Junctional Zone Research Articles

The treatment with Levonorgestrel Releasing Intrauterine System (LNG-IUS) in patients affected by menometrorrhagia, dysmenorrhea and adenomimyois: clinical and ultrasonographic reports.

Adenomyosis is the consequence of the myometrial invasion by endometrial glands and stroma. Transvaginal ultrasonography plays a decisive role in the diagnosis and monitoring of this pathology. Our study aims to evaluate the efficacy of LNG-IUS (Levonorgestrel Releasing Intrauterine System) as medical therapy. We analyzed both clinical symptoms and ultrasonographic aspects of menometrorrhagia and dysmenorrhea in patients with adenomyosis and the control group. A prospective cohort study was carried out on 28 patients suffering from symptomatic adenomyosis treated with LNG-IUS. Adenomyosis was diagnosed through transvaginal ultrasonography by an expert sonographer. A control group of 27 symptomatic patients (menorrhagia and dysmenorrhea) without a transvaginal ultrasonographic diagnosis of adenomyosis was treated in the same way. The two cohorts were compared to the efficacy of LNG-IUS on menorrhagia and dysmenorrhea. Patients are evaluated at the time of LNG-IUS insertion and six months after for: increased uterine volume, globulous uterine morphology, uterine symmetry, alterations in the junctional zone, heterogeneous myometrial texture, presence of myometrial cysts, hyperechogenic lines crossing the myometrium, adenomyomas, menstrual blood loss and dysmenorrhea. After six months, the uterine volume decreased significantly in both cohorts (p=0.005; p=0.005). Furthermore, uterine symmetry, visibility of the junctional zone, heterogeneity of myometrial texture, presence of myometrial cysts, hyperechogenic lines and adenomyomas improved in patients affected by adenomyosis (p>0.001; p>0.001; p>0.001; p=0.014; p=0.025; p=0.014). The blood loss decreased significantly in both the cohorts (p<0.001) and particularly in adenomyotic patients. Pain relief was observed in all the patients (p<0.001). LNG-IUS can be considered an effective treatment for managing symptoms and improving uterine morphology.

Sonographic and clinical features of adenomyosis in women in "early" (18-35) and "advanced" (&gt;35) reproductive ages

Adenomyosis has been considered for a long time a condition of advanced reproductive age. Recently, imaging techniques have allowed its diagnosis in young women. The aim of our study was to compare adenomyosis in early (18-35) and advanced (>35) reproductive age (ERA vs. ARA). Between May 2019 and October 2020, 928 consecutive women underwent transvaginal ultrasounds (TV-US) in our Department. We enrolled 134 women of reproductive age (18-55) presenting at least 2 US features of adenomyosis, according to the MUSA consensus. We compared the two reproductive age groups (ERA and ARA) about both clinical and US features of adenomyosis. Severe dysmenorrhea was more frequent in the ERA group (78.7% vs. 54.8%), while menorrhagia was more frequent in the ARA group (64.4% vs. 37.7%). At US, the ARA group had a higher frequency of altered junctional zone (67.1% vs. 39.3%), diffuse (76.7% vs. 39.3%) and severe adenomyosis (24.7% vs. 9.8%), and adenomyoma (16.4% vs. 1.6%). Adenomyosis may occur in young women, who present different clinical and sonographic features compared to older women. Young patients have a higher prevalence of severe dysmenorrhea and focal and mild adenomyosis at US, while older women present more frequently menorrhagia, and altered junctional zone, diffuse and severe adenomyosis at US. Early diagnosis in young women suffering from adenomyosis may help to interrupt the mechanisms that drive the development of adenomyosis, starting immediately the right treatment.

Initial Experience With Diffusion-Weighted Magnetic Resonance Imaging for the Evaluation of Endometrial Fibrosis.

This study aimed to determine the feasibility of diffusion-weighted imaging for detecting endometrial fibrosis in patients with intrauterine injury. This prospective study included 34 patients with endometrial fibrosis and 34 healthy controls. All participants underwent T2-weighted and diffusion-weighted magnetic resonance imaging with b values of 0 and 1000 s/mm2 during the periovulatory phase with a dominant follicle. The endometrial apparent diffusion coefficient (ADC) and uterine anatomical parameters (endometrial thickness [EMT], length of the uterine cavity [LUC], and junctional zone thickness [JZT]) were measured and compared. Performance of the uterine endometrial ADC and anatomical parameters in diagnosing endometrial fibrosis was evaluated. Patients with endometrial fibrosis showed a lower endometrial ADC, lower EMT, shorter LUC, and higher JZT than did healthy controls (all, P < 0.001). Endometrial ADC value and uterine anatomical parameters showed good performance in diagnosing endometrial fibrosis, with the areas under the receiver operating characteristic curves of 0.976, 0.870, 0.883, and 0.864, respectively. The area under the curve of ADC was significantly higher than those of EMT (z = 1.973, P = 0.0485), LUC (z = 2.059, P = 0.0395), and JZT (z = 2.484, P = 0.0130). Intraobserver and interobserver agreements of endometrial ADC value measurements were excellent for both patients (intraclass correlation coefficient = 0.987 and 0.983, respectively) and healthy women (intraclass correlation coefficient = 0.986 and 0.989, respectively). Our preliminary results suggest that diffusion-weighted imaging has the potential to be a noninvasive imaging tool for the quantitative assessment of endometrial fibrosis.

