐pressure group (VAS 3.00 [0.00–7.00] vs. 3.50 [0.00–9.00], p = 0.041). Additionally, high‐pressure procedures used less fluid compared to standard pressure procedures, which helps to reduce the risk of fluid‐related complications. Logistic regression analysis identified higher fluid volumes (odds ratio [OR] = 1.005, 95% confidence interval [CI] = 1.001–1.010) and the need for pressure increases (OR = 3.914, 95% CI = 1.157–13.238) as significant risk factors for severe pain.Higher intracavitary pressure levels (above 100 mmHg) in office hysteroscopy are associated with reduced pain, shorter procedure durations, and decreased fluid use, enhancing visualization and procedural efficiency while maintaining patient comfort. [ABSTRACT FROM AUTHOR]

Streptococcus (S.) equi subspecies (subsp.) zooepidemicus is an important facultative pathogen in horses and can cause severe infections in other species including humans. Facing the post-antibiotic era, novel antimicrobials are needed for fighting bacterial infections. Bacteriophages (phages) are the natural predators of bacteria and discussed as a promising antimicrobial treatment option. The objective of this study was to isolate and characterize S. equi subsp. zooepidemicus- specific phages for the first time and to evaluate their efficacy in vitro and ex vivo. In total, 13 phages with lytic activity were isolated and host ranges were determined. Two phages with broad host ranges and high efficiency of plating (vB_SeqZP_LmqsRe26-2 (lytic activity: 30/37 bacterial isolates) and vB_SeqZP_LmqsRe26-3 (lytic activity: 29/37 bacterial isolates)) and one phage with relatively low efficiency of plating (vB_SeqZP_LmqsRe26-1) were selected for further characterization, including electron microscopy and whole genome sequencing. In in vitro planktonic killing assays at two tested multiplicities of infection (MOI 1 and MOI 10), significant bacterial growth reduction was observed when the phages vB_SeqZP_LmqsRe26-2 and vB_SeqZP_LmqsRe26-3 were added. These phages were subsequently co-incubated with clinical S. equi subsp. zooepidemicus isolates in an equine endometrial explant model but did not achieve bacterial growth reduction at MOI 1 and MOI 10. However, helium ion microscopy revealed presence of particles adherent to the bacteria on the explant after incubation (25 h), suggesting possible phage-bacteria interactions. In conclusion, phages against S. equi subsp. zooepidemicus were successfully isolated and characterized. Promising results were observed in in vitro but no significant reduction was detected in ex vivo experiments, requiring additional investigations. However, after further adaptations (e.g., optimization of MOIs and phage administration or use of phage-antibiotic combination), phages could be a potential antimicrobial tool for future therapeutic use in S. equi subsp. zooepidemicus infections, although the available results do not currently support the therapeutic usage. [ABSTRACT FROM AUTHOR]

Simple Summary: Investigations during the last few years have shown the central importance of the microbiota of the female genital in pregnancy, both in health and disease. Great advances have been made in understanding the diverse microflora in the vagina and uterus, and significant differences have been found between the microbial densities in both loci, with the intra-uterine populations ordinarily being low mass. The very high sensitivity DNA detection methods employed to identify microbes have the drawback that in studies of low microbial density sites it becomes challenging to differentiate between DNA from contaminants and from resident microorganisms. This problem presents acutely in analyses of the intra-amniotic microbiome, to a degree that many investigators have concluded that there is not such microbiome in healthy pregnancies. In contrast, there are the findings of multiple studies claiming the characterisation of the intra-amniotic microbiome in various female populations. Thus, it became necessary to appraise the evidence in favour and against the existence of this microbiome in healthy pregnancies. This work presents the results of such enquiry and some recommendations to minimise the interference posed by DNA from contaminants. The existence of intra-amniotic and placental microbiomes during pregnancy has been the source of considerable debate, with research yielding conflicting evidence. This study evaluated investigations into the putative presence of these microbiomes in healthy pregnancies by identifying design and data interpretation issues, particularly concerning contamination in samples with low-density bacterial DNA. Positive findings from diverse populations suggest a consistent presence of microbiota in the intra-amniotic space. Negative conclusions regarding the existence of these prenatal microbiomes emphasise the impact of contamination in the analysis of samples with low-density bacterial DNA. This study concluded that there is no definitive evidence to refute the existence of intra-amniotic microbiomes in healthy pregnancies. Also, it provides suggestions for controlling potential contamination factors in future research on intra-amniotic and placental microbial populations. [ABSTRACT FROM AUTHOR]

