ABSTRACT
RATIONALE: Uterine arteriovenous fistula (UAVF) is a rare vascular abnormality that can cause severe and potentially life-threatening hemorrhage. Uterine artery embolization is a common treatment that may affect ovarian and uterine perfusion and cause fertility problems. We herein report our experience treating 2 patients with UAVF who underwent resection after temporary occlusion of both internal iliac arteries. PATIENT CONCERNS: Both patients presented with a large UAVF after incomplete miscarriages in the second trimester. Magnetic resonance imaging revealed a UAVF measuring 3.6â ×â 2.6â ×â 2.1 cm over the myometrium of the posterior uterine in case 1, and a UAVF of 7.1â ×â 4.1â ×â 4.5 cm was identified in case 2. DIAGNOSIS: Uterine arteriovenous fistula, retained products of conception. INTERVENTIONS: The patients underwent resection of UAVF with temporary occlusion of the internal iliac arteries and hysteroscopic removal of the retained products of conception. OUTCOMES: Intraoperative bleeding were minimal. Neither patient exhibited abnormal uterine bleeding at the 6-month follow-up. Follow-up ultrasonography and magnetic resonance imaging showed normal uterine myometrium and endometrium and no residual disease. LESSONS: UAVF resection after temporary occlusion of the internal iliac arteries is a promising treatment approach for UAVF. This technique can reduce intraoperative bleeding and remove the potential hemorrhage-related lesion while preserving fertility.
Subject(s)
Arteriovenous Fistula , Iliac Artery , Humans , Female , Iliac Artery/surgery , Iliac Artery/diagnostic imaging , Arteriovenous Fistula/surgery , Adult , Uterine Artery/surgery , Uterine Artery/diagnostic imaging , Pregnancy , Uterine Hemorrhage/etiology , Uterine Hemorrhage/surgery , Uterine Artery Embolization/methods , Magnetic Resonance Imaging , Uterus/blood supply , Uterus/surgeryABSTRACT
Placental protein 13 (PP13) exhibits a plasma concentration that increases gradually during normal gestation, a process that is disrupted in preeclampsia, which is characterized by elevated vascular resistance, reduced utero-placental blood flow, and intrauterine growth restriction. This study investigated PP13's role in vascular tone regulation and its molecular mechanisms. Uterine and subcutaneous arteries, isolated from both pregnant and non-pregnant women, were precontracted with the thromboxane analogue U46619 and exposed to PP13 using pressurized myography. The molecular mechanisms were further investigated, using specific inhibitors for nitric oxide synthase (L-NAME+LNNA at 10-4 M) and guanylate cyclase (ODQ at 10-5 M). The results showed that PP13 induced vasodilation in uterine arteries, but not in subcutaneous arteries. Additionally, PP13 counteracted U46619-induced vasoconstriction, which is particularly pronounced in pregnancy. Further investigation revealed that PP13's mechanism of action is dependent on the activation of the nitric oxide-cGMP pathway. This study provides novel insights into the vasomodulatory effects of PP13 on human uterine arteries, underscoring its potential role in regulating utero-placental blood flow. These findings suggest that PP13 may be a promising candidate for improving utero-placental blood flow in conditions such as preeclampsia. Further research and clinical studies are warranted to validate PP13's efficacy and safety as a therapeutic agent for managing preeclampsia.
Subject(s)
Pre-Eclampsia , Pregnancy Proteins , Uterine Artery , Humans , Female , Pre-Eclampsia/metabolism , Pregnancy , Uterine Artery/metabolism , Uterine Artery/drug effects , Adult , Pregnancy Proteins/metabolism , Pregnancy Proteins/pharmacology , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology , Vasodilation/drug effects , Nitric Oxide/metabolism , Vasoconstriction/drug effects , Cyclic GMP/metabolism , Placenta/metabolism , Placenta/blood supply , Placenta/drug effects , GalectinsABSTRACT
INTRODUCTION: To assess the placental biometry, placental biomarkers and uterine artery Doppler in each trimester of pregnancy for prediction of early-onset fetal growth restriction (EO FGR). METHODS: In this prospective cohort study placental biometry; biomarkers PAPP-A, sFLT-1, and PlGF along with the uterine artery blood flow evaluation was done serially at 11-14, 20-24 and 28-32 weeks of gestation. The above parameters were compared between women with early onset FGR and controls. RESULTS: Out of 1008 fully followed cases, the small for gestational age fetuses were 227/1008 (22.5 %), and EO FGR were 84/1008(8.3 %).The placental length, volume, and PlGF levels were significantly lower, whereas the uterine artery PI(Ut PI) was significantly higher at all time points among cases. The sFLT-1 level showed a significant increase among cases, whereas it decreased among controls from the first to the second trimester. The detection rate using PV/UtA PI was 60 % in the first trimester and 66.7 % in the second trimester at 30 % FPR. CONCLUSION: The PV/Ut PI in first and the second trimester was a good marker for the prediction of pregnancies at increased risk of developing EO FGR.
