Quantitative ultrasound measurement of uterine contractility in adenomyotic vs. normal uteri: a multicenter prospective study.

OBJECTIVE: To evaluate uterine contractility in patients with adenomyosis compared with healthy controls using a quantitative two-dimensional transvaginal ultrasound (TVUS) speckle tracking method. DESIGN: A multicenter prospective observational study took place in three European centers between 2014 and 2023. SETTING: One university teaching hospital, 1 teaching hospital and 1 specialised clinic. PATIENTS: A total of 46 women with a sonographic or magnetic resonance imaging diagnosis of adenomyosis were included. 106 healthy controls without uterine pathologies were included. INTERVENTION: Four-minute TVUS recordings were performed and four uterine contractility features were extracted using a speckle tracking algorithm. MAIN OUTCOMES MEASURES: The extracted features were contraction frequency (contractions/min), amplitude, velocity (mm/s), and coordination. Women with adenomyosis were compared with healthy controls according to the phase of the menstrual cycle. RESULTS: Throughout the different phases of the menstrual cycle, trends of increased amplitude, decreased frequency and velocity, and reduced contraction coordination were seen in patients with adenomyosis compared with healthy controls. These were statistically significant in the late follicular phase, with a higher amplitude (0.087 ± 0.042 vs. 0.050 ± 0.018), lower frequency and velocity (1.49 ± 0.22 vs. 1.68 ± 0.25 contractions/min, and 0.65 ± 0.18 vs. 0.88 ± 0.29 mm/s, respectively), and reduced contraction coordination (0.34 ± 0.08 vs. 0.26 ± 0.17), in the late luteal phase, with higher amplitude (0.050 ± 0.022 vs. 0.035 ± 0.013), lower velocity (0.51 ± 0.11 vs. 0.65 ± 0.13 mm/s), and reduced contraction coordination (0.027 ± 0.06 vs. 0.18 ± 0.07), and in the midfollicular phase, with decreased frequency (1.48 ± 0.21 vs. 1.69 ± 0.16 contractions/min) in patients with adenomyosis compared with healthy controls. During menses, a higher pain score was significantly associated with lower frequency and velocity and higher contraction amplitude. Results remained significant after correcting for age, parity, and body mass index. CONCLUSION: Uterine contractility differs in patients with adenomyosis compared with healthy controls throughout the phases of the menstrual cycle. This suggests an etiologic mechanism for the infertility and dysmenorrhea seen in patients with adenomyosis. Moreover, it presents new potential therapeutic targets and diagnostic markers.

Attenuated monoamine oxidase a impairs endometrial receptivity in women with adenomyosis via downregulation of FOXO1†.

The establishment of endometrial receptivity is a prerequisite for successful pregnancy. Women with adenomyosis possess a lower chance of clinical pregnancy after assisted reproductive technology, which is partially due to impaired endometrial receptivity. The establishment of endometrial receptivity requires the participation of multiple processes, and proper endometrial epithelial cell (EEC) proliferation is indispensable. Monoamine oxidase A (MAOA) is a key molecule that regulates neurotransmitter metabolism in the nervous system. In the present study, we demonstrated a novel role for MAOA in the establishment of endometrial receptivity in women with adenomyosis and in an adenomyotic mouse model. Attenuated MAOA impairs endometrial receptivity by promoting inappropriate proliferation of EECs via the downregulation of FOXO1 during the window of implantation. These results revealed that MAOA plays a vital role in endometrial receptivity in female reproduction.

Adenomyosis: An update regarding its diagnosis and clinical features.

Adenomyosis is a common gynecologic disease characterized by invasion of endometrial glands and stroma within the myometrium. Clinically, it can result in abnormal uterine bleeding, pelvic pain, and infertility. Adenomyosis has historically been diagnosed by histology of hysterectomy specimens. As a result of the development of imaging techniques, the diagnosis is nowadays possible by means of transvaginal pelvic ultrasound or pelvic magnetic resonance imaging. The use of pelvic imaging has demonstrated the existence of different forms of adenomyosis, notably allowing distinction between lesions of the external myometrium and those of the internal myometrium. The epidemiological and clinical characteristics may depend on the anatomical location of the adenomyosis lesions. In order to provide the best management for women with adenomyosis, the objective of this review is to provide an update regarding the diagnosis of adenomyosis and its clinical features according to the different adenomyosis phenotypes.

