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.

Kynurenine Relaxes Arteries of Normotensive Women and Those With Preeclampsia.

[Figure: see text].

Enhanced myometrial vascularity and AVM: A review on diagnosis and management.

Uterine Arteriovenous malformations (AVM) are vascular disorders characterized by complex high-flow tangles of abnormal vessels connecting arteries and veins with bypassing capillaries. Recently, the terminology applied to describe uterine AVMs has been modified. Most AVMs are acquired. The term enhanced myometrial vascularity (EMV) is used to describe any condition in which any uterine pathology may lead to increased myometrial vascularity regardless of the absence or presence of residual tissue of gestation.

Vascular effect of levonorgestrel intrauterine system on heavy menstrual bleeding: is it associated with hemodynamic changes in uterine, radial, and spiral arteries?

The aim of this study was to evaluate the clinical and blood flow changes associated with the use of a levonorgestrel-releasing intrauterine device (LNG-IUD) in patients with idiopathic heavy menstrual bleeding (HMB). LNG-IUD was inserted into a total of 91 patients (39.5 ± 5.4 years) who were diagnosed with HMB. Uterine volume, ovarian volume, uterine, radial and spiral artery blood flow, Pictorial Blood Loss Assessment Chart (PBAC) scores, and other clinical and laboratory parameters were evaluated before and 12 months after insertion of LNG-IUD. Compared to pre-insertion values, LNG-IUD dramatically improved haemoglobin, PBAC scores, and endometrial thickness. Mean resistance indices of radial and spiral arteries significantly increased 12 months after insertion. Our study results suggest that a significant increase in the resistance indices of the intra-myometrial arteries in LNG-IUD users one year after insertion may be due to its local progestational effects, indicating a possible mechanism of LNG-IUD in reducing menstrual blood flow.Impact StatementsWhat is already known on this subject? The mechanisms of action of LNG-IUD on heavy menstrual bleeding include atrophy, decidualization and vascular changes of in the endometrium, resulting endometrial suppression. However, the exact mechanism to stop bleeding is not clear.What do the results of this study add? The present study suggests that one of the effects of the LNG-IUD on heavy menstrual bleeding is its ability to increase the resistance indexes of the intra-myometrial arteries.What are the implications of these findings for clinical practice and/or further research? These results will foster further studies on the effects of LNG-IUD on intra-myometrial arteries and will further assure clinicians on the vascular effect of LNG-IUD during management of heavy menstrual bleeding which includes hysterectomy as a final step.

Diagnosis and treatment of women with radiologic findings suspicious for uterine arteriovenous malformations.

This study investigated the clinical outcomes for patients with pelvic ultrasound findings suspicious for uterine arteriovenous malformations (AVMs) at a single institution. We reviewed the electronic medical record to identify women with pelvic ultrasound reports read as possible uterine AVM, and used medical records to determine clinical outcomes. Among the 39 women with ultrasounds suspicious for AVM, 14 had subsequent MRIs, 10 had additional ultrasounds, and 10 underwent pelvic angiography. Five of the 39 women were ultimately diagnosed with AVMs. Of the 34 women who did not have an AVM, 12 were diagnosed with retained products of conception. Women may be receiving overtreatment for possible uterine AVMs; careful clinical consideration is warranted as the most common clinical diagnosis for women with radiologic findings suspicious of uterine AVM is retained products of conception.Impact statementWhat is already known on the subject: An acquired uterine arteriovenous malformation (AVM) is an abnormal arterio-venous connection in the myometrium that may cause life-threatening haemorrhage. Over the past decade, it has been noted that the characteristic ultrasound findings of uterine AVM may represent other causes of uterine hypervascularity including retained products of conception.What the results of this study add: As there is no consensus on the management of highly vascular myometrial lesions suspicious for uterine AVMs, this study reports our institution's experience with pelvic ultrasound findings suspicious for uterine AVMs. We found that further diagnostic workup, including MRI and angiography were common, but that the most frequent final diagnosis was retained products of conception.What the implications are of these findings for future clinical practice: This study contributes to the growing body of work noting spectrum of conditions with similar vascular ultrasound findings, and suggests that at least in this sample, women may be receiving overtreatment for these presumed uterine AVMs. Close collaboration among gynaecologists and radiologists is needed to interpret the significance of these radiographic images and to determine the appropriate intervention, as women with radiologic findings suspicious of uterine AVM will frequently have retained products of conception.

