Fetal vascular malperfusion score is linked with developing preeclampsia in women with gestational diabetes mellitus: a retrospective cohort study

SUMMARY OBJECTIVE: Fetal vascular malperfusion is associated with poor perinatal outcomes in women with preeclampsia and gestational diabetes mellitus. The aim of this study was to determine the association between fetal vascular malperfusion score and syncytiotrophoblast basement membrane thickness and clinicopathological variables, such as developing preeclampsia in women with gestational diabetes mellitus. METHODS: This retrospective cohort study included 65 pregnant participants (34 with gestational diabetes mellitus and 31 controls) between January 2019 and January 2022. Gestational diabetes mellitus was diagnosed as ≥2 of 4 elevated values on a 3-h, 100-g oral glucose tolerance test. The fetal vascular malperfusion score was evaluated by endothelial CD34 positivity in the villous stroma of the placenta. The association between fetal vascular malperfusion score and syncytiotrophoblast basement membrane thickness with clinicopathological variables in women with gestational diabetes mellitus was evaluated. RESULTS: It was revealed that the gestational diabetes mellitus group had greater fetal vascular malperfusion scores than the control group (gestational diabetes mellitus group fetal vascular malperfusion score: 34.2±9.1 and control group fetal vascular malperfusion score: 26.5±8.7, respectively, p=0.0009). Syncytiotrophoblast basement membrane thickness was correlated with the development of preeclampsia, trophoblast proliferation, and fetal vascular malperfusions (0.3952, p=0.0129; 0.3487, p=0.0211; and 0.4331, p=0.0082, respectively). On the contrary, fetal vascular malperfusions were correlated with the development of preeclampsia, villous edema, and trophoblast proliferation (0.3154, p=0.0343; 0.2922, p=0.4123; and 0.3142, p=0.0355, respectively). CONCLUSION: The gestational diabetes mellitus group displayed significantly higher fetal vascular malperfusion scores and thickening of the syncytiotrophoblast basement membrane than the control group. There is a correlation between developing preeclampsia and the fetal vascular malperfusion scores and the syncytiotrophoblast basement membrane thickness.

Higroma quístico retronucal como marcador de anomalías cromosómicas en el primer trimestre de la gestación - Actualización

Objetivo. Evaluar la asociación del higroma quístico retronucal (HQR) y anomalías cromosómicas fetales. Métodos. Estudio observacional retrospectivo de 323 fetos del primer trimestre con riesgo para anomalías cromosómicas diagnosticados por ecografía entre las 11 y 13,6 semanas. Resultados. De 323 fetos con riesgo para anomalías cromosómicas, se encontró 132 casos de anomalías cromosómicas (40,9%). Se identificaron 145 casos de HQR; en 64 (56,6%) se realizó biopsia de vellosidades coriales y en 81 (43,5%) amniocentesis, hallándose cariotipo anómalo en 82 (56,6%). De 88 fetos con HQR aislado, 33 casos (37,5%) tuvieron alguna anomalía cromosómica; en 58 fetos con HQR asociado a otros hallazgos anormales, se encontró que en 43 fetos (74,1%) hubo anomalías cromosómicas, y de ellos 24 (41,4%) tenían onda de flujo (OVF) anormal del ductus venoso, 17 (29,3%) tenían edema generalizado, 8 casos (13,8%) con cardiopatía, 7 (12,1%) ausencia del hueso nasal. Los valores predictivos del HQR fueron: sensibilidad (S) 62,1%, especificidad (E) 67%, valor predictivo positivo (VPP) 56,6%, valor predictivo negativo (VPN) 71,9%, p<0,001, OR: 3,3. El HQR asociado a otros hallazgos anormales, tuvo los siguientes valores predictivos: S 52,4%, E 76,2%, VPP 76,2%, OR: 3,5, LR+: 2,2, p<0,000. El edema generalizado y el ductus venoso anormal tuvieron los valores predictivos más altos: VPP 88,2% y 83,3%, respectivamente. Las anomalías cromosómicas encontradas con mayor frecuencia fueron: T21 (53,7%), monosomía X (18,3%), T18 (15,9%), T13 (6,1%). Conclusiones. El higroma quístico retronucal es un marcador de riesgo con alto valor predictivo para anomalías cromosómicas, siendo mayor cuando está asociado a otros hallazgos ecográficos anormales. La identificación ecográfica del HQR en el tamizaje prenatal del primer trimestre debería ser indicación para recomendar una prueba diagnóstica para anomalías cromosómicas.

Objective: To evaluate the association of retronucal cystic hygroma (RCH) and fetal chromosomal abnormalities. Methods: Retrospective observational study of 323 first trimester fetuses at risk for chromosomal abnormalities diagnosed by ultrasound between 11 and 13.6 weeks. Results: Of 323 fetuses at risk for chromosomal abnormalities, 132 cases of chromosomal abnormalities were found (40.9%). A total of 145 cases of RCH were identified; chorionic villus biopsy was performed in 64 (56.6%) and amniocentesis in 81 (43.5%); an abnormal karyotype was found in 82 (56.6%). Of 88 fetuses with isolated RCH, 33 (37.5%) had some chromosomal abnormality. In 58 fetuses with RCH associated with other abnormal findings, chromosomal abnormalities were found in 43 fetuses (74.1%) and of these 24 (41.4%) had abnormal ductus venosus flow wave (DVF), 17 (29.3%) had generalized edema, 8 cases (13.8%) with cardiopathy, 7 (12,1%) with absent nasal bone. The predictive values of RCH were sensitivity (S) 62.1%, specificity (Sp) 67%, positive predictive value (PPV) 56.6%, negative predictive value (NPV) 71.9%, p<0.001, OR: 3.3. RCH associated with other abnormal findings were S 52.4%, Sp 76.2%, PPV 76.2%, OR: 3.5, LR+: 2.2, p<0.000. Generalized edema and abnormal ductus venosus had the highest predictive values: PPV 88.2% and 83.3%, respectively. The most frequently found chromosomal abnormalities were T21 (53.7%), monosomy X (18.3%), T18 (15.9%), T13 (6.1%). Conclusions: Retronucal cystic hygroma is a risk marker with high predictive value for chromosomal abnormalities, being higher when associated with other abnormal ultrasound findings. Ultrasonographic identification of RCH in first trimester prenatal screening should be an indication to recommend diagnostic testing for chromosomal abnormalities.

