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.

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.

Minimally invasive surgical treatment of Robert's uterus with missed miscarriage: case report.

Robert's uterus was firstly reported in 1970, it's a rare Müllerian duct anomaly with 2 intra-uterine cavities divided by asymmetrical septum. One of the cavities is completely obstructed to cervix by septum and menstruation fluid retents in this blind cavity, periodical pelvic pain during menstruation can lead attendance to hospital. We report a gravida of Robert's uterus with missed abortion in the blind cavity, who had mild dysmenorrhoea since adolescent age, diagnosed and treated by minimally invasive surgical methods. To our knowledge, it's a previously unreported case which gynaecologists terminated pregnancy in blind cavity of Robert's uterus without resecting the septum while dysmenorrhoea relieved entirely and postoperative volume of menstruation stayed the same as preoperative.

Coagulation Status in Women with a History of Missed Abortion.

The purpose of this study assess the status of coagulation function in a large series of reproductive-age women with a history of missed abortion in China. Likewise, we want to explore the association between coagulation and missed abortions, in order to evaluate whether they could be used as early predictive factors for missed abortions. A total of 11,182 women who suffered from missed abortion from Peking University Third Hospital and 5298 healthy age-matched reproductive-age women were enrolled in our study. Coagulation function tests (prothrombin time, activated partial thromboplastin time), fibrinolysis status detection (fibrinogen, D-Dimer), anticoagulation function tests (protein C, protein S and antithrombin III), and lupus anticoagulants (LAC) were examined. In addition, platelet counts were detected by automated hematology analyzer. Platelet aggregation (PAgT) was tested by light transmission aggregometry (LTA). Compared with healthy reproductive-age women, the level of D-Dimer, dRVVT-R, PC, PAgT, and platelet count was higher, and the antithrombin III (AT-III) activity was lower in women with a history of missed abortion. (P < 0.05). A total of 13.1% patients with a history of missed abortion were positive for LAC, and platelet aggregation rates were increased in 47.4% patients. Moreover, multivariate logistic regression analysis showed that D-Dimer, dRVVT-R, AT-III, PC, and PAgT had significant predictive value for missed abortion. In addition, a model based on coagulation function tests for predicting missed abortion was developed. These findings provide evidence of hypercoagulability in patients with a history of missed abortion. Lupus anticoagulant, PAgT, and D-Dimer were the strongest predictors of missed abortion.was to.

Genetic analysis of chorionic villus tissues in early missed abortions.

Chromosomal abnormalities are the most common etiology of early spontaneous miscarriage. However, traditional karyotyping of chorionic villus samples (CVSs) is limited by cell culture and its low resolution. The objective of our study was to investigate the efficiency of molecular karyotyping technology for genetic diagnosis of early missed abortion tissues. Chromosome analysis of 1191 abortion CVSs in early pregnancy was conducted from August 2016 to June 2021; 463 cases were conducted via copy-number variations sequencing (CNV-seq)/quantitative fluorescent-polymerase chain reaction (QF-PCR) and 728 cases were conducted using SNP array. Clinically significant CNVs of CVSs were identified to clarify the cause of miscarriage and to guide the couples' subsequent pregnancies. Among these, 31 cases with significant maternal cell contamination were removed from the study. Among the remaining 1160 samples, 751 cases (64.7%) with genetic abnormalities were identified, of which, 531 (45.8%) were single aneuploidies, 31 (2.7%) were multiple aneuploidies, 50 (4.3%) were polyploidies, 54 (4.7%) were partial aneuploidies, 77 (6.6%) had submicroscopic CNVs (including 25 with clinically significant CNVs and 52 had variants of uncertain significance), and 8 cases (0.7%) were uniparental disomies. Our study suggests that both SNP array and CNV-seq/QF-PCR are reliable, robust, and high-resolution technologies for genetic diagnosis of miscarriage.

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.

The role of mifepristone on first trimester miscarriage treatment - A double-blind randomized controlled trial - MiFirsT.

