Trophoblast Vessel Research Articles

Trophoblastic volumetric bloodflow evaluation in women with trombophylia on 7–10th week of pregnancy

Spontaneous abortion occur in 15–20% of all detected pregnancies, and 45–70% of all spontaneous miscarriages take place up to 10 weeks. Thrombophilia is one of the main causes of miscarriage and its effect on the course of pregnancy remains poorly understood. In this regard, there is great interest in the problem of diagnosing thrombophilia and further prevention of thrombosis in obstetric practice.Purpose. Compare the parameters of volumetric blood flow in the chorion with different types of trophoblastic blood flow disturbance in pregnant women with thrombophilia in the first trimester for their quantitative verification.Materials and methods. The study included 129 pregnant women at the 7th to 10th week of gestation with a diagnosis of thrombophilia and a control group - pregnant women with a normal course of this pregnancy and a successful outcome of past pregnancies.The patients were divided into III clinical groups:I. Pregnant women with a normal course of this pregnancy and a successful outcome of past pregnancies (n = 33) – comparison group;II. Pregnant women with thrombophilia, in whom current pregnancy occurred on anticoagulant therapy (n = 28);III. Pregnant women with thrombophilia without taking anticoagulant drugs before registration of pregnancy (n = 68).Ultrasound was performed on Voluson E8 and S8 machines. All pregnant women underwent transabdominal and transvaginal ultrasound in B-mode, in color-doppler (CD) mode, and volumetric reconstruction of chorion was performed using the VOCAL program. In B-mode, the state of the embryo and extraembryonic structures were examined. The identification of trophoblastic vessels was carried out using the CD – region of interest was placed in the trophoblast area detected in B-mode, size and shape was adapted for a particular section.Using three-dimensional echography, the chorion volume was performed. The degree of blood supply in chorionic volume were calculated; vascularization index (VI), flow index (FI) and perfusion index (VFI) were displayed on a histogram with quantitative indicators.ResultsIn the CD mode, the types of trophoblastic blood flow were identified in the chorionic vessels:1) continuous type – blood flow loci are continuously identified over the entire area of the basal surface of the trophoblast;2) intermittent type – blood flow loci are unevenly identified along the basal surface of the trophoblast;3) single loci – single blood flow loci are identified along the basal surface of the trophoblast;4) lack of blood flow – blood flow loci are not determined along the basal surface of the trophoblast.Assessment of the quantitative parameters of the volumetric blood flow was used in the corresponding type of blood flow to verify the classification of types of trophoblastic blood flow in the CD mode.Statistical analysis of the volumetric blood flow indices using three-dimensional chorionic reconstruction showed a high degree of reliability (p < 0.0001) in the VI and VFI values between all corresponding types of blood flow.Discussion. High incidence of spontaneous abortion and the significant role of thrombophilia in this pathology leads to necessity of expanding the research in this area. There has been a lot of research done over the past decade. The quantitative threshold values of the resistance indices in the chorionic vessels were calculated using pulse-wave Doppler, the chorionic blood supply indices were determined using volumetric reconstruction for various pathologies.However, we have not previously met the classification of chorionic blood supply in the CD mode. This technique is very simple to perform and is a highly informative for predicting miscarriage in the first trimester. For the first time, we proposed the above classification of trophoblastic blood flow; for the first time, we proved the reliability of the classification developed by us using the method of volumetric reconstruction of the chorion with an assessment of trophoblastic blood flow, which allows us to recommend its use when writing a protocol for ultrasound of the fetus in the first trimester in pregnant women with thrombophilia.Conclusion. The classification of trophoblastic blood flow was verified by three-dimensional echography with quantitative indicators of the volumetric blood flow of the trophoblast vessels, with a high degree of reliability (p < 0.001) which to indicates the reliability of this classification. It can be recommended to conduct a multicenter study for investigating fetal ultrasound with the additional use of the CD in the first trimester in pregnant women with a diagnosis of thrombophilia.