A clinical observational study on the efficacy of subcutaneous etonogestrel implants for adenomyosis in 20 patients.

Objective: To evaluate the efficacy of subcutaneous etonogestrel implants for adenomyosis.Methods: We conducted a clinical observational study of 20 patients suffering from adenomyosis treated with subcutaneous etonogestrel implants from August 2015 to July 2017 and followed up for 36 months. We evaluated the efficacy of subcutaneous etonogestrel implants primarily based on the following indicators: the pictorial blood loss assessment chart (PBAC) for menstrual blood volume, changes in bleeding patterns, the visual analog scale (VAS) pain score for dysmenorrhea, uterine volume, serum cancer antigen 125 (CA125) levels, hemoglobin levels and side effects.Results: During the 3 years of follow-up, subcutaneous etonogestrel implants were removed from six patients, among whom one was diagnosed with endometrial cancer, four had an increased menstrual blood volume, and one entered menopause. In total, 14 patients were treated with subcutaneous etonogestrel implants for 3 years. Among these patients, the number of patients with heavy menstrual bleeding and high PBAC and VAS scores and serum CA125 levels was significantly decreased after implantation compared with that before implantation. In the eight patients with anemia, hemoglobin levels increased gradually. However, the uterine volumes did not significantly change. Bleeding patterns were changed but were tolerable.Conclusion: Subcutaneous etonogestrel implants represent a new option for the clinical treatment of adenomyosis for patients who refuse surgery.

Upregulated Talin1 synergistically boosts ß-estradiol-induced proliferation and pro-angiogenesis of eutopic and ectopic endometrial stromal cells in adenomyosis.

Adenomyosis (ADS) is an estrogen-dependent gynecological disease with unspecified etiopathogenesis. Local hyperestrogenism may serve a key role in contributing to the origin of ADS. Talin1 is mostly identified to be overexpressed and involved in the progression of numerous human carcinomas through mediating cell proliferation, adhesion and motility. Whether Talin1 exerts an oncogenic role in the pathogenesis of ADS and puts an extra impact on the efficacy of estrogen, no relevant data are available yet. Here we demonstrated that the adenomyotic eutopic and ectopic endometrial stromal cells (ADS_Eu_ESC and ADS_Ec_ESC) treated with ß-estradiol (ß-E2) presented stronger proliferative and pro-angiogenetic capacities, accompanied by increased expression of PCNA, Ki67, VEGFB and ANGPTL4 proteins. Meanwhile, these promoting effects were partially abrogated by Fulvestrant (ICI 182780, an estrogen-receptor antagonist). Aberrantly upregulation of Talin1 mRNA and protein level was observed in ADS endometrial specimens and stromal cells. Through performing functional experiments in vitro, we further determined that merely overexpression of Talin1 (OV-Talin1) also enhanced ADS stromal cell proliferation and pro-angiogenesis, while the most pronounced facilitating effects were found in the co-intervention group of OV-Talin1 plus ß-E2 treatment. Results from the xenograft nude mice model showed that the hypodermic endometrial lesions from co-intervention group had the highest mean weight and volume, compared with that of individual OV-Talin1 or ß-E2 treatment. The expression levels of PCNA, Ki67, VEGFB and ANGPTL4 in the lesions were correspondingly elevated the most in the co-intervention group. Our findings unveiled that overexpressed Talin1 might cooperate withß-E2 in stimulating ADS endometrial stromal cell proliferation and neovascularization, synergistically promoting the growth and survival of ectopic lesions. These results may be beneficial to provide a new insight for clarifying the pathogenesis of ADS.

Impaired decidualization of human endometrial stromal cells from women with adenomyosis†.

Differentiation of endometrial stromal cells (ESCs) into secretory decidualized cells (dESCs) is essential for embryo implantation. Adenomyosis is a common benign gynecological disease that causes infertility. However, whether adenomyosis affects decidualization of human ESCs is elusive. Primary eutopic ESCs were obtained from patients with adenomyosis (n = 9) and women with nonendometrial diseases (n = 12). We determined the capacity of decidualization of human ESCs by qRT-PCR, Edu proliferation assay, cytokine array, and ELISA assay. We found that the expression of decidualization markers (IGFBP1 and PRL) in ESCs of adenomyosis was reduced, concomitant with increased cell proliferation. Differential secretion of cytokines in dESCs, including CXCL1/2/3, IL-6, IL-8, MCP-1, VEGF-A, MIP-3α, OPN, SDF-1α, HGF, and MMP-9, was observed between adenomyosis and nonadenomyosis. Moreover, the expression of decidualization regulators (HOXA10 at both mRNA and protein levels, FOXO1, KLF5, CEBPB, and HAND2 at mRNA levels) in the eutopic endometrium of adenomyosis was lower than that of nonadenomyosis. We propose that ESCs from adenomyosis have defected ability to full decidualization, which may lead to a nonreceptive endometrium.

Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis.

Chronic inflammatory processes affecting the endometrium, as encountered in endometriosis, adenomyosis, and chronic endometritis, alter endometrial receptivity. These disorders are associated with early pregnancy losses and possibly recurrent pregnancy losses (RPL). In the cases of endometriosis, other factors associated with the disease also are susceptible of causing miscarriages and possibly RPL, such as an impact of intrapelvic inflammatory processes affecting the oocyte and embryo in case of natural conception. Conversely these latter effects obviously are bypassed in case of assisted reproductive technology. Chronic inflammation of the endometrium in the condition known as chronic endometritis also causes early pregnancy losses and RPL with beneficial effects achieved when specific treatment is undertaken.

Adenomyosis and infertility: the role of the junctional zone.

OBJECTIVE: Adenomyosis is a benign uterine disorder characterized by the invasion of the endometrium within the myometrium, starting from the junctional zone (JZ), the inner hormone dependent layer of the myometrium that plays an important role in sperm transport, implantation and placentation. The resulting histological abnormalities and functional defects may represent the pathogenic substrate for infertility and pregnancy complications. The objective of this paper is to review the literature to evaluate the correlation between inner myometrium alterations and infertility and to assess the role of JZ in the origin of adverse obstetric outcomes of both spontaneous and in vitro fertilization (IVF) pregnancies. METHODS: we searched Pubmed for all original and review articles in the English language from January1962 until December 2019, using the MeSH terms of 'adenomyosis', 'junctional zone', combined with 'infertility', 'obstetrical outcomes', 'spontaneous conception', 'in vitro fertilization' and 'classification'. The review was divided into three sections to assess this pathogenic correlation, evaluating also the importance of classification of the disease. RESULTS AND CONCLUSIONS: Absent or incomplete remodeling of the JZ can affect uterine peristalsis, alter vascular plasticity of the spiral arteries and activate inflammatory pathways, all related to adverse obstetric outcomes. Despite these observations, there is still limited evidence whether adenomyosis is a cause of infertility. However, it is reasonable to screen patients for adenomyosis, to consider pregnant women with diffuse adenomyosis at high risk of adverse obstetric outcomes, and to evaluate the importance of a noninvasive validated classification in the management of women with adenomyosis.

TGF-ß1 Neutralization Improves Pregnancy Outcomes by Restoring Endometrial Receptivity in Mice with Adenomyosis.

The objective of this research is to study the effects of TGF-ß1 inhibition on endometrial receptivity and pregnancy outcomes in mice with adenomyosis. Experiments were done using a mouse model of adenomyosis which took place in a hospital-affiliated laboratory. The mouse model used for this research is ICR mouse. Adenomyosis was induced by oral gavage of tamoxifen (TAM) from postnatal days (PNDs) 1 to 4 in ICR mice. Bilateral intrauterine injection of anti-TGF-ß1-neutralizing antibody or isotype IgG or PBS was performed at PND42. The mice were then either sacrificed or mated at PND64 followed by sacrificing at gestational day (GD) 4 or proceeding to delivery. Implantation numbers, rate of dams with live birth, live birth numbers, survival at 1 week old, and pup mortality rate after weaning were recorded. Collagen was demonstrated by Masson's trichrome and Van Gieson's stains. Uterine expression of a receptivity marker, leukemia inhibitory factor (LIF), was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry (IHC). Anti-TGF-ß1 treatment increased the mean implantation numbers, fecundity rate, the rate of dams with live birth, pup survival rate at 1 week old, and pup mortality rate after weaning. Collagen expression in uteri with adenomyosis was attenuated by anti-TGF-ß1 treatment. Increased LIF expression by anti-TGF-ß1 treatment was detected by qRT-PCR, Western blot, and IHC. The results suggest that inhibition of TGF-ß1 improves pregnancy outcomes by restoring endometrial receptivity in mice with adenomyosis.