Subject(s)
Fetal Growth Retardation , Placenta , Pregnancy Trimester, First , Pregnancy Trimester, Second , Uterine Artery , Vascular Endothelial Growth Factor Receptor-1 , Humans , Female , Pregnancy , Fetal Growth Retardation/diagnostic imaging , Prospective Studies , Placenta/metabolism , Placenta/diagnostic imaging , Adult , Uterine Artery/diagnostic imaging , Vascular Endothelial Growth Factor Receptor-1/blood , Ultrasonography, Prenatal , Biomarkers/blood , Placenta Growth Factor/blood , Placenta Growth Factor/metabolism , Pregnancy-Associated Plasma Protein-A/metabolism , Pregnancy-Associated Plasma Protein-A/analysis , Cohort Studies , Young AdultABSTRACT
OBJECTIVE: While there have been numerous innovations recently for the management of postpartum haemorrhage (PPH), a limited body of research supports their application during this critical complication, which contributes significantly to maternal mortality worldwide. This randomized controlled trial (RCT) aimed to evaluate the effectiveness of three interventions - transvaginal uterine artery clamp (TVUAC), vacuum-assisted uterine contraction using a suction cannula (SC), and condom tamponade (CT) - in the management of atonic PPH. METHODS: An open-label RCT was conducted among women who delivered vaginally and developed atonic PPH at a tertiary care obstetric facility. Block randomization with sealed envelopes was used to allocate eligible participants into three interventional arms with a 1:1:1 ratio. The exclusion criteria were twin deliveries, haemodynamically unstable patients, and individuals who did not provide informed consent. The primary outcome variables assessed were blood loss post-application, total blood loss, time taken for application, and time required to achieve haemostasis within each trial arm. The secondary outcomes were the need for a second instrument or surgical intervention to control bleeding, and requirement for blood transfusion. Effectiveness outcomes were analysed as intention-to-treat, whilst safety outcomes were analysed as as-treated. RESULTS: Sixteen participants were randomized to each intervention group (n = 48). TVUAC and SC demonstrated comparable outcomes, while CT lagged in all examined parameters. Following device application, blood loss was similar in both the TVUAC (235 ± 187 ml) and SC (246.5 ± 189 ml) groups. However, following the use of CT, there was blood loss of 431 ± 427 ml, although this difference was not significant (p = 0.113). When considering total blood loss, the TVUAC group (903 ± 234 ml) showed slightly higher values than the SC group (887 ± 184 ml). However, the CT group exhibited notably higher total blood loss (1068 ± 455 ml) than the TVUAC and SC groups. In terms of application time, both TVUAC (1.8 ± 1.1 min) and SC (1.6 ± 0.9 min) significantly outperformed CT (3 ± 1.3 min) (p = 0.002). Furthermore, the time interval from the diagnosis of PPH to achieving haemostasis (defined as the time taken for active haemostasis) was significantly shorter in the TVUAC group (6 ± 4 min) and the SC group (5.7 ± 1.6 min) compared with the CT group (9.7 ± 3.8 min) (p = 0.002). CONCLUSIONS: TVUAC and SC are more effective for the management of PPH than CT. However, both TVUAC and SC have advantages and disadvantages. While these results suggest a potential preference for TVUAC and SC over CT for the management of PPH, further research is necessary to validate these findings.
Subject(s)
Postpartum Hemorrhage , Uterine Artery , Humans , Female , Postpartum Hemorrhage/therapy , Adult , Pregnancy , Condoms/statistics & numerical data , Uterine Balloon Tamponade/methods , Uterine Balloon Tamponade/instrumentation , Young Adult , Treatment OutcomeABSTRACT
OBJECTIVES: To observe the differences in the effects of different dosages of grain-sized moxibustion on uterine artery blood flow in patients with cold and dampness primary dysmenorrhea (PD). METHODS: A total of 60 patients with PD were randomly divided into 3 groups with 20 cases in each group. Acupoints Sanyinjiao (SP6), Diji (SP8) and Xuehai (SP10) were selected in all the 3 groups, and different dosages of grain-sized moxibustion were used (3 moxa cones, 6 moxa cones, 9 moxa cones) respectively. Treatment started 7 days before menstruation for 3 times, lasting for a total of 3 menstrual cycles. The values of uterine artery blood flow parameters including pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio (S/D) were recorded before and after treatment. The visual analog scale (VAS) score and cox menstrual symptom scale (CMSS) score (including severity ï¼»CMSS-Sï¼½ and time of duration ï¼»CMSS-Tï¼½) were evaluated before treatment, at the end of each menstrual cycle, and one menstrual cycle after treatment. RESULTS: The values of uterine artery blood flow parameters (PI, RI, S/D) after treatment in the 9 moxa cones group were lower than those before treatment, as well as lower than those in the 3 and 6 moxa cones groups after treatment (P<0.05). The VAS scores of the 3 moxa cones group were lower than those before treatment in the first and second cycle (P<0.05). The VAS scores of the 6 and 9 moxa cones groups were lower than those before treatment at each observation point (P<0.05), and were lower than those of the 3 moxa cones group in the third cycle of treatment and follow-up period (P<0.05). And the VAS score of the 9 moxa cones group was lower than that of the 6 moxa cones group during the follow-up period (P<0.05). Compared with the scores before treatment, the CMSS-T scores at each observation point after treatment were lower in the 9 moxa cones group (P<0.05)ï¼the CMSS-T scores in the second and third cycle after treatment, and follow-up period were lower in the 6 moxa cones group (P<0.05), with the CMSS-S scores in the second and third cycle after treatment, and follow-up period lower in the 6 and 9 moxa cones groups (P<0.05). The CMSS-T and CMSS-S scores of the 6 and 9 moxa cones groups were lower than those of the 3 moxa cones group in the third cycle and follow-up period (P<0.05). The CMSS-T and CMSS-S scores of the 9 moxa cones group were lower than those of the 6 moxa cones group during the follow-up period (P<0.05). CONCLUSIONS: Grain-Sized moxibustion has dose-effect relationship in the treatment of PD. Compared with 3 and 6 moxa cones groups, 9 moxa cones group has advantages in improving uterine artery blood flow parameters and alleviating dysmenorrhea symptoms in PD patients.
