Ultrasound and magnetic resonance imaging-based investigation of the role of perfusion and oxygen availability in menstrual pain.

BACKGROUND: The mechanisms responsible for menstrual pain are poorly understood. However, dynamic, noninvasive pelvic imaging of menstrual pain sufferers could aid in identifying therapeutic targets and testing novel treatments. OBJECTIVE: To study the mechanisms responsible for menstrual pain, we analyzed ultrasonographic and complementary functional magnetic resonance imaging parameters in dysmenorrhea sufferers and pain-free controls under multiple conditions. STUDY DESIGN: We performed functional magnetic resonance imaging on participants with and those without dysmenorrhea during menses and outside menses. To clarify whether regional changes in oxygen availability and perfusion occur, functional magnetic resonance imaging R2∗ measurements of the endometrium and myometrium were obtained. R2∗ measurements are calculated nuclear magnetic resonance relaxation rates sensitive to the paramagnetic properties of oxygenated and deoxygenated hemoglobin. We also compared parameters before and after an analgesic dose of naproxen sodium. In addition, we performed similar measurements with Doppler ultrasonography to identify if changes in uterine arterial velocity occurred during menstrual cramping in real time. Mixed model statistics were performed to account for within-subject effects across conditions. Corrections for multiple comparisons were made with a false discovery rate adjustment. RESULTS: During menstruation, a notable increase in R2∗ values, indicative of tissue ischemia, was observed in both the myometrium (beta ± standard error of the mean, 15.74±2.29 s-1; P=.001; q=.002) and the endometrium (26.37±9.33 s-1; P=.005; q=.008) of participants who experienced dysmenorrhea. A similar increase was noted in the myometrium (28.89±2.85 s-1; P=.001; q=.002) and endometrium (75.50±2.57 s-1; P=.001; q=.003) of pain-free controls. Post hoc analyses revealed that the R2∗ values during menstruation were significantly higher among the pain-free controls (myometrium, P=.008; endometrium, P=.043). Although naproxen sodium increased the endometrial R2∗ values among participants with dysmenorrhea (48.29±15.78 s-1; P=.005; q=.008), it decreased myometrial R2∗ values among pain-free controls. The Doppler findings were consistent with the functional magnetic resonance imaging (-8.62±3.25 s-1; P=.008; q=.011). The pulsatility index (-0.42±0.14; P=.004; q=.004) and resistance index (-0.042±0.012; P=.001; q=.001) decreased during menses when compared with the measurements outside of menses, and the effects were significantly reversed by naproxen sodium. Naproxen sodium had the opposite effect in pain-free controls. There were no significant real-time changes in the pulsatility index, resistance index, peak systolic velocity, or minimum diastolic velocity during episodes of symptomatic menstrual cramping. CONCLUSION: Functional magnetic resonance imaging and Doppler metrics suggest that participants with dysmenorrhea have better perfusion and oxygen availability than pain-free controls. Naproxen sodium's therapeutic mechanism is associated with relative reductions in uterine perfusion and oxygen availability. An opposite pharmacologic effect was observed in pain-free controls. During menstrual cramping, there is insufficient evidence of episodic impaired uterine perfusion. Thus, prostaglandins may have protective vasoconstrictive effects in pain-free controls and opposite effects in participants with dysmenorrhea.

Enhanced myometrial vascularity: case presentation and review.

OBJECTIVE: To describe the etiology of arteriovenous malformations (AVM) and enhanced myometrial vascularity (EMV), and review updates in management for patients with retained products of conception (RPOC) associated with EMV through a case presentation. DESIGN: A 6-minute narrated video discusses the recent distinction between EMV and AVM. The etiology, symptoms, imaging findings/interpretation, and management based on symptoms are reviewed in detail. As this represents a single case report, it does not meet the definition of research according to the regulations at 45 CFR 46.102(l); therefore, institutional review board approval was not required. SETTING: Tertiary referral center. PATIENT(S): Eight weeks after suction dilation and curettage (D&C) for an incomplete abortion, a 28-year-old gravida 1, para 0 patient presented to an outside facility with RPOC, menorrhagia, and an acute decrease in hemoglobin. After uterine AVM was diagnosed, she was transferred to our facility for further care. INTERVENTION(S): After transfer to our center, ultrasound demonstrated RPOC, with prominent internal vasculature containing peak systolic velocity >20 cm/s. A diagnosis of EMV was made. Magnetic resonance imaging confirmed a prominent serpentine vessel at the endometrium and RPOC within the uterine cavity (Fig. 1). Due to her anemia, she underwent uterine artery embolization (UAE) followed by suction D&C (Fig. 2). Hysteroscopy was performed before and after suction D&C and after curettage, a large vascular bundle was appreciated at the surface of the endometrium. MAIN OUTCOME MEASURE(S): None. RESULT(S): The patient presented to the clinic 2 weeks postoperatively with the resolution of abnormal uterine bleeding symptoms and a negative ß-human chorionic gonadotropin test. CONCLUSION(S): Management of patients with EMV is dependent on the extent of their symptoms. If significant bleeding is present, surgical management is required. Previous reports suggested that patients with EMV and RPOC should undergo UAE before D&C, but more recent studies suggest that D&C may be initiated without UAE, as EMV associated with RPOC may be a normal transient placentation phenomenon and have less risk of hemorrhage than previously suspected. However, in patients with significant preoperative bleeding and/or anemia, we propose that UAE should still be considered. Each patient requires individualized management based on symptoms, signs, imaging, and plans for future fertility. The ideal management of patients with RPOC and EMV remains to be determined.