Proteomic Analysis of Uterine Tissues During Peri-Implantation Period in Mice with Experimentally Induced Adenomyosis that Treated with anti-Ngf: Implications for Cell-Cell Adhesion and Metabolic Processes.

Nerve growth factor (NGF) has been verified to be expressed with higher level in adenomyosis uteri, and its neutralizing antibody has a strong inhibitory influence on inflammation. The present study aimed to explore the effect of anti-NGF on the expression of proteins in uteri of mice-induced adenomyosis and assessed its potential role in improving pregnancy rate. In this study, we established a mouse model of adenomyosis and administrated NGF-neutralizing antibody into mice. The mass spectrometry (MS) analysis of the uteri during the implantation window was performed to explore the essential proteins participating in therapy. Besides, embryos of healthy mice were transferred into the uteri to assess the implantation rate. The results of MS analysis demonstrated that 119 proteins were changed in the adenomyosis group compared with control group, and 126 proteins were differentially expressed in the anti-NGF group compared with the adenomyosis group (fold change > 1.5, P < 0.05. After performing cluster analysis using Mfuzz package, we found that a group of proteins participated in cell-cell adhesion and metabolic processes, which were attenuated in the adenomyosis group, while those were successfully recovered by anti-NGF treatment. Western blotting confirmed that the expression levels of integrin alpha-1 (ITGA1), integrin beta-1 (ITGB1), laminin subunit gamma-1 (LAMC1), and creatine kinase M-type (CKM) were decreased in adenomyosis group, whereas those levels were elevated after anti-NGF treatment. Embryo implantation rate in the adenomyosis group was significantly decreased compared with that in the control group (2.31% vs. 26.15%, P < 0.001) and anti-NGF treatment slightly enhanced the embryo implantation rate in mice with experimentally induced adenomyosis (9.23% vs. 2.31%, P = 0.017). Our results revealed that anti-NGF therapy can improve fertility of mice with experimentally induced adenomyosis, possibly through promoting integrin-related proteins.

Symptoms of Adenomyosis and Overlapping Diseases.

To summarize and update our current knowledge regarding adenomyosis diagnosis, prevalence, and symptoms. Systematic review of PubMed between January 1972 and April 2020. Search strategy included: "adenomyosis [MeSH Terms] AND (endometriosis[MeSH Term OR prevalence study [MeSH Terms] OR dysmenorrhea[Text Word] OR prevalence[Text Word] OR young adults [Text Word] OR adolesce* [Text Word] OR symptoms[Text Word] OR imaging diagnosis [Text Word] OR pathology[Text Word]. Articles published in English that addressed adenomyosis and discussed prevalence, diagnosis, and symptoms were included. Included articles described: pathology diagnosis, imaging, biopsy diagnosis, prevalence and age of onset, symptoms, and concomitant endometriosis. Sixteen articles were included in the qualitative analysis. The studies are heterogeneous when diagnosing adenomyosis with differing criteria, protocols, and patient populations. Prevalence estimates range from 20% to 88.8% in symptomatic women (average 30-35%) with most diagnosed between 32-38 years old. The correlation between imaging and pathology continues to evolve. As imaging advances, newer studies report younger symptomatic women are being diagnosed with adenomyosis based on both magnetic resonance imaging (MRI) and/or transvaginal ultrasound (TVUS). High rates of concomitant endometriosis create challenges when discerning the etiology of pelvic pain. Symptoms that are historically attributed to endometriosis may actually be caused by adenomyosis. Adenomyosis remains a challenge to identify, assess and research because of the lack of standardized diagnostic criteria, especially in women who wish to retain their uterus. As noninvasive diagnostics such as imaging and myometrial biopsies continue to improve, younger women with variable symptoms will likely create criteria for diagnosis with adenomyosis. The priority should be to create standardized histopathological and imaging diagnoses to gain deeper understandings of adenomyosis.

Eye to the Future in Adenomyosis Research.

Adenomyosis is a poorly understood and clinically underappreciated gynecologic disorder associated with substantial morbidity including dysmenorrhea, pelvic pain, heavy menstrual bleeding, infertility, and poor pregnancy outcomes. Substantial gaps persist in our understanding of essentially all aspects of this disorder - epidemiology, risk factors, pathogenesis, pathophysiology, diagnosis, and treatment. In this article, we summarize current thoughts on future directions in basic, translational, and clinical adenomyosis research.