Subject(s)
Dysmenorrhea , Moxibustion , Humans , Female , Dysmenorrhea/therapy , Dysmenorrhea/physiopathology , Adult , Young Adult , Uterine Artery/physiopathology , Acupuncture Points , AdolescentABSTRACT
PURPOSE: To describe the management of uterine artery (pseudo)aneurysm, ruptured or unruptured, during pregnancy. METHODS: After reporting a case about this rare pathology, a review of the literature was performed. The search was applied to PubMed databases. RESULTS: A total of eighteen articles met the inclusion criteria. Eighteen patients were reported. Eight (44.4 %) patients didn't have prior medical or surgical history. Fifteen (83.3 %) beneficed interventional radiology method during pregnancy including two cases (13.3 %) with repeated embolization because of recanalization of the (pseudo)aneurysm. Nine patients (50 %) beneficed a planned cesarean between 34 and 39 weeks of gestation. One (15.8 %) patient was diagnosed with fetal death before treatment of the uterine artery (pseudo)aneurysm. CONCLUSION: The decision to proceed to the treatment of the (pseudo)aneurysm must consider several factors, associated or not with a good fetal vitality and a hemodynamically stable patient. Embolization appears to be the method of choice. Mode of delivery and term remain not clear and contraindication of expulsive efforts in case of a uterine artery (pseudo)aneurysm merit further investigations.
Subject(s)
Aneurysm, False , Uterine Artery Embolization , Uterine Artery , Female , Humans , Pregnancy , Aneurysm, False/therapy , Aneurysm, False/diagnostic imaging , Pregnancy Complications, Cardiovascular/therapy , Uterine Artery/diagnostic imaging , Uterine Artery Embolization/methodsABSTRACT
Fetal growth restriction (FGR) is associated with uteroplacental insufficiency, and neurodevelopmental and structural brain deficits in the infant. It is currently untreatable. We hypothesised that treating the maternal uterine artery with vascular endothelial growth factor adenoviral gene therapy (Ad.VEGF-A165) normalises offspring brain weight and prevents brain injury in a guinea pig model of FGR. Pregnant guinea pigs were fed a restricted diet before and after conception and received Ad.VEGF-A165 (1 × 1010 viral particles, n = 18) or vehicle (n = 18), delivered to the external surface of the uterine arteries, in mid-pregnancy. Pregnant, ad libitum-fed controls received vehicle only (n = 10). Offspring brain weight and histological indices of brain injury were assessed at term and 5-months postnatally. At term, maternal nutrient restriction reduced fetal brain weight and increased microglial ramification in all brain regions but did not alter indices of cell death, astrogliosis or myelination. Ad.VEGF-A165 increased brain weight and reduced microglial ramification in fetuses of nutrient restricted dams. In adult offspring, maternal nutrient restriction did not alter brain weight or markers of brain injury, whilst Ad.VEGF-A165 increased microglial ramification and astrogliosis in the hippocampus and thalamus, respectively. Ad.VEGF-A165 did not affect cell death or myelination in the fetal or offspring brain. Ad.VEGF-A165 normalises brain growth and markers of brain injury in guinea pig fetuses exposed to maternal nutrient restriction and may be a potential intervention to improve childhood neurodevelopmental outcomes in pregnancies complicated by FGR.
Subject(s)
Adenoviridae , Brain , Fetal Growth Retardation , Genetic Therapy , Microglia , Uterine Artery , Vascular Endothelial Growth Factor A , Animals , Guinea Pigs , Pregnancy , Female , Genetic Therapy/methods , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Fetal Growth Retardation/therapy , Fetal Growth Retardation/metabolism , Adenoviridae/genetics , Brain/metabolism , Brain/pathology , Microglia/metabolism , Fetal Development/physiology , Genetic VectorsABSTRACT
OBJECTIVE: Studies have shown that members of the salusin family regulate the migration and proliferation of arterial smooth muscle cells and increase the tendency to atherosclerosis through fibrosis and calcification in the vascular wall. However, the effect of salusins on the uterine artery has not yet been investigated. This study was conducted to investigate whether serum salusin alpha and beta concentrations in the first trimester are associated with diastolic notching in uterine artery Doppler. METHODS: This non-interventional cohort study was conducted on 88 pregnant women, 44 of whom had diastolic notching on unilateral or bilateral uterine artery Doppler, and 44 of whom did not have diastolic notching on uterine artery Doppler. The uterine artery notch positive and negative groups were compared in terms of serum salusin alpha and beta concentrations. RESULTS: The two groups were similar in terms of demographic characteristics (p < 0.05). The median salusin alpha concentration was found to be 689.4 pg/ml in the uterine artery notch positive group, while it was 734.6 pg/ml in the uterine artery notch negative group (p = 0.608). The median salusin beta concentration was found to be 674.5 pg/ml in the uterine artery notch positive group, while it was 693.8 pg/ml in the uterine artery notch negative group (p = 0.453).Participants were regrouped into normal and high uterine artery resistance and compared in terms of serum salusin alpha and beta concentrations. The median salusin alpha concentration was found to be 994.5 pg/ml in the high uterine artery PI group, while it was 685.2 pg/ml in the normal uterine artery PI group (p = 0.698). The median salusin beta concentration was found to be 1,100.8 pg/ml in the high uterine artery PI group, while it was 669.1 pg/ml in the normal uterine artery PI group (p = 0.584). CONCLUSION: Although the sample size was too small to draw a definitive conclusion, our results indicate that uterine artery diastolic notching or increased resistance in the uterine artery does not appear to be associated with serum salusin alpha or beta concentrations.