Objective measures of adenomyosis on MRI and their diagnostic accuracy-a systematic review & meta-analysis.

Magnetic resonance imaging (MRI) diagnosis of adenomyosis is considered the most accurate non-invasive technique, but remains subjective, with no consensus on which diagnostic parameters are most accurate. We aimed to systematically review the literature on how adenomyosis can be objectively quantified on MRI in a scoping manner, to review the diagnostic performance of these characteristics compared with histopathological diagnosis, and to summarize correlations between measures of adenomyosis on MRI and clinical outcomes. We searched databases Pubmed, Embase, and Cochrane for relevant literature up to April 2020 according to PRISMA guidelines. We included studies that objectively assessed adenomyosis on MRI, and separately assessed studies investigating the diagnostic performance of MRI vs histopathology for inclusion in a meta-analysis. The QUADAS-2 tool was used for risk of bias, with many studies showing an unclear or high risk of bias. Eighty studies were included, of which 14 assessed the diagnostic performance of individual MRI parameters, with four included in the meta-analysis of diagnostic accuracy. Common MRI parameters were: junctional zone (JZ) characteristics, such as maximum JZ thickness-pooled sensitivity 71.6% (95% CI 46.0%-88.2%), specificity 85.5% (52.3%-97.0%); JZ differential-pooled sensitivity 58.9% (95% CI 44.3%-72.1%), specificity 83.2% (95% CI 71.3%-90.8%); and JZ to myometrial ratio-pooled sensitivity 63.3% (95% CI 51.9%-73.4%), specificity 79.4% (95% CI 42.0%-95.4%); adenomyosis lesion size, uterine morphology (pooled sensitivity 42.9% (95% CI 15.9%-74.9%), specificity 87.7%, (95% CI 37.9-98.8) and changes in signal intensity-eg, presence of myometrium cysts; pooled 59.6% (95% CI 41.6%-75.4%) and specificity of 96.1% (95% CI 80.7%-99.3%). Other MRI parameters have been used for adenomyosis diagnosis, but their diagnostic performance is unknown. Few studies attempted to correlate adenomyosis MRI phenotype to clinical outcomes. A wide range of objective parameters for adenomyosis exist on MRI; however, in many cases their individual diagnostic performance remains uncertain. JZ characteristics remain the most widely used and investigated with acceptable diagnostic accuracy. Specific research is needed into how these objective measures of adenomyosis can be correlated to clinical outcomes.

Estrogen 17β‑estradiol accelerates the proliferation of uterine junctional zone smooth muscle cells via the let‑7a/Lin28B axis in adenomyosis.

The estrogen 17β‑estradiol has been proven to serve an indispensable role in the occurrence and development of adenomyosis(ADS). The let‑7a/Lin28B axis can control cell proliferation by acting as a tumor‑inhibiting axis in numerous types of cancer. However, its role in ADS remains unknown. The present study aimed i)to elucidate the role of let‑7a in regulating the proliferation of human uterine junctional zone(JZ) smooth muscle cells (SMCs) in ADS, ii)to evaluate whether 17β‑estradiol modifies the expression levels of let‑7a and Lin28B in JZ SMCs in ADS, and iii)to establish how 17β‑estradiol affects the function of the let‑7a/Lin28B axis in the proliferation of JZ SMCs in ADS. A total of 36premenopausal women with ADS were enrolled as the experimental group and 34women without ADS were recruited as the control group. Reverse transcription‑quantitative PCR was used to evaluate the expression level of let‑7a, and western blotting was performed to determine the Lin28B expression levels. Lentiviral null vector, let‑7a overexpression lentiviral vector GV280 and let‑7a inhibition lentiviral vector GV369 were used to infect cells to alter the expression of let‑7a for further functional experiments. 17β‑estradiol and Cell Counting Kit‑8 assays were conducted to determine how 17β‑estradiol affects the function of the let‑7a/Lin28B axis in the proliferation of JZ SMCs in ADS. The results demonstrated that let‑7a was downregulated and Lin28B was upregulated in the JZ SMCs of ADS compared with the control cells (P<0.0001). Moreover, a lower expression of let‑7a led to faster proliferation of JZ SMCs (P<0.05), and 17β‑estradiol affected the let‑7a/Lin28B axis to accelerate the proliferation of JZ SMCs in ADS (P<0.05). These data suggested that 17β‑estradiol collaborates with the let‑7a/Lin28B axis to affect the development of ADS.