Does Enoxaparin treatment have any effects on the placenta in women with unexplained histories of habitual abortion? A case control study

ABSTRACT BACKGROUND: It is very common to offer low molecular weight heparin (LMWH) medications to women with unexplained habitual abortion, to increase the livebirth rate. Although no benefit from LMWH has been clearly demonstrated, examination of the effects of enoxaparin on placental structure is lacking. OBJECTIVE: To assess placental structural changes in pregnancies treated with enoxaparin, compared with controls. DESIGN AND SETTING: Case-control study in an obstetrics and gynecology unit of a tertiary-level university hospital in Turkey. METHODS: Forty patients who had had term pregnancies and live births but also histories of habitual abortion were recruited for this study. Placentas were sampled using a systematic random sampling method. Tissue samples were obtained, embedded and sectioned for routine histological analyses. Hematoxylin and eosin staining was used. Surface area and length estimates from placental components were evaluated by using Image J. Cell proliferation and apoptosis were also assessed via immunohistochemistry. RESULTS: There were no significant differences between the groups regarding maternal age, abortion rate, birth weight or gestational age. Comparison of the enoxaparin and control groups showed that there were no significant differences in terms of surface area and ratios of placental components. We found that Bcl-2 was generally expressed at high levels in the enoxaparin group, while there was no difference in terms of Ki-67 between the groups. CONCLUSIONS: This study demonstrates that enoxaparin did not show any significant effect on the placental structure of cases that had histories of habitual abortion.

A study of tubal ectopic pregnancy based on the histopathology of fallopian tubes in the age group of 20-35 years

Purpose: Ectopic pregnancy is a life-threatening condition for the mother. Disruptions of the fallopian tube are considered to be important in its pathogenesis. The present study was conducted to observe the histopathology of this dreaded disease which could lead to the development of suitable remedies. Methods: Cases diagnosed with ectopic gestation in the fallopian tube who subsequently underwent salpingectomy were considered for the study. Histopathology of sections from the affected fallopian tubes was studied under the light microscope after staining with H and E. Results: Most cases presented with amenorrhoea, whereas others had dysmenorrhoea, menorrhagia, and menometrorrhagia. Histopathologic findings included the presence of salpingitis (acute and chronic), calcification, sclerosed vessel and. Conclusion: Past history of inflammatory diseases, especially PID plays an important role in the subsequent development of ectopic pregnancy. Its prevention and treatment can lead to a decrease in the incidence of ectopic pregnancy.

First-trimester chorionic villus sampling: genetic analysis of 985 cases / 中华围产医学杂志

Objective@#To investigate the value and safety of first-trimester chorionic villus sampling (CVS) in prenatal diagnosis.@*Methods@#This study retrospectively analyzed the clinical data of 985 cases undergoing CVS and prenatal diagnosis with karyotyping and fluorescence in situ hybridization (FISH) in the Department of Obstetrics and Gynecology of Peking University First Hospital from January 2012 to December 2017. The success rate of cell culture, indications for prenatal diagnosis, karyotyping results, and complications of CVS were described.@*Results@#Among the 985 cases, 970 (98.48%) underwent FISH and 893 (90.66%) received karyotyping, and 878 (89.14%) accepted both. After CVS, the success rate of cell culture was 96.64% (863/893). Abnormal ultrasonographic findings (42.64%, 420/985) were the most common indications for prenatal diagnosis. In this study, 181 cases of chromosomal abnormalities were detected, including numerical and structural abnormalities, accounting for 18.38% of all 985 cases. Those cases with abnormal ultrasonographic images had the highest detection rate of chromosomal abnormalities (31.90%, 134/420), followed by those with adverse pregnant history (11.83%, 20/169) and advanced maternal age (8.21%, 11/134). In addition, there was a discrepancy between karyotyping and FISH results, which might due to 16 cases of placental mosaicism and 13 cases of maternal cell contamination (MCC). Embryonic demises were reported in six cases (0.61%, 6/985), including four with chromosomal numerical abnormalities within four weeks after CVS. No other short- or long-term postoperative complications were found in the rest 979 cases (99.39%).@*Conclusions@#CVS in the first trimester is a safe and reliable invasive method for prenatal diagnosis, which can help to obtain an earlier diagnosis in a certain population such as those with abnormal ultrasonographic findings, thus improve the pertinence and efficiency of prenatal diagnosis. However, the potential influences of placental mosaicism and MCC on the diagnostic results should not be ignored.