We used human-centered design to explore preferred consumer experiences for obtaining mifepristone for medication abortion care from a pharmacy. We conducted a two-part virtual workshop series with the same 10 participants in March and April of 2022 to initiate the discovery phase of a human-centered design process. Most participants were residents of Illinois and all participants had uteruses and had either sought abortion care or supported someone who had. Co-developed and co-facilitated with a local abortion fund, workshops engaged participants to provide formative data for the development of recommendations for community health center clinicians and pharmacists. A simulated medication abortion care counseling session grounded group activities and discussions that explored the experience of filling a medication abortion prescription at a pharmacy or by mail. Data were analyzed for key themes and recommendations. Qualitative data were collected from the workshops. Data analysis was conducted in three iterative, parallel stages: 1) virtual whiteboard results from both workshops were analyzed deductively through spreadsheets and visualizations; 2) close reading was conducted for workshop transcripts and participant evaluations; and 3) document analysis was used to triangulate data across formats. Data were discussed periodically among the research team until consensus was reached. Five primary categories of questions and preferences emerged from workshop data concerning: logistics, privacy, cost, pharmacist refusal, and follow-up care. Researchers found that participants desired certain questions and concerns to be answered by specific provider types. Participants indicated a desire for further research and opportunities that prioritize lived experience and use storytelling and/or design methods to collect data. Despite existing patient-oriented medication abortion resources, there is a need for patient resources to support pharmacy dispensing, and a corresponding need for clinician and pharmacist resources. These can help in-person and mail-order pharmacy dispensing to be as consumer friendly as possible. [ABSTRACT FROM AUTHOR]

Women suffering from absolute uterine factor infertility (AUFI), due to either lack of a uterus or one unable to sustain neonatal viability, presented as one of the last frontiers in conquering infertility. Following systematic animal research for over a decade, uterus transplantation was tested as a treatment for AUFI in 2012, which culminated in the first human live birth in 2014. The development of uterus transplantation from mouse to human has followed both the Moore criteria for introduction of a surgical innovation and the IDEAL concept for evaluation of a novel major surgical procedure. In this article we review the important preclinical animal and human studies that paved the way for the successful introduction of human uterus transplantation a decade ago. We discuss this in the context of the Moore criteria and describe the different procedures of preparation, surgeries, postoperative monitoring, and use of assisted reproduction in human uterus transplantation. We review the worldwide activities and associated results in the context of the IDEAL concept for evaluation of surgical innovation and appraise the ethical considerations relevant to uterus transplantation. We conclude that rigorous application of the Moore criteria and strict alignment with the IDEAL concept have resulted in the establishment of uterus transplantation as a novel, safe, and effective infertility therapy that is now being used worldwide for the treatment of women suffering from AUFI. [ABSTRACT FROM AUTHOR]