A rare case of extensive placenta accreta in twin pregnancy after GnRH agonist treatment of adenomyosis

BackgroundAdenomyosis remains an enigma for the reproductive endocrinologist. It is thought to contribute to sub-fertility, and its only curative treatment is hysterectomy. However, studies have documented increased live birth rates in women with adenomyosis who were treated with gonadotropin releasing hormone agonist (GnRHa).CaseHere we present a case of a 52-year-old woman with adenomyosis who had three failed frozen embryo transfers (FETs) prior to initiating a 6-month trial of GnRHa. GnRHa therapy resulted in a decrease in uterine size from 11.5 × 7.9 × 7.0 cm to 7.8 × 6.2 × 5.9 cm and a decrease in the junctional zone (JZ) thickness from 19 to 9 mm. Subsequently, she underwent her fourth FET, which resulted in live birth of twins. The delivery was complicated by expansive accretas of both placentas requiring cesarean hysterectomy. The final pathology of the placentas demonstrated an extensive lack of decidualized endometrium that was even absent outside the basal plate.ConclusionsGnRHa therapy in patients with adenomyosis may improve implantation rates after FET. Previous molecular studies indicate that genetic variance in the expression of the gonadotropin releasing hormone receptor (GnRHR) could explain the expansive lack of decidualized endometrium after GnRHa therapy. Further investigations are needed to determine if GnRHa therapy contributes to the pathologic process of placenta accreta.

ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development

Invasive trophoblast cells are critical to spiral artery remodeling in hemochorial placentation. Insufficient trophoblast cell invasion and vascular remodeling can lead to pregnancy disorders including preeclampsia, preterm birth, and intrauterine growth restriction. Previous studies in mice identified achaete-scute homolog 2 (ASCL2) as essential to extraembryonic development. We hypothesized that ASCL2 is a critical and conserved regulator of invasive trophoblast cell lineage development. In contrast to the mouse, the rat possesses deep intrauterine trophoblast cell invasion and spiral artery remodeling similar to human placentation. In this study, we investigated invasive/extravillous trophoblast (EVT) cell differentiation using human trophoblast stem (TS) cells and a loss-of-function mutant Ascl2 rat model. ASCL2 transcripts are expressed in the EVT column and junctional zone, which represent tissue sources of invasive trophoblast progenitor cells within human and rat placentation sites, respectively. Differentiation of human TS cells into EVT cells resulted in significant up-regulation of ASCL2 and several other transcripts indicative of EVT cell differentiation. Disruption of ASCL2 impaired EVT cell differentiation, as indicated by cell morphology and transcript profiles. RNA sequencing analysis of ASCL2-deficient trophoblast cells identified both down-regulation of EVT cell-associated transcripts and up-regulation of syncytiotrophoblast-associated transcripts, indicative of dual activating and repressing functions. ASCL2 deficiency in the rat impacted placental morphogenesis, resulting in junctional zone dysgenesis and failed intrauterine trophoblast cell invasion. ASCL2 acts as a critical and conserved regulator of invasive trophoblast cell lineage development and a modulator of the syncytiotrophoblast lineage.

Specific sagittal alignment patterns are already present in mild adolescent idiopathic scoliosis

PurposeThe complex three-dimensional spinal deformity in AIS consists of rotated, lordotic apical areas and neutral junctional zones that modify the spine’s sagittal profile. Recently, three specific patterns of thoracic sagittal ‘malalignment’ were described for severe AIS. The aim of this study is to define whether specific patterns of pathological sagittal alignment are already present in mild AIS.MethodsLateral spinal radiographs of 192 mild (10°–20°) and 253 severe (> 45°) AIS patients and 156 controls were derived from an international consortium. Kyphosis characteristics (T4–T12 thoracic kyphosis, T10–L2 angle, C7 slope, location of the apex of kyphosis and of the inflection point) and sagittal curve types according to Abelin-Genevois were systematically compared between the three cohorts.ResultsEven in mild thoracic AIS, already 49% of the curves presented sagittal malalignment, mostly thoracic hypokyphosis, whereas only 13% of the (thoraco) lumbar curves and 6% of the nonscoliosis adolescents were hypokyphotic. In severe AIS, 63% had a sagittal malalignment. Hypokyphosis + thoracolumbar kyphosis occurred more frequently in high-PI and primary lumbar curves, whereas cervicothoracic kyphosis occurred more in double thoracic curves.ConclusionsPathological sagittal patterns are often already present in curves 10°–20°, whereas those are rare in non-scoliotic adolescents. This suggests that sagittal ‘malalignment’ patterns are an integral part of the early pathogenesis of AIS.