OBJECTIVES: To evaluate the efficacy of combined mifepristone and misoprostol compared to misoprostol alone in outpatient medical treatment of first trimester miscarriage. Additionally, the study intends to compare the rate of complications, adverse effects, and treatment acceptability between groups. STUDY DESIGN: Single-center double-blind randomized placebo-controlled trial including women with diagnosis of missed first trimester miscarriage up to 9 weeks of gestation. RESULTS: Between April 2019 and November 2021, 216 women diagnosed with first trimester miscarriage up to 9 weeks of gestation were randomly assigned to mifepristone group or to misoprostol-alone group. Data from 105 women in mifepristone group and 103 women in misoprostol-alone group were analyzed, with no differences in baseline characteristics. The median time between medications (oral mifepristone/placebo and vaginal misoprostol) was nearly 43 h in both groups (p = 0.906). The median time to first follow-up was 2.6 weeks (IQR 1.0) in mifepristone group and 2.4 weeks (IQR 1.0) in misoprostol-alone group (p = 0.855). The overall success rate of medical treatment was significantly higher in the mifepristone-group comparing to misoprostol-alone group (94.3% vs. 82.5%, RR 1.14, 95% CI, 1.03-1.26; p = 0.008). Accordingly, the rate of surgical treatment was significantly lower in the mifepristone-group (5.7% vs.14.6%, RR 0.39, 95% CI, 0.16-0.97; p = 0.034). The composite complication rate was similar and lower than 4% in both groups. No case of complicated pelvic infection, hemodynamic instability or inpatient supportive treatment was reported. There were no significant differences in the rates of adverse events, median score for vaginal bleeding intensity or analgesics use. Despite the same median value, the score of abdominal pain intensity was significantly higher in the mifepristone-group (p = 0.011). In both groups, more than 65% of the women classified the treatment as "good" and 92% would recommend it to a friend on the same clinical situation. CONCLUSION: The mifepristone plus vaginal misoprostol combined treatment for medical resolution of first trimester miscarriage resulted in significant higher success rate and lower rate of surgical uterine evacuation comparing to misoprostol-alone treatment, with no relevant differences in adverse events or treatment acceptability.

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.

Exposure to pesticide components causes recurrent pregnancy loss by increasing placental oxidative stress and apoptosis: a case-control study.

We investigated the plasma levels of pesticides components namely polychlorinated biphenyls (PCBs), dieldrin, dichlorodiphenyldichloroethylene (DDE), ethion, malathion, and chlorpyrifos in recurrent pregnancy loss (RPL) cases, and tested their associations with placental oxidative stress (OS) biomarkers [nitric oxide (NO.), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and superoxide dismutase (SOD)] and with placental apoptotic/antiapoptotic indices (Bcl-2 and caspase-3), and evaluated their possible cut-off points to distinguish RPL cases. The study recruited 101 pregnant women divided into; G1 [n = 49, control, normal 1st-trimester pregnancy, normal obstetric history with at least one previous normal live birth], G2 [n = 26, cases with missed abortion (< 3 abortions) before 24 weeks of gestation], and G3 [n = 26, cases with missed abortion (≥ 3 abortions) before 24 weeks of gestation]. The plasma pesticide levels were analyzed by gas chromatography-mass spectrometry. Plasma human chorionic gonadotrophin (HCG), placental OS, Bcl-2, and caspase-3, were analyzed by their corresponding methods and kits. Plasma PCBs, DDE, dieldrin, and ethion levels were significantly higher in RPL cases than in normal pregnancies (p ≤ 0.001). These levels correlated positively with placental OS and apoptosis and negatively with plasma HCG levels. Also, these levels were reliable markers of risk to RPL. Malathion and chlorpyrifos were not detected in any of the study's participants. Pesticides may be risk factors in cases of spontaneous RPL cases. They are associated with an increasing placental OS and placental apoptosis. Specific measures should be taken to decrease maternal exposure to these pollutants' sources, especially in underdeveloped and developing countries.

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.

Prediction model for missed abortion of patients treated with IVF-ET based on XGBoost: a retrospective study.

Aim: In this study, we established a model based on XGBoost to predict the risk of missed abortion in patients treated with in vitro fertilization-embryo transfer (IVF-ET), evaluated its prediction ability, and compared the model with the traditional logical regression model. Methods: We retrospectively collected the clinical data of 1,017 infertile women treated with IVF-ET. The independent risk factors were screened by performing a univariate analysis and binary logistic regression analysis, and then, all cases were randomly divided into the training set and the test set in a 7:3 ratio for constructing and validating the model. We then constructed the prediction models by the traditional logical regression method and the XGBoost method and tested the prediction performance of the two models by resampling. Results: The results of the binary logistic regression analysis showed that several factors, including the age of men and women, abnormal ovarian structure, prolactin (PRL), anti-Müllerian hormone (AMH), activated partial thromboplastin time (APTT), anticardiolipin antibody (ACA), and thyroid peroxidase antibody (TPO-Ab), independently influenced missed abortion significantly (P < 0.05). The area under the receiver operating characteristic curve (AUC) score and the F1 score with the training set of the XGBoost model (0.877 ± 0.014 and 0.730 ± 0.019, respectively) were significantly higher than those of the logistic model (0.713 ± 0.013 and 0.568 ± 0.026, respectively). In the test set, the AUC and F1 scores of the XGBoost model (0.759 ± 0.023 and 0.566 ± 0.042, respectively) were also higher than those of the logistic model (0.695 ± 0.030 and 0.550 ± 049, respectively). Conclusions: We established a prediction model based on the XGBoost algorithm, which can accurately predict the risk of missed abortion in patients with IVF-ET. This model performed better than the traditional logical regression model.