Introduction: The contribution of tubal factors to infertility is up to 30%. One of the tests used to evaluate tubal factor infertility is Doppler saline Sonosalpingography (SSG). The basic principle of SSG is to distend the uterine cavity with isotonic saline, which helps identify the uterine contour, intrauterine pathology, endometrial thickness and the presence of fluid in the Pouch of Douglas (POD). Adding Doppler increases its efficiency and accuracy. Aim: To ascertain the role of Doppler saline SSG in tubal infertility. Materials and Methods: This cross-sectional study was done for 18 months in the Obstetrics and Gynaecology Department of Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India involving 200 women with either primary or secondary infertility. These women were recruited in the midfollicular phase after obtaining written informed consent. Patients underwent Doppler SSG to assess tubal patency and the findings were compared with Diagnostic Hysterolaparoscopy (DHL). Diagnostic tests were used to calculate sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV). Inter-rater kappa agreement was used to find out the strength of the association between Doppler Saline SSG and diagnostic laparoscopy. A p-value of less than 0.05 was considered significant. The data was entered into an MS Excel spreadsheet and analysis was done using the licensed version of Statistical Package for Social Sciences (SPSS) version 21.0. Results: The mean age and mean duration of infertility were reported to be 29 years and five years, respectively. The sensitivity of Doppler SSG for tubal patency was reported as 85.4%, the specificity as 95.8%, PPV as 95.3%, NPV as 86.8% and the accuracy for tubal patency was 90.6%. Doppler SSG and laparoscopic chromopertubation findings had substantial association (k value -0.62). Conclusion: Doppler SSG is a reliable method for the assessment of tubal factors and can be used as a screening modality with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Stress-inducible heat shock protein 70 (Hsp70), which functions as a molecular chaperone and is frequently overexpressed in different cancer cell types, is present on the cell surface of tumor cells and is actively released into the circulation in free and extracellular lipid vesicle-associated forms. Since the exact pathomechanism of endometriosis has not yet been elucidated (although it has been associated with the development of endometrial and ovarian cancer), we asked whether extracellular Hsp70 and circulating endometriotic cells (CECs) reflect the presence and development of endometriosis. Therefore, circulating levels of free and lipid microvesicle-associated Hsp70 were measured using the Hsp70-exo ELISA, and the presence of circulating CECs in the peripheral blood of patients with endometriosis was determined using membrane Hsp70 (mHsp70) and EpCAM monoclonal antibody (mAb)-based bead isolation approaches. Isolated CECs were further characterized by immunofluorescence using reagents directed against cytokeratin (epithelial marker), CD45 (leukocyte marker), CD105/CD44 (mesenchymal stemness markers) and by comparative RNA analysis. Similar to the situation in patients with cancer, the levels of circulating Hsp70 were elevated in the blood of patients with histologically proven endometriosis compared to a healthy control cohort, with significantly elevated Hsp70 levels in endometriosis patients with lesions outside the uterine cavity. Moreover, CECs could be isolated using the cmHsp70.1 mAb-based, and to a lesser extent EpCAM mAb-based, bead approach in all patients with endometriosis, with the highest counts obtained using the mHsp70-targeting procedure in patients with extra-uterine involvement. The longevity in cell culture and the expression of the cytokeratins CD105 and CD44, together with differentially expressed genes related to epithelial-to-mesenchymal transition (EMT), revealed similarities between mHsp70-expressing CECs and circulating tumor cells (CTCs) and suggest a mesenchymal stem cell origin. These findings support the involvement of mHsp70-positive stem cell-like cells in the development of endometriotic lesions. In summary, elevated levels of Hsp70 and CECs in the circulation could serve as liquid biopsy markers for endometriosis with extra-uterine involvement and help to elucidate the underlying pathomechanism of the disease. [ABSTRACT FROM AUTHOR]