AMPK activation in pregnant human myometrial arteries from high-altitude and intrauterine growth-restricted pregnancies.

High-altitude (>2,500 m) residence increases the incidence of intrauterine growth restriction (IUGR) due, in part, to reduced uterine artery blood flow and impaired myometrial artery (MA) vasodilator response. A role for the AMP-activated protein kinase (AMPK) pathway in protecting against hypoxia-associated IUGR is suggested by genomic and transcriptomic studies in humans and functional studies in mice. AMPK is a hypoxia-sensitive metabolic sensor with vasodilatory properties. Here we hypothesized that AMPK-dependent vasodilation was increased in MAs from high versus low-altitude (<1,700 m) Colorado women with appropriate for gestational age (AGA) pregnancies and reduced in IUGR pregnancies regardless of altitude. Vasoreactivity studies showed that, in AGA pregnancies, MAs from high-altitude women were more sensitive to vasodilation by activation of AMPK with A769662 due chiefly to increased endothelial nitric oxide production, whereas MA responses to AMPK activation in the low-altitude women were endothelium independent. MAs from IUGR compared with AGA pregnancies had blunted vasodilator responses to acetylcholine at high altitude. We concluded that 1) blunted vasodilator responses in IUGR pregnancies confirm the importance of MA vasodilation for normal fetal growth and 2) the increased sensitivity to AMPK activation in AGA pregnancies at high altitude suggests that AMPK activation helped maintain MA vasodilation and fetal growth. These results highlight a novel mechanism for vasodilation of MAs under conditions of chronic hypoxia and suggest that AMPK activation could provide a therapy for increasing uteroplacental blood flow and improving fetal growth in IUGR pregnancies.NEW & NOTEWORTHY Intrauterine growth restriction (IUGR) impairs infant well- being and increases susceptibility to later-in-life diseases for mother and child. Our study reveals a novel role for AMPK in vasodilating the myometrial artery (MA) from women residing at high altitude (>2,500 m) with appropriate for gestational age pregnancies but not in IUGR pregnancies at any altitude.

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 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.

Separating fetal and maternal placenta circulations using multiparametric MRI.

PURPOSE: The placenta is a vital organ for the exchange of oxygen, nutrients, and waste products between fetus and mother. The placenta may suffer from several pathologies, which affect this fetal-maternal exchange, thus the flow properties of the placenta are of interest in determining the course of pregnancy. In this work, we propose a new multiparametric model for placental tissue signal in MRI. METHODS: We describe a method that separates fetal and maternal flow characteristics of the placenta using a 3-compartment model comprising fast and slowly circulating fluid pools, and a tissue pool is fitted to overlapping multiecho T2 relaxometry and diffusion MRI with low b-values. We implemented the combined model and acquisition on a standard 1.5 Tesla clinical system with acquisition taking less than 20 minutes. RESULTS: We apply this combined acquisition in 6 control singleton placentas. Mean myometrial T2 relaxation time was 123.63 (±6.71) ms. Mean T2 relaxation time of maternal blood was 202.17 (±92.98) ms. In the placenta, mean T2 relaxation time of the fetal blood component was 144.89 (±54.42) ms. Mean ratio of maternal to fetal blood volume was 1.16 (±0.6), and mean fetal blood saturation was 72.93 (±20.11)% across all 6 cases. CONCLUSION: The novel acquisition in this work allows the measurement of histologically relevant physical parameters, such as the relative proportions of vascular spaces. In the placenta, this may help us to better understand the physiological properties of the tissue in disease.

Placental bed research: I. The placental bed: from spiral arteries remodeling to the great obstetrical syndromes.