The cannabinoid receptor CB1 affects the proliferation and apoptosis of adenomyotic human uterine smooth muscle cells of the junctional zone: a mechanism study

BackgroundThe denomyotic junctional zone (JZ) plays an important role in the pathogenesis of adenomyosis. Proliferating cell nuclear antigen (PCNA) is an important nuclear marker of cell proliferation. This study aimed to evaluate the effects of the cannabinoid receptor CB1 on proliferation and apoptosis in the JZ in women with and without adenomyosis.MethodsJZ smooth muscle cells (JZSMCs) of the adenomyosis and control groups were collected and cultivated. Immunohistochemistry and immunoblotting were used for protein localization and expression detection of CB1 and PCNA. Additionally, qRT-PCR was used to quantitatively analyse the mRNA expression of the two. AM251 and ACEA were used to regulate the function of CB1 receptors, and CCK-8 assay and flow cytometry assay were used to verify the proliferation and apoptosis of JZSMCs after regulation.ResultsWe demonstrated that in normal JZSMCs CB1 and PCNA messenger RNA (mRNA) and protein expression was significantly higher in the proliferative phase of the menstrual cycle than in the secretory phase. CB1 and PCNA expression in JZSMCs from women with ADS was significantly higher than that in control women and did not significantly differ across the menstrual cycle. CB1 receptor antagonist AM251 inhibited the proliferation of adenomyotic JZSMCs in a dose-dependent manner. The CB1 receptor agonist ACEA significantly promoted the proliferation of adenomyotic JZSMCs. The apoptosis rate of adenomyotic JZSMCs treated with AM251 was significantly higher than that of JZSMCs from the untreated control group. The apoptosis rate was significantly decreased in the ACEA group compared with that in the untreated control group. Furthermore, AM251 suppressed the phosphorylation of AKT and Erk1/2 in adenomyotic JZSMCs. The CB1 agonist ACEA significantly promoted the phosphorylation of AKT and Erk1/2.ConclusionsOur results indicated that the levels of CB1 and PCNA were increased in patients with adenomyosis and that cyclic changes were lost. CB1 may affect uterine JZ proliferation and apoptosis in adenomyosis by enhancing AKT and MAPK/Erk signalling.

75 AKT1 deficiency is linked to placental, fetal, and postnatal growth restriction

The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is involved in many biological processes including cell differentiation and migration. AKT1 is a serine/threonine kinase that has been implicated in fetal, placental, and postnatal growth. However, little is known about the role of AKT1 in trophoblast cell invasion and trophoblast-guided spiral artery remodeling. The objective of this project is to examine the role of AKT1 in the rat, a model of hemochorial placentation. A germline mutant Akt1 rat model using CRISPR/Cas9 genome editing was created. Mating of heterozygotes produced the expected Mendelian ratio. Western blotting was used to determine concentrations of AKT1, total AKT, and phosphorylated AKT (Ser473) proteins. Postnatal growth of AKT1 null male and female progeny was compared to wild-type progeny. Placental and fetal weights were examined. Gene expression within placentation sites was assessed. The AKT1 protein was not detected in homozygous Akt1 mutant placentas. Akt1 null male and female progeny showed significant deficits in postnatal growth. Growth restriction associated with AKT1 deficiency began in utero and was characterized by small fetuses and placentas. Postnatal growth deficiency persisted through 8 weeks of development. Interrogation of placentation sites identified growth restriction of the junctional zone and the labyrinth zone compartments of placentas from Akt1 null rats. AKT1 deficiency affected the transcriptomic phenotype of invasive trophoblast cells and trophoblast cells within the junctional zone. AKT1 is required for fetal and placental development and postnatal growth in the rat model of hemochorial placentation. AKT1 serves as a regulator of junctional zone development, the site of invasive trophoblast progenitor cells, and the invasive trophoblast cell lineage. (Supported by NIH grants HD020676, HD099638, and the Sosland Foundation).

