Missed abortion in the 11-21-week period: Fetal autopsy and placental histopathological analysis of 794 cases.

INTRODUCTION: Missed abortion (MA) is a type of miscarriage with multiple etiological factors that refers to fetal death with a failure of the retained intrauterine product of conception to be discharged spontaneously. Currently fetal death in missed abortion is categorized according to three main causes: Fetal, placental, and maternal factors. The aim of the current study was to contribute and increase knowledge in clinical practice of late first and second trimester MA (Gestational age: week 11 + 0 - week 20 + 6). MATERIAL AND METHODS: This retrospective case series study includes 794 cases of fetuses and matching placentas sent to the Section of Perinatal Pathology, Department of Pathology, Karolinska Hospital between 2003 and 2019 from five different gynecology departments in the Stockholm region, Sweden. RESULTS: The cases were divided into two groups according to gestational length; gestational week 11 + 0-14 + 6 (group A) and 15 + 0-20 + 6 (group B) respectively, and comparisons were made between groups. Fetal growth restriction and placental pathology were more common in late MA, but number of cases with malformation were higher in early MA. Cord pathology was seen in approximately 40 % of the cases and equally distributed in the gestational weeks included. DISCUSSION: Fetal growth restriction and placental pathology were more common in late second trimester MA. This might demonstrate an early placental dysfunction affecting fetal growth and may be associated to maternal comorbidity such as autoimmune disease and cardiovascular disease. It is advisable to investigate maternal factors more closely after late second trimester MA before a future pregnancy. The risk for recurrent MA is believed to be low in cases of significant cord pathology. CONCLUSION: Cord complications were over-represented in missed abortion suggesting a probable etiopathogenetic link to fetal demise in this condition.

Expression of HLA-G and KIR2DL4 receptor in chorionic villous in missed abortion.

OBJECTIVE: Human leukocyte antigen-G (HLA-G) is a molecule that was first known to confer protection to the fetus from destruction by the immune system of its mother. HLA-G expression is mainly restricted to the fetal-maternal interface on the extravillous cytotrophoblast, placenta, amnion.Methods: The purpose of this study is to investigate the HLA-G and KIR2DL4 expression in chorionic villous among 2 groups with missed abortion: group 1 - 27cases with normal karyotype and group 2 - 22 with fetal polyploidy. Criteria of inclusion: abortive material from two groups of women with missed abortion; 6-12 weeks gestational age, singleton pregnancy, cytogenetic of chorionic villous was obligatory - normal fetal karyotype and polyploidy of fetus.Results: During IHC investigations the average relative area of HLA-G expression in trophoblast was counted (in 1st group 33.9 ± 3.5 and in 2nd group 38.6 ± 2.8). Expression of HLA-G the most verified in extravillous chorion stroma. The average relative area of KIR2DL4 receptor was not statistically different among two groups (31.6 ± 2.4 and 32.2 ± 1.7). CONCLUSIONS: These results suggest the role of HLA-G for the progression in early reproductive losses. Low expression of HLA-G is associated with pregnancy complications and can be one of the reasons for spontaneous abortion.

Distinct mRNA and long non-coding RNA expression profiles of decidual natural killer cells in patients with early missed abortion.

Early non-chromosome-related missed abortion (MA) is commonly associated with an altered immunological environment during pregnancy. Human decidual natural killer (dNK) cells, the most abundant lymphocyte population within the first-trimester maternal-fetal interface, are vital maternal regulators of immune tolerance mediating successful embryo implantation and placentation. Previous studies have shown that dNK cells may play a role in MA. However, the gene expression status and specific altered manifestations of dNK cells in patients with early MA remain largely unknown. Here, we show that MA dNK cells have distinct mRNA and lncRNA expression profiles through RNA sequencing, with a total of 276 mRNAs and 67 lncRNAs being differentially expressed compared with controls. Protein-protein interaction analysis of differentially expressed mRNAs was performed to identify hub genes and key modules. An lncRNA-mRNA regulatory network characterized by the small-world property was constructed to reveal the regulation of mRNA transcription by differential hub lncRNAs. Functional annotation of differentially expressed mRNAs and lncRNAs was performed to disclose their potential roles in MA pathogenesis. Our data highlight several enriched biological processes (immune response, inflammatory response, cell adhesion, and extracellular matrix [ECM] organization) and signaling pathways (cytokine-cytokine receptor interaction, ECM-receptor interaction, Toll-like receptor signaling pathway, and phosphatidylinositol signaling system) that may influence MA. This study is the first to demonstrate the involvement of altered mRNA and lncRNA expression profiles in the dNK cell pathogenesis of early MA, facilitating a better understanding of the underlying molecular mechanisms and the development of novel MA therapeutic strategies targeting key mRNAs and lncRNAs.