[Interaction of polycyclic aromatic hydrocarbon DNA adducts and telomere length on missed abortion].

Objective: To analyze the contribution and interaction of polycyclic aromatic hydrocarbons (PAH)-DNA adducts and changes of telomere length (TL) on missed abortion. Methods: From March to December 2019, patients with missed abortion in the First Hospital of Shanxi Medical University and pregnant women with normal pregnancy but voluntary abortion in the same department during the same period were selected and divided into a case group and a control group. Questionnaire was used to investigate the general situation and the pregnancy situation of the subjects. The abortion villi were collected and the content of PAH-DNA adducts and TL was detected. Logistic regression model was used to analyze the associated factors of missed abortion. R epiR package and Mediation package were used to analyze the effect and relationship between PAH-DNA adducts and TL on missed abortion. Results: The age of the subjects was(29.92±5.69)years old. The M(Q1,Q3)of PAH-DNA adducts was 453.75(404.61, 504.72) pg/ml. The M(Q1,Q3)of TL was 1.21(0.77, 1.72). The content of PAH-DNA adducts in the case group was higher than that in the control group (Z=-2.10, P=0.036), while the TL was lower than that in the control group (Z=-4.05, P<0.001). Multivariate logistic regression showed that low, medium and high levels of PAH-DNA adducts (OR=3.17,95%CI:1.41-7.14;OR=2.85,95%CI:1.25-6.52;OR=2.46,95%CI:1.07-5.64), and long, medium and short levels of TL (OR=2.50,95%CI:1.11-5.63;OR=3.32,95%CI:1.45-7.56;OR=3.22,95%CI:1.42-7.26) were all risk factors for missed abortion. The medium level of PAH-DNA adducts had a 2.76-fold higher risk of shortened TL than those with the lowest level, and no mediating role of TL was found. The stratified analysis showed that when the TL level was longer (>1.21), the low and high levels of PAH-DNA adducts were associated with missed abortion (all P<0.05); when the TL level was shorter (<1.21), the medium level of PAH-DNA adducts was associated with abortion (P=0.025). At lower levels of PAH-DNA adducts, no effect of TL on missed abortion was observed, while, at higher levels, TL was strongly associated with missed abortion (OR=7.50,95%CI:1.95-28.82;OR=6.04,95%CI:1.54-23.65;OR=9.05,95%CI:2.34-35.04). The interaction analysis found that the AP was 0.72 (95%CI: 0.46-0.99), and the SI was 5.21 (95%CI: 2.30-11.77). Conclusion: The high level of PAH-DNA adducts and shortened TL may increase the risk of missed abortion, and there may be a positive additive interaction between the two factors on missed abortion.

Single-cell profiling of the microenvironment in decidual tissue from women with missed abortions.

OBJECTIVE: To define the decidual microenvironment in euploid and aneuploid missed abortions and elective termination of pregnancies. DESIGN: Prospective, multicenter, observational study. SETTING: Tertiary hospital and descriptive analysis of transcriptomic data. PATIENT(S): A total of 34 patients experienced abortions, including 6 women who underwent elective terminations of pregnancy of unplanned pregnancies and 28 cases with missed abortions. All patients underwent their operations from Sep, 2021 to Sep, 2022. INTERVENTION(S): All women underwent villous copy number variation sequencing. Meanwhile, single-cell RNA sequencing were performed in the decidual tissues of 16 women, and reverse transcription quantitative polymerase chain reaction were performed in the decidual tissues of 18 women. MAIN OUTCOME MEASURE(S): Single-cell RNA sequencing was used to explore the changes in the microenvironment of decidual tissues in abortions. RESULT(S): Single-cell RNA sequencing indicated that the microenvironment of the decidual tissue of the missed-abortion group was altered, and that the stromal cells (SCs), natural killer cells, macrophages, and epithelial cells all reflected functional imbalances compared with the elective terminations of pregnancy group. We also noted a correlation between the proportion of senescent SCs and chromosomal abnormalities in missed-abortion embryos. The proportion of senescent decidual SCs in the decidual tissue of missed-abortion patients with common chromosomal abnormalities of the fetus was higher, and this was not conducive to fetal growth and was closely related to missed abortion. In addition, we ascertained that the strength of the HLA-KIR interaction between NK1 and NK2 subsets and non-senescent stromal cell subsets in the missed abortion decidual tissues was weakened, potentially playing a role in the occurrence of missed abortion. CONCLUSION(S): The decidualization of SCs in the missed-abortion decidual tissues was impaired, the clearance of senescent SCs by NK cells was weakened, the killing toxicity of non-senescent SCs was enhanced, macrophages were insufficiently resident at the maternal-fetal interface, and epithelial cell differentiation was unbalanced-all creating a maternal microenvironment that was not conducive to fetal growth. We posit that interfering with the expression of dysregulated genes in the missed-abortion decidual tissues and reversing the maternal microenvironment might constitute an effective means toward improving the clinical outcome of missed abortions. Intriguingly, we observed a correlation between stromal cell senescence and embryonic chromosomal abnormalities. Thus, we hypothesize that the DIO2 marker of senescent SCs can be used as a risk indicator for the occurrence of missed miscarriages with chromosomal abnormalities of the embryos, and that it can be applied to guide the clinical diagnosis and treatment of recurrent abortion. CLINICAL TRIAL REGISTRATION NUMBER: NCT04425317.