Association of 2D and 3D transvaginal ultrasound findings with adenomyosis in symptomatic women of reproductive age: a prospective study

OBJECTIVE:To evaluate the association of two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasound (TVUS) findings with adenomyosis symptoms.METHODS:This prospective study conducted between January and December 2018 enrolled 78 women aged 18 to 40 years with abnormal uterine bleeding (AUB), infertility, and/or pelvic pain. All patients underwent 2D and 3D TVUS. Signs of adenomyosis on TVUS were identified according to the consensus of the Morphological Uterus Sonographic Assessment group.RESULTS:The prevalence of adenomyosis on TVUS was 55.12%. Patients with adenomyosis were older (p=0.002) and had more dysmenorrhea, AUB, and endometriosis than those without adenomyosis. When comparing the presence of symptoms with each adenomyosis feature, on 2D TVUS, severe dyspareunia was significantly associated with the presence of a poorly defined junctional zone (JZ) (p=0.023) and on 3D TVUS, patients with AUB had a more irregular (p=0.003), poorly defined (p=0.028), and interrupted JZ (p=0.011). After logistic regression analysis, signs of adenomyosis on TVUS remained significantly associated only with age over 30 years (OR: 1.2; 95% CI: 1.0-1.2) and AUB (OR: 7.65; 95% CI: 2-29). Patients with diffuse adenomyosis were older and presented with more infertility and AUB than patients with focal or no adenomyosis.CONCLUSION:The findings of adenomyosis by 2D and 3D TVUS showed association with age and AUB. 3D TVUS alterations in the JZ were associated with AUB and dyspareunia. Diffuse adenomyosis was associated with older age, a greater prevalence of infertility, and AUB.

Аденомиоз и бесплодие. Подходы к лечению

Aim: to improve the rate of pregnancy in women with adenomyosis and infertility. Patients and Methods: this prospective comparative study included 150 women aged 24–38 years. Among them, 120 women were diagnosed with infertility and adenomyosis, and 30 healthy women planned pregnancy (control group). 60 women (study group 1) underwent surgery for adenomyosis, 30 women were followed up only (study subgroup 1A) and 30 women received Dienogest 2 mg for 6 months (study subgroup 1B). Women of study group 2 (n =60) underwent no surgery, 30 women were followed up only (study subgroup 2A) and 30 women received Dienogest 2 mg for 6 months (study subgroup 2B). After 3 and 6 months, blood levels of hormones, junctional zone thickness (measured by ultrasound), and the rate and time of pregnancy were assessed. Results: at baseline, women with adenomyosis were reported to have high levels of estradiol (p&lt;0.05 compared to the control group). After 3 and 6 months, the level of estradiol gradually reduced to 432.5±27.4 pmole/l and 364.3±16.2 pmole/l in study subgroup 2A and 314.3±22.7 pmole/l and 264.7±18.6 pmole/l in study subgroup 2B (p&lt;0.05). Pregnancy occurred, on average, after 6.1±1.6 (3–8) months in study subgroup 1A, 5.3±1.1 (4–7) months in study subgroup 2A, 4.1±1.4 (2–7) months in study subgroup 1B (p≤0.05 compared to study subgroup 1A and study group 2), and 5.1±1.2 (3–7) months in study subgroup 2B. In study groups 1 and 2, pregnancy occurred 1.5- and 1.4-times more commonly in women who received Dienogest. Conclusions: surgery and further hormone therapy is an optimal management strategy for adenomyosis and infertility. KEYWORDS: adenomyosis, infertility, Dienogest, junctional zone, pregnancy. FOR CITATION: Esedova A.E., Medzhidova A.M. Adenomyosis and infertility. Management strategies. Russian Journal of Woman and Child Health. 2021;4(2):110–114. DOI: 10.32364/2618-8430-2021-4-2-110-114.

Stereological analysis of the New Zealand rabbits (Oryctolagus cuniculus) placenta.

The onset of gestation is characterized by growth, morphological and functional changes of the placenta. We aim to evaluate the placental compartments in New Zealand rabbits by means of stereological methods. The fetal and maternal portion of placenta (12, 14, 18 and 20 gestational days) was randomly sampled for the stereological analysis. Histological sections were scanned to estimate fetal (labyrinth and junctional) and maternal (decidua) compartment volumes. The total volume of the placenta for the ages of 12, 14, 18 and 20 days was, respectively, 320 mm3, 340 mm3, 940 mm3 and 1300 mm3. The volume of the labyrinth was 56 mm3, 119 mm3, 231 mm3 and 481 mm3, respectively. The volume of junctional zone was 75 mm3, 76 cm3, 238 mm3 and 314 mm3, respectively. The volume of decidua was 174 mm3, 143 mm3, 469 mm3 and 504 mm3, respectively. We concluded that the rabbit´s placenta compartments varied according to the gestational period, increasing continuously over the 20 gestational days. However, on the onset of the development of the placenta the decidua presented faster growth, whereas after the 20 days of development, the labyrinth developed more quickly. This study represents an aid to the understanding of placentation in humans.

Hyperglycemia results in significant pathophysiological changes of placental spiral artery remodeling and angiogenesis, further contributing to congenital defects.