Endometriosis is a common chronic disorder characterized by the growth of endometrium-like tissue outside the uterine cavity. The disease is associated with chronic inflammation and pelvic pain and may have an impact on the patient's fertility. The causative factors and pathophysiology of the disease are still poorly recognized. The dysregulation of the immune system, aberrant tissue remodeling, and angiogenesis contribute to the disease progression. In endometriosis patients, the proteins regulating the breakdown and reorganization of the connective tissue, e.g., collagenases, and other proteases, as well as their inhibitors, show an incorrect pattern of expression. Here, we report that the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK), one of the inhibitors of connective tissue proteases, is elevated in endometrioma cysts as compared to normal endometrium from unaffected women. We also demonstrate a reduced level of miR200b in endometriotic tissue that correlates with RECK mRNA levels. Furthermore, we employ the 12Z cell line, derived from a peritoneal endometriotic lesion, and the Ishikawa cell line, originating from endometrial adenocarcinoma to identify RECK as a direct target of miR200b. The described effect of miR200b on RECK, together with the aberrant expression of both genes in endometrioma, may help to understand the role played by the tissue remodeling system in the pathogenesis of endometriosis. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical and ultrasonographic features of uterine perivascular epithelioid cell tumor (PEComa) using standardized terminology. Methods: This was a retrospective analysis of patients with uterine PEComa diagnosed and confirmed by pathology and immunohistochemistry at West China Second University Hospital, Sichuan University, Sichuan, China, between January 2010 and September 2023. The Morphological Uterus Sonographic Assessment (MUSA) consensus and the International Endometrial Tumor Analysis (IETA) consensus were utilized for the standardized description of the sonographic characteristics of uterine PEComa. We summarized the clinical and ultrasound features of uterine PEComa in cases from our center and those found in a review of the literature conducted using PubMed from 1 January 2013 to 30 September 2023 (inclusive). Results: Five patients, aged 33–57 (median, 52) years, with a total of six uterine PEComa lesions were included in our cohort. All cases had complete ultrasonographic and pathological images. None of the patients had a history of tuberous sclerosis complex. Two patients had malignant PEComa (one patient had two lesions) and three had benign PEComa, originating from the cervix, myometrium or uterine cavity. Patients presented with symptoms including increased vaginal discharge, vaginal bleeding and pelvic or abdominal pain. The three patients with benign PEComa underwent total hysterectomy and bilateral adnexectomy, tumor excision and conservative management, respectively, while both malignant cases underwent total hysterectomy and bilateral adnexectomy followed by chemotherapy. Regular follow‐up (from 6 to 24 months) revealed recurrence in one case. Two lesions were misdiagnosed as uterine fibroids, two as cervical cancer, one as metastatic cervical cancer (with myometrial invasion) and one was indeterminate. Ultrasound examination showed that most lesions displayed regular round or ovoid shape (66.7%), uniform echoes (66.7%) and hypoechogenicity (66.7%), with one (16.7%) malignant PEComa showing cystic areas and one (16.7%) benign PEComa showing punctate calcifications. All lesions lacked shadowing and the majority showed moderate to abundant vascularity (color score of 3–4, 83.3%). The color score was 2–4 in the periphery in 100% of cases and internally in 83.3% of cases. The three benign PEComas showed similar characteristics in vascular distribution, with scattered internal vessels and peripheral vessels exhibiting a circular pattern. The literature search identified 11 articles describing the ultrasonographic appearance of 18 cases of uterine PEComa, with similar characteristics to those in our cohort. Conclusions: The sonographic features of uterine PEComa include a uniform or non‐uniform hypoechogenic mass, typically round or ovoid with regular margins, occasionally containing cystic areas or calcifications, lacking shadowing and often showing moderate to abundant vascularity. Although the preoperative ultrasound diagnosis of uterine PEComa remains challenging, particularly given the non‐specific nature of the sonographic characteristics described here, dispersed intratumoral vessels and a peripheral circular vascular distribution may serve as diagnostic clues for uterine PEComa, but more cases are needed for confirmation. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

• Mayer–Rokitanski–Kuster–Hauser syndrome is a congenital aplasia of uterus and vagina. • It causes absolute infertility, determining psychological disorders. • Psychological evaluation is needed to plan a management strategy and support patients and partners. Mayer–Rokitanski–Kuster–Hauser (MRKH) syndrome consists of a congenital aplasia of the uterus and the upper part of the vagina. It is the most frequent congenital cause of absolute uterine factor infertility, determining psychological disorders due to infertility and reduced quality of sexual activity. Being the necessity of baseline and prolonged assessments, clinicians need evaluation parameters for the monitoring of patients to plan a suitable management strategy and for efficient support before and after interventions, such as neovagina and uterus transplantation. Research of the literature was performed in PubMed and SCOPUS by searching for the terms "Mayer-Rokitanski-Kuster-Hauser" AND "psychological disorders"; from the 60 articles obtained, only 35 articles regarding neovagina creation and uterus transplantation were considered for the present manuscript. Based on the literature, management of MRKH syndrome by neovagina creation, either surgically or not, can restore a satisfactory sexual life and to reduce stress, signs of mental disorder and depression and improve sexual activity and quality of life. A psychological assessment of candidates to UT and of their partners is necessary. Recipients had low levels of anxiety compared to the normal population at baseline but a transiently lowered physical quality of life 1 year after surgery; elevated anxiety scores are associated with childlessness in the long-term evaluation. Further research is necessary to develop suitable evaluation protocols and adequate supportive services, to improve the outcomes of patients who undergo neovagina creation and uterus transplantation. [ABSTRACT FROM AUTHOR]