Hystero-embryoscopy: evaluation and evacuation of spontaneous missed abortions.

OBJECTIVE: To demonstrate the steps for hystero-embryoscopic evaluation of a 7-week spontaneous missed abortion and evacuation of the products of conception. Illustrate the surgical technique and highlight its advantages in improving the evaluation of spontaneous missed abortions. DESIGN: Video case presentation and demonstration of surgical technique. SETTING: Tertiary referral center. PATIENT(S): The patient provided consent for the video and its publication. INTERVENTION(S): Following vaginoscopy, the cervix was approached without prior blind cervical dilation. Navigation from the endocervix to the endometrial cavity was performed using a 2.9-mm diameter hysteroscope. The endometrial cavity was thoroughly inspected revealing an intact gestational sac and submucosal fibroids. An operative grasper was introduced, the chorion and amnion were penetrated, and embryoscopy was performed. In-flow was reduced for external morphological inspection of the embryo, which was then grasped and retrieved. The procedure was continued by introducing of a 26-french bipolar resectoscope, after which the products of conception were excised without electricity and sent for histologic and genetic analyses. MAIN OUTCOME MEASURE(S): This procedure allowed for proper embryonic evaluation and hysteroscopic evacuation of products of conception was successfully performed. RESULT(S): Cytogenic analysis of this case revealed a female embryo with trisomy 15. No maternal and fetal cell admixture was noted in the analysis, allowing a precise diagnosis. CONCLUSION(S): Hystero-embryoscopy is a valuable diagnostic and therapeutic procedure for cases of missed abortion. It may reveal embryonic morphological abnormalities, expand the diagnostic spectrum in the evaluation of pregnancy loss, and avoid potential complications from blind curettage.

Clinical presentation, investigation, underlying causes, and subsequent pregnancy outcomes among different phenotypes of second trimester miscarriage.

AIM: To evaluate the causes of miscarriage and subsequent pregnancy outcomes among different phenotypes of second trimester miscarriage. METHODS: Retrospective analysis of 170 consecutive second trimester miscarriages between 14 + 0 and 23 + 6 weeks recorded in the Clinical Data Analysis and Reporting System from 2012 to 2021. Cases were excluded if miscarriages occurred before 14 + 0 weeks of gestation, data were incomplete, or passage of the fetus happened before the clinical assessment. Cases were classified with a stepwise approach into three phenotypic groups including silent miscarriages (ST-SM), rupture of membranes (ST-ROM), and inevitable miscarriages (ST-IM) depending on the fetal heart pulsation and leakage of liquor at presentation. Clinical investigation of the underlying causes and the outcome of the subsequent pregnancy was then reviewed. RESULTS: There were 97 cases of ST-SM, 21 cases of ST-ROM, and 52 cases of ST-IM. Placental histology and karyotype examination were more likely to yield significant results in the cases of ST-ROM and ST-SM (p < 0.05). The phenotypic examination identified different underlying causes including fetal anomaly, suspected cervical insufficiency, diabetes mellitus, and unknown causes (p < 0.001). Sixty-four cases achieved a subsequent pregnancy. Although women with history of ST-ROM and ST-IM received more cervical length monitoring and cervical cerclage than those with ST-SM (66.7% vs. 44.4% vs. 7.5%, p = 0.0002; and 16.7% vs. 22.2% vs. 2.5%, p = 0.031, respectively), the risk of recurrent second trimester miscarriage was higher in ST-ROM and ST-IM than in ST-SM (16.7% vs. 0%, p = 0.018). CONCLUSION: The classification can differentiate different second trimester miscarriage phenotypes, which offers essential information to guide investigation panels of the underlying cause of miscarriages, and the prognosis and management of subsequent pregnancy. Future researches focused on second trimester miscarriage should report their findings according to different phenotypes.