Subject(s)
Intercellular Signaling Peptides and Proteins , Pregnancy Trimester, First , Uterine Artery , Humans , Female , Uterine Artery/diagnostic imaging , Pregnancy , Intercellular Signaling Peptides and Proteins/blood , Adult , Pregnancy Trimester, First/blood , Ultrasonography, Doppler , Ultrasonography, Prenatal , Case-Control Studies , Young AdultABSTRACT
Pregnancy is characterized by longitudinal maternal, physiological adaptations to support the development of a fetus. One of the cardinal maternal adaptations during a healthy pregnancy is a progressive increase in uterine artery blood flow. This facilitates sufficient blood supply for the development of the placenta and the growing fetus. Regional hemodynamic changes in the uterine circulation, such as a vast reduction in uterine artery resistance, are mainly facilitated by changes in uterine artery reactivity and myogenic tone along with remodeling of the uterine arteries. These regional changes in vascular reactivity have been attributed to pregnancy-induced adaptations of cell-to-cell communication mechanisms, with an emphasis on the interaction between endothelial and vascular smooth muscle cells. Perivascular adipose tissue (PVAT) is considered the fourth layer of the vascular wall and contributes to the regulation of vascular reactivity in most vascular beds and most species. This review focuses on mechanisms of uterine artery reactivity and the role of PVAT in pregnancy-induced maternal vascular adaptations, with an emphasis on the uterine circulation.
Subject(s)
Adaptation, Physiological , Adipose Tissue , Uterine Artery , Female , Pregnancy , Humans , Uterine Artery/physiology , Adipose Tissue/blood supply , Adipose Tissue/physiology , Adaptation, Physiological/physiology , AnimalsABSTRACT
BACKGROUND: Fetal Medicine Foundation (FMF) studies suggest that preterm preeclampsia can be predicted in the first trimester by combining biophysical, biochemical, and ultrasound markers and prevented using aspirin. We aimed to evaluate the FMF preterm preeclampsia screening test in nulliparous women. METHODS: We conducted a prospective multicenter cohort study of nulliparous women recruited at 11 to 14 weeks. Maternal characteristics, mean arterial blood pressure, PAPP-A (pregnancy-associated plasma protein A), PlGF (placental growth factor) in maternal blood, and uterine artery pulsatility index were collected at recruitment. The risk of preterm preeclampsia was calculated by a third party blinded to pregnancy outcomes. Receiver operating characteristic curves were used to estimate the detection rate (sensitivity) and the false-positive rate (1-specificity) for preterm (<37 weeks) and for early-onset (<34 weeks) preeclampsia according to the FMF screening test and according to the American College of Obstetricians and Gynecologists criteria. RESULTS: We recruited 7554 participants including 7325 (97%) who remained eligible after 20 weeks of which 65 (0.9%) developed preterm preeclampsia, and 22 (0.3%) developed early-onset preeclampsia. Using the FMF algorithm (cutoff of ≥1 in 110 for preterm preeclampsia), the detection rate was 63.1% for preterm preeclampsia and 77.3% for early-onset preeclampsia at a false-positive rate of 15.8%. Using the American College of Obstetricians and Gynecologists criteria, the equivalent detection rates would have been 61.5% and 59.1%, respectively, for a false-positive rate of 34.3%. CONCLUSIONS: The first-trimester FMF preeclampsia screening test predicts two-thirds of preterm preeclampsia and three-quarters of early-onset preeclampsia in nulliparous women, with a false-positive rate of ≈16%. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02189148.
