Association between ACE1 and missed abortion: ACE1 promotes H2O2-induced trophoblast cell injury in vitro†.

The aim of this study was to evaluate the role of angiotensin-converting enzyme 1 (ACE1) in H2O2-induced trophoblast cell injury and the potential molecular mechanisms. Oxidative stress was modeled by exposing HTR-8/SVneo cells to 200 µM H2O2. Western blot and real-time quantitative PCR methods were used to detect protein and mRNA expression level of ACE1 in chorionic villus tissue and trophoblast HTR-8/SVneo cell. Inhibition of ACE1 expression was achieved by transfection with small interfering RNA. Then flow cytometry, Cell Counting Kit-8, and Transwell assay was used to assess apoptosis, viability, and migration ability of the cells. Reactive oxygen species (ROS) were detected by fluorescent probes, and malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) activities were determined by corresponding detection kits. Angiotensin-converting enzyme 1 expression was upregulated in chorionic villus tissue of patients with missed abortion (MA) compared with individuals with normal early pregnancy abortion. H2O2 induced elevated ACE1 expression in HTR-8/SVneo cells, promoted apoptosis, and inhibited cell viability and migration. Knockdown of ACE1 expression inhibited H2O2-induced effects to enhance cell viability and migration and suppress apoptosis. Additionally, H2O2 stimulation caused increased levels of ROS and MDA and decreased SOD and GSH activity in the cells, whereas knockdown of ACE1 expression led to opposite changes of these oxidative stress indicators. Moreover, knockdown of ACE1 attenuated the inhibitory effect of H2O2 on the Nrf2/HO-1 pathway. Angiotensin-converting enzyme 1 was associated with MA, and it promoted H2O2-induced injury of trophoblast cells through inhibiting the Nrf2 pathway. Therefore, ACE1 may serve as a potential therapeutic target for MA.

The Success of Mifepristone and Misoprostol in the Management of Early Pregnancy Loss at a Community Hospital: A Prospective Study.

OBJECTIVES: This prospective single-arm study was conducted to understand the expulsion rate of the gestational sac in the management of early pregnancy loss (EPL). METHODS: We recruited 441 participants; 188 met the eligibility criteria. Participants were 18 years of age and older who experienced a confirmed EPL (<12 weeks gestational age) defined by an intrauterine pregnancy with a non-viable embryonic or anembryonic gestational sac with no fetal heart activity. Participants were given 200 mg of mifepristone pre-treatment orally followed by 2 doses of misoprostol 800 µg vaginally after 24 and 48 hours. Participants were seen in follow-up on day 14 to confirm the absence of a gestational sac, classified as treatment success. For failed treatment (defined by retained gestational sac), we offered expectant management or a third dose of misoprostol and/or dilatation and curettage. We followed all participants for 30 days. We collected data on overtreatment for retained products of conception and hospital admissions for adverse events. RESULTS: Overall, 181 participants followed the protocol and 169 (93.3%) participants had a complete expulsion of the gestational sac by the second visit (day 14). Twelve (6.6%) failed the treatment and 1 had an adverse event of heavy vaginal bleeding requiring dilatation and curettage. Despite the expulsion of the gestational sac, 29 cases (17.1%) at subsequent follow-up were diagnosed as retained products of conception based on ultrasound assessment of thickened endometrium. CONCLUSIONS: Pretreatment with mifepristone followed by 2 doses of misoprostol with a 14-day follow-up resulted in a high expulsion rate and is a safe management option for EPL.

Medical treatment of miscarriage using misoprostol-a retrospective study.