• Hysteroscopy is the gold-standard approach for treating most intrauterine lesions. • Hysteroscopic visualization may not suffice for optimal management in complex cases. • Intraoperative ultrasound in hysteroscopy reduces uterine perforation risk. • Ultrasound-guided hysteroscopy increases the rate of complete resection of lesions. Hysteroscopy stands as the gold-standard approach for managing intrauterine pathology. However, in complex clinical cases, hysteroscopic evaluation alone may prove insufficient for the safest and successful patient management. Intraoperative ultrasound (IOUS) has emerged as a valuable adjunct to hysteroscopic surgery, offering real-time visualization of endometrial cavity, uterine walls and instruments within the uterine cavity, enabling precise delineation of anatomical structures, and helping to assess the extent of pathology during intricate interventions. This review aims to comprehensively assess the applications, efficacy and utility of IOUS in hysteroscopic surgery. Available evidence indicates that in hysteroscopic myomectomy, IOUS significantly reduces the risk of uterine perforation, particularly in submucosal FIGO 2 myomas, and enhances the likelihood of a single-step procedure. During hysteroscopic metroplasty, ultrasound guidance decreases the chance of incomplete uterine septum resection. In the hysteroscopic management of severe Asherman syndrome, IOUS reduces the risk of uterine perforation or false passage. For cesarean scar pregnancy (CSP), ultrasound is crucial in defining the most appropriate surgical approach and is effective in guiding the hysteroscopic treatment of endogenic CSP. The use of IOUS in hysteroscopy proves valuable in complex cases where the risk of uterine perforation or incomplete procedure is increased. [ABSTRACT FROM AUTHOR]

Introduction: We present the rare case of an 18-year-old patient with a Dicer-1 mutation-associated sarcoma of the cervix uteri. Case: The patient presented with irregular vaginal bleeding in July 2022. The clinical examination showed an exophytic tumor of the cervix, uterus and ovaries were normal in sonogram. The tumor of the cervix was resected, followed by a diagnostic hysteroscopy and abrasion of the uterine cervix and cavity. Hysteroscopy showed normal findings of the cervix and uterus. After diagnosis of a highly malignant Dicer-1 mutation-associated sarcoma of the cervix, cryopreservation of oocytes was realized. Based on the principle of obtaining maximum oncological safety while preserving fertility in this 18-year-old patient, we recommended chemotherapy rather than radiation with its far severe implications on the patient´s reproductive organs. 4 cycles of chemotherapy consisting of doxorubicin and ifosfamide were applied until December 2022. After re-staging in December 2022 via CT scan and MRI, the abdomen and pelvis as well as control hysteroscopy and abrasion were unremarkable. Until now, the patient is tumor free. Discussion: Primary sarcomas of the cervix are very rare. Recent literature hints towards a distinct DICER-1 sarcoma entity characterized by specific mutational clusters. Limited follow-up data suggested that DICER1-mutant tumors might exhibit a less aggressive clinical course than DICER1-wild-type tumors. Conclusion: Decision-making in case of rare histological entities with sparse recommendations in the literature poses a challenge to the treating physician. Treatment strategies should consider oncological safety as well as options of preserving fertility. Gonadotoxic potential of different strategies should be taken into consideration and discussed in detail with the affected patient. [ABSTRACT FROM AUTHOR]

Undifferentiated uterine sarcoma is an extremely rare cytologically challenging finding in pleural effusions undistinguished from the more common causes of malignant effusions. Cellblock is a valuable diagnostic tool when combined with certain diagnostic clues, relevant immunoprofile and knowledge of the patient's history. [ABSTRACT FROM AUTHOR]