Introduction: Hyperglycemic conditions achieved during pregnancy have been shown to have detrimental effects to fetal development and increase the prevalence of childhood comorbidities. However, the mechanisms in which diabetic pregnancies affect placental development and subsequently contribute to adverse health effects on the mother and offspring remain unclear. Research design and methods: Streptozotocin was used to induce gestational diabetes in mice. In this model, hyperglycemia was established at embryonic day 3.5 (E3.5). Pregnancy mass was collected at E10.5, E12.5, E14.5, and E16.5 for different assessments. Results: Both placental and embryonic weights were found to be significantly elevated at E16.5. At E14.5, a significantly larger junctional zone with increased number of glycogen trophoblasts was found in the placentas from hyperglycemic pregnancies (HG group) compared to the placentas from normoglycemic pregnancies (NG group). Importantly, the HG placenta exhibited decreased trophoblast giant cell (TGC) association and TUNEL+ cells, and increased expression of α-SMA on the spiral artery, suggesting arterial remodeling was impacted. Moreover, the interhemal membrane of the labyrinth layer, was found to be thicker in the HG placentas. Furthermore, hyperglycemia resulted in more offspring congenital defects, which were associated with a thicker interhemal membrane. Conclusions: Together, these results suggest that gestational diabetes perturbs proper placental development and function, specifically spiral artery remodeling and angiogenesis, thereby negatively impacting embryonic development.

Pregnancy outcomes in patients with uterine junctional zone thickening

Hypothesis/aims of study. Overcoming infertility and miscarriage in adenomyosis is a complex practical problem in obstetrics and gynecology. It is likely that one of the signs of the disease is a thickening of the transitional zone between the endometrium and the myometrium (J-zone), which can be visualized using magnetic resonance imaging (MRI). The data on the influence of the biometric characteristics of the J-zone on the course and outcome of pregnancy in patients with adenomyosis is ambiguous. This study was aimed to assess the effect of J-zone thickness on pregnancy outcomes in patients with adenomyosis.&#x0D; Study design, materials and methods. This is a prospective study, which included 102 patients aged 22-39 years with ultrasound signs of adenomyosis who were going to conceive. The patients were divided into two groups: Group 1 (n = 58) consisted of nulliparous patients with no history of previous intrauterine interventions; Group 2 (n = 58) comprised multiparous women with any of those, such as curettage of the uterine cavity for a non-developing or unwanted pregnancy and separate diagnostic curettage for a reason not related to pregnancy. Using MRI, J-zone maximum thickness was measured at the thickest part. We evaluated the relationship between J-zone thickness and pregnancy outcomes, while estimating J-zone thresholds for subfertility outcomes in the both groups.&#x0D; Results. The average value of J-zone maximum thickness in Group 2 was significantly higher than that in Group 1 and amounted to 12.1 4.2 mm and 10.3 3.9 mm, respectively (p 0.05). The pregnancy rate in the both groups did not differ significantly and amounted to 43.1% in Group 1 and 38.6% in Group 2 (p 0.05). The frequency of retrochorial hematoma was diagnosed in 13.8% and 22.7% of cases, respectively, and did not differ significantly in the both groups (p 0.05). The frequency of spontaneous miscarriage in Group 1 and Group 2 did not differ, either (6.9% and 6.8%, p 0.05). The J-zone thresholds for unfavorable pregnancy outcomes were determined with a probability of 60% in Group 1 (9.1 mm) and Group 2 (10.0 mm).&#x0D; Conclusion. J-zone thickness may be used as a prognostic marker of pregnancy outcome in patients with adenomyosis.

Insulin-regulated aminopeptidase deficiency impairs cardiovascular adaptations and placental development during pregnancy.

Insulin-regulated aminopeptidase (IRAP), an enzyme that cleaves vasoactive peptides including oxytocin and vasopressin, is suggested to play a role in pregnancy and the onset of preeclampsia. Our aim was to examine the contribution of IRAP to arterial pressure regulation and placental development during pregnancy in mice. Mean arterial pressure and heart rate were measured via radiotelemetry in 12-week-old female wild-type and IRAP knockout mice. Females were time-mated with males of the same genotype. Placentae were collected at embryonic day 18.5 for histological analysis. Basal heart rate was ∼40 bpm lower in IRAP knockout females compared with wild-type females. The increase in heart rate across gestation was greater in IRAP knockout females than wild-type females. Neither basal nor gestational mean arterial pressure was different between wildtype and IRAP knockout females. Urine output and water intake of IRAP knockout mice were ∼45% less than wild-type mice at late gestation. IRAP deficiency had no effect on fetal weight. Morphological assessment of placentae revealed that IRAP deficiency was associated with reduced labyrinth surface area and accumulation of glycogen in the junctional zone. Our data demonstrate that IRAP deficiency alters maternal fluid handling and impairs placental labyrinth expansion at late gestation, indicating that IRAP contributes to the normal adaptions to pregnancy.