Kynurenine Relaxes Arteries of Normotensive Women and Those With Preeclampsia.

[Figure: see text].

The role of ultrasound in prediction of intra-operative blood loss in cases of placenta accreta spectrum disorders.

PURPOSE: To assess the value of various grey-scale ultrasound, 2D color Doppler, and 3D power Doppler sonographic markers in predicting major intraoperative blood loss during planned cesarean hysterectomy for cases diagnosed with placenta accreta spectrum (PAS) disorders. METHODS: 50 women diagnosed with PAS were scanned the day before planned delivery and hysterectomy for various sonographic markers indicative of placental invasion. These women were then later divided according to blood loss in two groups: group A (minor hemorrhage, < 2500 ml), and group B (major hemorrhage, > 2500 ml), and the data were analyzed. RESULTS: The odds ratio (OR) for major hemorrhage was as follows for the following sonographic markers: 'number of lacunae > 4' OR 3.8 95% CI (1.0-13.8) (p = 0.047); 'subplacental hypervascularity' OR 10.8 95% CI (1.2-98.0) (p = 0.035); 'tortuous vascularity with 'chaotic branching' OR 10.8 95%CI (1.2-98.0) (p = 0.035); 'numerous coherent vessels involving the serosa-bladder interface OR 14.6 95% CI (2.7-80.5) (p = 0.002); and 'presence of bridging vessels OR 2.9 95% CI (1.4-6.9) (p = 0.005). Only the presence of numerous coherent vessels involving the bladder-serosal interface (p = 0.002) was proven to be independent predictor of major hemorrhage during hysterectomy. CONCLUSION: The use of 2D color Doppler and 3D power Doppler can help predict massive hemorrhage in cases of PAS disorders.

Use of hysteroscopy in diagnosis and follow-up of acquired uterine enhanced myometrial vascularity.

OBJECTIVE: To describe the role of hysteroscopy in diagnosis and subsequent follow-up of uterine enhanced myometrial vascularity (EMV). Uterine EMV, previously known as arteriovenous malformation (AVM), is a rare but cannot-miss finding often associated with prior pregnancy or uterine surgery and is typically suspected when a vascular mass is found on ultrasound. Color Doppler imaging will demonstrate high-velocity, low-impedance flow, with more significant shunts demonstrating higher peak systolic velocity (PSV). If not already diagnosed by ultrasound, accurate recognition during hysteroscopy is mandatory prior to any uterine instrumentation, as biopsy or curettage can lead to unanticipated massive hemorrhage. While many cases of EMV may resolve spontaneously, actively bleeding patients may require treatment with embolization, a procedure that may decrease ovarian reserve and impair fertility, though favorable reproductive outcomes have been reported. Others have reported success with hysteroscopic management using a bipolar electrosurgical loop. DESIGN: Case report. SETTING: Academic hospital system. PATIENT(S): We describe a 22-year-old G2P1011 who presented to the emergency department with heavy vaginal bleeding and a negative urine human chorionic gonadotropin 9 weeks following a first-trimester termination of pregnancy. Her ultrasound demonstrated a heterogeneous 2.6×2.3×2.6 cm vascular mass in the endometrial canal that was initially interpreted as retained products of conception. Unfortunately, PSV in the lesion was not measured. During observation, bleeding continued, and her hemoglobin dropped from 8.3 g/dL to 6.9 g/dL the next morning. She was transfused 2 units of blood and taken to the operating room for hysteroscopic evaluation and possible uterine curettage. INTERVENTION(S): Hysteroscopy revealed a large pulsating 2cm bluish vascular mass that was recognized as a uterine EMV and the procedure was terminated with the plan for embolization. Given fertility concerns, the diagnosis was confirmed with MRI/MRA, which identified a 2.7cm mass-like process with early post-contrast enhancement in the arterial phase. An angiogram demonstrated bilaterally enlarged tortuous uterine arteries perfusing a hypervascular EMV that was treated with selective bilateral uterine artery embolization. MAIN OUTCOME MEASURE(S): Further bleeding or evidence of EMV. RESULT(S): Follow-up office hysteroscopy at 2 weeks demonstrated a 2 cm raised area of tissue without pulsations. At 6 weeks post-procedure, bleeding had ceased, and office hysteroscopy revealed only a small 0.5 cm calcified nodule with a circumferential pseudo-decidual reaction. CONCLUSION(S): Hysteroscopy may be used to diagnose EMV when ultrasound is not conclusive. Recognition of the pulsating vascular appearance of EMV on hysteroscopy is critical in preventing hemorrhage from inappropriate curettage. Resolution of the lesion following embolization can be readily demonstrated with office hysteroscopy.

Natural history of pregnancy-related enhanced myometrial vascularity following miscarriage.