Adenomyosis: Mechanisms and Pathogenesis.

Adenomyosis is a common disorder of the uterus, and is associated with an enlarged uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility. It is characterized by endometrial epithelial cells and stromal fibroblasts abnormally found in the myometrium where they elicit hyperplasia and hypertrophy of surrounding smooth muscle cells. While both the mechanistic processes and the pathogenesis of adenomyosis are uncertain, several theories have been put forward addressing how this disease develops. These include intrinsic or induced (1) microtrauma of the endometrial-myometrial interface; (2) enhanced invasion of endometrium into myometrium; (3) metaplasia of stem cells in myometrium; (4) infiltration of endometrial cells in retrograde menstrual effluent into the uterine wall from the serosal side; (5) induction of adenomyotic lesions by aberrant local steroid and pituitary hormones; and (6) abnormal uterine development in response to genetic and epigenetic modifications. Dysmenorrhea, HMB, and infertility are likely results of inflammation, neurogenesis, angiogenesis, and contractile abnormalities in the endometrial and myometrial components. Elucidating mechanisms underlying the pathogenesis of adenomyosis raise possibilities to develop targeted therapies to ameliorate symptoms beyond the current agents that are largely ineffective. Herein, we address these possible etiologies and data that support underlying mechanisms.

Focal adenomyosis is associated with primary infertility.

OBJECTIVE: To study the association between adenomyosis and infertility, according to the adenomyosis phenotype as diagnosed by magnetic resonance imaging (MRI). DESIGN: A single-center, cross-sectional study. SETTING: University hospital-based research center. PATIENT(S): Patients between 18 and 42 years of age who were surgically explored for benign gynecological conditions at our institution between May 2005 and May 2018. Only women with uterine MRIs performed by a senior radiologist were retained for this study. INTERVENTION(S): Primary and secondary infertile women were compared with women without infertility. In addition, the women were diagnosed according to the MRI findings as having adenomyosis (focal adenomyosis of the outer myometrium [FAOM] and/or diffuse adenomyosis phenotypes) or no adenomyosis. MAIN OUTCOME MEASURE(S): Primary and secondary infertility-associated factors. RESULT(S): A total of 496 women were included in the study population. Three groups were compared: a no infertility group (n = 361), a primary infertility group (n = 84), and a secondary infertility group (n = 51). Among them, 248 women did not present adenomyosis lesions and 248 women had a radiological diagnosis of adenomyosis. The presence of FAOM was significantly associated with primary infertility. Diffuse adenomyosis was not found to be associated with infertility. The distribution of endometriosis or leiomyomas was not significantly different between the groups. After a multinomial regression model including the women's age and associated endometriosis or leiomyoma, the presence of FAOM was identified as an independent associated factor of primary infertility (adjusted odds ratio 1.9; 95% confidence interval 1.1-3.3). CONCLUSION(S): The presence of FAOM was associated with primary infertility. This study opens the door to future clinical and basic studies aimed at better characterization of FAOM and its infertility-related physiopathology.

Menstruation: science and society.