PURPOSE: The treatment of early miscarriage with medication is effective and low in side effects. Nevertheless, no uniform dosage regimen has yet been established, nor has it been possible to determine whether previous pregnancies and births with their respective modes of delivery play a role in the effectiveness of Misoprostol. This study aimed to find predictive parameters for successful treatment with Misoprostol in early miscarriage. METHODS: In a retrospective study at the Otto von Guericke University Women's Hospital, records of patients with early miscarriage and medical treatment using Misoprostol from 2018 to 2021 were reviewed for this purpose. The need for a curettage subsequent to treatment was scored as a parameter of failure. The data were analyzed using Statistical Package for the Social Science Version 28.0. The significance level was set to 0.050. RESULTS: We found that successful therapy with misoprostol was seen in 86% (n = 114). 14% (n = 20) of the patients had curettage after taking Misoprostol as advised. Out of 134 women, 16% (n = 21) reported mild side effects, with nausea as the leading one (9.2% (n = 12)). Significance was found comparing the measurement of double endometrial stripe thickness after the second cycle of Misoprostol in women with and without curettage after medical treatment (exact value two-sided 0.035 at p < 0.05). A cutoff value at 8.8 mm was calculated using ROC Analysis. CONCLUSIONS: Our results indicate that the treatment of early miscarriage in the first trimester with Misoprostol is effective and has few side effects. The measurement of the endometrial stripe thickness after the second cycle of Misoprostol via transvaginal ultrasound could present a predictive marker during therapy.

HLA-G Expression/Secretion and T-Cell Cytotoxicity in Missed Abortion in Comparison to Normal Pregnancy.

The main role of HLA-G is to protect the semi-allogeneic embryo from immune rejection by proper interaction with its cognate receptors on the maternal immune cells. Spontaneous abortion is the most common adverse pregnancy outcome, with an incidence rate between 10% and 15%, with immunologic dysregulation being thought to play a role in some of the cases. In this study, we aimed to detect the membrane and soluble HLA-G molecule at the maternal-fetal interface (MFI) and in the serum of women experiencing missed abortion (asymptomatic early pregnancy loss) in comparison to the women experiencing normal early pregnancy. In addition, the proportion of T cells and their cytotoxic profile was evaluated. We observed no difference in the spatial expression of HLA-G at the MFI and in its serum levels between the women with missed abortions and those with normal early pregnancy. In addition, comparable numbers of peripheral blood and decidual total T and γδT cells were found. In addition, as novel data we showed that missed abortion is not associated with altered extravilous invasion into uterine blood vessels and increased cytotoxicity of γδT cells. A strong signal for HLA-G on non-migrating extravilous trophoblast in the full-term normal placental bed was detected. In conclusion, HLA-G production at the MFI or in the blood of the women could not be used as a marker for normal pregnancy or missed abortions.

PRM-based quantitative proteomics analysis of altered HSP abundance in villi and decidua of patients with early missed abortion.

OBJECTIVE: In this study, we aimed to identify differentially expressed heat shock protein (HSP) profiles in the villi and decidua from patients with early missed abortion (EMA). METHODS: By using high-throughput and high-precision parallel reaction monitoring (PRM)-based targeted proteomics techniques, this study examined the abundance of HSPs in the villi and decidua of 10 patients with EMA and 10 controls. Moreover, the abundance of 3 HSPs in the villi of another 22 patients with EMA and 22 controls was verified with Western blotting and immunohistochemistry (IHC). RESULTS: There were potential differences in the abundance of 16 HSPs and 42 polypeptides in human villi and decidua compared with those of the control group. Among them, HSP90AB1, HSPD1 and HSPA13 were downregulated in abundance in villi of patients with EMA, with a statistically significant difference, which was consistent with the verification results of Western blots and IHC. CONCLUSION: Using a PRM-based targeted proteomics technique, this study is the first to screen and quantitatively analyze the expression profile of HSPs in the villi and decidua of patients with EMA. The significant downregulation of HSP90AB1, HSPD1 and HSPA13 was found to have a potentially intimate association with the occurrence of EMA. The findings in our study may provide novel potential research targets related to HSPs for the pathogenesis, prevention and treatment of EMA.

High Expression and Significance of Siglec10/CD24 in Unexplained Missed Abortion.