Comparison of the diagnostic value of histopathological examinations of miscarriage products after pharmacological induction of miscarriage and curettage.

OBJECTIVES: For early miscarriage (pregnancy loss ≤ 12 weeks of gestation), two types of therapeutic treatment are offered (pharmacotherapy and curettage of the uterine cavity) depending on the presence and severity of clinical symptoms as well as patient choice. Our study aimed to assess the diagnostic value of the results of histopathological examinations of miscarriage products in relation to the administered treatments. MATERIAL AND METHODS: 850 medical records from patients diagnosed with missed miscarriage or empty gestational sac were analyzed retrospectively. Patients underwent surgical treatment or pharmacotherapy. Inefficacy of pharmacotherapy resulted in subsequent curettage. The results of histopathology were evaluated for their diagnostic value and classified: subgroup 1 - high value specimen (the studied specimen included fetal tissues, and villi), and subgroup 2 - no-diagnosis (the studied specimen included maternal tissues, autolyzed tissues, blood clots). Data were compared with chi-squared test. Differences was considered significant at p < 0.05. RESULTS: 1128 histopathological test results were analyzed; 569 (50.4%) were obtained during pharmacotherapy and 559 (49.6%) after curettage; out of the latter 497 after the initial pharmacotherapy and 62 after surgery. In the pharmacotherapy group, high value specimens comprised 231 cases (40.59%) while no diagnosis was obtained in 338 cases (59.4%). Considering specimens obtained in the course curettage, high value specimens were found in 364 cases (65.1%) while results that did not allow a diagnosis to be made were found in 195 cases (34.9%). CONCLUSIONS: Tissue specimens of high diagnostic value are obtained significantly more often during surgical treatment of miscarriage than during pharmacotherapy.

Mast cell involvement in human cervical ripening.

OBJECTIVE: Cervical ripening resembles an inflammatory process in many aspects, involving invasion of inflammatory cells, collagen breakdown and remodelling of the extracellular matrix. Mast cells produce a variety of inflammatory agents and are attributed a functional role in cervical ripening. The aim of this study was to examine if cervical mast cells are increased in number and stimulated during pregnancy. STUDY DESIGN: Cervical biopsies were obtained with a biopsy needle prior to surgical termination of pregnancy in the first trimester, surgery for first-trimester miscarriage, elective caesarean section, and benign gynaecological surgery in non-pregnant women. After fixation, semithin sections were prepared and stained with toluidine blue. The number of mast cells was counted under a light microscope and their secretory activity was scored (0.5-4) according to specified criteria and further visualised with electron microscopy. For pairwise comparison between groups Fisher's nonparametric permutation test was used. RESULTS: The number of mast cells was increased from 3.4 ± 1.65 mast cells per 10 visual fields in non-pregnant women to 7.70 ± 0.35 per 10 visual fields in first trimester control women (p < 0.05). The highest number of mast cells was observed at term with 10.8 ± 2.1 per 10 visual fields, a number that was significantly higher than in first trimester control women (p < 0.05). At term mast cell activity scores were 3.39 ± 0.37 compared with 2.69 ± 0.27 in control first trimester women and 2.21 ± 0.86 in women with missed miscarriage (p < 0.05). The percentage of mast cells with activity score 4 was significantly higher at term compared with in the first trimester. Free mast cell granules were predominantly observed in areas with disorganized collagen fibres. CONCLUSION: The findings confirm that an increased influx of mast cells to the cervix occurs during pregnancy. The stimulated mast cell secretory activity in conditions associated with cervical tissue remodelling, such as term pregnancy and symptomatic miscarriage, provides further evidence that mast cells play a physiological role in cervical ripening.