OBJECTIVES: Our primary aim was to report the incidence of enhanced myometrial vascularity (EMV) in consecutive women attending our early pregnancy assessment unit, following first-trimester miscarriage. We aimed further to evaluate the clinical presentation and complications associated with expectant and surgical management of EMV in these women. METHODS: This was a prospective cohort study conducted in a London teaching hospital between June 2015 and June 2018, including consecutive patients with an observation of EMV on transvaginal ultrasonography following first-trimester miscarriage. The diagnosis was made following the subjective identification of EMV using color Doppler ultrasonography and a peak systolic velocity (PSV) ≥ 20 cm/s within the collection of vessels. Women were followed up with repeat scans every 14 days. Management was expectant unless intervention was indicated because of excessive or prolonged bleeding, persistent presence of retained tissue in the endometrial cavity or patient choice. The final clinical outcome was recorded. Time to resolution of EMV was defined as the interval from detection of EMV until resolution. RESULTS: During the study period, there were 2627 first-trimester fetal losses in the department and, of these, 40 patients were diagnosed with EMV, hence the incidence of EMV following miscarriage was 1.52%. All cases were associated with ultrasound evidence of retained products of conception (RPOC) at presentation (mean dimensions, 22 × 20 × 20 mm). Thirty-one patients opted initially for expectant management, of which 18 had successful resolution without intervention, five were lost to follow-up and eight subsequently had surgical evacuation due to patient choice. No expectantly managed case required emergency intervention. Nine patients chose surgical evacuation as primary treatment. No significant correlation was seen between PSV within the EMV at presentation and blood loss at surgery. Median PSV was 47 (range, 20-148) cm/s. The estimated blood loss in all cases managed surgically ranged from 20-300 mL. Presence of RPOC was confirmed in all specimens that were sent for analysis following surgery. For cases successfully managed expectantly, the mean time to resolution was 48 (range, 21-84) days. In the nine cases managed surgically from the beginning, the mean time to resolution of EMV was 10.6 (range, 3-29) days. CONCLUSIONS: This study suggests that EMV is an uncommon finding following miscarriage and is associated with the presence of RPOC. Expectant management was a safe option in our cohort, with minimal bleeding, although it was associated with protracted time to resolution. In patients who opted for surgery, the maximum blood loss was 300 mL and no patient required blood transfusion or embolization. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The importance of pseudocapsule preservation during hysteroscopic myomectomy.

Minimally invasive techniques for myomectomy are based on the rationale of preserving the myometrial integrity, in order to spare muscular and fibro-neurovascular myometrial fibers and ensure complete and bloodless myoma removal. Post-operative myometrial vascularization is crucial in injured muscle regeneration. The post-surgical myometrial healing is needful for uterine reproductive function. Neurotransmitters and neurofibers were analyzed in the myoma pseudocapsule surrounding fibroid. They activate signaling molecule synthesis and release which, in turn, promote cell activation and induce muscle regeneration and growth. Pseudocapsule damage during myomectomy may lead to a reduction of neuropeptides and neurofibers at the hysterotomic site, to a poor physiological myometrial healing, with more fibrosis due to hypoxia, ischemia and necrosis. These pathophysiological events cause deficit in myometrial neurotransmission, muscular impulse and contractility, with ultimately impaired uterine muscle function during pregnancy, labor and delivery. Hence, during myomectomy, all manipulations should be performed as precisely and bloodlessly as possible, avoiding extensive, high wattage diathermocoagulation or excessive tissue manipulation or muscular trauma. Any iatrogenic pseudocapsule damage may alter neurotransmitter function during successive myometrial healing, impacting negatively on uterine repair and on eventual pregnancies. Hence the reasoned myomectomy on a biological basis, the "intracapsular myomectomy", satisfied these surgical and physiological requirements. It was described precisely and firstly by the hysteroscopy, with the image magnification of the preservation of the myoma pseudocapsule. The "intracapsular hysteroscopic myomectomy" demonstrated the safe and effective removal of submucous myomas with intramural development. It allowed to completely remove the myoma in one or two surgical steps, saving the pseudocapsule and the surrounding healthy myometrium. The respect of the myometrium and the reduced thermal injury, a part the excellent outcomes in terms of surgical complications prevention, post-surgical fibrosis and intrauterine synechiae reduction, highlighted the physiological development of a successive pregnancy, without any myometrial complications during pregnancy, labor and delivery.

Conservative surgery of diffuse adenomyosis with TOUA: Single surgeon experience of one hundred sixteen cases and report of fertility outcomes.

The aim of this study is to evaluate the clinical outcomes of conservative adenomyomectomy with TOUA for diffuse uterine adenomyosis and to determine the feasibility and safety. One hundred and sixteen patients with symptomatic diffuse uterine adenomyosis underwent adenomyomectomy with TOUA by a single surgeon at Ulsan University Hospital between May 2011 and March 2016. Surgical outcomes included operative time, intraoperative injury and operative blood loss. We assessed the degree of improvement in dysmenorrhea and menorrhagia at the 7-month follow-up visit after the operation. The mean age of patients was 37.49 years (range: 26-49). The mean total surgical time was 116.12 min (range: 60-300, SD: 37.27). The mean estimated blood loss was 207.22 mL (range: 30-1200, SD: 161.08) and there were no cases of injury to the uterine arteries or pelvic nerves. The mean duration of hospital stay was 5.05 days (range: 4-7, SD: 0.68) and the mean follow-up period of 16.67 months (range: 6-49, SD: 12.77). At the 7-month follow-up after adenomyomectomy with TOUA, dysmenorrhea and menorrhagia were improved in 100% and 89% of the patients, respectively. In patients with diffuse uterine adenomyosis, even when the whole uterus is involved, for relief of severe adenomyosis-related symptoms, adenomyomectomy with TOUA could be a safe and effective surgical treatment option for those who want to preserve their fertility.