OBJECTIVE: To investigate the expression of Siglec10 and CD24 in normal early pregnancy and missed abortion, and their significance in the maternal-fetal interface. METHODS: For our research, we employed Q-PCR and WB techniques to evaluate the traits and expression of Siglec10 and CD24 in the nonpregnant endometrium, as well as in the villus and decidua of women in their 6-10 weeks of normal early pregnancy and those who experienced missed abortion. Additionally, we utilized ELISA to determine the levels of Siglec10 and CD24 in the peripheral blood of pregnancy, missed abortion, and non-pregnant individuals. T-test and ANOVA were used to compare groups. RESULTS: 1. Villous tissues in early pregnancy showed high expression of Siglec10 and CD24, with a significant increase in expression in the missed abortion group (P < 0.01).2. Nonpregnant endometrial tissue showed low expression of Siglec10 and CD24, while early pregnancy decidua showed high expression, with even higher expression in missed abortion (all P < 0.05).3. Serum levels of Siglec10 and CD24 in normal early pregnancy were significantly higher than non-pregnancy (P < 0.01). However, the missed abortion group showed significantly higher levels than normal pregnancy (P < 0.01).4. CD24 expression in serum of missed abortion increases with Siglec10 expression, indicating a significant positive correlation (r = 0.500, P < 0.01). CONCLUSION: Siglec10 and CD24 expression in villus, decidua, and peripheral blood are up-regulated in unexplained missed abortions than those of women with normal pregnancies. This suggests that the levels of serum Siglec10 and CD24 can be used as an effective predictor of missed abortion.

Quantitative proteomics and functional analysis identified novel targets for missed abortion.

Missed abortion (MA) is a special form of spontaneous abortion that is increasing in incidence. However, the precise molecular mechanisms underlying MA, especially regarding the decidua, are poorly understood. Herein, we identified molecular signaling pathways related to MA by comparing the decidua of women experiencing normal pregnancy and MA using a quantitative proteomics approach based on HPLC-MS/MS and iTRAQ labeling. Integrated bioinformatics analysis of villi and decidua was performed to reveal potential crosstalk signals in closely related tissues. We identified 2277 proteins with high confidence in decidua, of which 232 were differentially expressed in MA samples. Specifically, we reported that integrated quantitative proteomic and bioinformatic analysis revealed altered proteins in MA and the mechanisms underpinning MA involved numerous pathways, especially ribosome and cellular metabolism signaling. Moreover, Importin 9, Cullin 1 and COX6C are critical for MA, and their altered expression might contribute to the pathophysiology of MA. In particular, COX6C was dramatically down-regulated in both decidua and villi of MA. COX6C was also found to be highly expressed in syncytiotrophoblastic and cytotrophoblastic cells in villi and widely expressed in decidua of the control group, but dramatically decreased in the MA group. Functional analysis showed that knockdown of COX6C inhibited apoptosis process in both HTR-8 and SiHa cells, suggesting that COX6C may play protective effects in MA. Thus, this study could help to map the regulatory protein network related to MA and contribute to the pathophysiological mechanisms of MA.

The association between history of retained placenta and success rate of misoprostol treatment for early pregnancy failure.

BACKGROUND: To date, the association between retained placenta and treatment success rate of misoprostol for early pregnancy failure has yet to be evaluated. The aim of this study was to evaluate this association and further investigated the connection between medical, clinical and sonographic parameters and treatment success. METHODS: We conducted a retrospective cohort study of women with early pregnancy failure treated with misoprostol from 2006 to 2021. The success rate of misoprostol treatment was compared between patients with history of retained placenta including women who underwent manual lysis of the placenta following delivery or patients who were found to have retained products of conception during their post-partum period (study group) and patients without such history (controls). Demographic, clinical, and sonographic characteristics as well as treatment outcomes were compared between the groups. RESULTS: A total of 271 women were included in the study (34 women in the study group compared to 237 women in the control group). Two-hundred and thirty-three women (86.0%) presented with missed abortion, and 38 (14.0%) with blighted ovum. Success rates of misoprostol treatment were 61.8% and 78.5% for the study and control groups, respectively (p = 0.032). Univariate analysis performed comparing successful vs. failed misoprostol treatment showed advanced age, gravidity, parity and gestational sac size (mm) on TVUS were associated with higher misoprostol treatment failure rate. Following a multivariate logistic regression model these variables did not reach statistical significance. CONCLUSION: Women who have an event of retained placenta following childbirth appear to have decreased success rate of treatment with misoprostol for early pregnancy failure. Larger studies are needed to confirm this finding.