Effect of assisted reproductive technology on the molecular karyotype of missed abortion tissues.

Missed abortion is one of the common complications of assisted reproductive technology (ART). Genetic abnormality is the most important factor. However, the effect of ART on the molecular karyotype of products of conception (POC) remains unknown. We explored the effect of ART on the molecular karyotype of POC in miscarriage. POC were obtained from women undergoing ART. Single nucleotide polymorphism (SNP) microarray was used to analyze the molecular karyotype. A total of 1493 POC were collected for SNP array analysis. The total rate of karyotypic abnormalities was 63.1% (943/1493). The proportion of karyotypic abnormalities was 70.4% (193/416) in >35-year-old group, which was significantly higher than that (60.6%) (343/566) in <30-year-old group and that (60%) (307/511) in the 30-35-year-old group. In natural conception (NC) group, the proportion of karyotypic abnormalities was 64.6% (201/311), whereas in ART group it was 62.7% (742/1182) and, there was no significant difference. The ratio between male and female fetuses was 1:1.13 (698/795). The rate of karyotypic abnormalities in male was 62.9% (439/698) and that in female was 63.4% (504/795), and these values did not differ significantly (P=0.84). Molecular karyotypic abnormality is the most important reason in miscarriage, and female age is a significant factor influencing the karyotypic abnormalities. Comparison with NC, ART, and gender of aborted embryos may not increase the rate of molecular karyotypic abnormality in miscarriage.

Early missed abortion is associated with villous angiogenesis via the HIF-1α/VEGF signaling pathway.

PURPOSE: To analyze the effects of the hypoxia-inducible factor 1-alpha (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway on villous angiogenesis in early missed abortion. METHODS: Immunohistochemical assays were performed to detect the expression of micro-vessel density (MVD), HIF-1α, and VEGF in villous tissue samples from 30 missed abortions and 30 elective abortions in early pregnancy. We further analyzed the correlation between HIF-1α/VEGF and MVD. HTR8/SVneo cells were cultured under hypoxic (1%) or normoxic (20%) conditions, tube formation was investigated, and protein and mRNA level of HIF-1α/VEGF were determined using western blot and qRT-PCR. Finally, HIF-1α was knocked down with siRNA introduced into HTR8/SVneo cell line under hypoxia, and HIF-1α/VEGF expression and HTR8/SVneo tube formation were investigated. RESULTS: The expression of HIF-1α, VEGF, and MVD was lower in the missed abortion than in the elective abortion group. Correlational analysis showed that the expression of HIF-1α and VEGF was positively correlated with MVD in both groups. The levels of HIF-1α/VEGF mRNA and protein in HTR8/SVneo cells were significantly enhanced under hypoxia. HIF-1α knockdown with siRNA inhibited HIF-1α/VEGF mRNA and protein levels of HTR8/SVneo cells induced by hypoxia. Tube formation of HTR8/SVneo cells was significantly enhanced in hypoxic culture and was inhibited by HIF-1α knockdown with siRNA. CONCLUSIONS: Our results reveal a novel role for HIF-1α/VEGF in regulating villous angiogenesis in early pregnancy and suggest that it may be a novel biomarker for missed abortion.

Whole­exome sequencing analysis of products of conception identifies novel mutations associated with missed abortion.

Missed abortion (MA) refers to a pregnancy in which there is fetal demise without outside intervention, and additionally no uterine activity that may expel the product of conception (POC) prior to 20 weeks of gestation. Chromosomal abnormalities are the primary cause of MA and single gene defects in the POC may additionally be associated with MA; however, few studies have been conducted on the identification of mutations by whole­exome sequencing. In the present study, 19 unrelated MA POCs were collected and whole­exome sequencing was performed on the POC. Bioinformatics analysis was performed on sequence variants from a list of 286 selected candidate genes that were associated with early embryonic lethality and MA. A total of 36 sequence variants in 32 genes potentially associated with MA were identified in 15 out of 19 patients. Gene Ontology analysis suggested that these genes were enriched in biological processes in early embryonic development, including 'chordate embryonic development', 'cell proliferation' and 'forebrain development'. Further strict in silico bioinformatics analysis predicted that the LIM domain­binding protein 1 (c.662C>T; p.S221L) variant was a highly pathogenic variant. In conclusion, the results of the present study provide researchers and clinicians with a better understanding of the etiology and molecular mechanism of human embryonic lethality and MA.