First-trimester chorionic villus sampling: genetic analysis of 985 cases / 中华围产医学杂志

Objective To investigate the value and safety of first-trimester chorionic villus sampling (CVS) in prenatal diagnosis.Methods This study retrospectively analyzed the clinical data of 985 cases undergoing CVS and prenatal diagnosis with karyotyping and fluorescence in situ hybridization (FISH) in the Department of Obstetrics and Gynecology of Peking University First Hospital from January 2012 to December 2017.The success rate of cell culture,indications for prenatal diagnosis,karyotyping results,and complications of CVS were described.Results Among the 985 cases,970 (98.48％) underwent FISH and 893 (90.66％) received karyotyping,and 878 (89.14％) accepted both.After CVS,the success rate of cell culture was 96.64％ (863/893).Abnormal ultrasonographic findings (42.64％,420/985) were the most common indications for prenatal diagnosis.In this study,181 cases of chromosomal abnormalities were detected,including numerical and structural abnormalities,accounting for 18.38％ of all 985 cases.Those cases with abnormal ultrasonographic images had the highest detection rate of chromosomal abnormalities (31.90％,134/420),followed by those with adverse pregnant history (11.83％,20/169) and advanced maternal age (8.21％,11/134).In addition,there was a discrepancy between karyotyping and FISH results,which might due to 16 cases of placental mosaicism and 13 cases of maternal cell contamination (MCC).Embryonic demises were reported in six cases (0.61％,6/985),including four with chromosomal numerical abnormalities within four weeks after CVS.No other short-or long-term postoperative complications were found in the rest 979 cases (99.39％).Conclusions CVS in the first trimester is a safe and reliable invasive method for prenatal diagnosis,which can help to obtain an earlier diagnosis in a certain population such as those with abnormal ultrasonographic findings,thus improve the pertinence and efficiency of prenatal diagnosis.However,the potential influences of placental mosaicism and MCC on the diagnostic results should not be ignored.

Morphological features of the human placenta and its free chorionic villi in normal pregnancies and those with diabetes and high blood pressure: literature review / Características morfológicas de la placenta humana y sus vellosidades coriales libres en gestas normales y con diabetes e hipertensión arterial: revisión de la literatura

The most prevalent pathologies during pregnancy, such as hypertension, gestational diabetes mellitus (GDM), and intrauterine growth restriction (IUGR), can determine modifications in macro- and microscopic morphological features of the placenta and its free chorionic villi. In the fetus it may be accompanied by pathological manifestations, with the embryo's future quality of life, and even its viability, at risk. The aim of this work is to perform a review of the morphological alterations that the placenta exhibits in pregnancies with GDM. A search on the topic in the scientific literature and specialized textbooks was carried out. The terms "placenta", "diabetes mellitus gestational" and "gestational diabetes mellitus" were used to define the search. Among the morphological modifications it was found that the placental weight/fetal weight ratio is higher in GDM and is associated mainly with histological changes. The distance between maternal and fetal circulation is increased because of an increase in the chorionic villi on the surface as well as greater thickness of the syncytiotrophoblast basal membrane due to an increased type IV collagen deposition. The stroma between the villi is edematous, which modifies the metabolic and endocrinal function of these placentas. Moreover, the capillary surface is enlarged due to the phenomena of vascular neoformation and a greater penetration of these vessels within the villi. Low oxygen partial pressure (pO2) was detected, which would produce a compensatory hyperplasia of terminal chorionic villi. In GDM the placenta undergoes alterations in its formation, structure, and function. According to the review, these alterations are related to an oxygenation deficiency in the fetus and changes in the transplacental transport of nutrients and other alterations, causing fetal overgrowth by increasing their availability in addition to other consequences to the developing fetus. In the case of high blood pressure during pregnancy, this produces accelerated maturation and rapid aging of the chorionic villi, with the risk of inducing a placental abruption. In addition, placental circulation is reduced by a third, decreasing oxygen saturation in the umbilical vessels and placing the health of the fetus at risk.

Las patologías de la gestación más prevalentes, como hipertensión, diabetes mellitus gestacional (DMG) y restricción del crecimiento uterino, pueden determinar modificaciones en las características morfológicas macro y microscópicas de la placenta y sus vellosidades coriales libres,y en el feto se puede acompañar de manifestaciones patológicas, con riesgo para su calidad de vida futura, e incluso su viabilidad. El objetivo de este trabajo consiste en realizar una revisión acerca de las alteraciones morfológicas que presenta la placenta en gestaciones con DMG. Se llevó a cabo una búsqueda sobre la temática en literatura científica y libros de texto especializados. Se utilizaron los términos "placenta", "diabetes mellitus gestacional" y "gestational diabetes mellitus" para orientar la búsqueda. Entre las modificaciones morfológicas se encontró que la relación peso placentario/peso fetal está aumentado en la DMG y se asocia principalmente a cambios histológicos. La distancia entre la circulación materna y la fetal está aumentada debido a un aumento de la superficie entre las vellosidades coriales, así como al mayor grosor de la membrana basal del sincitiotrofoblasto por un depósito elevado de colágeno tipo IV. El estroma entre las vellosidades se encuentra edematoso lo que va a modificar la función metabólica y endocrina de estas placentas. También hay aumento de la superficie capilar por fenómenos de neoformación vascular y una mayor penetración de estos vasos dentro de las vellosidades. Se detectó baja presión parcial de oxígeno (pO2), que produciría una hiperplasia compensatoria de vellosidades coriónicas terminales. En la DMG la placenta experimenta alteraciones en su formación, estructura y función. Según lo revisado, estas alteraciones están relacionadas con déficit en la oxigenación del feto, cambios en el transporte transplacentario de los nutrientes y otras alteraciones, ocasionando sobrecrecimiento fetal por aumento de su disponibilidad, entre otras consecuencias al feto en desarrollo. Y en el caso de la hipertensión arterial durante la gestación produce una maduración acelerada y envejecimiento rápido de las vellosidades coriales, con el riesgo de inducir un desprendimiento prematuro de placenta. Además se reduce la circulación placentaria en un tercio, disminuyendo la saturación de oxígeno en los vasos umbilicales del, poniendo en riesgo la salud del feto.