Association between HIF-1α, BNIP3, and autophagy in the chorionic villi of missed abortion.

AIM: To investigate the expression of autophagy mediated by the hypoxia-inducible factor 1α (HIF-1α)/BNIP3 signaling pathway in villus tissues of missed abortion and HTR-8/SVneo cells and to elucidate the association of HIF-1α and BNIP3 in autophagy of missed abortion. METHODS: Villus tissues from 30 healthy women with induced abortion and 35 patients with missed abortion were collected, and HTR-8/SVneo cells were cultured under hypoxia and transfected with HIF-1α-siRNA. Real-time polymerase chain reaction was utilized to measure the mRNA levels of HIF-1α and BNIP3; Western blotting was performed to determine the protein levels of HIF-1α, BNIP3, LC3 II/I, and Beclin 1 in villus tissues and HTR-8/SVneo cells. Cellular invasion activity was detected by transwell matrigel assay. The level of autophagy was confirmed by transmission electron microscopy of autophagosome formation. RESULTS: The mRNA levels of HIF-1α and BNIP3 were significantly lower in the missed abortion villi than in the induced abortion samples. The protein levels of HIF-1α, BNIP3, Beclin 1, and LC3II/I were significantly decreased in villus tissues from missed abortion, and autophagosomes were significantly decreased in villus tissues from missed abortion. Under hypoxia, the mRNA expression of HIF-1α and BNIP3 was inhibited after silencing HIF-1α by RNAi, while the protein expression of HIF-1α, BNIP3, Beclin1, and LC3II/I was significantly downregulated. The number of invading cells was significantly decreased, and autophagosomes were significantly decreased after silencing HIF-1α by RNAi in HTR-8/SVneo cells. CONCLUSIONS: Autophagy mediated by the HIF-1α/BNIP3 signaling pathway in villous trophoblast cells may be associated with the progression and development of missed abortion.

Interactions between Benzo(a)pyrene exposure and genetic polymorphisms of AhR signaling pathway on missed abortion.

Benzo(a)pyrene (BaP) is an environmental pollutant widely exposed to human beings. While the relationship between BaP and missed abortion is few understood. To explore the association between missed abortion and BaP, genetic polymorphisms of AhR pathway, we recruited 112 cases women with missed abortion and 137 controls women with normal pregnancy from Shanxi, China. The BPDE-DNA adducts level in the case group was higher than that in the control group (P < 0.001). The subjects were categorized according to the tertiles of BPDE-DNA adduct concentrations: T1 (

Could maternal serum MFG-E8 level predict adverse first trimester pregnancy outcome? A preliminary study.

BACKGROUND: Milk fat globule-epidermal growth factor 8 (MFG-E8) is expressed in the endometrial epithelium and its expression increases during the implantation process. Due to this knowledge, we aimed to investigate the maternal serum MFG-E8 levels on both healthy pregnant women in the first trimester and pregnant women complicated with missed abortion and threatened abortion in the first trimester. METHODS: This prospective, cross-sectional study was conducted in a tertiary referral hospital, department of obstetrics between July 2020 and February 2021 after ethical committee approval. The study population was consisted of 30 healthy pregnant women (HP) in the first trimester, 30 pregnant women suffering from threatened abortion (TA) in the first trimester and 30 pregnant women suffering from missed abortion (MA) in the first trimester. Maternal serum MFG-E8 levels were analyzed with enzyme linked immunosorbent assay. Delivery and neonatal outcomes of the study population was evaluated. The continuous variables were compared among three groups with variance analysis with post hoc tests. The categorical variables were compared with chi-square and Fisher's exact tests where applicable. RESULTS: The mean age of the study population was 29.36 ± 5.31 years. There was no significant difference among three groups for parameters of age, body mass index, parity number, and gestational week. Despite being within normal ranges, the mean neutrophil and international normalized ratio values of the three groups showed statistically significant difference (p < 0.05). The mean maternal serum MFG-E8 levels of MA, TA, and HP groups were 270 ± 152.3, 414.7 ± 236.7, and 474 ± 222.5 ng/mL, respectively (p = 0.001). It was found that mean of MFG-E8 of the MA group was statistically significantly lower than those of the other two groups (p < 0.05). DISCUSSION: Although maternal serum MFG-E8 level seems to be a parameter that differ between live and nonlive pregnancies, studies with large number of cases are needed to discuss our results and to determine a cut-off value for prediction.