Subject(s)
Pre-Eclampsia , Pregnancy Trimester, First , Pregnancy-Associated Plasma Protein-A , Humans , Female , Pregnancy , Pre-Eclampsia/diagnosis , Prospective Studies , Adult , Pregnancy-Associated Plasma Protein-A/analysis , Pregnancy-Associated Plasma Protein-A/metabolism , Parity , Placenta Growth Factor/blood , Biomarkers/blood , Uterine Artery/diagnostic imaging , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
OBJECTIVES: The purpose of this study was to investigate the association between first-trimester uterine artery pulsatility index (UtA-PI) and crown-rump length discordance (CRLD) with growth discordance (GD) in twins and analyze the influence of chorionicity in these parameters. METHODS: This retrospective analysis integrated data from the twin pregnancy database of Centro Hospitalar São João (2019-2023), including 184 fetuses, with 19 monochorionic and 73 dichorionic gestations. To determine the association between UtA-PI and CRLD with GD, correlation analyses were computed and linear regression models were carried out. Separate analyses were conducted for each type of placentation. Logistic regression analysis was carried out to determine the association of mean UtA-PI and CRLD with severe GD, defined as discordance ≥25â¯%. RESULTS: GD≥25â¯% was detected in 9.80â¯% of pregnancies. A statistically significant difference between monochorionic and dichorionic gestations was found in crown-rump length (p=0.009), CRLD (p<0.001) and birth weight (p=0.025), but not in mean UtA-PI (p=0.853) or GD (p=0.556). Mean UtA-PI was significantly higher in discordant than in concordant pairs (p<0.001), but that association was not seen in CRLD (p=0.931). Mean UtA-PI and GD were correlated by the regression line "GD=3.844 × UtA-PI + 6.638", with R2 0.027. CRLD and GD were correlated by the regression line "GD=0.280 × CRLD + 10.79", with R2 0.010. Mean UtA-PI, but not CRLD, was significantly associated with severe GD (odds ratio, 22.753; p=0.002). CONCLUSIONS: Mean UtA-PI, but not CRLD, is associated with GD. The prevalence of severe GD increases significantly with increasing mean UtA-PI.
Subject(s)
Crown-Rump Length , Fetal Growth Retardation , Pregnancy Trimester, First , Ultrasonography, Prenatal , Uterine Artery , Humans , Female , Pregnancy , Retrospective Studies , Uterine Artery/diagnostic imaging , Ultrasonography, Prenatal/methods , Adult , Fetal Growth Retardation/diagnostic imaging , Pregnancy, Twin , Pulsatile Flow , Ultrasonography, Doppler/methodsABSTRACT
BACKGROUND: The uterine artery pulsatility index (UtA PI) is associated with blood flow to the placenta. Its increased values imply impaired placentation. This study aimed to evaluate UtA PI measurements in first-trimester ultrasound in pregnancies after kidney (KTx) or liver transplantation (LTx) and its relationship with perinatal outcome. MATERIALS AND METHODS: A retrospective analysis of 72 pregnancies in female kidney (35) or liver (37) transplant recipients between 2017 and 2023 was performed. Data concerning UtA PI were available for 17 kidney and 19 liver recipients. Statistical analysis of variables between KTx and LTx groups and the correlation with perinatal outcomes was performed using Student's t test and Pearson's correlation with P < .05 considered statistically significant. RESULTS: The mean UtA PI results were similar, and there were no statistical differences between the group of pregnant kidney and liver recipients with mean values of 1.46 (SD 0.44] and 1.73 (SD 0.51] respectively (P = .10). The mean neonate birth weight was lower in KTx group (2158 g ([SD 723 g]) compared with the LTx group (2780 g [SD 754g]; P =.02). In the KTx and LTx groups, mean UtA PI was in negative correlation with Apgar score in the first minute (P = .04, P = .01 respectively). CONCLUSIONS: Uterine artery Doppler is useful in predicting perinatal outcomes in the general population and organ recipient pregnancies, even in the early stages of pregnancy, as we observed the correlation between UtA PI and Apgar score. Pregnant kidney recipients remain at higher risk for complications and more unpredictable outcomes than liver recipients.
Subject(s)
Kidney Transplantation , Liver Transplantation , Pregnancy Outcome , Pulsatile Flow , Uterine Artery , Humans , Pregnancy , Female , Uterine Artery/diagnostic imaging , Retrospective Studies , Adult , Ultrasonography, Prenatal , Infant, NewbornABSTRACT
BACKGROUND: Preeclampsia is a significant pregnancy disorder with an unknown cause, mainly attributed to impaired spiral arterial remodeling. METHODS: Using RNA sequencing, we identified key genes in placental tissues from healthy individuals and preeclampsia patients. Placenta and plasma samples from pregnant women were collected to detect the expression of TPBG (trophoblast glycoprotein). Pregnant rats were injected with TPBG-carrying adenovirus to detect preeclamptic features. HTR-8/SVneo cells transfected with a TPBG overexpression lentiviral vector were used in cell function experiments. The downstream molecular mechanisms of TPBG were explored using RNA sequencing and single-cell RNA sequencing data. TPBG expression was knocked down in the lipopolysaccharide-induced preeclampsia-like rat model to rescue the preeclampsia features. We also assessed TPBG's potential as an early preeclampsia predictor using clinical plasma samples. RESULTS: TPBG emerged as a crucial differentially expressed gene, expressed specifically in syncytiotrophoblasts and extravillous trophoblasts. Subsequently, we established a rat model with preeclampsia-like phenotypes by intravenously injecting TPBG-expressing adenoviruses, observing impaired spiral arterial remodeling, thus indicating a causal correlation between TPBG overexpression and preeclampsia. Studies with HTR-8/SVneo cells, chorionic villous explants, and transwell assays showed TPBG overexpression disrupts trophoblast/extravillous trophoblast migration/invasion and chemotaxis. Notably, TPBG knockdown alleviated the lipopolysaccharide-induced preeclampsia-like rat model. We enhanced preeclampsia risk prediction in early gestation by combining TPBG expression with established clinical predictors. CONCLUSIONS: These findings are the first to show that TPBG overexpression contributes to preeclampsia development by affecting uterine spiral artery remodeling. We propose TPBG levels in maternal blood as a predictor of preeclampsia risk. The proposed mechanism by which TPBG overexpression contributes to the occurrence of preeclampsia via its disruptive effect on trophoblast and extravillous trophoblast migration/invasion on uterine spiral artery remodeling, thereby increasing the risk of preeclampsia.