Aspectos morfocuantitativos de las vellosidades coriales libres en gestas normales, con diabetes, hipertensión arterial y restricción del crecimiento intrauterino / Morphoquantitative characteristics of free corial vellosities in normal births, with diabetes, hypertension and restriction of intrauterine growth

Las patologías de la gestación como la hipertensión, diabetes mellitus gestacional, o restricción del crecimiento intrauterino, pueden determinar modificaciones en las características morfológicas macro y microscópicas de la placenta y sus vellosidades coriales libres, y en el feto se puede acompañar de manifestaciones patológicas, con riesgo para su calidad de vida futura, e incluso su viabilidad. El objetivo de este trabajo consistió en describir aspectos morfométricos e histológicos de las vellosidades coriales libres en gestas normales, con diabetes e hipertensión arterial. Se utilizaron 30 placentas humanas y fueron separadas, según presencia o ausencia de patologías en el embarazo, en tres grupos: Normal (N), Síndrome Hipertensivo del Embarazo (SHE), Diabetes (D) y Restricción del Crecimiento Intrauterino (RCIU). Se usó ficha para registrar peso placentario y del recién nacido Todas las muestras fueron fijadas en formalina tamponada al 10 %. De cada una fueron extraídas 5 muestras, obteniendo 25 cortes por cada placenta. Posteriormente, fueron teñidas con H&E, Azul Alcián y Tricrómico de Masson. Además, se efectuó el análisis histológico y morfométrico (ImageJ®) de las vellosidades coriales. El análisis estadístico fue realizado utilizando ANOVA. Entre los cambios morfológicos, se encontró una relación peso placentario/peso del recién nacido aumentada en la Diabetes Mellitus Gestacional asociada a cambios histológicos. No hubo cambios morfométricos significativos entre placentas N, SHE y D. Hubo un aumento en el número de vasos coriales en placentas del grupo D (P < 0,05) y de la superficie entre las vellosidades coriales. En el grupo SHE hubo aumento moderado de nudos sinciciales y presencia de fibrina en el estroma. Las placentas con Diabetes Mellitus Gestacional experimentan alteraciones histológicas, como consecuencia de cambios estructurales y funcionales. Además, el aumento de vasos sanguíneos en placentas con diabetes se produce por neoformación vascular y mayor penetración de vasos sanguíneos dentro de las vellosidades. En el caso del SHE las alteraciones placentarias se relacionan con la gravedad de la enfermedad.

Gestational pathologies such as hypertension, gestational diabetes mellitus and restriction of intrauterine growth can determine changes in the macro and microscopic morphological characteristics of the placenta and its free chorionic villi. In the fetus it can be accompanied by pathological manifestations with risk to its viability and future quality of life. The aim of this work was to describe morphometric and histological aspects of free chorionic villi in normal pregnancies associated with diabetes, hypertension and restriction of intrauterine growth. Thirty human placentas were used and were separated into three groups: Normal (N), Hypertensive Pregnancy Syndrome (SHE), Diabetes (D), and Restriction of Intrauterine Growth (RIG) according to evident pathologies or absence thereof during pregnancy. Tab was used to record placental and newborn weight. All samples were fixed in 10 % buffered formalin. From each, 5 samples were extracted, obtaining 25 cuts for each placenta. Subsequently, they were stained with H & E, Alcian Blue and Masson's Trichrome. In addition, histological and morphometric analysis (ImageJ®) of the chorion villus was carried out. Statistical analysis was performed using ANOVA. Among the morphological changes, an increased placental weight / weight ratio of the newborn was found in Gestational Diabetes Mellitus associated with histological changes. There were no significant morphometric changes between placentas N, SHE and D. There was an increase in the number of corial vessels in placentas of group D (P <0.05) and of the surface between the chorion villi. In the SHE group there was a moderate increase in syncytial nodes and presence of fibrin in the stroma. Placentas with Gestational Diabetes Mellitus experience histological alterations, as a consequence of structural and functional changes. In addition, the increase of blood vessels in placentas D is produced by vascular neoformation and increased penetration of blood vessels into the villi. In the case of SHE, placental alterations are related to the severity of the disease.

Placental osseous metaplasia associated with abortion in a mare: case report / Metaplasia óssea placentária associada a aborto em uma égua: relato de caso

The aim of this report is to describe a case of marked osseous metaplasia in the placenta associated with abortion in a mare. A 19-year-old Campolina mare with a history of multiple parturitions and absence of reproductive failure, aborted a fetus with approximately six months of gestation. There were no gross changes in the fetus and the placenta. Microscopically, there was multifocal replacement of fetal connective mesenchyme of the chorionic villi with well differentiated and partially mineralized osseous tissue (confirmed by von Kossa staining). To further characterize the collagenous component of the lesion, sections of the placenta were stained with Masson's trichrome and Picrosirius red. Osseous tissue deposition had abundance of type I collagen. To the best of our knowledge, this is the first report of osseous metaplasia in the placenta of a mare associated with abortion at mid gestation, presumably due to placentary insufficiency.(AU)

O objetivo deste relato é descrever um caso de metaplasia óssea em placenta equina, associada a aborto. Uma égua da raça Campolina, com aproximadamente 19 anos de idade, após múltiplas gestações e sem histórico de alterações reprodutivas, abortou feto com idade aproximada de seis meses. Não foram observadas alterações macroscópicas no feto e na placenta. Microscopicamente, havia substituição do mesênquima de vilosidades coriônicas por tecido ósseo bem diferenciado e parcialmente mineralizado (confirmada pela coloração de von Kossa). Para caracterização do componente colagenoso, foram realizadas colorações de tricrômico de Masson e picrosirius red. O tecido ósseo tinha predominância de colágeno do tipo I. Este é o primeiro relato de metaplasia óssea na placenta equina, associada a aborto no terço médio da gestação, presumivelmente devido à insuficiência placentária.(AU)