Alteration of the Gut Microbiota in Missed Abortion.

There is a symbiotic relationship between gut microbiota and human beings. Imbalance of the gut microbiota will cause pathological damages to humans. Although many risk factors are associated with missed abortion (MA), the pathological mechanism of it is still unclear. Here, we analyzed gut flora of the patients with MA by S16 high-throughput sequencing. The possible pathogenic mechanisms of the MA were explored. Fecal samples from 14 healthy controls and 16 MA patients were collected to do 16S rRNA gene high-throughput sequencing analysis. The abundance of the Bacteroidetes, Proteobacteria, Actinobacteria, Escherichia, Streptococcus_ Salivarius, and Lactobacillus was significantly reduced in the MA group, while, the abundance of the Klebsiella was significantly increased in the MA patients. The Ruminococcaceae and [Eubacterium]_coprostanoligenes_group were found only in the specimens of the MA patients. The Fabrotax function prediction analysis showed that four photosynthesis function bacteria (cyanobateria, oxygenic_photoautotrophy, photoautotrophy, and phototrophy) only existed in the MA group. In the analysis of the BugBase microbiome function prediction, the Escherichia of the MA group is significantly reduced compared to that of the healthy controls in the items of that Contains_Mobile_Elements, Facultatively_Anaerobic, Forms_Biofilms, Potentially_Pathogenic.png, Gram_Nagative, and Stress_Tolerant_relabundance. These alterations may affect the stability of the host's immune, neural, metabolic and other systems by interfering with the balance of the gut microbiota or by the metabolites of those bacteria, causing the MA. This study explored the possible pathogenic factors of the gut microbiota of the MA. The results provide evidence to figure out the pathogenesis of the MA.

Protocol for Increasing the Sensitivity of MS-Based Protein Detection in Human Chorionic Villi.

An important step in the proteomic analysis of missing proteins is the use of a wide range of tissues, optimal extraction, and the processing of protein material in order to ensure the highest sensitivity in downstream protein detection. This work describes a purification protocol for identifying low-abundance proteins in human chorionic villi using the proposed "1DE-gel concentration" method. This involves the removal of SDS in a short electrophoresis run in a stacking gel without protein separation. Following the in-gel digestion of the obtained holistic single protein band, we used the peptide mixture for further LC-MS/MS analysis. Statistically significant results were derived from six datasets, containing three treatments, each from two tissue sources (elective or missed abortions). The 1DE-gel concentration increased the coverage of the chorionic villus proteome. Our approach allowed the identification of 15 low-abundance proteins, of which some had not been previously detected via the mass spectrometry of trophoblasts. In the post hoc data analysis, we found a dubious or uncertain protein (PSG7) encoded on human chromosome 19 according to neXtProt. A proteomic sample preparation workflow with the 1DE-gel concentration can be used as a prospective tool for uncovering the low-abundance part of the human proteome.

Risk factors for missed abortion: retrospective analysis of a single institution's experience.