Endometrial vascular development in heavy menstrual bleeding: altered spatio-temporal expression of endothelial cell markers and extracellular matrix components.

STUDY QUESTION: Are there any phenotypic and structural/architectural changes in the vessels of endometrium and superficial myometrium during the normal menstrual cycle in healthy women and those with heavy menstrual bleeding (HMB)? SUMMARY ANSWER: Spatial and temporal differences in protein levels of endothelial cell (EC) markers and components of the extracellular matrix (ECM) were detected across the menstrual cycle in healthy women and these are altered in HMB. WHAT IS KNOWN ALREADY: HMB affects 30% of women of reproductive age with ~50% of cases being idiopathic. We have previously shown that the differentiation status of endometrial vascular smooth muscle cells (VSMCs) is altered in women with HMB, suggesting altered vessel maturation compared to controls. Endometrial arteriogenesis requires the co-ordinated maturation not only of the VSMCs but also the underlying ECs and surrounding ECM. We hypothesized that there are spatial and temporal patterns of protein expression of EC markers and vascular ECM components in the endometrium across the menstrual cycle, which are altered in women with HMB. STUDY DESIGN, SIZE, DURATION: Biopsies containing endometrium and superficial myometrium were taken from hysterectomy specimens from both healthy control women without endometrial pathology and women with subjective HMB in the proliferative (PP), early secretory (ESP), mid secretory (MSP) and late secretory (LSP) phases (N = 5 for each cycle phase and subject group). Samples were fixed in formalin and embedded in paraffin wax. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serial sections (3µm thick) were immunostained for EC markers (factor VIII related antigen (F8RA), CD34, CD31 and ulex europaeus-agglutinin I (UEA-1) lectin), structural ECM markers (osteopontin, laminin, fibronectin and collagen IV) and for Ki67 to assess proliferation. Immunoreactivity of vessels in superficial myometrium, endometrial stratum basalis, stratum functionalis and luminal region was scored using either a modified Quickscore or by counting the number of positive vessels. MAIN RESULTS AND THE ROLE OF CHANCE: In control samples, all four EC markers showed a dynamic expression pattern according to the menstrual cycle phase, in both endometrial and myometrial vessels. EC protein marker expression was altered in women with HMB compared with controls, especially in the secretory phase in the endometrial luminal region and stratum functionalis. For example, in the LSP expression of UEA-1 and CD31 in the luminal region decreased in HMB (mean quickscore: 1 and 5, respectively) compared with controls (3.2 and 7.4, respectively) (both P = 0.008), while expression of F8RA and CD34 increased in HMB (1.4 and 8, respectively) compared with controls (0 and 5.8, respectively) (both P = 0.008). There was also a distinct pattern of expression of the vascular structural ECM protein components osteopontin, laminin, fibronectin and collagen IV in the superficial myometrium, stratum functionalis and stratum basalis during the menstrual cycle, which was altered in HMB. In particular, compared with controls, osteopontin expression in HMB was higher in stratum functionalis in the LSP (7.2 and 11.2, respectively P = 0.008), while collagen IV expression was reduced in stratum basalis in the MSP (4.6 and 2.8, respectively P = 0.002) and in stratum functionalis in the ESP (7 and 3.2, respectively P = 0.008). LIMITATIONS, REASONS FOR CAUTION: The protein expression of vascular EC markers and ECM components was assessed using a semi-quantitative approach in both straight and spiral arterioles. In our hospital, HMB is determined by subjective criteria and levels of blood loss were not assessed. WIDER IMPLICATIONS OF THE FINDINGS: Variation in the protein expression pattern between the four EC markers highlights the importance of choice of EC marker for investigation of endometrial vessels. Differences in expression of the different EC markers may reflect developmental stage dependent expression of EC markers in endometrial vessels, and their altered expression in HMB may reflect dysregulated vascular development. This hypothesis is supported by altered expression of ECM proteins within endometrial vessel walls, as well as our previous data showing a dysregulation in VSMC contractile protein expression in the endometrium of women with HMB. Taken together, these data support the suggestion that HMB symptoms are associated with weaker vascular structures, particularly in the LSP of the menstrual cycle, which may lead to increased and extended blood flow during menstruation. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Wellbeing of Women (RG1342) and Newcastle University. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Surgery in adenomyosis.