Subject(s)
Cell Movement , Pre-Eclampsia , Trophoblasts , Female , Pre-Eclampsia/genetics , Pre-Eclampsia/metabolism , Pregnancy , Trophoblasts/metabolism , Animals , Rats , Humans , Disease Models, Animal , Uterine Artery/metabolism , Uterine Artery/pathology , Rats, Sprague-Dawley , Vascular Remodeling/physiology , Vascular Remodeling/genetics , Placenta/metabolism , Glycoproteins/genetics , Glycoproteins/metabolism , AdultABSTRACT
AIMS: Accurate prediction of preeclampsia could improve maternal outcomes. However, the role of uterine artery Doppler ultrasound in predicting preeclampsia remains unclear. MATERIALS AND METHODS: We comprehensively searched several electronic databases, including PubMed, EMBASE, the Cochrane Library, and Web of Science, covering studies published from the time of database creation to September 23, 2023. Studies on the predictive value of uterine artery Doppler ultrasound for preeclampsia were included. The primary pregnancy outcome was preeclampsia. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scoring scale. RESULTS: The use of resistance index (RI) for predicting preeclampsia demonstrated the highest sensitivity of 0.73 (95% confidence interval [CI], 0.30-0.94) and specificity of 0.90 (95% CI, 0.72-0.97), with a pooled area under the curve value of 0.91 (95% CI, 0.88-0.93). The use of pulsatility index (PI) for predicting preeclampsia showed a sensitivity of 0.65 (95% CI, 0.45-0.81) and specificity of 0.88 (95% CI, 0.77-0.94). Furthermore, preeclampsia prediction via notching showed a sensitivity of 0.54 (95% CI, 0.38-0.68) and specificity of 0.89 (95% CI, 0.79-0.95). CONCLUSIONS: These findings highlight the varying predictive performance of different preeclampsia indices. PI and RI demonstrated moderate-to-high sensitivity and specificity, whereas notching exhibited relatively lower sensitivity but comparable specificity. Further research and validation are warranted to consolidate these results and enhance the accuracy of preeclampsia prediction.
Subject(s)
Pre-Eclampsia , Ultrasonography, Doppler , Uterine Artery , Female , Humans , Pregnancy , Pre-Eclampsia/diagnostic imaging , Predictive Value of Tests , Sensitivity and Specificity , Ultrasonography, Doppler/methods , Ultrasonography, Prenatal/methods , Uterine Artery/diagnostic imagingABSTRACT
Objectives: This study aims to correlate pelvic ultrasound with female puberty and evaluate the usual ultrasound parameters as diagnostic tests for the onset of puberty and, in particular, a less studied parameter: the Doppler evaluation of the uterine arteries. Methods: Cross-sectional study with girls aged from one to less than eighteen years old, with normal pubertal development, who underwent pelvic ultrasound examination from November 2020 to December 2021. The presence of thelarche was the clinical criterion to distinguish pubescent from non-pubescent girls. The sonographic parameters were evaluated using the ROC curve and the cutoff point defined through the Youden index (J). Results: 60 girls were included in the study. Uterine volume ≥ 2.45mL had a sensitivity of 93%, specificity of 90%, PPV of 90%, NPV of 93% and accuracy of 91% (AUC 0.972) for predicting the onset of puberty. Mean ovarian volume ≥ 1.48mL had a sensitivity of 96%, specificity of 90%, PPV of 90%, NPV of 97% and accuracy of 93% (AUC 0.966). Mean PI ≤ 2.75 had 100% sensitivity, 48% specificity, 62% PPV, 100% NPV and 72% accuracy (AUC 0.756) for predicting the onset of puberty. Conclusion: Pelvic ultrasound proved to be an excellent tool for female pubertal assessment and uterine and ovarian volume, the best ultrasound parameters for detecting the onset of puberty. The PI of the uterine arteries, in this study, although useful in the pubertal evaluation, showed lower accuracy in relation to the uterine and ovarian volume.