OBJECTIVE: To explore the risk factors including the difference between mean gestational sac diameter and crown-rump length for missed abortion. METHODS: Hospitalized patients with missed abortion and patients with continuing pregnancy to the second trimester from Chengdu Women's and Children's Central Hospital from June 2018 to June 2021 were retrospectively analyzed. The best cut-off value for age and difference between mean gestational sac diameter and crown-rump length (mGSD-CRL) were obtained by x-tile software. Univariate and multivariate logistic regression analysis were adopted to identify the possible risk factors for missed abortion. RESULTS: Age, gravidity, parity, history of cesarean section, history of recurrent abortion (≥ 3 spontaneous abortions), history of ectopic pregnancy and overweight or obesity (BMI > 24 kg/m2) were related to missed abortion in univariate analysis. However, only age (≥ 30 vs < 30 years: OR = 1.683, 95%CI = 1.017-2.785, P = 0.043, power = 54.4%), BMI (> 24 vs ≤ 24 kg/m2: OR = 2.073, 95%CI = 1.056-4.068, P = 0.034, power = 81.3%) and mGSD-CRL (> 20.0vs ≤ 11.7 mm: OR = 2.960, 95% CI = 1.397-6.273, P = 0.005, power = 98.9%; 11.7 < mGSD-CRL ≤ 20.0vs > 20.0 mm: OR = 0.341, 95%CI = 0.172-0.676, P = 0.002, power = 84.8%) were identified as independent risk factors for missed abortion in multivariate analysis. CONCLUSION: Patients with age ≥ 30 years, BMI > 24 kg/m2 or mGSD-CRL > 20 mm had increasing risk for missed abortion, who should be more closely monitored and facilitated with necessary interventions at first trimester or even before conception to reduce the occurrence of missed abortion to have better clinical outcomes.

The association between vaginal microbiota disorders and early missed abortion: A prospective study.

INTRODUCTION: The objective of this study was to explore the association between disordered vaginal microbiota and missed abortion to ascertain potential causes of missed abortion related to vaginal microbiology. MATERIAL AND METHODS: This study was a prospective cohort study with a comparison group (reference group). Vaginal secretions from the posterior fornix of women in the early stages of pregnancy were collected in the Xiangya Third Hospital of Central South University in Changsha, Hunan, China, from November 2018 to November 2019. A total of 54 cases of missed abortion (case group) and 50 cases of normal pregnancy requiring induced abortion (reference group) were analyzed. Bacterial DNA was extracted, hybridized with gene-specific primers, and then detected using a bacterial chip. The composition and relative abundance of vaginal microbiota in the two groups were compared using α-diversity analysis, ß-diversity analysis, and the linear discriminant analysis effect size method. RESULTS: The α-diversity analysis showed that the Simpson index of the case group was lower than that of the reference group, whereas the Shannon index in the case group was higher. The relative abundance of Firmicutes in the case group (42.52%) was lower than in the reference group (51.03%, p < 0.05), as was the relative abundance of Lactobacillus (case group 16.51%, reference group 23.00%; p < 0.05). Interestingly, levels of Mycoplasma genitalium and Ureaplasma were lower in the case group (p < 0.05). The relative abundance of Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus gasseri was also significantly lower in the case group than in the reference group (p < 0.05). The pathways enriched in the case group were predominantly related to metabolism, whereas the genetics-related pathways were predominantly enriched in the reference group. CONCLUSIONS: Bacteria are more diverse and unevenly distributed in patients with missed abortion. Decreases in the proportion of vaginal Lactobacillus and changes in Lactobacillus species in these patients may increase the chance of genital tract pathogenic bacterial infection. To our knowledge, our study was the first to observe that a decrease of Firmicutes levels in the vaginal microbiota might impair energy metabolism and have an association with missed abortion.

National register data are of value in studies on miscarriage-Validation of the healthcare register data in Finland.