INTRODUCTION: Adenomyosis is defined as the presence of endometrial glands and stroma within the myometrium. The true prevalence is unknown and has been reported to range from 1 to 70%. It has a significantly negative impact on women's quality of life, causing abnormal uterine bleeding, dysmenorrhea, and chronic pelvic pain. The definitive treatment for adenomyosis is hysterectomy, although it does not contemplate patients who wish to preserve their fertility. The aim of this paper is to discuss the latest evidence on the surgical techniques for the treatment of adenomyosis published in medical-scientific databases. METHOD: A comprehensive literature search for articles published from 1996 to 2017 related to surgery for adenomyosis was made in Pubmed, Medline, the Cochrane Library, and Google Scholar, in English, by the following MeSH terms: adenomyosis, surgery, pathogenesis, dysmenorrhea and infertility. RESULTS: There is extensive evidence on several surgical approaches for the improvement of adenomyosis-related symptoms; however, there is no robust evidence that they are effective for infertility. CONCLUSION: The management of adenomyosis is quite complex and controversial. Complications after extensive uterine reconstruction, such as uterine rupture, should be considered and discussed with the patient. There are still limited data to support surgery effectiveness, especially for infertility, and further well-designed studies are required.

Hypervascular retained product of conception: Characteristic magnetic resonance imaging and possible relationship to placental polyp and pseudoaneurysm.

The cases of two patients who developed myometrial vascularization following dilatation and curettage are described. In case 1, pathological diagnosis was possible with the resected specimens. This patient had hypervascular retained products of conception (RPOC). In case 2, the natural course of this pathological condition was observed, confirming a process of regression during repeated withdrawal bleeding. The three principal magnetic resonance imaging (MRI) findings in these cases were: (i) presence of a remnant; (ii) breaking of the junctional zone in contact with the remnant; and (iii) vascularization/flow voids infiltrating into the myometrium from the broken junctional zone. These three MRI findings differed in degree and varied in combination in each case of RPOC. Uterine artery pseudoaneurysms have been reported as intrauterine vascularization after abortion or delivery with subsequent spontaneous regression. These reports may include cases of hypervascular RPOC.

HDlive Flow silhouette mode for the diagnosis of uterine enhanced myometrial vascularity/arteriovenous malformations.

We present our initial experience of using the HDlive Flow silhouette mode to construct images of two cases of uterine enhanced myometrial vascularity/arteriovenous malformations (EMV/AVMs). In the first case, the HDlive Flow silhouette mode clearly depicted a fused vascular tumor with irregular contour in the posterior myometrium. In the second case, a large hypervascular mass occupying the entire fundal lesion of the uterus was clearly identified using the HDlive Flow silhouette mode. Moreover, spatial relationships among the hypervascular mass, intrauterine blood collection, and dilated, spiral-shaped right uterine artery enabled the clear localization of the mass. The HDlive Flow silhouette mode provides a novel, unique sonographic image of uterine EMV/AVMs, and might facilitate their diagnosis and localization in the myometrium.

Suturing method as a factor for uterine vascularity after laparoscopic myomectomy.

OBJECTIVE: To evaluate the vascularity of the myometrium after laparoscopic myomectomy sutured by two different methods using contrast-enhanced Magnetic Resonance Imaging. STUDY DESIGN: Twenty-eight women who had symptomatic leiomyomas and underwent laparoscopic myomectomy between June 2013 and July 2014 were included in the present study. In the first half period, continuous sutures were used in 12 patients, and in the latter half period, single interrupted sutures were used in 16 patients. Contrast-enhanced Magnetic Resonance Imaging was used 3 or 6 months after surgery to evaluate vascularity after laparoscopic myomectomy. We defined avascularity index as the percentage of avascular area after surgery to cross sectional area of myoma before surgery. The Wilcoxon rank-sum test was applied to compare avascularity indeces in the two study groups. RESULTS: At 3 months after surgery, avascularity index in continuous sutures group was significantly higher than that in single interrupted sutures group (median 5.0 vs.1.2, p<0.001), suggesting a poorer vascular recovery of the myometrium sutured continuously. CONCLUSION: Simple interrupted suturing might be superior to continuous suturing in terms of vascularity evaluated using contrast enhanced Magnetic Resonance Imaging.

Temporarily Blocking the Uterine Artery to Dig Out a Diffused Adenomyosis Lesion Treated Laparoscopically.