Chorionic villus cell culture and karyotype analysis in 1983 cases of spontaneous miscarriage / 中华妇产科杂志

Objective To investigate the relationship between spontaneous miscarriage and embryonic chromosome abnormalities,and to evaluate the clinical application of karyotype analysis by chorionic villus cell culture. Methods The chorionic villus karyotype of 1983 cases of miscarriage from January 2010 to July 2016 in Guangzhou Women and Children′ s Mecical Center were analyzed retrospectively. The miscarried chorionic villi were obtained by curettage under sterilized condition. The chromosome specimens were prepared after chorionic villus cell culture. Karyotype analysis was performed by G-banding technique. Results In the 1983 samples, successful karyotype analysis was performed in 1770 cases, with the successful rate of 89.98%. Chromosomal abnormalities were found in 1038 cases (58.64%,1038/1770). Chromosomal structural abnormalities were found in 37 cases. The numeral abnormalities were more common than structural abnormalities, and most of the numeral abnormalities were aneupoidies. In turn, they were trisomy 16, 45,X, trisomy 22, trisomy 2, trisomy 21, trisomy 15. The most common structural abnormality was balanced translocation, including Robersonian translocation. Female embryoes accounted for 61.02%(1080/1770) miscarriages and for 57.4%(596/1770) of chromosomal abnormalities, while male embroyes acoounted for 61.02%(1080/1770),57.4%(596/1770)respectively. The proportion of female embryoes was higher than male embryoes. The median age of the patients was 30 years old(16-46 years old). As the maternal age increased, the proportion chromosomal abnormalities increased. The incidence of chromosomal abnormalities in the advanced age group (≥35 years) was 68.38%(240/351), which was significantly higher than that in the younger group (56.24% ,798/1419; χ2=17.10, P<0.01). Conclusions Embryonic chromosomal abnormalities are the most common cause of early spontaneous miscarriage. The abnormalities centralize in some karyotypes. There is certain relationship between maternal age and the incidence of miscarriage, as well as the embryonic gender. Chorionic villus cell culture and karyotype analysis are helpful in finding the cause of miscarriage and counsel the patients.

Chromosome abnormality analysis of 7 036 chorionic villi inspontaneous miscarriage cases by multiplex ligation-dependent probe amplification / 中华检验医学杂志

Objective To investigate chromosomal aneuploidy of chorionic villior tissue from embryo arrestor spontaneous miscarriage by the method of multiplex ligation-dependent probe amplification(MLPA), and to provide genetic etiology data for recurrent spontaneous abortion(RSA) and embryo arrest.Methods The clinical retrospective analysis was used during November 2013 to October 2016 in Shenzhen Maternity and Child Healthcare Hospital.The genomic DNA of 7 036 chorionic villi or tissue samples from embryo arrestor pregnancy loss were extracted by resin and Proteinase K, following detected by multiplex ligation-dependent probe amplification, and then analyzed by descriptive and frequency statistic using SPSS17.0 software.Results Totally 2 984 samples (42.41%) with chromosomal aneuploidy were detected, of which, the top five were trisomy 16(826)11.74%, monosomy X (Turner,401)5.70%, trisomy 22(247)3.51%, trisomy 13(149)2.12% and trisomy 21(144)2.05%.Aneuploidy 19 or 17 were rare,just 1 and 3 cases respectively.The aneuploidy of chromosome 1 was not discovered yet.There were 161 samples (2.28%) for segmental deletion and/or duplication cases.Besides of the monosomy X(Turner,401), monsomy 21 was also high frequency(17,0.24%).In addition, 56 samples(0.80%)were double trisomic,while 2 samples(0.03%)were tris-trisomy.Thirteen samples(0.18%)were heterosome trisomy,and five samples(0.07%)were Turner combined trisomy.Fifteen samples(0.21%) were unbalanced translocation of the arm,while 20 samples(0.28%) were nonhomologous chromosome translocation.Conclusions Trisome and monosome were the majority of chromosome abnormality (above 90%), as well as the main cause of spontaneous miscarriage.Meanwhile the chromosome aneuploidy (including segment deletion or duplication) could be screened by MLPA quickly, thoroughly and efficiently, further more discover the carrier of balanced translocation in couples and provide valuable genetic information for next pregnancy.

Roee of long non-coding RNAs maternally imprinted genes 3 in human villi development / 第二军医大学学报

Objective To study the effect of long non-coding RNAs (lncRNAs) maternally imprinted genes 3 (MEG3) on human abortion vilii development and to explore the related molecular mechanisms. Methods We collected the vilii samples from 15 spontaneous abortion (SA) and 15 induced abortion (IA) patients. Immunohistochemistry was applied to detect the expressions of apoptosis factor Bax and apoptosis inhibitory factor Bcl-2 in vilii samples. Real-time quantitative polymerase chain reaction (qPCR) was used to analyze the levels of MEG3 of vilii samples. Overexpression of MEG3 in human trophoblast cell line HTR-8/SVneo was identified by qPCR; the invasion ability of HTR-8/SVneo cells was examined by matrigel invasion assay in MEG3 overexpression and control groups. Results Immunohistochemistry showed that the expression of Bax in IA group was lower than that in SA group, while the expression of Bcl-2 was higher (P<0.01). The level of MEG3 in IA group was significantly higher than that in SA group (P<0.01). The expression of MEG3 was obviously increased and invasion ability was inhibited in MEG3 overexpressed HTR-8/SVneo cells (P<0.01). Conclusion LncRNAs MEG3 may regulate the apoptosis and invasive ability of bizarre trophoblastic cells and influence on the development of human villi.