INTRODUCTION: Despite the high prevalence of miscarriages, they are not systematically registered and few epidemiological studies have been done. As Finnish health registries are comprehensive and widely used in research, we validated the Finnish register data concerning diagnostics and treatment of miscarriage, and treatment-related adverse events. MATERIAL AND METHODS: We conducted a validation study regarding miscarriage-related codes of diagnoses and surgical procedures in a Finnish National Hospital Discharge Registry (NHDR) by comparing the information from the NHDR with that of the hospital records. We selected a random sample of 4 months during 1998-2016 from three hospitals, comprising 687 women aged 15-49 experiencing a first miscarriage during follow-up. Women with diagnoses unrelated to miscarriage, or proven to be other than miscarriage, were excluded. The final sample consisted of 643 women with confirmed miscarriage, which was used for analyses regarding the diagnosis, treatment and adverse events of miscarriage treatment. RESULTS: The majority of miscarriages registered in the NHDR were confirmed by the hospital records (positive predictive value [PPV] = 93.6% [95% confidence interval [CI] 91.8%-95.4%]). Different types of miscarriage were also reliably identified; spontaneous abortion with PPV = 85.6% (95% CI 80.9%-89.2%), missed abortion with PPV = 92.7% (95% CI 88.8%-95.3%) and blighted ovum with PPV = 91.1% (95% CI 84.3%-95.1%). The PPV of surgical treatment (62.2% [95% CI 55.7%-68.3%]) was lower than the PPV of non-surgical treatment (93.3% [95% CI 90.5%-95.3%]). The diagnoses regarding adverse events of miscarriage treatment could be reliably identified. The PPV for clinical infections was 76.0% (95% CI 56.6%-88.5%) and for retained products of conception or/and vaginal bleeding 96.8% (95% CI 83.8%-99.4%). CONCLUSIONS: The coverage of the NHDR was good concerning identification of miscarriages, different types of miscarriages and non-surgical treatment. Nevertheless, there is a need for clearly defined procedural codes concerning to medical treatment of miscarriage. The register-based data are reliable and practicable for both clinical evaluation and research concerning miscarriage.

Circulating levels of Elabela in pregnant women with missed abortion.

ObjectiveThis study aimed to detect Elabela concentrations in the serum of Missed abortion (MA) and compare them with the healthy pregnancies.Materials and methodsThis retrospective case-control study was performed in the second affiliated hospital, Xi'an Jiaotong University March 2019 to September 2019. A total of 108 healthy (35 early, 36 middle and 37 late) pregnant women and 25 (early gestational stage) MA patients were involved. Demographic and clinical characteristics were recorded. The concentration of plasma Elabela was examined using ELISA.ResultsThe level of plasma Elabela was increased in early and middle stages and decreased in late stage of healthy pregnant women. Maternal serum Elabela levels were significantly lower in MA patients (4.59 ± 1.23 ng/mL) compared to healthy pregnant women (5.77 ± 1.21 ng/mL, p < 0.01).ConclusionMaternal circulating levels of Elabela were significantly lower in MA patients than in healthy pregnant women. We consider that Elabela might be a crucial biomarker of the pathophysiologic process in MA.

Intravaginal misoprostol versus uterine curettage for missed abortion: A cost-effectiveness analysis.

PURPOSE: To evaluate the cost-effectiveness of a strategy based on direct-acting uterine curettage (UC) versus a pre-direct-acting misoprostol (1600 mg) in patients with missed abortion (MA), from the perspective of a National Health System. METHODS: An open prospective cohort study was carried out at Reina Sofía University Hospital (Córdoba, Spain) from January 1, 2019 to December 31, 2019 in 180 patients diagnosed with MA. The patients chose medical treatment with intravaginal misoprostol (800 µg/4 h) or UC after receiving complete and detailed information. The effectiveness, clinical characteristics of the patients, costs of treating and managing the disease, and satisfaction with the procedures were recorded. RESULTS: One hundred and forty-five patients (80.6%) chose misoprostol versus 35 patients (19.4%) who chose UC. The effectiveness of misoprostol has been 42% evaluated at 48 h; UC success rate has been 100%. The incidence of side effects is significantly higher in patients treated with misoprostol (p < 0.05); as well as the number of care received by the patient (p < 0.05). Satisfaction is higher in patients treated with UC (p < 0.05). However, the cost is almost 5-folds higher in patients treated with UC (p < 0.05). CONCLUSION: UC has a higher success rate, greater satisfaction, and a lower incidence of side effects, although significantly increases the cost compared to misoprostol in MA.

The role of p53-MDM2 signaling in missed abortion and possible pathogenesis.