Women's health concerns are generally underrepresented in basic and translational research, but reproductive health in particular has been hampered by a lack of understanding of basic uterine and menstrual physiology. Menstrual health is an integral part of overall health because between menarche and menopause, most women menstruate. Yet for tens of millions of women around the world, menstruation regularly and often catastrophically disrupts their physical, mental, and social well-being. Enhancing our understanding of the underlying phenomena involved in menstruation, abnormal uterine bleeding, and other menstruation-related disorders will move us closer to the goal of personalized care. Furthermore, a deeper mechanistic understanding of menstruation-a fast, scarless healing process in healthy individuals-will likely yield insights into a myriad of other diseases involving regulation of vascular function locally and systemically. We also recognize that many women now delay pregnancy and that there is an increasing desire for fertility and uterine preservation. In September 2018, the Gynecologic Health and Disease Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development convened a 2-day meeting, "Menstruation: Science and Society" with an aim to "identify gaps and opportunities in menstruation science and to raise awareness of the need for more research in this field." Experts in fields ranging from the evolutionary role of menstruation to basic endometrial biology (including omic analysis of the endometrium, stem cells and tissue engineering of the endometrium, endometrial microbiome, and abnormal uterine bleeding and fibroids) and translational medicine (imaging and sampling modalities, patient-focused analysis of menstrual disorders including abnormal uterine bleeding, smart technologies or applications and mobile health platforms) to societal challenges in health literacy and dissemination frameworks across different economic and cultural landscapes shared current state-of-the-art and future vision, incorporating the patient voice at the launch of the meeting. Here, we provide an enhanced meeting report with extensive up-to-date (as of submission) context, capturing the spectrum from how the basic processes of menstruation commence in response to progesterone withdrawal, through the role of tissue-resident and circulating stem and progenitor cells in monthly regeneration-and current gaps in knowledge on how dysregulation leads to abnormal uterine bleeding and other menstruation-related disorders such as adenomyosis, endometriosis, and fibroids-to the clinical challenges in diagnostics, treatment, and patient and societal education. We conclude with an overview of how the global agenda concerning menstruation, and specifically menstrual health and hygiene, are gaining momentum, ranging from increasing investment in addressing menstruation-related barriers facing girls in schools in low- to middle-income countries to the more recent "menstrual equity" and "period poverty" movements spreading across high-income countries.

Evaluation of adenomyosis after gonadotrophin-releasing hormone agonist therapy using ultrasound post-processing imaging: a pilot study.

OBJECTIVE: We explored a method for the quantitative sonographic analysis of myometrial texture using computer-aided image analysis software to assess outcomes following treatment with gonadotrophin-releasing hormone (GnRH) agonist for adenomyosis in women with infertility. METHOD: Data for patients with ultrasound images of the myometrium obtained at Taipei Medical University Hospital from 1 September 2018 to 5 April 5 2019 were analyzed. Only 10 patients with 20 ultrasound images matched the eligibility criteria. The images were divided into pre-treatment (n = 10) and post-treatment images (n = 10) and quantitative grayscale histograms were obtained from the ultrasound images using publicly available ImageJ computer-aided image analysis software. We analyzed the differences between the pre- and post-treatment images using the Mann-Whitney test and compared the results with outcomes assessed by serum CA-125 levels. RESULTS: Image analysis of the grayscale histograms revealed significant differences between before and after treatment. The classification of the myometrium pre-treatment and post-treatment was similar using CA-125 and histogram grayscale analysis. CONCLUSION: Computer-aided image analysis of grayscale histograms of the myometrium obtained from ultrasound images is an alternative method for assessing myometrial conditions after GnRH agonist treatment in patients with adenomyosis.

Three-dimensional ultrasound diagnosis of adenomyosis is not associated with adverse pregnancy outcome following single thawed euploid blastocyst transfer: prospective cohort study.

OBJECTIVES: The objectives of this study were (1) to assess the prevalence of ultrasound (US) features of adenomyosis in an infertile population undergoing in-vitro fertilization (IVF), (2) to define the inter- and intrarater agreement of three-dimensional (3D) US assessment of adenomyosis, and (3) to evaluate sonographic features of adenomyosis with respect to pregnancy outcome following transfer of a single thawed euploid blastocyst. METHODS: This was a prospective cohort study. Subjects scheduled to undergo a single thawed euploid blastocyst transfer between April and December 2017 at a large IVF center were eligible for inclusion. Enrolled subjects underwent endometrial preparation for frozen embryo transfer. 3D-US was performed on the day prior to embryo transfer, with images stored for subsequent evaluation. Subjects then underwent transfer of a single thawed euploid blastocyst, and pregnancy outcomes were collected. All 3D-US volumes were de-identified and reviewed independently by five reproductive endocrinologists/infertility specialists with expertise in gynecological US for the presence of seven sonographic features of adenomyosis: global uterine enlargement, myometrial wall asymmetry, heterogeneous echogenicity, irregular junctional zone, myometrial cysts, fan-shaped shadowing and ill-defined myometrial lesions. Adenomyosis was considered to be present if the majority of the reviewers noted at least one of the seven sonographic features. Inter- and intrarater agreement was evaluated using Fleiss's kappa. Clinical and cycle characteristics of subjects with and those without adenomyosis were compared. The primary outcome of interest was live birth rate. Secondary outcomes included clinical pregnancy rate and miscarriage rate. Logistic regression analysis was performed to account for potential confounders. RESULTS: A total of 648 subjects were included. The prevalence of adenomyosis on US was 15.3% (99/648). On retrospective chart review, very few patients with adenomyosis had symptoms. The inter- and intrarater agreement amongst five independent specialists conducting the 3D-US assessments of adenomyosis were poor (κ = 0.23) and moderate (κ = 0.58), respectively. Subjects with adenomyosis were older (37.1 vs 35.9 years, P = 0.02) and more likely to undergo a gonadotropin-releasing hormone agonist downregulation protocol when compared with those without adenomyosis (12.1% vs 5.1%, P = 0.02). Clinical pregnancy (80.0% vs 75.0%) and live birth (69.5% vs 66.5%) rates were similar between the groups. When adjusting for potential confounders, there was no difference in the rate of clinical pregnancy (adjusted odds ratio (aOR), 1.47 (95% CI, 0.85-2.56)), miscarriage (aOR, 1.3 (95% CI, 0.62-2.72)) or live birth (aOR, 1.28 (95% CI, 0.78-2.08)) between subjects with and those without adenomyosis. No individual sonographic marker of adenomyosis was predictive of pregnancy outcome. CONCLUSIONS: The inter-rater agreement of 3D-US assessment of adenomyosis is poor. Furthermore, sonographic markers of adenomyosis in asymptomatic patients may not be associated with altered pregnancy outcome following transfer of a single thawed euploid blastocyst. These findings suggest that routine screening for asymptomatic adenomyosis in an unselected infertile patient population undergoing frozen embryo transfer may not be warranted. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Factors associated with physiological postoperative pyrexia.