STUDY OBJECTIVE: To show the tips and tricks of a simpler technique for temporary blocking of the uterine artery in laparoscopic resection of a diffuse adenomyosis lesion to make the procedure more efficient and reproducible. DESIGN: This study is designed to be a step-by-step explanation of the technique using videos and pictures (Canadian Task Force classification III). SETTING: Changzhou Maternal and Child Health Hospital, Changzhou, China. PATIENTS: Three patients (age 39-42 years, 41±1.73) were diagnosed with diffuse adenomyosis with severe secondary dysmenorrhea willing to reserve the uterus and a poor response to medical management. Gynecologic examination revealed that the uteri sizes were 9 to 14 weeks. Transvaginal ultrasonography revealed that the lesions were 4 to 7 cm in size. INTERVENTIONS: Laparoscopic resection of the diffuse adenomyosis lesion was conducted after temporary blocking of the uterine artery with a rubber belt. MEASUREMENTS AND MAIN RESULTS: The traditional methods for injecting diluted vasopressin in the myometrium around the affected area and a half-life period of 30 minutes were used. Many adenomyosis patients with severe dysmenorrhea and menometrorrhagia have a large lesion; thus, the operating time is longer. The maximum dose of vasopressin is 20 units daily, and hypertensive patients have a contraindication. We made an incision of the broad ligament of the avascular area near the uterine artery and pulled the rubber pressure pulse ligation tightly through to temporarily block the uterine artery without vasopressin completely through the laparoscopic resection of the diffuse adenomyosis lesion. Intraoperative blood loss was only 120 to 230 mL. In this video, we show a simpler technique for temporarily blocking the uterine artery in laparoscopic resection of diffuse adenomyosis with a stepwise expiation. A levonorgestrel-releasing intrauterine system (Mirena; Bayer, Leverkusen, Germany) was placed in the uterus from the vagina immediately after surgery. At the 3-25 month (10.67±12.42) follow-up, visual analog scale scores were obviously reduced, and the menstrual quantity and amenorrhea dramatically declined after the surgery. All patients had no recurrence and no Mirena loss as assessed by vaginal ultrasound and the visual analog scale [1]. Estrogen was maintained at the normal level after 3 months. This study was approved by the Institutional Review Board of the Changzhou Maternal and Child Health Hospital Affiliated to Nanjing Medical University. CONCLUSION: The incidence of adenomyosis is a newer trend that is being used in patients with a poor response to medical management of uterine lesions and large lesions in China. Using the rubber belt to temporarily block the uterine artery in laparoscopic resection of the diffuse adenomyosis lesion offers the possibility of the rubber belt being effective, safe, and reproducible. Minimally invasive surgery in expert hands is the preferred solution of an increasing number of patients after drug treatment failure.

Angiogenesis and pro-angiogenic factors in uterine fibroids - facts and myths.

Uterine leiomyomata present major problem for females. Although they are benign tumors their frequency is associated with many symptoms like infertility, abdominal pain, menorrhagia. Authors based on their own morphological studies and review of the literature try to indicate main factors causing angiogenesis within leiomyomata and its influence on tumor growth. The strongest proangiogenic factor seems to be hypoxia, which stimulates up- and down-regulation of numerous genetically determined substances. Also mechanical pressure acting upon newly growing vessels is one of the factors which may determine formation of so called "vascular pseudocapsule" around the lesion.

Reliability of First-Trimester Ultrasonic Biopsy for the Evaluation of Placental and Myometrial Blood Perfusion and the Prediction of Preeclampsia.

OBJECTIVE: Low placental vascularization measured by three-dimensional (3-D) ultrasound with power Doppler can predict preeclampsia. We evaluated the reliability and reproducibility of the ultrasonic sphere biopsy (USSB) technique to evaluate placental and subplacental myometrium vascularization in the first trimester. METHODS: We performed a secondary analysis of a case-control study nested in a prospective cohort of women with a singleton pregnancy undergoing ultrasound at 11 to 14 weeks' gestation. Women who developed preeclampsia (n = 20) and randomly selected controls (n = 60) were compared. Other controls (n = 60) were also randomly selected to evaluate intra- and inter-observer reproducibility. Using 3-D power Doppler, the vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured from the volume of the whole placenta and the subplacental myometrium and from their respective USSB. Pearson's correlation coefficients (cc) with their P-values were calculated. RESULTS: We observed that USSB is reliable in estimating the vascularization of the whole placenta in the first trimester (cc of VI 0.83; of FI 0.62; and of VFI 0.78; P < 0.001 for all) but was not as reliable for estimating subplacental myometrium vascularization (cc of VI 0.71; of FI 0.35; and of VFI 0.73). Measurement of placental vascularization using USSB showed good to excellent intra- and inter-observer reproducibility (cc of VI 0.86 and 0.85, respectively; of FI 0.75 and 0.75, respectively; and of VFI 0.83 and 0.83, respectively; P < 0.001 for all). Finally, we observed that women who subsequently developed preeclampsia had lower placental USSB VI (2.1 vs 4.8, P = 0.02), FI (32.4 vs. 42.5, P = 0.002), and VFI (0.8 vs. 2.1, P = 0.01) than controls. CONCLUSION: First-trimester USSB of the placenta using 3-D power Doppler is a reliable and reproducible procedure for estimating placental vascularization and could be used to predict preeclampsia.

Ultrasound diagnosis and management of acquired uterine enhanced myometrial vascularity/arteriovenous malformations.