Arias-Stella Reaction With Signet Ring-Like Cell Histomorphology.

Cells with their nucleus pushed to the periphery in a crescent-like fashion by intracytoplasmic vacuole(s) are referred to as signet ring cells when the vacuole(s) contain mucin and signet ring-like cells when they are empty or contain a material other than mucin. Signet ring cells are commonly associated with adenocarcinomas. These cells are uncommon in the endometrium and have been found to be associated with both malignant and benign processes. We report the first case of signet ring-like cells within endometrial glands with Arias-Stella reaction.

The Expression of PDCD4 in Patients With Missed Abortion and Its Clinical Significance.

Missed abortion is a special form of spontaneous abortion and its incidence shows a rising trend. Immunological factor is one of the most common reasons. Tumor suppressor gene programmed cell death 4 ( PDCD4) also participates in some immune-mediated inflammation, such as atherosclerosis, and so on, but the role of PDCD4 in missed abortion remains unclear. Here, the expression of PDCD4 was detected in decidual and chorionic tissues, as well as peripheral blood mononuclear cells from patients with missed abortion and healthy controls using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry. The expression of cytokines was also detected in decidual tissues using qRT-PCR. The levels of serum estradiol and progesterone were measured by radioimmunoassay. In addition, the correlations of PDCD4 expression with cytokines and hormones were analyzed. The results demonstrated that PDCD4 expression was reduced in decidual tissues from the missed abortion group compared with the control group. The levels of tumor necrosis factor α were significantly higher in decidual tissues of missed abortion patients than those in normal controls. We also found serum estradiol and progesterone levels were significantly lower in the missed abortion group than those in the control group, and serum progesterone level was inversely related to PDCD4 messenger RNA level. The data suggested that reduced PDCD4 expression may be involved in the occurrence of missed abortion. This may facilitate the potential development of novel diagnostic and therapeutic strategies for the treatment of missed abortion.

[The morphology, typical combinations of polymorphic genes of hemostasis, and specific features of the pathogenesis of retrochorial hematoma in missed abortion]. / Morfologiya, kharakternye sochetaniya polimorfnykh genov gemostaza i osobennosti patogeneza retrokhorial'noi gematomy pri nerazvivayushcheisya beremennosti.

AIM: to identify mutations and hemostatic gene polymorphisms typical for retrochorial hematoma (RCH) and to study its pathogenesis in missed abortion. SUBJECTS AND METHODS: A PCR assay was used to detect the genetic forms of thrombophilia in 270 patients with ultrasonographically verified RCH. Logistic regression analysis revealed that with the F7 (proconvertin, coagulation factor (CF) VII G10976A polymorphism or with the F13 (fibrinase, CF XIII) G>T, or FGB (fibrinogen ß-chain) G455A polymorphism, the risk of RCH was 2.72, 2.16, and 1.92 times higher, respectively. First trimester missed abortion was found in 42 (15.5%) cases; among them there were 24 (8.8%) women with different polymorphism combinations: F7 (G10976A), F13 (fibrinase, G>T), FGB (G455A). A total of 18 cases of missed abortion due to morphologically verified endometritis, endocrinopathies, and antiphospholipid syndrome were excluded from the sample. RESULTS: Compared to the morphology of medical abortions of the same period (16 women), patients with polymorphic genes of hemostasis were found to have statistically significant incomplete endometrial decidualization, thinning or absence of a Rohr's fibrinoid layer, a smaller number and shortening of syncytiotrophoblast microvilli, and the maximum amount of dissecting hemorrhage and RCH in the utero-chorionic region. The stages of RCH pathogenesis were determined; these included penetration of maternal erythrocytes deep into the decidua ~ dissociation of a layer of decidual cells with impairment of a «hemostatic envelope¼ ~ formation of RCH with a dense network of fibrin threads ~ final necrosis of surrounding cells and tissues. CONCLUSION: The investigators identified for the first time the typical combinations of polymorphic genes of predisposition to a high risk for RCH; its complete formation requires additional changes in maternal and placental components that provide local hemostasis.