Subject(s)
Puberty , Humans , Female , Cross-Sectional Studies , Child , Puberty/physiology , Adolescent , Child, Preschool , Uterus/diagnostic imaging , Uterus/blood supply , Infant , Sensitivity and Specificity , Uterine Artery/diagnostic imaging , Ovary/diagnostic imaging , Ovary/blood supply , Pelvis/diagnostic imaging , Pelvis/blood supply , Ultrasonography , ROC CurveABSTRACT
Fetal growth restriction is a hallmark of Fetal Alcohol Syndrome (FAS) and is accompanied by maternal uterine circulatory maladaptation. FAS is the most severe form of Fetal Alcohol Spectrum Disorder (FASD), a term for the range of conditions that can develop in a fetus when their pregnant mother consumes alcohol. Alcohol exerts specific direct effects on lipids that control fundamental developmental processes. We previously demonstrated that direct in vitro application of phosphatidic acid (PA, the simplest phospholipid and a direct target of alcohol exposure) to excised uterine arteries from alcohol-exposed rats improved vascular function, but it is unknown if PA can rescue end organ phenotypes in our FASD animal model. Pregnant Sprague-Dawley rats (n = 40 total dams) were gavaged daily from gestational day (GD) 5 to GD 19 with alcohol or maltose dextrin, with and without PA supplementation, for a total of four unique groups. To translate and assess the beneficial effects of PA, we hypothesized that in vivo administration of PA concomitant with chronic binge alcohol would reverse uterine artery dysfunction and fetal growth deficits in our FASD model. Mean fetal weights and placental efficiency were significantly lower in the binge alcohol group compared with those in the control (p < 0.05). However, these differences between the alcohol and the control groups were completely abolished by auxiliary in vivo PA administration with alcohol, indicating a reversal of the classic FAS growth restriction phenotype. Acetylcholine (ACh)-induced uterine artery relaxation was significantly impaired in the uterine arteries of chronic in vivo binge alcohol-administered rats compared to the controls (p < 0.05). Supplementation of PA in vivo throughout pregnancy reversed the alcohol-induced vasodilatory deficit; no differences were detected following in vivo PA administration between the pair-fed control and PA alcohol groups. Maximal ACh-induced vasodilation was significantly lower in the alcohol group compared to all the other treatments, including control, control PA, and alcohol PA groups (p < 0.05). When analyzing excitatory vasodilatory p1177-eNOS, alcohol-induced downregulation of p1177-eNOS was completely reversed following in vivo PA supplementation. In summary, these novel data utilize a specific alcohol target pathway (PA) to demonstrate a lipid-based preventive strategy and provide critical insights important for the development of translatable interventions.
Subject(s)
Disease Models, Animal , Ethanol , Fetal Alcohol Spectrum Disorders , Fetal Growth Retardation , Phosphatidic Acids , Rats, Sprague-Dawley , Uterine Artery , Animals , Female , Pregnancy , Fetal Growth Retardation/drug therapy , Fetal Growth Retardation/physiopathology , Uterine Artery/drug effects , Fetal Alcohol Spectrum Disorders/physiopathology , Phosphatidic Acids/pharmacology , Rats , Binge Drinking/complications , Placenta/blood supply , Placenta/drug effects , Placenta/metabolismABSTRACT
OBJECTIVE: To evaluate the performance of maternal factors, biophysical and biochemical markers at 11-13 + 6 weeks' gestation in the prediction of gestational diabetes mellitus with or without large for gestational age (GDM ± LGA) fetus and great obstetrical syndromes (GOS) among singleton pregnancy following in-vitro fertilisation (IVF)/embryo transfer (ET). MATERIALS AND METHODS: A prospective cohort study was conducted between December 2017 and January 2020 including patients who underwent IVF/ET. Maternal mean arterial pressure (MAP), ultrasound markers including placental volume, vascularisation index (VI), flow index (FI) and vascularisation flow index (VFI), mean uterine artery pulsatility index (mUtPI) and biochemical markers including placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 11-13 + 6 weeks' gestation. Logistic regression analysis was performed to determine the significant predictors of complications. RESULTS: Among 123 included pregnancies, 38 (30.9%) had GDM ± LGA fetus and 28 (22.8%) had GOS. The median maternal height and body mass index were significantly higher in women with GDM ± LGA fetus. Multivariate logistic regression analysis demonstrated that in the prediction of GDM ± LGA fetus and GOS, there were significant independent contributions from FI MoM (area under curve (AUROC) of 0.610, 95% CI 0.492-0.727; p = 0.062) and MAP MoM (AUROC of 0.645, 95% CI 0.510-0.779; p = 0.026), respectively. CONCLUSION: FI and MAP are independent predictors for GDM ± LGA fetus and GOS, respectively. However, they have low predictive value. There is a need to identify more specific novel biomarkers in differentiating IVF/ET pregnancies that are at a higher risk of developing complications.
Subject(s)
Diabetes, Gestational , Placenta , Pregnancy Trimester, First , Ultrasonography, Prenatal , Humans , Female , Pregnancy , Adult , Prospective Studies , Placenta/diagnostic imaging , Placenta/blood supply , Ultrasonography, Prenatal/methods , Fertilization in Vitro , Biomarkers/blood , Fetal Macrosomia/diagnostic imaging , Placenta Growth Factor/blood , Predictive Value of Tests , Gestational Age , Embryo Transfer , Uterine Artery/diagnostic imaging , Pregnancy Complications/diagnostic imaging , Reproductive Techniques, AssistedABSTRACT
The aim of the study was to study robotic cervical radical trachelectomy, aimed at standardizing and optimizing surgical procedures, thereby facilitating the learning process. All surgical procedures were based on the anatomy of the embryonic compartments, which not only help prevent tumor spillage due to disruption of the embryonic compartments, but also maximize the avoidance of inadequate resection margins. Using robotics to perform radical trachelectomy, combined with the concept of membrane anatomy, not only enables a bloodless surgical process, but also streamlines and simplifies the procedure, making it more efficient and precise. Utilizing robotics for radical hysterectomy can lead to a more meticulous and refined outcome. Precise surgical techniques contribute to standardizing and optimizing surgical procedures, thereby facilitating the learning process.