The term placental bed was coined to describe the maternal-fetal interface (ie, the area in which the placenta attaches itself to the uterus). Appropriate vascularization of this area is of vital importance for the development of the fetus; this is why systematic investigations of this area have now been carried out. Initially, the challenge was the identification and classification of the various successive branching of uterine arteries in this area. These vessels have a unique importance because failure of their physiological transformation is considered to be the anatomical basis for reduced perfusion to the intervillous space in women with preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, abruptio placentae, and fetal death. To investigate in depth the pathophysiology of the placental bed, some 60 years ago, a large number of placental bed biopsies, as well as of cesarean hysterectomy specimens with placenta in situ, from both early and late normotensive and hypertensive pregnancies, were carefully dissected and analyzed. Thanks to the presence of a series of specific physiological changes, characterized by the invasion and substitution of the arterial intima by trophoblast, this material allowed the identification in the placental bed of normal pregnancies of the main vessels, the uteroplacental arteries. It was then discovered that preeclampsia is associated with defective or absent transformation of the myometrial segment of the uteroplacental arteries. In addition, in severe hypertensive disease, atherosclerotic lesions were also found in the defective myometrial segment. Finally, in the basal decidua, a unique vascular lesion, coined acute atherosis, was also identified This disorder of deep placentation, coined defective deep placentation, has been associated with the great obstetrical syndromes, grouping together preeclampsia, intrauterine growth restriction, preterm labor, preterm premature rupture of membranes, late spontaneous abortion, and abruptio placentae. More recently, simplified techniques of tissue sampling have been also introduced: decidual suction allows to obtain a large number of decidual arteries, although their origin in the placental bed cannot be determined. Biopsies parallel to the surface of the basal plate have been more interesting, making possible to identify the vessels' region (central, paracentral, or peripheral) of origin in the placental bed and providing decidual material for immunohistochemical studies. Finally, histochemical and electron microscopy investigations have now clarified the pathology and pathogenetic mechanisms underlying the impairment of the physiological vascular changes.

Cutaneous small-vessel vasculitis following hysterosalpingo-foam sonography (HyFoSy).

We present a case of diffuse skin immune reaction, diagnosed as cutaneous small-vessel vasculitis, following assessment of tubal patency by contrast ultrasound, which appears to be the first reported case of hypersensitivity reaction to sonographic tubal patency testing, based on a literature search. A 32-year-old woman presented with non-thrombocytopenic palpable purpura the day after assessment of tubal patency by two-/three-dimensional hysterosalpingo-foam sonography (HyFoSy) using ExEm® Foam. During real-time ultrasound, the observer identified flow in only the right tube when using saline with air as contrast medium; however, the same observer identified flow in both tubes after injecting ExEm Foam and the woman left the clinic without any complications. The next day, the patient was admitted with a complaint of a red-purple skin rash noticed the same morning, associated with moderate leg pain. Slow-motion analysis of the recorded videos and three-dimensional ultrasound datasets showed previously unnoticed venous intravasation of ExEm Foam into the myometrial vessels. Palpable purpura is typically found in vasculitis as a result of extravasation of red cells outside the inflamed blood vessel. This previously unreported side effect of tubal patency testing by HyFoSy, its potential rare organ consequences, as well as unknown consequences of venous intravasation by foam, should be included in the informed consent prior to the examination. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

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.

First-trimester detection of abnormally invasive placenta in high-risk women: systematic review and meta-analysis.

OBJECTIVES: The primary aim of this systematic review was to ascertain whether ultrasound signs suggestive of abnormally invasive placenta (AIP) are present in the first trimester of pregnancy. Secondary aims were to ascertain the strength of association and the predictive accuracy of such signs in detecting AIP in the first trimester. METHODS: An electronic search of MEDLINE, EMBASE, CINAHL and Cochrane databases (2000-2016) was performed. Only studies reporting on first-trimester diagnosis of AIP that was subsequently confirmed in the third trimester either during operative delivery or by pathological examination were included. Meta-analysis of proportions, random-effects meta-analysis and hierarchical summary receiver-operating characteristics curve analysis were used to analyze the data. RESULTS: Seven studies, involving 551 pregnancies at high risk of AIP, were included. At least one ultrasound sign suggestive of AIP was detected in 91.4% (95% CI, 85.8-95.7%) of cases with confirmed AIP. The most common ultrasound feature in the first trimester of pregnancy was low implantation of the gestational sac close to a previous uterine scar, which was observed in 82.4% (95% CI, 46.6-99.8%) of cases. Anechoic spaces within the placental mass (lacunae) were observed in 46.0% (95% CI, 10.9-83.7%) and a reduced myometrial thickness in 66.8% (95% CI, 45.2-85.2%) of cases affected by AIP. Pregnancies with a low implantation of the gestational sac had a significantly higher risk of AIP (odds ratio, 19.6 (95% CI, 6.7-57.3)), with a sensitivity and specificity of 44.4% (95% CI, 21.5-69.2%) and 93.4% (95% CI, 90.5-95.7%), respectively. CONCLUSIONS: Ultrasound signs of AIP can be present during the first trimester of pregnancy, even before 11 weeks' gestation. Low anterior implantation of the placenta/gestational sac close to or within the scar was the most commonly seen early ultrasound sign suggestive of AIP, although its individual predictive accuracy was not high. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Diagnosis and management of patients with enhanced myometrial vascularity associated with retained products of conception.