Adenomyosis of the inner and outer myometrium are associated with different clinical profiles.

Do adenomyosis phenotypes such as external or internal adenomyosis, as diagnosed by MRI, have the same clinical characteristics? External adenomyosis was found more often in young and nulliparous women and was associated with deep infiltrating endometriosis, whereas, in contrast, internal adenomyosis was more often associated with heavy menstrual bleeding (HMB) but no differences were noted in terms of pain symptoms. Adenomyosis is characterized by the presence of endometrial glands and stroma deep within the myometrium, giving rise to dysmenorrhea, pelvic pain and menorrhagia. Various forms have been described, including adenomyosis of the outer myometrium (external adenomyosis), which corresponds to lesions separated from the junctional zone (JZ), and adenomyosis of the inner myometrium (internal adenomyosis), which is mostly characterized by endometrial implants scattered throughout the myometrium and enlargement of the JZ. Although the pathogenesis of adenomyosis is not clearly understood, several lines of evidence suggest that these two phenotypes could have distinct origins. The clinical presentation of different forms of adenomyosis in patients warrants further investigation. This was an observational study that used data collected prospectively in non-pregnant patients aged between 18 and 42 years who had undergone surgical exploration for benign gynecological conditions at our institution between May 2005 and May 2018. Only women with a pelvic MRI performed by a senior radiologist during the preoperative work-up were retained for this study. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon in the month preceding the surgery. The women's histories (notably their age, gravidity, history of surgery and associated endometriosis), as well as clinical symptoms such as the pain intensity, presence of menorrhagia and infertility, were noted. A pelvic MRI was performed in 496 women operated at our center for a benign gynecological disease who had provided signed informed consent. Of these, 248 women had a radiological diagnosis of adenomyosis. Based on the MRI findings, the women were diagnosed as having external and/or internal adenomyosis. The women were allocated to two groups according to the adenomyosis phenotype (only external adenomyosis vs only internal adenomyosis). Women exhibiting an association of both adenomyosis forms were analyzed separately. In all, following the MRI findings, 109 women (44.0%) exhibited only external adenomyosis, while 78 (31.5%) had only internal adenomyosis. The women with external adenomyosis were significantly younger (mean ± SD; 31.9 ± 4.6 vs 33.8 ± 5.2 years; P = 0.006), more often nulligravid (P ≤ 0.001) and more likely to exhibit an associated endometriosis (P < 0.001) compared to the women in the internal adenomyosis group. Moreover, the women exhibiting internal adenomyosis significantly more often had a history of previous uterine surgery (P = 0.002) and HMB (62 (80%) vs 58 (53.2%), P < 0.001) compared to the women with external adenomyosis. No differences in the pain scores (i.e. dysmenorrhea, non-cyclic pelvic pain and dyspareunia) were observed between the two groups. The exclusive inclusion of surgical patients could constitute a possible selection bias, as the women referred to our center may have suffered from particularly severe clinical symptoms. Further studies are needed to explore the pathogenesis by which these types of adenomyosis occur. This could help with the development of new treatment strategies specific for each entity. none. N/A.

Something old, something new: digital quantification of uterine vascular remodelling and trophoblast plugging in historical collections provides new insight into adaptation of the utero-placental circulation.