Application of copy number variation analysis based on next-generation sequencing in the genetic analysis of missed abortion chorionic villi / 中华妇产科杂志

Objective To investigate the value of copy number variation analysis based on next-generation sequencing (NGS-CNVA) in the genetic analysis of missed abortion chorionic villi. Methods From August 2012 to May 2014, chorionic villi from 74 cases of missed abortion at 6-13 gestational weeks in Haidian Maternal and Child Health Hospital were collected and analyzed by karyotype analysis and NGS-CNVA. The results of the two methods were compared. Results (1) Karyotype analysis was carried out for the villi from the 74 missed abortion patients. Thirty cases were euploid, 26 cases were aneuploid, while 18 cases had structural abnormalities. The resolution of the karyotyping was 320 bands and the average report time was 22 days. (2) All of the 74 samples obtained NGS-CNVA results and the report time was 7-10 days. (3) The NGS-CNVA results of 56 cases were consistent with karyotype. Among them, 28 cases (28/56, 50%) had no copy number variants (CNV), and 19 cases (19/56, 34%)had CNV between 1 Mb and 10 Mb. 9 cases (9/56,16%) had CNV≥10 Mb found by NGS-CNVA, but not found by karyotyping. (4) According to the results of NGS-CNVA, karyotype were reviewed. The reviewed results found 7 cases with CNV<10 Mb and 3 cases with CNV≥10 Mb in 30 cases which got normal karyotype results at the first analysis. (5) Among the 18 cases of structural abnormalities, 6 cases were Robertsonian translocation. Sequencing technology could confirm the specific area of chromosome deletion/duplication in 8 cases, but could not locate them. Conclusions NGS-CNVA has lower failure rate, higher resolution, lower specimen requirement and shorter report time than karyotype analysis when used for the genetic analysis of missed chorionic villi . NGS-CNVA could be a useful genetic analysis method for the missed abortion villi.

Quantitative fluorescent polymerase chain reaction for rapid prenatal diagnosis of fetal aneuploidies in chorionic villus sampling in a single institution

OBJECTIVE: To validate quantitative fluorescent polymerase chain reaction (QF-PCR) via chorionic villus sampling (CVS) for the diagnosis of fetal aneuploidies. METHODS: We retrospectively reviewed the medical records of consecutive pregnant women who had undergone CVS at Cheil General Hospital between December 2009 and June 2014. Only cases with reported QF-PCR before long-term culture (LTC) for conventional cytogenetic analysis were included, and the results of these two methods were compared. RESULTS: A total of 383 pregnant women underwent QF-PCR and LTC via CVS during the study period and 403 CVS specimens were collected. The indications of CVS were as follows: abnormal first-trimester ultrasonographic findings, including increased fetal nuchal translucency (85.1%), advanced maternal age (6.8%), previous history of fetal anomalies (4.2%), and positive dual test results for trisomy 21 (3.9%). The results of QF-PCR via CVS were as follows: 76 (18.9%) cases were identified as trisomy 21 (36 cases), 18 (33 cases), or 13 (seven cases), and 4 (1.0%) cases were suspected to be mosaicism. All results of common autosomal trisomies by QF-PCR were consistent with those of LTC and there were no false-positive findings. Four cases suspected as mosaicism in QF-PCR were confirmed as non-mosaic trisomies of trisomy 21 (one case) or trisomy 18 (three cases) in LTC. CONCLUSION: QF-PCR via CVS has the advantage of rapid prenatal screening at an earlier stage of pregnancy for common chromosomal trisomies and thus can reduce the anxiety of parents. In particular, it can be helpful for pregnant women with increased fetal nuchal translucency or abnormal first-trimester ultrasonographic findings.

Pulmonary Placental Transmogrification Presenting as a Small Lung Nodule / 대한내과학회지

Pulmonary placental transmogrification (PT) is a rare lung disease that takes on the histologic appearance of placental chorionic villi. We herein report a case of PT in a 66-year-old woman who presented with a single nodule on chest radiography performed during a routine health examination. She had no complaints of any symptoms. Chest radiography showed a focal ill-defined nodular opacity in the right lower lobe; chest computed tomography revealed a 17-mm lobulated, focal irregular mass with fissural retraction in the right lower lobe, suggestive of lung cancer. Pathology of a percutaneous needle aspiration biopsy revealed papillary structures resembling placental villi. These were lined by cytotrophoblast-like cells and syncytiotrophoblasts. This characteristic pathologic finding led to a diagnosis of PT. PT of the lung is found mainly in bullous or cystic lesions. However, this patient presented with a single nodule on chest radiography.

EXERCISE EFFECT ON PLACENTAL COMPONENTS: SYSTEMATIC REVIEW AND META-ANALYSIS / EFEITO DO EXERCÍCIO NOS COMPONENTES PLACENTÁRIOS: REVISÃO SISTEMÁTICA E META-ANÁLISE / EFECTO DEL EJERCICIO EN COMPONENTES PLACENTARIOS: REVISIÓN SISTEMÁTICA Y META-ANÁLISIS

Physical exercise has been demonstrated a positive effect on many pregnancy outcomes. Placental components are important for exchanging oxygen and nutrients between mother and fetus. This study aimed to systematic review and meta-analysis whether physical exercise could induce a morphological adjustment on placenta components. We systematically searched PubMed database until October 30th, 2014. We included randomized and non-randomized studies with control group, which aimed to investigate the effect of the physical exercise (water, aerobic and resistance) on placental components (placental weight and volume, villous volume and vascular volume, intervillous space and stem villi). Initially, we identified 222 articles, of which 9 articles were used for full text analysis. Finally, four articles were included in the systematic review and meta-analysis. Meta-analysis demonstrated that exercise appeared to affect placental weight (95% CI, 39.73g [4.66-74.80]), placental volume (95% CI, 47.11 cm3 [37.99-56.23]), intervillous space (95% CI, 16.76 cm3 [12.66-20.68]), villous volume (95% CI, 46.01 cm3 [40.21-51.81]), villous vascular volume (95% CI, 15.95 cm3 [7.83-24.07]) and stem villi (95% CI, 6.00 cm3[4.25-7.75]). Apparently, physical exercise has a positive effect on placental components. However, this conclusion is based on a limited number of studies. Clearly, it stands the necessity of larger samples and better methodology quality.