Subject(s)
Robotic Surgical Procedures , Trachelectomy , Uterine Artery , Uterine Cervical Neoplasms , Humans , Female , Robotic Surgical Procedures/methods , Trachelectomy/methods , Uterine Cervical Neoplasms/surgery , Uterine Artery/surgery , Organ Sparing Treatments/methods , Cervix Uteri/surgeryABSTRACT
Performing a minimally invasive surgery comes with a significant advantage regarding rehabilitating the patient after the operation. But it also causes difficulties, mainly for the surgeon or expert who performs the surgical intervention, since only visual information is available and they cannot use their tactile senses during keyhole surgeries. This is the case with laparoscopic hysterectomy since some organs are also difficult to distinguish based on visual information, making laparoscope-based hysterectomy challenging. In this paper, we propose a solution based on semantic segmentation, which can create pixel-accurate predictions of surgical images and differentiate the uterine arteries, ureters, and nerves. We trained three binary semantic segmentation models based on the U-Net architecture with the EfficientNet-b3 encoder; then, we developed two ensemble techniques that enhanced the segmentation performance. Our pixel-wise ensemble examines the segmentation map of the binary networks on the lowest level of pixels. The other algorithm developed is a region-based ensemble technique that takes this examination to a higher level and makes the ensemble based on every connected component detected by the binary segmentation networks. We also introduced and trained a classic multi-class semantic segmentation model as a reference and compared it to the ensemble-based approaches. We used 586 manually annotated images from 38 surgical videos for this research and published this dataset.
Subject(s)
Algorithms , Laparoscopy , Neural Networks, Computer , Ureter , Uterine Artery , Humans , Laparoscopy/methods , Female , Ureter/diagnostic imaging , Ureter/surgery , Uterine Artery/surgery , Uterine Artery/diagnostic imaging , Image Processing, Computer-Assisted/methods , Semantics , Hysterectomy/methodsABSTRACT
Fall-calving primiparous beef females [body weight (BW): 451â ±â 28 (SD) kg; body condition score (BCS): 5.4â ±â 0.7] were individually-fed either 100% (control; CON; nâ =â 13) or 70% (nutrient restricted; NR; nâ =â 13) of metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to parturition. Doppler ultrasonography of both uterine arteries was conducted pre-treatment and every 21 d from days 181 to 265 of gestation. Expelled placentas were collected, and ipsilateral cotyledonary tissue was sampled to assess relative messenger ribonucleic acid (mRNA) expression. Placentas were separated into ipsilateral and contralateral sides, dissected (cotyledonary vs. intercotyledonary), and dried. Data were analyzed with nutritional plane, treatment initiation date, and calf sex (when Pâ <â 0.25) as fixed effects. Uterine blood flow included day and nutritional planeâ ×â day as repeated measures. We previously reported that post-calving, NR dams weighed 64 kg less and were 2.0 BCS lower than CON, but calf birth weight was not affected. Maternal heart rate was less (Pâ <â 0.001) for NR dams than CON after nutritional planes began. Nutritional plane did not affect (Pâ ≥â 0.20) uterine artery hemodynamics, but all variables were affected (Pâ ≤â 0.04) by day. Contralateral cotyledonary and placental weight were less (Pâ ≤â 0.04) and contralateral intercotyledonary weight and number of cotyledons tended to be less (Pâ ≤â 0.10) for NR dams than CON, but ipsilateral and whole placental weights were not affected (Pâ ≥â 0.13). Ipsilateral placental weight as a percentage of total placental weight was greater (Pâ =â 0.03) for NR dams than CON. Whole placental cotyledonary: intercotyledonary weight was less (Pâ =â 0.01) for NR dams than CON. Placental efficiency was not affected (Pâ =â 0.89) by nutritional plane. Cotyledonary relative mRNA expression of GLUT3 and SNAT2 was greater (Pâ ≤â 0.05) and relative expression of GLUT1, GLUT4, and NOS3 tended to be greater (Pâ ≤â 0.07) for NR dams than CON. Nutritional plane did not affect (Pâ ≥â 0.13) relative mRNA expression of GLUT5, 4F2hc, CAT1, LAT1, LAT2, VEGFA, FLT1, KDR, GUCY1B3, and PAG2. Despite less contralateral placental growth, beef heifers experiencing late gestational nutrient restriction maintained uterine artery blood flow and total placental mass and had 4 nutrient transporters and 1 angiogenic factor upregulated in cotyledons, all of which likely contributed to conserving fetal growth.
Nutrient requirements increase substantially during late gestation in the beef female to support fetal, uteroplacental, and mammary growth, and in the still-growing heifer, nutrients are also needed for maternal tissue growth. During pregnancy, the placenta serves as the interface for the metabolism and transport of nutrients, gases, and wastes between maternal and fetal circulations. Inadequate gestational nutrition can result in placental insufficiency and intrauterine growth restriction of the offspring, resulting in postnatal consequences. How late gestational undernutrition in beef heifers impacts the factors involved in placental nutrient transport capacity is poorly understood. We observed that late gestational nutrient restriction in heifers decreased maternal heart rate, but total uterine artery blood flow was not affected. Additionally, total placental mass was maintained, while cotyledonary expression of 4 nutrient transporters and an angiogenic factor were upregulated in placentas of nutrient restricted dams, which collectively allowed for similar calf birth weights as adequately-fed dams.