Embryoscopic diagnostics of endometrial defects in missed abortion after IVF.

High incidence of missed abortion induces to search for its causes. Apart from genetic and anatomic uterine factors, the state of the decidual endometrium and implantation zone of chorionic structures of the gestational sac are of particular interest. Direct visualization of the intact decidual endometrium is possible with embryoscopy, however, there is lack of presented data of normal and pathological signs of the endometrium during pregnancy. This paper describes the changes of the endometrium in missed abortion obtained by hysteroscopy in 160 women with nonprogressive pregnancy after ART protocols. High incidence of vascular disorders is determined, namely perivascular hemorrhage (70%), thrombosis of small-caliber endometrial vessels (36.9%), necrosis of the decidual endometrium and areas of the endometrium ejection beyond the implantation zone as a source of vaginal bleeding (10%). In addition, a high incidence of capsular decidual membrane defects are detected, namely, dystrophy, thinning and necrosis (60.6%).

Sublingual misoprostol for management of empty sac or missed miscarriage: The first two years' experience at a metropolitan Australian hospital.

BACKGROUND: Misoprostol management of miscarriage is only now becoming widely used in Australia. AIMS: To review the efficacy, safety and the popularity of outpatient sublingual misoprostol in empty sac/missed miscarriage management over its first two years of availability in a metropolitan Australian hospital. MATERIALS AND METHODS: A retrospective cohort review was undertaken of women choosing sublingual misoprostol 600 µg (three tablets) × three doses for miscarriage management. Principal outcomes assessed were miscarriage resolution without the need for curettage and complications. Additionally, the relative popularity of misoprostol versus surgery by place of birth and over time, and the return of pregnancy tissue for histology were analysed. RESULTS: Between 1 December 2012 and 30 November 2014, 279 women chose sublingual misoprostol for nonurgent miscarriage management, while 420 chose surgery (40 and 60%, respectively). Of the misoprostol cohort, 269 had complete data; 239 of 269 (88.8%) had resolution without curettage, nine (3.3%) had acute curettage, 21 (7.8%) had nonacute curettage, 30 (11.15%) had unplanned emergency department presentation, 11 (4.1%) had unplanned admission, three (1.1%) had blood transfusion and one (0.4%) had an infection requiring admission. Misoprostol was as popular with Australian-born as overseas-born women; 53.5% of patients returned histopathology specimens; one (0.7%) demonstrated partial hydatidiform mole. CONCLUSIONS: Outpatient management of missed/empty gestational sac miscarriage using sublingual misoprostol is associated with a high rate of avoiding curettage and the low rate of complication. It is equally popular with Australian-born and overseas-born women. Just over 50% returned pregnancy tissue for analysis.

[Transcervical Embryoscopy after Missed Abortion in Monoamniotic Twins with Discordant Exencephaly]. / Transzervikale Embryoskopie nach verhaltenem Abort in monoamnioten Zwillingen mit diskordanter Exenzephalie.