O exercício físico tem demonstrado efeito positivo nos muitos desfechos da gravidez. Componentes da placenta são importantes para a troca de oxigênio e nutrientes entre mãe e feto. O objetivo deste estudo foi revisar de forma sistemática e realizar uma meta-análise para verificar se o exercício físico pode induzir um ajuste morfológico nos componentes da placenta. A pesquisa foi feita sistematicamente no banco de dados PubMed até 30 de outubro de 2014. Foram incluídos estudos randomizados e não-randomizados com grupo controle, que tiveram como objetivo investigar o efeito do exercício físico (água, aeróbico e resistência) em componentes da placenta (peso e volume placentário, volume vascular e volume viloso, espaço interviloso e troncos vilosos). Inicialmente, identificamos 222 artigos, dos quais nove artigos foram utilizados para a análise de texto completo. Por último, quatro artigos foram incluídos na revisão sistemática e meta-análise. A meta-análise demostrou que o exercício parece afetar o peso da placenta (95% IC, 39,73g [4,66-74,80]), o volume placentário (IC 95%, 47,11 cm3 [37,99-56,23]), o espaço interviloso (IC 95%, 16,76 cm3 [12,66-20,68]), o volume viloso (IC 95%, 46,01 cm3 [40,21-51,81]), o volume vascular viloso (95% IC, 15,95 cm3 [7,83-24,07]) e o tronco viloso (95% IC, 6,00 cm3[4,25-7,75]). Aparentemente, o exercício físico tem efeito positivo sobre os componentes da placenta. No entanto, esta conclusão é baseada em um número limitado de estudos. Claramente, destaca-se a necessidade de amostras maiores e melhor qualidade de metodologia.

El ejercicio físico ha demostrado efecto positivo en los muchos resultados del embarazo. Los componentes de la placenta son importantes para el intercambio de oxígeno y nutrientes entre la madre y el feto. El objetivo de este estudio fue revisar de forma sistemática y realizar un meta-análisis para comprobar si el ejercicio físico puede inducir la adaptación morfológica en los componentes de la placenta. La encuesta se realizó sistemáticamente en la base de datos PubMed hasta 30 de octubre de 2014. Se incluyeron ensayos aleatorios y no aleatorizados con grupo control, que tenían como objetivo investigar el efecto del ejercicio físico (agua, aeróbico y de resistencia) en los componentes de la placenta (peso y volumen de la placenta, el volumen vascular y volumen velloso, espacio intervelloso y troncos vellosos). Inicialmente, se identificaron 222 artículos, de los cuales nueve artículos fueron utilizados para el análisis de texto completo. Finalmente, cuatro artículos fueron incluidos en la revisión sistemática y meta-análisis. El meta-análisis mostró que el ejercicio parece afectar el peso de la placenta (IC del 95%, 39,73g [4,66-74,80]), el volumen de la placenta (IC del 95%, 47,11 cm3 [37,99-56,23]), el espacio intervelloso (IC del 95%, 16,76 cm3 [12,66-20,68]), el volumen velloso (IC del 95%, 46,01 cm3 [40,21-51,81]), el volumen vascular velloso (95 IC%, 15,95 cm3 [7,83-24,07]) y el tronco velloso (IC 95%, 6,00 cm3 [4,25-7,75]). Aparentemente, el ejercicio físico tiene un efecto positivo sobre los componentes de la placenta. Sin embargo, esta conclusión se basa en un número limitado de estudios. Claramente, hay una necesidad para mayores tamaños de muestra y una mejor calidad de la metodología.

Prenatal diagnosis of single gene disorders and role of multidisciplinary cooperative mode / 中华围产医学杂志

Objective To evaluate the trend in prenatal diagnosis of single gene disorders (SGD) and role ofmultidisciplinary cooperative mode.Methods In January l,2012,amultidisciplinarycooperativemode for SGD diagnosis was established in the Peking University First Hospital,involving Departments of Obstetrics,Pediatrics,Neurology,Dermatology and Central Laboratory.For each pregnant woman with a family history of SGD for prenatal diagnosis,propositus should be diagnosed in the relevant departments,and then further diagnosed,managed and followed up by the Obstetrics Department.Up to December 31,2014,of 6 681 women for prenatal diagnosis,279 women had a family history of SGD:76 of them received chorionic villus sampling (CVS) at 11-14 gestational weeks,and 203 received amniocentesis (AC) at 16-22 gestational weeks.The trend in SGD diagnosis and the safety of CVS and AC were analyzed using Chi-square test.Results The proportion of SGD family history in AC group was 3.2％ (203/6 355),which stayed stable with 2.3％ (47/2 054) in 2012,3.9％ (78/2 023) in 2013 and 3.4％ (78/2 278) in 2014,and there was no significant difference between 2013 and 2014 (x2=0.571,P=0.463).In CVS group,the proportion of SGD family history was 23.3％ (76/326),showing an increasing trend with 18.2％ (8/44) in 2012,17.6％ (19/108) in 2013 and 28.2％ (49/174) in 2014,and there were significant differences between 2013 and 2014 (x2=4.067,P=0.046).The proportion of SGD family history in CVS group was higher than in AC group in year 2012,2013 and 2014 (x2＝42.626,44.531 and 201.400,all P=0.000).Among the 279 cases of SGD family history,no complications and adverse outcome were observed except an intra-uterine fetal death occurring 6 months after CVS in one woman,but 3 fetuses were found to have chromosome anomalies with one trisomy 18,one 45,X,and one mosaicism of 45,X/46,XY which was determined to be normal by AC.Conclusions SGD family history is one of the important indicators in prenatal diagnosis,and CVS is feasible for prenatal diagnosis of SGD family history as early as in the first trimester.Multidisciplinary cooperative mode is helpful in SGD family history diagnosis.