BACKGROUND: Arteriovenous malformation is a short circuit between an organ's arterial and venous circulation. Arteriovenous malformations are classified as congenital and acquired. In the uterus, they may appear after curettage, cesarean delivery, and myomectomy among others. Their clinical feature is usually vaginal bleeding, which may be severe, if curettage is performed in unrecognized cases. Sonographically on 2-dimensional grayscale ultrasound scanning, the pathologic evidence appears as irregular, anechoic, tortuous, tubular structures that show evidence of increased vascularity when color Doppler is applied. Most of the time they resolve spontaneously; however, if left untreated, they may require involved treatments such as uterine artery embolization or hysterectomy. In the past, uterine artery angiography was the gold standard for the diagnosis; however, ultrasound scanning has diagnosed successfully and helped in the clinical management. Recently, arteriovenous malformations have been referred to as enhanced myometrial vascularities. OBJECTIVES: The purpose of this study was to evaluate the role of transvaginal ultrasound scanning in the diagnosis and treatment of acquired enhanced myometrial vascularity/arteriovenous malformations to outline the natural history of conservatively followed vs treated lesions. METHODS: This was a retrospective study to assess the presentation, treatment, and clinical pictures of patients with uterine Enhanced myometrial vascularity/arteriovenous malformations that were diagnosed with transvaginal ultrasound scanning. We reviewed both (1) ultrasound data (images, measured dimensions, and Doppler blood flow that were defined by its peak systolic velocity and (2) clinical data (age, reproductive status, clinical presentation, inciting event or procedure, surgical history, clinical course, time intervals that included detection to resolution or detection to treatment, and treatment rendered). The diagnostic criteria were "subjective" with a rich vascular network in the myometrium with the use of color Doppler images and "objective" with a high peak systolic velocity of ≥20 cm/sec in the vascular web. Statistical analysis was performed and coded with statistical software where necessary. RESULTS: Twenty-seven patients met the diagnostic criteria of uterine enhanced myometrial vascularity/arteriovenous malformation. Mean age was 31.8 years (range, 18-42 years). Clinical diagnoses of the patients included 10 incomplete abortions, 6 missed abortions, 5 spontaneous complete abortions, 5 cesarean scar pregnancies, and 1 molar pregnancy. Eighty-nine percent of patients had bleeding (n = 24/27), although 1 patient was febrile, and 2 patients were asymptomatic. Recent surgical procedures were performed in 55.5% patients (15/27) that included curettage (n = 10), cesarean deliveries (n = 5), or both (n = 1); 4 patients had a remote history of uterine surgery that included myomectomy. Treatment was varied and included expectant treatment alone in 48% of the patients with serial ultrasound scans and serum human chorionic gonadotropin until resolution (n = 13/27 patients), uterine artery embolization (29.6%; 8/27 patients), methotrexate administration (22.2%; 6/27 patients), hysterectomy (7.4%; 2/27 patients), and curettage (3.7%; 1/27 patients). Three patients required a blood transfusion. Of the 9 patients whose condition required embolization, the conditions of 7 patients resolved after the procedure although 1 patient's condition required operative hysteroscopy and 1 patient's condition required hysterectomy for intractable bleeding. Average peak systolic velocity after embolization in the 9 patients was 85.2 cm/sec (range, 35-170 cm/sec); the average peak systolic velocity of the 16 patients with spontaneous resolution was 58.5 cm/sec (range, 23-90 cm/sec). CONCLUSIONS: Acquired enhanced myometrial vascularity/arteriovenous malformations occurred after unsuccessful pregnancies or treatment procedures that included uterine curettage, cesarean delivery, or cesarean scar pregnancy. Triage of patients for expectant treatment vs intervention with uterine artery embolization based on their clinical status, which was supplemented by objective measurements of blood velocity measurement in the arteriovenous malformation, appears to be a good predictor of outcome. Ultrasound evaluation of patients with early pregnancy failure and persistent bleeding should be considered for evaluation of a possible enhanced myometrial vascularity/arteriovenous malformation.

Corroborating evidence for platelet-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis.

STUDY QUESTION: Do platelets play any role in the development of adenomyosis? SUMMARY ANSWER: As in endometriosis, adenomyotic lesions show significantly increased platelet aggregation, increased expression of transforming growth factor (TGF)-ß1, phosphorylated Smad3, markers of epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT), and smooth muscle metaplasia (SMM), in conjunction with increased fibrosis as compared with normal endometrium. WHAT IS KNOWN ALREADY: Both EMT and FMT are known to play vital roles in fibrogenesis in general and in endometriosis in particular. EMT has been implicated in the development of adenomyosis. SMM is universally seen in endometriosis and also in adenomyosis, and is correlated positively with the extent of fibrosis. However, there has been no published study on the role of platelets in fibrogenesis in adenomyosis, even though adenomyotic lesions undergo repeated cycles of tissue injury and repair, which suggests the involvement of platelets and their possible roles in fibrogenesis. STUDY DESIGN, SIZE, DURATION: Cross-sectional studies of ectopic endometrial and control endometrial tissue samples from three sets of women with and without adenomyosis (n= 34 and 20, 12 and 10, and 8 and 8, respectively) were carried out from 2014 to 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Immunohistochemistry analysis of ectopic endometrial tissues from women with (n= 34) and without (n= 20) adenomyosis with respect to biomarkers of EMT, FMT and highly differentiated smooth muscle cells as well as TGF-ß1, phosphorylated Smad3, markers of proliferation, angiogenesis and extracellular matrix (ECM) deposits. Masson trichrome staining, Van Gieson staining and Pico-Sirius staining were performed to evaluate and quantify the extent of fibrosis in lesions. Progesterone receptor isoform B (PR-B) staining also was performed. In addition, CD42b-positive platelets in ectopic (n= 12) and control (n= 10) endometrium were counted by confocal microscopy and compared. The protein expression levels of TGF-ß1 and phosphorylated Smad3 in both ectopic (n= 8) and control (n= 8) endometrium were measured by western blot analysis. Immunofluorescent staining of both platelets and hepatocyte growth factor (HGF) was also performed for adenomyotic tissue samples (n= 10). MAIN RESULTS AND THE ROLE OF CHANCE: Adenomyotic lesions had a significantly higher extent of platelet aggregation and increased staining for TGF-ß1 and phosphorylated Smad3 (both P-values <0.001 versus control). In addition, E-cadherin staining was decreased while vimentin staining in adenomyotic epithelial cells was increased, along with increased staining of proliferating cell nuclear antigen, vascular endothelial growth factor and CD31 (all P-values <0.001), markers of proliferation and angiogenesis. Staining for α-SMA, a marker for myofibroblast, desmin, smooth muscle myosin heavy chain and oxytocin receptor was significantly increased in adenomyotic lesions versus control, concomitant with increased staining of collagen I and lysyl oxidase (all P-values <0.001). Histochemistry analysis indicates that the extent of fibrosis is high in adenomyotic lesions (P < 0.001), and the extent appeared to correlate negatively with the microvessel density (P < 0.05). PR-B staining was significantly decreased in adenomyotic lesion as compared with control endometrium (P < 0.001). Platelets and HGF were co-localized mostly in the stromal component of adenomyotic lesions, near the glandular epithelium. LIMITATIONS, REASONS FOR CAUTION: The results are limited by the cross-sectional nature of the study and the use of histochemistry and immunohistochemistry analyses only, but nonetheless is a validation of our previous finding in mouse experiments. WIDER IMPLICATIONS OF THE FINDINGS: The data presented are consistent with the notion that platelet-induced activation of the TGF-ß/Smad signaling pathway may be a driving force in EMT, FMT and SMM in the development of adenomyosis, leading to fibrosis. This study provides the first piece of evidence that adenomyotic lesions are wounds that undergo repeated injury and healing, and, as such, platelets play critical roles in the development of adenomyosis by promoting proliferation, angiogenesis, increasing ECM deposits, and SMM, resulting in fibrosis. Platelets may also be involved in uterine hyperactivity and myometrial hyperinnervation. Our results provide one explanation as to why adenomyosis is a challenge for medical treatment, and shed new light onto the pathophysiology of adenomyosis. STUDY FUNDING/COMPETING INTERESTS: Support for data collection and analysis was provided by grants from the National Science Foundation of China. None of the authors has anything to disclose.