Telocytes (TCs) are characterized by a small oval-shaped cell body with long prolongations that are called telopods (Tps). PDGFR-β and c-kit markers may assist for the immunohistochemical identification of TCs; however, by these means they cannot be identified with absolute specificity. Transmission electron microscopy (TEM) is considered as a gold standard method for TCs observation. Studies on TCs in the female reproductive system are limited, and there is a lack of awareness regarding TCs in rat ovaries. We aimed to demonstrate the existence and morphology of TCs in rat ovaries, alongside previously studied TCs in rat uteri. Thus, ovaries and uteri from young adult Sprague–Dawley female rats (n = 8) with regular estrous cycles were collected. Then, left ovaries and uteri were proccessed for TEM analysis, while the right ones were used for immunohistochemistry. As a result, TCs were seen throughout the rat's ovarian stroma with their characteristic cell bodies, Tps, podomes (Pds) and podomers (Pdms). Tps were situated within the thecal layer of the follicles, surrounding the corpus luteum and blood vessels. Ovarian TCs were recognized to have relationship with other TCs/stromal cells. Subsequently, TCs were seen in stroma of endometrium with surrounding blood vessels and uterine glands, myometrium and perimetrium in rat uteri. There was also no statistical significance between the number of c-kit+ and PDGFR-β+ telocyte-like cells in both rat ovarian (p = 0.137) and endometrial stroma (p = 0.450). Further investigation of the roles and functions of TCs in the female reproductive system is needed. [ABSTRACT FROM AUTHOR]

This paper evaluates the effects of hydro-alcohol extract of Englerina drummomdii Balla ex Polhil & Wiens leaves on the histology of ovaries and uterine tissues of female Wistar rats using appropriate standard methods with forty-nine (49) Wistar rats weighing between 160g to 180g were used for the study. Data obtained show that hydro-alcohol extract of Englerina drummomdii Balla ex Polhil & Wiens leaves when administered at a dose of 200mg/kg of extract, shows numerous viable follicles. Ovarian tissue shows atretic (AF) and degenerated follicles (DF) when treated with Monosodium glutamate (MSG) alone. And when MSG is co-administered with extract at a dose of 200mg/kg, it causes partial or complete blocks of ovarian tissues. 100mg of extract only caused degeneration of follicles with atretic follicles (AF). When mistletoe extract in low dose (extract 100mg/kg + MSG 800mg/kg) was co-administered with MSG 800mg/kg, it shows recovered secondary follicles (SF), mature ova (MO), germinal and growing follicles follicles, (GF). Mistletoe at low dose, high dose cause degeneration of ovarian and uterine tissues and when extract at 100mg/kg and MSG 800mg/kg is co-administered, it tends to restore the alterations in the histology of both the ovaries and uterine tissues. [ABSTRACT FROM AUTHOR]

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The American Institute of Ultrasound in Medicine (AIUM) has developed the Practice Parameter for the Performance of Ultrasound of the Female Pelvis, which provides recommendations for high-quality ultrasound examinations in this specialty area. The document outlines indications for pelvic sonography, qualifications and responsibilities of personnel, preparation for the examination, and detailed specifications for evaluating the uterus, adnexae (ovaries and fallopian tubes), and cul-de-sac. It emphasizes the importance of accurate documentation, equipment specifications, quality assurance, safety, infection control, and adherence to the ALARA principle. The parameter was developed in collaboration with various organizations and committees, reflecting a multidisciplinary approach to advancing the safe and effective use of ultrasound in medicine. [Extracted from the article]