Detection of chromosome abnormality by next-generation sequencing technology of miscarried embryo in the first-trimester / 天津医药

Objective To investigate the clinical values of next-generation sequencing (NGS) technology in diagnosis of miscarried chorionic villi genetic disorders. Methods Patients who underwent miscarriage (n=87) were enrolled in this study. Among all patients, 32 cases were of recurrent miscarrage and 55 cases were of sporadic miscarriage. In all collected patients, 35 women were 35 years or older while other 52 women were less than 35 years old. Positive detection rate and the abnormal detection rate were compared between these two methods. Chromosomes abnormal rates were also compared among different types of miscarrage and different ages. All aborted villi tissue were analyzed by NGS of whole genome and G-band?ing karyotype. Results The successful detection rate of chorionic villi by NGS (100.00%) was higher than that of G-band?ing karyotype (74.71%), and the detection rate of abnormal chorionic villi by NGS (58.62%) was also higher than that of G-banding karyotype (50.77%). Three cases of chromosome structure anomaly were found in those 51 chromosome anomalies (5.88%). Other 48 cases of chromosome anomalies were aneuploidy anomalies (94.12%) include 39 cases of trisomy, 2 cases of double trisomy and 1 case of triple trisomy and 6 cases of monomer. On the other hand, 32 cases of chromosome aneuploi?dy anomalies were found in 33 chromosome anomalies by G-banding karyotype, which include 24 cases of trisomy, 2 cases of double trisomy, 1 case of triple trisomy, 5 cases of monomer and 1 case of chromosome structure anomaly. Most NGS re?sults (n=64) were in agreement with G-banding karyotype but with 1 case of discrepancy. Chromosomal abnormality rate de?tected by NGS in sporadic miscarrage group and recurrent spontaneous miscarrage group were 60.00%and 56.25%respective?ly. There was no significant difference (P>0.05). Chromosomal abnormality rate picked by NGS in women aged≥35 years old (71.43%) was higher than that in women<35 years old (50.00%) with statistically significant difference (P<0.05). Conclu?sion NGS technology showed highly accuracy in detecting chromosomal abnomality from villi tissue. Therefore, it could help to detect genetic disorders of miscarrage. It is useful to determine the reasons of miscarrage and guide the next pregnancy.

Study of Trophoblasts and Histological Changes of Fallopian Tube in Tubal Pregnancy and Anatomical Considerations for Its Early Rupture.

Fertilisation takes place in the lumen of fallopian tube, from where, aided by the ciliated columnar epithelium of the tube, the fertilised ovum makes its way into uterine cavity and the implantation occurs. The passage of fertilised ovum into uterine cavity is delayed or obstructed by developmental, mechanical or other defects which lead to tubal gestation. The incidence varies from 1 in 300 to 1 in 150 pregnancies and it contributes significantly to the maternal mortality and morbidity. Early diagnosis and therapy has helped to reduce the maternal death due to ectopic pregnancy. However, study on histological changes of early ectopic pregnancy are rather scarce and therefore, the present study was conducted on 25 patients of ectopic pregnancy specimens observed for the mode and extent of invasion of chorionic villi, and the histological changes in wall of the fallopian tubes to evaluate the causes of early tubal rupture as well as estimation of gestational age by the study of chorionic villi.

Expression and regulatory mechanism of microRNA-155 in the villi of patients with unexplained recurrent spontaneous abortion patients / 中华妇产科杂志

Objective To study the expression and the mechanism of miR-155in the villi of patients with unexplained recurrent spontaneous abortion (URSA).Methods The expression of miR-155 in the villi of 36 cases with URSA (URSA group) and 25 women with normal early pregnancy (control group) were detected by stem-loop real-time reverse transcription (RT) qPCR.Expression of hypoxia inducible factor-1 (HIF-1α),vascular endothelial cell growth factor(VEGF) and micro lymphatic vessel density (MVD) in the villi of were measured by immnohistochemical staining among two groups.Results (1) miR-155 expression:the mean miR-155 expression were 1.456 (0.489,2.459) in URSA group and 2.833 (1.740,3.794) in control group,which reached statistical difference (P ＜0.05).The mean expression of miR-155 of 1.683 (0.902,2.459) in URSA group with abortion times (≤ 3) was significantly higher than 1.229 (0.489,1.719) in URSA group with more than 4 times abortion (P ＜ 0.05).(2) Indexes:the expression of HIF-1α,VEGF and MVD value were 121 ± 12,134 ± 12,36 ± 6 in URSA group and 99 ± 10,109 ± 10,28 ±4 in control group,which reached statistical difference(P ＜ 0.01).The expression of HIF-1α,VEGF and MVD value of 119 ± 12,134 ± 12,35 ± 5 in URSA group with less than 3 times abortion was significantly lower than 128 ± 12,138 ± 12,43 ± 6 in URSA group with more than 4 times abortion (P ＜ 0.01).Conclusions The expression of miR-155 and HIF-1α is topically stimulated by oxygen signal.HIF-1α adjusts the transcription and translation of VEGF,which together involved in placental trophoblast invasion and placental angiogenesis.The low expression of miR-155 could interfere with expression of HIF-1α and VEGF,which might be involved in villous vascular dysplasia in URSA.