Diffusion-weighted MR imaging of uterine leiomyomas following uterine artery embolization.

PURPOSE: To test whether variations in apparent diffusion coefficient (ADC) values of uterine leiomyomas after uterine artery embolization (UAE) may correlate with outcome and assess the effects of UAE on leiomyomas and normal myometrium with magnetic resonance imaging (MRI). METHODS: Data of 49 women who underwent pelvic MRI before and after UAE were retrospectively reviewed. Uterine and leiomyoma volumes, ADC values of leiomyomas, and normal myometrium were calculated before and after UAE. RESULTS: By comparison with baseline ADC values, a significant drop in leiomyoma ADC was found at 6-month post-UAE (1.096 × 10(-3) mm(2)/s vs. 0.712 × 10(-3) mm(2)/s, respectively; p < 0.0001), but not at 48-h post-UAE. Leiomyoma devascularization was complete in 40/49 women (82 %) at 48 h and in 37/49 women (76 %) at 6 months. Volume reduction and leiomyoma ADC values at 6 months correlated with the degree of devascularization. There was a significant drop in myometrium ADC after UAE. Perfusion defect of the myometrium was observed at 48 h in 14/49 women (28.5 %) in association with higher degrees of leiomyoma devascularization. CONCLUSION: Six months after UAE, drop in leiomyoma ADC values and volume reduction correlate with the degree of leiomyoma devascularization. UAE affects the myometrium as evidenced by a drop in ADC values and initial myometrial perfusion defect. KEY POINTS: • A drop in leiomyoma ADC values is observed 6 months after UAE. • Drop in leiomyoma ADC value is associated with leiomyoma devascularizarion after UAE. • MR 48 h post-UAE allows assessing leiomyoma devascularization. • Myometrium perfusion defect occurs more often in women with a smaller uterus.

Myometrial artery calcifications and aging.

OBJECTIVE: This study aims to determine whether myometrial artery calcifications increase with age and whether uterine sections are an appropriate model for studying vascular aging. METHODS: An observational study of 172 women (aged 45 y or older) who underwent hysterectomy for benign indications at the University Hospital (Newark, NJ) between July 1, 2009 and June 1, 2012 was performed. Women with a history of malignancy, undocumented last menstrual period, or unavailable uterine tissue slides were excluded. H&E-stained uterine sections were evaluated for myometrial artery calcifications (defined as the presence of acellular densely basophilic material within the media of vessels) by a single pathologist in a blinded manner. RESULTS: Between July 1, 2009 and June 1, 2012, hysterectomies were performed on 441 women, 172 of whom met inclusion criteria. Seventeen women (9.9%) had myometrial artery calcifications detectable on H&E-stained tissue sections. None of 84 women aged 45 to 49 years, 2 of 51 women (3.9%) aged 50 to 59 years (aged 56 and 58 y), 10 of 27 women (37%) aged 60 to 69 years, and 5 of 10 women (50%) aged 70 to 81 years had myometrial artery calcifications. The prevalence of myometrial artery calcifications significantly increased with advancing age (P = 0.022). CONCLUSIONS: Myometrial artery calcifications increase with advancing age. Histological sections of uterine tissue from hysterectomy specimens seem to be a useful model for evaluating vascular aging markers.