AIM: Postoperative pyrexia is generally a physiological response to surgery. It is a common problem and burden for both patients and surgeons. This study aimed to investigate the incidence and duration of physiological postoperative pyrexia and to retrospectively identify the prognostic factors associated with it. METHODS: We reviewed the medical records of 462 patients who underwent surgery for adenomyosis under general anesthesia. Postoperative pyrexia was defined as an axillary temperature of at least 38°C occurring for at least 4 h after the surgery up to the next morning. Long-duration pyrexia was defined as a fever recovery period of >3 days. RESULTS: Of the 367 patients included in this study, 234 (64%) developed postoperative pyrexia and 260 (71%) needed >3 days to recover the normal temperature (<37°C). Multivariate analyses revealed that the administration of an amino acid-enriched solution and non-administration of flurbiprofen were associated with postoperative pyrexia. Scale of surgery (bleeding volume + weight of removed adenomyosis and other tissue), body mass index, and decreased body temperature during surgery were not associated with postoperative pyrexia. Long-duration pyrexia was associated with the scale of surgery but not with the administration of an amino acid-enriched solution and flurbiprofen. CONCLUSION: More than half of the patients developed postoperative pyrexia. Postoperative pyrexia was related to the administration of an amino acid-enriched solution and flurbiprofen. Long-duration pyrexia was associated with the scale of surgery.

Transcriptome sequencing of adenomyosis eutopic endometrium: A new insight into its pathophysiology.

The eutopic endometrium has been suggested to play a crucial role in the pathogenesis of adenomyosis. However, the specific genes in eutopic endometrium responsible for the pathogenesis of adenomyosis still remain to be elucidated. We aim to identify differentially expressed genes (DEGs) and molecular pathways/networks in eutopic endometrium from adenomyosis patients and provide a new insight into disease mechanisms at transcriptome level. RNA sequencing (RNA-Seq) was performed with 12 eutopic endometrium from adenomyosis and control groups. Differentially expressed genes in adenomyosis were validated by quantitative real-time PCR (qPCR) and immunochemistry. Functional annotations of the DEGs were analysed with Ingenuity Pathway Analysis (IPA). Quantitative DNA methylation analysis of CEBPB was performed with MassArray system. A total of 373 differentially expressed genes were identified in the adenomyosis eutopic endometrium compared to matched controls. Bioinformatic analysis predicted that IL-6 signalling and ERK/MAPK signalling were activated in adenomyosis endometrium. We also found that the increased expression and DNA hypomethylation of CEBPB were associated with adenomyosis. Our results revealed key pathways and networks in eutopic endometrium of adenomyosis. The study is the first to propose the association between C/EBPß and adenomyosis and can improve the understanding of the pathogenesis of adenomyosis.