INTRODUCTION: Monoamniotic twins are considered a cause of high-risk pregnancies. Thereby, discordant malformations do occur rarely. A discordant exencephaly has been described in only a few cases. Transcervical embryoscopy can be performed in cases of monoamniotic twins with missed abortion directly before the abort-curettage. CASE REPORT: The case of a 35-year-old G1/P0 women in the 12(th) week of pregnancy is described. She had a monoamniotic twin pregnancy with discordant exencephaly and missed abortion diagnosed at 11+2 weeks. A transcervical embryoscopy was performed immediately before the abort-curettage and identified the discordant exencephaly and an additional umbilical cord knot of the 2 foetuses as a probable cause for the abortion. DISCUSSION: The transcervical embryoscopy lead in our case report to the diagnosis of a umbilical cord knot in a monoamniotic twin pregnancy with missed abortion. We also identified a discordant exencephaly by embryoscopy. With blunt access to the amniotic cavity, the transcervical embryoscopy applies only a minor additional risk to the abort-curettage. However, it should only be performed when the patient explicitly asks for enhanced diagnostics. CONCLUSION: Transcervical embryoscopy can be performed as an additional diagnostic tool in cases of monoamniotic twins with missed abortion. However, a detailed risk-benefit analysis should be done upfront in consultation with the patient.

A comparison of the molecular distribution of proangiogenic factors in endometrium of missed abortions and of voluntary first trimester termination cases.

OBJECTIVE: The authors aimed to evaluate the angiogenic changes that occur in the cases with missed abortions compared with the voluntary termination of pregnancy as control group, with this controlled clinical study. MATERIALS AND METHODS: The study included fifteen healthy volunteer women with unwanted pregnancy less than 10th gestational week in an academic research environment. The patients were 19 women between 6th and 11th gestational weeks diagnosed with missed abortion as the patient group. Immunohistochemistry was utilized to examine temporal and spatial expression of vascular endothelial growth factor (VEGF) and their two receptors: VEGF-R1 (Flt-1) and VEGF-R2 (Flk-1/KDR), and Trombospondin-1, eNOS, iNOS, and HIF-1α in the both deciduas and placenta of the both groups. RESULTS: This study discovered the significant difference (p < 0.005) between the groups of controlled and missed abortion in the decidual and placental cell components, and has put forward that thrombospondin and iNOS have an impact on abortion through antiangiogenic effect in cases of missed abortions. CONCLUSIONS: The potential role of molecules affecting angiogenesis in the etiology of missed abortion has been evaluated and the authors aimed for this to be a guide for studies on further treatments and on the prevention of the development of missed abortions.

Expression of GRIM-19 in missed abortion and possible pathogenesis.

OBJECTIVE: To study the expression of a gene associated with retinoid-interferon (IFN)-induced mortality 19 (GRIM-19) in the villi of patients with missed abortion and possible pathogenesis. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): Villous samples were collected from a total of 50 women with missed abortion and 50 women with normal pregnancies. INTERVENTION(S): Villous samples from the missed-abortion group were collected by curettage or manual vacuum aspiration. The control villous samples were obtained by vacuum aspiration. MAIN OUTCOME MEASURE(S): Protein and messenger RNA levels of GRIM-19 in villous samples were measured by Western blot and real-time polymerase chain reaction, and the location of GRIM-19 in trophoblasts was detected by immunohistochemistry. Apoptotic cells and microvessel density in villous sample were assayed by TUNEL and immunostaining. Mitochondrial membrane potential and apoptotic changes of the HTR-8/SVneo cell line in response to down-regulation of GRIM-19 were evaluated by 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide and annexin V/propidium iodide. Vascular endothelial growth factor production was measured by ELISA. RESULT(S): GRIM-19 protein and messenger RNA levels in the villi from women with missed abortion were found to be significantly lower than in women who had normal pregnancies. Many more apoptotic cells and lower microvessel density were detected in villi from patients with missed abortion. Knockdown of GRIM-19 in HTR-8/SVneo cells gave rise to a collapse of mitochondrial membrane potential and increase in apoptosis. Simultaneously, the vascular endothelial growth factor secretion in the HTR-8/SVneo cells culture medium decreased as GRIM-19 became down-regulated. CONCLUSION(S): The GRIM-19 deficiency in the villus may be associated with missed abortion via increasing apoptosis and affecting angiogenesis.

The role of Hofbauer cells on the pathogenesis of early pregnancy loss.