Histopathology manifestation and imaging characteristics of in vivo confocal microscopy for diagnosis of ocular surface squamous neoplasia

Objective: To study the histopathology manifestation and imaging characteristics of in vivo confocal microscopy (IVCM) for diagnosis of ocular surface squamous neoplasia (OSSN) and analyze the reliability of IVCM in differential diagnosis from OSSN cases. Methods: A prospective study. Twenty-three patients (23 eyes) with OSSN were collected from September 2015 to November 2017 in Beijing Tongren Eye center. They were underwent the examinations sequentially as follows: visual examination; slit-lamp microscope examination and ocular surface photography; color fundus image; anterior segment optical coherence tomography examination; IVCM examination and histopathology examination after surgery. With histopathology diagnosis, all subjects were divided into two groups: conjunctival intraepithelial neoplasm (CIN) and squamous cell carcinoma (SCC). Compared with histopathological findings, the IVCM results (cell morphology, cytoplasm and nucleus) of OSSN were analyzed. The difference analysis between the count data of two groups was carried out by the chi square test or Fisher's exact test. Receiver operating characteristic curve and area under the curve (AUC) were used to describe the accuracy of each parameter to differentiate SCC from OSSN. Results: There were 12 males and 11 females among the 23 patients aged (62±15) years. With the histopathological diagnosis, there were 15 cases (15 eyes) in the CIN group and 8 cases (8 eyes) in the SCC group. Eye redness, pain, foreign body sensation and tears were the symptoms of OSSN. There was no significant difference in clinical symptoms between the CIN and SCC groups. The size of tumors and the incidence of trophoblastic vessels in the SCC group were greater than those in the CIN group [8.5(6.5-15.5) mm vs. 5.8(4.0-8.5)mm, Z=4.702,P=0.029; 7/8 vs. 5/15, χ2=6.135, P=0.013). In histopathology, multilayered epithelia with cellular polymorphism, varied cytoplasm staining, and slightly thicker nuclei were observed in the CIN group. The corneal epithelial cells of SCC patients were markedly heterogeneous, and the intercellular bridge structure can be detected. Proliferative cells appeared with spindle shaped cells, nuclear mitotic figures and syncytial cells in the SCC group. The IVCM examination in the CIN group and SCC group showed that the cytoplasm was high and the ratio of nuclear plasma increased. There was no significant difference between the two groups in the size of epithelial cells, cytoplasm reflectivity, and nuclear cytoplasm ratio (P=0.053, 0.108, 0.067). The proportions of nuclear mitotic figures, spindle or chimeric cells, nests of whirlpool cells and the abnormal cells of the superficial stroma layer (8/8, 8/8, 8/8 and 8/8) in the SCC group was higher than those (2/15, 1/15, 4/15 and 0/15) in the CIN group, and the difference was statistically significant (P=0.001, 0.001, 0.003; P<0.001). Among these IVCM parameters, the abnormal cells of the superficial stroma layer had the highest diagnostic ability with the AUC value of 1.000, and the following AUC values were 0.933 for mitotic or double nuclei, 0.901 for spindle or chimeric cells, and 0.867 for the nests of whirlpool cells. Conclusions: The IVCM characteristics of OSSN are the dysplastic cells, hyper-reflective cytoplasm and increased nuclear plasma ratio in the corneal epithelium. Dysplastic cells appearing in the superficial stroma layer, nuclear mitotic figures and nests of vortex cells are the main IVCM parameters to support the malignant change of OSSN lesions. (Chin J Ophthalmol, 2018, 54: 652-660).