BACKGROUND: Missed abortion is one of the common obstetrical and gynecological complications, angiogenesis is the most important factor in fetal and placental development. However, the definite etiology and pathogenesis are not fully understood. METHODS: The mRNA levels of p53, MDM2, VEGF, and HIF-lα were detected in 60 villous samples of missed abortion patients and 64 healthy controls by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Immunohistochemistry was used to explore the expression and correlation of p53, MDM2, VEGF, and HIF-lα in villous tissues. Furthermore, we upregulated MDM2 expression in JEG-3 and BeWo cells under hypoxia, combined with Nutlin3, the cell cycle was determined using flow cytometry and the expressions of p53, MDM2, VEGF, and HIF-1α were determined by qRT-PCR and western blot. RESULTS: qRT-PCR demonstrated that the expressions of p53, MDM2, and HIF-1α were significantly increased and VEGF was decreased in missed abortion group compared with normal pregnancies. Correlation analysis found that p53 was positively correlated with MDM2 and HIF-1α, and negatively correlated with VEGF in missed abortion group. After administration of Nutlin3, overexpression of MDM2 could arrest cell cycle in G1 phase and reduce the proportion of S phase. The expression of p53 and MDM2 of JEG-3 cells and BeWo cells which transfected with pcDNA3.1-MDM2 plasmid were markedly increased after Nutlin3 addition under hypoxic conditions, while the expression of VEGF and HIF-1α decreased. CONCLUSION: Our data indicated that during the development of villi in early pregnancy, p53-MDM2 signaling regulate cell cycle and angiogenesis through interaction with HIF-1α and VEGF, which may be a crucial factor affecting pregnancy outcomes.

A novel method for office aspiration curettage in cases of retained products of conception: A randomized controlled trial.

INTRODUCTION: Missed abortion can be treated with medication or aspiration curettage. A Karman aspiration cannula is another option. We evaluated its success in evacuating retained products of conception (RPOC) based on symptoms, endometrial thickness, endometrial irregularity, and blood flow seen on Doppler ultrasound (indicative of placenta). MATERIAL AND METHODS: This prospective, randomized, nonblinded trial was conducted in a university-affiliated medical center. It included 40 women diagnosed with missed abortion and two failed courses of 600 µg buccal misoprostol, one  week apart, randomly assigned to treatment or controls. One week after the second misoprostol course, immediately after evaluating endometrial thickness, endometrial irregularity using Doppler ultrasound, and with blood flow indicative of RPOC, women in the aspiration group underwent endometrial suction with a Karman aspiration cannula. The 5-6 mm cannula attached to a 60 mL syringe was inserted into the uterus under ultrasound guidance. The contents were aspirated until the uterus was empty. Control group patients did not receive additional treatment. All were scheduled for ambulatory, operative hysteroscopy under anesthesia 1 month later (departmental protocol). On that day, all women with RPOC on Doppler ultrasound underwent hysteroscopy. Bleeding days, days with pain, pain according to visual analog scale, length of hospitalization, and infection rate were recorded. NIH clinical trial registration number NCT02917785. RESULTS: In the study group, 90% did not need hysteroscopy, compared with 50% of controls (p = 0.014). No complications were noted. At all visits, we used Doppler ultrasound to exclude or confirm RPOC. Pathology revealed RPOC in all women who underwent aspiration. Average visual analog scale score for office aspiration (n = 20) was 4.9 ± 3.6. vs. 6.3 ± 3.4 for the first (p = 0.157) and 4.7 ± 3.3 for the second (p = 0.836) misoprostol treatment cycle. The treatment group experienced 6.1 days of bleeding and the control group experienced 1.4 days (p = .006). CONCLUSIONS: Based on our criteria of diagnosing RPOC according to symptoms, endometrial thickness, endometrial irregularity, and blood flow indicative of placental tissue seen on Doppler ultrasound and histo-pathological confirmation, aspiration using Karman cannula can be an effective therapeutic approach. It may be a safe alternative for women with RPOC after misoprostol failure.