Intrauterine adhesion (IUA) is a common complication of surgical manipulation of the uterine cavity such as abortion. The pathology of IUA is characterized by fibrosis, but the pathogenesis is not fully understood. The function of Apelin-13 in IUA and related mechanisms were investigated in this study. The IUA rat model was established. The pathological changes and fibrosis degree of rat uterine tissues were detected by HE and Masson staining after intraperitoneal injection of Apelin-13. Epithelial–mesenchymal transition (EMT) of endometrial epithelial cells and endothelial–mesenchymal transition (EnMT) of vein endothelial cells were induced by TGF-β1. Tube-forming assay using HUVEC was implemented to detect the effect of Apelin-13 upon angiogenesis. IHC staining, immunofluorescence staining, and Western blot were conducted to detect the expression levels of EMT markers, angiogenesis, and key proteins of the TGF-β1/Smad signaling. Apelin-13 significantly alleviated IUA and fibrosis, and increased endometrial thickness and gland number in IUA rats. In addition, Apelin-13 significantly reversed EMT and EnMT induced by IUA modeling and TGF-β1, promoted the tube-forming ability of HUVEC, and up-regulated the expression of angiogenesis-related proteins. Mechanistically, Apelin-13 significantly suppressed smad2/3 phosphorylation and inhibited the TGF-β1/Smad signaling via its receptor APJ. Apelin-13 might alleviate IUA via repressing the TGF-β1/Smad pathway and is expected to be a potent therapeutic option for the clinical treatment of IUA. [ABSTRACT FROM AUTHOR]

Embryo survival and pre‐implantation development depend on uterine luminal fluid, which is believed to play a role in early embryonic death and infertility in cows. Extracellular vesicles (EVs) in the uterine luminal fluid contain microRNAs (miRNAs), crucial mediators of intercellular communication. miRNAs regulate conceptus–maternal interactions and participate in embryonic development by suppressing gene expression. Therefore, we hypothesized that miRNAs in the intrauterine EVs of low‐fertility cows would hinder embryonic survival and development. EVs were collected from the bovine uterine luminal fluid of both normal‐ and low‐fertility cows 7 days post‐estrus. Small RNA‐sequencing analysis of miRNAs isolated from these EVs identified eight miRNAs that were highly expressed in normal‐fertility cows (normal‐fertility miRNAs) and eight with elevated expression in low‐fertility cows (low‐fertility miRNAs). These two sets of miRNAs were transfected into hatched blastocysts via lipofection. RNA‐seq following lipofection with low‐fertility miRNAs identified 424 differentially expressed genes (DEGs) relative to the control; in contrast, following lipofection with normal‐fertility miRNAs, seven DEGs were identified. Pathway analysis of the DEGs identified following lipofection with low‐fertility miRNAs revealed substantial enrichment of mitogen‐activated protein kinase (MAPK) signaling. Expression of activator protein 1 (AP1) and interferon‐tau (IFNT) mRNA was significantly lower in the low‐fertility miRNA transfection group than in the control. IFNT is essential for maternal pregnancy recognition. Therefore, miRNAs in intrauterine EVs from low‐fertility cows at 7 days post‐estrus may inhibit embryo development and suppress IFNT expression by altering MAPK signaling. [ABSTRACT FROM AUTHOR]

Sexual reproduction requires the choreographed interaction of female cells and molecules with sperm and seminal fluid. In internally fertilizing animals, these interactions are managed by specialized tissues within the female reproductive tract (FRT), such as a uterus, glands, and sperm storage organs. However, female somatic reproductive tissues remain understudied, hindering insight into the molecular interactions that support fertility. Here, we report the identification, molecular characterization, and analysis of cell types throughout the somatic FRT in the premier Drosophila melanogaster model system. We find that the uterine epithelia is composed of 11 distinct cell types with well-delineated spatial domains, likely corresponding to functionally specialized surfaces that interact with gametes and reproductive fluids. Polyploidy is pervasive: More than half of lower reproductive tract cells are =4C. While seminal fluid proteins (SFPs) are typically thought of as male products that are transferred to females, we find that specialized cell types in the sperm storage organs heavily invest in expressing SFP genes. Rates of amino acid divergence between closely related species indicate heterogeneous evolutionary processes acting on male-limited versus female-expressed seminal fluid genes. Together, our results emphasize that more than 40% of annotated seminal fluid genes are better described as shared components of reproductive transcriptomes, which may function cooperatively to support spermatozoa. More broadly, our work provides the molecular foundation for improved technologies to catalyze the functional characterization of the FRT. [ABSTRACT FROM AUTHOR]