What is the physiological extent of vascular remodelling in and trophoblast plugging of the uterine circulation across the first half of pregnancy? All levels of the uterine vascular tree (arcuate, radial and spiral arteries (SAs)) dilate ∼2.6- to 4.3-fold between 6 and 20 weeks of gestation, with significant aggregates of trophoblasts persisting in the decidual and myometrial parts of SAs beyond the first trimester. In early pregnancy, endovascular trophoblasts form 'plugs' in the SAs, transiently inhibiting blood flow to the placenta, whilst concurrently the uterine vasculature undergoes significant adaption to facilitate increased blood delivery to the placenta later in gestation. These processes are impaired in pregnancy disorders, but quantitative understanding of the anatomical changes even in normal pregnancy is poor. Serial sections of normal placentae in situ (n = 22) of 6.1-20.5 weeks of gestation from the Boyd collection and Dixon collection (University of Cambridge, UK) were digitalized using a slide scanner or Axio Imager.A1 microscope. Spiral (n = 45), radial (n = 40) and arcuate (n = 39) arteries were manually segmented. Using custom-written scripts for Matlab® software, artery dimensions (Feret diameters; major axes; luminal/wall area) and endovascular trophoblast plug/aggregate (n = 24) porosities were calculated. Diameters of junctional zone SAs within the myometrium (n = 35) were acquired separately using a micrometre and light microscope. Decidual thickness and trophoblast plug depth was measured using ImageJ. By all measures, radial and arcuate artery dimensions progressively increased from 6.1 to 20.5 weeks (P < 0.01). The greatest increase in SA calibre occurred after 12 weeks of gestation. Trophoblast aggregates were found to persist within decidual and myometrial parts of SA lumens beyond the first trimester, and up to 18.5 weeks of gestation, although those present in the second trimester did not appear to prevent the passage of red blood cells to the intervillous space. Trophoblasts forming these aggregates became more compact (decreased in porosity) over gestation, whilst channel size between cells increased (P = 0.01). Decidual thickness decreased linearly over gestation (P = 0.0003), meaning plugs occupied an increasing proportion of the decidua (P = 0.02). N/A. Although serial sections were assessed, two-dimensional images cannot completely reflect the three-dimensional properties and connectivity of vessels and plugs/aggregates. Immersion-fixation of the specimens means that vessel size may be under-estimated. Uterine vascular remodelling and trophoblast plug dispersion is a progressive phenomenon that is not completed by the end of the first trimester. Our quantitative findings support the concept that radial arteries present a major site of resistance until mid-gestation. Their dimensional increase at 10-12 weeks of gestation may explain the rapid increase in blood flow to the placenta observed by others at ∼13 weeks. Measured properties of trophoblast plugs suggest that they will impact on the resistance, shear stress and nature of blood flow within the utero-placental vasculature until mid-gestation. The presence of channels within plugs will likely lead to high velocity flow streams and thus increase shear stress experienced by the trophoblasts forming the aggregates. Quantitative understanding of utero-placental vascular adaptation gained here will improve in silico modelling of utero-placental haemodynamics and provide new insights into pregnancy disorders, such as fetal growth restriction. This work was supported by a Royal Society Te Aparangi Marsden Grant [18-UOA-135]. A.R.C. is supported by a Rutherford Discovery Fellowship [14-UOA-019]. The authors have no conflict of interest to declare.

Effects of In Utero Exposure to Perfluorooctane Sulfonate on Placental Functions.

Perfluorooctane sulfonate (PFOS) is a metabolic-disrupting chemical. There is a strong association between maternal and cord blood PFOS concentrations, affecting metabolism in early life. However, the underlying effects have not been fully elucidated. In this study, using the maternal-fetal model, we investigated the impact of gestational PFOS exposure on the placental structure and nutrient transport. Pregnant mice were oral gavaged with PFOS (1 or 3 μg PFOS/g body weight) from gestational day (GD) 4.5 until GD 17.5. Our data showed a significant reduction in fetal body weight at high dose exposure. There were no noticeable changes in placental weights and the relative areas of junctional and labyrinth zones among the control and exposed groups. However, a placental nutrient transport assay showed a significant reduction in maternal-fetal transport of the glucose and amino acid analogues. Western blot analysis showed a significant decrease in the expression levels of placental SNAT4 upon PFOS exposure. Moreover, in the high-dose exposed group, placenta and fetal livers were found to have significantly higher corticosterone levels, a negative regulator of fetal growth. The perturbation in the placental transport function and corticosterone levels accounted for the PFOS-induced reduction of fetal body weights.

Progression of adenomyosis magnetic resonance imaging features under ulipristal acetate for symptomatic fibroids

Research questionWhat is the evolution of adenomyosis on magnetic resonance imaging (MRI) after a 3-month treatment course of daily 5 mg doses of ulipristal acetate (UPA) for symptomatic fibroids? DesignA monocentric prospective pilot study on patients who underwent a 3-month treatment course of UPA for symptomatic fibroids between January 2014 and December 2017. Patients underwent pelvic MRI shortly before (pre-MRI) and after treatment (post-MRI). The diagnosis of adenomyosis on MRI was defined by the observation of intramyometrial cysts and/or haemorrhagic foci within these cystic cavities and/or a thickening of the junctional zone >12 mm. The progression of adenomyosis was defined by the presence of at least one of the aforementioned criteria of adenomyosis on the pre-MRI and by at least one of the following on the post-MRI: (i) increased thickness of the junctional zone ≥20% and/or (ii) increased number of intramyometrial cysts. The appearance of adenomyosis was defined by the absence of the aforementioned criteria of adenomyosis on the pre-MRI and the presence of at least one of these criteria on the post-MRI. ResultsSeventy-two patients were included. The MRI features of adenomyosis progressed for 12 of 15 patients (80.0%) for whom adenomyosis was identified on the pre-MRI. An appearance of adenomyosis was identified after treatment for 15 of 57 patients (26.3%) for whom adenomyosis was not identified on the pre-MRI. ConclusionsA 3-month treatment course of daily 5 mg doses of UPA could provoke a short-term progression or an emergence of typical adenomyosis intramyometrial cysts on MRI examinations.