OBJECTIVES: To assess the complication rate, including estimated amount of blood loss, in patients undergoing dilation and curettage (D&C) for the treatment of retained products of conception with markedly enhanced myometrial vascularity mimicking arteriovenous malformation. METHODS: This was a retrospective medical-records review study of patients with retained products of conception with enhanced myometrial vascularity presenting to our ultrasound unit between August 2015 and August 2017. Color/power Doppler imaging was used subjectively to identify the degree and extent of vascularity. All patients underwent D&C, and their operative reports and medical records were reviewed to see if ultrasound guidance was used, to ascertain estimated blood loss and to identify complications during or after the procedure. RESULTS: The study group included 31 patients, of whom seven had retained products of conception after a vaginal delivery and 24 had retained products of conception after a first-trimester termination or miscarriage. The largest dimension of the region of enhanced myometrial vascularity ranged from 10 mm to 53 mm, with 14/31 having a width of ≥ 20 mm. Fifteen patients underwent a standard D&C procedure, 13 an ultrasound-guided procedure and three hysteroscopy. Estimated operative blood loss varied from negligible to a maximum of 400 mL. There were no intraoperative complications, although one patient was treated for presumed endometritis. CONCLUSIONS: An increasing number of studies describe the enhanced myometrial vascularity associated with retained products of conception as 'acquired arteriovenous malformation', with some recommending management with uterine-artery embolization. Our study demonstrates that the enhanced myometrial vascularity is associated with retained products of conception, and surgical removal by D&C, possibly with the aid of ultrasound guidance or hysteroscopy, is a safe treatment option. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation: a systematic review and meta-analysis.

INTRODUCTION: Our objective was to elucidate the overall diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation (AIP). MATERIAL AND METHODS: Medline, Embase, CINAHL and The Cochrane databases were searched. The ultrasound signs explored were: loss of hypoechoic (clear) zone in the placental-uterine interface, placental lacunae, bladder wall interruption, myometrial thinning, focal exophitic mass, placental lacunar flow, subplacental vascularity, and uterovesical hypervascularity. RESULTS: Twenty studies (3209 pregnancies) were included. Ultrasound had an overall good diagnostic accuracy in identifying the depth of placental invasion with sensitivities of 90.6%, 93.0%, 89.5%, and 81.2% for placenta accreta, increta, accreta/increta, and percreta, respectively; the corresponding specificities were 97.1%, 98.4%, 94.7%, and 98.9%. Placental lacunae had sensitivities of 74.8%, 88.6%, and 76.3% for the detection of placenta accreta, increta, and percreta, respectively. Sensitivity and specificity of loss of the clear zone in identifying placenta accreta were 74.9% and 92.0%, whereas the corresponding figures for placenta increta and percreta were 91.6% and 76.9%, and 88.1% and 71.1%. Lacunar flow had sensitivities of 81.2%, 84.3%, and 45.2% for the detection of placenta accreta, increta, and percreta respectively; the corresponding figures for specificity were 84.0%, 79.7%, and 75.3%. Sensitivity of uterovesical hypervascularity was low for the detection of placenta accreta (12.3%) but high for placenta increta (94.4%) and percreta (86.2%); the corresponding figures for specificity were 90.8%, 88.0% and 88.2%, respectively. CONCLUSIONS: Ultrasound has an overall good diagnostic accuracy in recognizing the depth and the topography of placental invasion.

Exposure to omentum adipose tissue conditioned medium from obese pregnant women promotes myometrial artery dysfunction.