Characteristic Growth of Human Choriocarcinoma Xenografts in Nude Mice

In order to investigate the mechanisms and regulation of trophoblast vessel invasion, we established a model using malignant trophoblast cells grown in nude mice. The human choriocarcinoma cell line Jeg-3 established fast-growing tumours within 2 weeks after subcutaneous injection into nude mice. Interestingly, instead of neoangiogenesis the tumours were characterized by large blood-filled lacunae. Staining for hCG-β and for mouse panendothelial antigen revealed that the majority of the lacunae were lined by trophoblast cells. The blood supply of the lacunae resulted from invasion of the choriocarcinoma cells into the host vessels at the junctional zone between tumour and mouse tissue. These large blood-filled lacunae led to a much faster expansion of tumours with less necrotic areas compared to tumours of non-trophoblastic origin (Hec-1A and HeLa), which revealed neovascularization. Jeg-3 choriocarcinoma cells eroded host vessels and replaced the endothelial lining in a similar way to trophoblast cells during the establishment of a haemochorial placenta. This model can be useful in investigating the cell biological mechanisms of trophoblast vessel invasion and replacement of the endothelium by trophoblast cells.

Doppler ultrasonography in early pregnancy does not predict adverse pregnancy outcome.

A transvaginal color and pulsed Doppler study was performed on 330 pregnancies at 7-16 weeks of gestation. Blood flow velocity waveforms were recorded from the main uterine arteries and their branches (arcuate and trophoblastic vessels) and from the umbilical arteries. The systolic/diastolic velocity ratio and the pulsatility index were calculated as indices of vascular resistance, respectively, at uterine and umbilical levels. A total of 282 patients had an uneventful pregnancy outcome, 19 developed an early pregnancy failure (missed abortion, n = 8; anembryonic pregnancy, n = 11) and 29 developed later complications such us hypertension (n = 10), fetal growth retardation (n = 13) or both n = 6). In normal pregnancies, Doppler-measured vascular resistances significantly decreased with advancing gestation at the level of both uterine and umbilical circulations. When the Doppler indices of the patients with early pregnancy failure or with later complications were compared to those of normal pregnancies, no evident differences were found in either of the vascular districts considered. However, in the patients who developed hypertension and/or fetal growth retardation, abnormal velocity waveforms were frequently present in uterine and umbilical arteries during second- or third-trimester examinations. Our results suggest a limited clinical value of Doppler velocimetry in early pregnancy.

Transvaginal Colour Doppler ultrasound in normal and abnormal early pregnancy

The value of transvaginal colour and pulse wave Doppler in the diagnosis of pathologic early intrauterine and tubal pregnancy was assessed. Forty-one normal pregnancies, 6 blighted ovum, 6 missed abortions, and 22 suspected ectopic pregnancies (13 proven tubal pregnancies) were examined. Single 5 MHz transvaginal colour and pulse wave Doppler probe was used and once clear signals from uterine vessels, umbilical artery or trophoblastic vessels were obtained. Resistance Index (peak systole--end diastole/peak systole, RI) from the corresponding waveforms was calculated. In 41 normal pregnancies (examined before termination of pregnancy) with gestational age ranged from 6 to 10 weeks mean RI in uterine artery was 0.81 (SD 0.06), in the umbilical artery 1 (SD 0), and 0.48 (0.08) in the trophoblastic vessels. Mean RI from uterine arteries in six pregnancies with blighted ovum and six with missed abortion were 0.77 (SD 0.11) and 0.69 (SD 0.13) respectively. In 2 out of 6 cases of blighted ovum and 4 out of 6 cases of missed abortion flow in trophoblastic vessels could not be detected. These findings suggest ineffective early placentation in pathologic pregnancy. Twenty-two patients with suspected ectopic pregnancy (raised serum beta HCG with empty uterus, amenorrhoea with abdominal pain and/or palpable abdominal mass) were examined. In 13 cases tubal pregnancy was confirmed by laparoscopy and/or laparotomy. In the remaining nine cases the diagnosis was excluded by means of laparoscopy or subsequent negative beta HCG. Doppler diagnosis of ectopic pregnancy was made when colour flow in adnexa with RI less than 0.56 was revealed.(ABSTRACT TRUNCATED AT 250 WORDS)