INTRODUCTION: Hofbauer cells (HC) are the placental macrophages that play a significant role in many important placental events. The aim of this retrospective study is to investigate the role of HC in the pathogenesis of early pregnancy loss (EPL). METHODS: The slides were obtained from archival blocks of missed abortion (MA, n = 15) and blighted ovum (BO, n = 15) cases. Unwanted pregnancies materials constituted the control group (n = 15). HC and endothelial cells were identified using immunohistochemical methods. HC were counted under light microscope. The extent of villous vasculature was evaluated using two methods; the Chalkey method and microvessel scoring. RESULTS: The mean number of villous HC was found to be significantly higher in both MA and BO groups in contrast to the control group. MA group also showed a higher number of HC in comparison with the BO group. Higher microvessel scoring was also found in MA group in contrast to other two groups. Chalkey method revealed no significant difference in the extent of villous vasculature for the control group in comparison with MA and BO. DISCUSSION: As we identified relatively low quantity of HC in BO associated with defective vasculature, we hypothesize that an inadequate microvessel formation after hypoxic insult can explain the pathogenesis of BO. We believe that HC are increased in MA due to their divergent roles on immunity and inflammation. CONCLUSION: We therefore conclude that HC may be of biological importance in the pathogenesis of EPL.

Association of Dll4/notch and HIF-1a -VEGF signaling in the angiogenesis of missed abortion.

BACKGROUND: Dll4/Notch and HIF-1a-VEGF have been shown to play an important role during angiogenesis, but there are no data about their roles and association in missed abortion. In this study, we investigated the association of Dll4/Notch and HIF-1a-VEGF signaling in missed abortion. METHODS: Women with missed abortion (n=27) and healthy controls (n=26) were included in the study. Real-time Reverse Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of Dll4/Notch and HIF-1a-VEGF signaling molecules. The protein level for Dll4 was measured by immunohistochemistry. RESULTS: Compared with induced abortion, the expression of VEGF was statistically reduced while the level of VEGFR1 and Notch1 was significantly up-regulated in missed abortion. Though other molecules (VEGFR2 and Dll4) were marginally higher in missed abortion, no statistical difference was observed. The expression of HIF-1a was significantly up-regulated, and close negatively correlated with VEGF in missed abortion. Both in induced abortion and missed abortion, Dll4 was positively correlated with Notch1. CONCLUSIONS: The early pregnancy is in a hypoxic environment, this may encourage the angiogenesis, but severe hypoxic may inhibit the angiogenesis. Aberrant Dll4/Notch and HIF-1a-VEGF signaling may have a role in missed abortion.

[Forensic medical assessment of the origin of the missed early post-traumatic abortions].

The objective of the present study was to develop an algorithm for the forensic medical assessment of the origin of the missed early post-traumatic abortions. The analysis of the available data on the main variants of traumatic pregnancy interruption was carried out. Diagnostic features of the missed early post-traumatic abortions are considered along with the possible errors in the use of the current approaches to forensic medical assessment of their origin. The proposed algorithm for the forensic medical assessment of the origin of the missed early post-traumatic abortions takes into consideration the specific features of the objects of interest and includes the analysis of the results of ultrasonic studies of the uterine cavity and histological investigations of the scraps of endometrial tissue. Absolute and probabilistic criteria for spontaneous and traumatic origin of the missed early post-traumatic abortions. The proposed algorithm is recommended for the use in routine clinical practice for the elucidation of the causes of the missed early post-traumatic abortions.

Fetal mediastinal tumor of neuroepithelial origin in a case of missed abortion.

We report a rare case of a primitive embryonal tumor discovered in the upper anterior mediastinum during routine autopsy of a macerated fetus at the 18th week of gestation. Our diagnosis was based on autopsy findings and histologic examination, which showed neuroepithelial differentiation of the tumor with frequent ependymal-type rosette formation; no structures of other germ cell layer origin were revealed. Additional positive immunohistochemical staining for CD56, CD57, and neurofilament protein confirmed the neural origin of the tumor, whereas the genetic analysis showed no MYCN gene amplification and no 11q23 deletion or rearrangement of EWS locus (22q12). Our findings exclude the possibility of teratoma and support the diagnosis of undifferentiated primitive tumor of neuroepithelial origin uncommonly located in the anterior mediastinum at the early 2nd trimester of gestation in a case of missed abortion.