AIM: Underlying mechanisms of poor pregnancy outcome in obese (OB) mothers (body mass index [BMI] ≥ 30 kg/m2 ) are unknown. Our studies demonstrate that OB pregnant women have altered myometrial artery (MA) function related to the thromboxane and nitric oxide pathways. In obesity, increased central fat mass is associated with an altered endocrine milieu. We tested the hypothesis that in OB pregnant women the omentum, a central fat store, releases factors that promote dysfunction in normal MAs. METHODS: Myometrial and omental adipose tissue biopsies were obtained from women with uncomplicated term pregnancies. Omental adipose tissue explants from six normal weight (NW; BMI 18.5-24.9 kg/m2 ) and six OB (BMI ≥ 30 kg/m2 ) women were cultured and the conditioned medium collected and pooled to produce NW medium and OB medium. Adipokine concentrations were measured using enzyme-linked immunosorbent assays. Wire myography was used to assess the effect of conditioned medium (NW or OB; N = 7) or leptin (100 nM; N = 5) exposure on MA responses to U46619 (thromboxane-mimetic) and bradykinin (endothelial-dependent vasodilator). RESULTS: OB medium had higher leptin and lower adiponectin levels than NW medium. U46619 and bradykinin concentration response curves shifted upwards in MAs exposed to OB medium but were unaffected by leptin. CONCLUSIONS: Omental adipose tissue from OB pregnant women produced altered concentrations of adipokines. Acute OB medium exposure induced MA dysfunction, an effect not mirrored by exposure to leptin. These data suggest that an aberrant endocrine environment created by increased central adiposity in OB pregnant women induces vascular endothelial dysregulation, which may predispose them to a poor pregnancy outcome.

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.

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.

Early first trimester uteroplacental flow and the progressive disintegration of spiral artery plugs: new insights from contrast-enhanced ultrasound and tissue histopathology.

STUDY QUESTION: Does the use of a vascular contrast agent facilitate earlier detection of maternal flow to the placental intervillous space (IVS) in the first trimester of pregnancy? SUMMARY ANSWER: Microvascular filling of the IVS was demonstrated by contrast-enhanced ultrasound from 6 weeks of gestation onwards, earlier than previously believed. WHAT IS KNOWN ALREADY: During placental establishment and remodeling of maternal spiral arteries, endovascular trophoblast cells invade and accumulate in the lumen of these vessels to form 'trophoblast plugs'. Prior evidence from morphological and Doppler ultrasound studies has been conflicting as to whether the spiral arteries are completely plugged, preventing maternal blood flow to the IVS until late in the first trimester. STUDY DESIGN, SIZE, DURATION: Uteroplacental flow was examined across the first trimester in human subjects given an intravenous infusion of lipid-shelled octofluoropropane microbubbles with ultrasound measurement of destruction and replenishment kinetics. We also performed a comprehensive histopathological correlation using two separately archived uteroplacental tissue collections to evaluate the degree of spiral artery plugging and evaluate remodeling of the upstream myometrial radial and arcurate arteries. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnant women (n = 34) were recruited in the first trimester (range: 6+3 to 13+6 weeks gestation) for contrast-enhanced ultrasound studies with destruction-replenishment analysis of signal intensity for assessment of microvascular flux rate. Histological samples from archived in situ (Boyd Collection, n = 11) and fresh first, second, and third trimester decidual and post-hysterectomy uterine specimens (n = 16) were evaluated by immunohistochemistry (using markers of epithelial, endothelial and T-cells, as well as cell adhesion and proliferation) and ultrastructural analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Contrast agent entry into the IVS was visualized as early as 6+3 weeks of gestation with some variability in microvascular flux rate noted in the 6-7+6 week samples. Spiral artery plug canalization was observed from 7 weeks with progressive disintegration thereafter. Of note, microvascular flux rate did not progressively increase until 13 weeks, which suggests that resistance to maternal flow in the early placenta may be mediated more proximally by myometrial radial arteries that begin remodeling at the end of the first trimester. LIMITATIONS REASONS FOR CAUTION: Gestational age was determined by crown-rump length measurements obtained by transvaginal ultrasound on the day of contrast-enhanced imaging studies, which may explain the variability in the earliest gestational age samples due to the margin of error in this type of measurement. WIDER IMPLICATIONS OF THE FINDINGS: Our comprehensive in situ histological analysis, in combination with the use of an in vivo imaging modality that has the sensitivity to permit visualization of microvascular filling, has allowed us to reveal new evidence in support of increasing blood flow to the IVS from 6 weeks of gestation. Histologic review suggested the mechanism may be blood flow through capillary-sized channels that form through the loosely cohesive 'plugs' by 7 weeks gestation. However, spiral artery remodeling on its own did not appear to explain why there is significantly more blood flow at 13 weeks gestation. Histologic studies suggest it may be related to radial artery remodeling, which begins at the end of the first trimester. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by the Oregon Health and Science University Knight Cardiovascular Institute, Center for Developmental Health and the Struble Foundation. There are no competing interests.

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.