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 (

Interaction of polycyclic aromatic hydrocarbon DNA adducts and telomere length on missed abortion / 中华预防医学杂志

Objective: To analyze the contribution and interaction of polycyclic aromatic hydrocarbons (PAH)-DNA adducts and changes of telomere length (TL) on missed abortion. Methods: From March to December 2019, patients with missed abortion in the First Hospital of Shanxi Medical University and pregnant women with normal pregnancy but voluntary abortion in the same department during the same period were selected and divided into a case group and a control group. Questionnaire was used to investigate the general situation and the pregnancy situation of the subjects. The abortion villi were collected and the content of PAH-DNA adducts and TL was detected. Logistic regression model was used to analyze the associated factors of missed abortion. R epiR package and Mediation package were used to analyze the effect and relationship between PAH-DNA adducts and TL on missed abortion. Results: The age of the subjects was(29.92±5.69)years old. The M(Q1,Q3)of PAH-DNA adducts was 453.75(404.61, 504.72) pg/ml. The M(Q1,Q3)of TL was 1.21(0.77, 1.72). The content of PAH-DNA adducts in the case group was higher than that in the control group (Z=-2.10, P=0.036), while the TL was lower than that in the control group (Z=-4.05, P<0.001). Multivariate logistic regression showed that low, medium and high levels of PAH-DNA adducts (OR=3.17,95%CI:1.41-7.14;OR=2.85,95%CI:1.25-6.52;OR=2.46,95%CI:1.07-5.64), and long, medium and short levels of TL (OR=2.50,95%CI:1.11-5.63;OR=3.32,95%CI:1.45-7.56;OR=3.22,95%CI:1.42-7.26) were all risk factors for missed abortion. The medium level of PAH-DNA adducts had a 2.76-fold higher risk of shortened TL than those with the lowest level, and no mediating role of TL was found. The stratified analysis showed that when the TL level was longer (>1.21), the low and high levels of PAH-DNA adducts were associated with missed abortion (all P<0.05); when the TL level was shorter (<1.21), the medium level of PAH-DNA adducts was associated with abortion (P=0.025). At lower levels of PAH-DNA adducts, no effect of TL on missed abortion was observed, while, at higher levels, TL was strongly associated with missed abortion (OR=7.50,95%CI:1.95-28.82;OR=6.04,95%CI:1.54-23.65;OR=9.05,95%CI:2.34-35.04). The interaction analysis found that the AP was 0.72 (95%CI: 0.46-0.99), and the SI was 5.21 (95%CI: 2.30-11.77). Conclusion: The high level of PAH-DNA adducts and shortened TL may increase the risk of missed abortion, and there may be a positive additive interaction between the two factors on missed abortion.

[Observation on effect of five evolutive phases and six climatic factors on pregnancy and sterility].

Objective： To verify statements about the effect of five evolutive phases and six climatic factors in 《huang di nei jing》 on pregnancy and sterility. Methods： Data of missed abortion from Nanjing Maternity and Child Health Care Hospital between 2006-2020 and Yangzhou Maternity and Child Health Care Hospital between 2012-2020 were collected. According to Chinese sexagenary cycle heavenly stems and earthly branches of each year between 2006-2020 was determined. And then based on the heavenly stems and earthly branches, evolutive phases and six climatic factors of each year were established. After that data of missed abortion in each year was compared. According to relative statements in 《huang di nei jing》 , it was observed whether the number of missed abortion cases in someone year increased significantly. Results: Totally there were 28059 cases of missed abortion from the two hospital were collected between 2006-2020 and 2012-2020 respectively. It was found that in the year of Shaoyang phase fire sitian and Jueyin wind wood in the spring (that is the year of 2010 and 2016) the number of missed abortion cases was higher obviously than the other year. When the year of Taiyang cold water in the spring (that is the year of 2009 and 2015), there was a relatively increased number of missed abortion cases. Conclusions: Five evolutive phases and six climatic factors have impacts on human pregnancy and sterility. It was an adverse condition for human reproduction in the year of Shaoyang phase fire sitian and Jueyin wind wood in the spring as well as Taiyang cold water in the spring. Until to now we can still verify statements about the effect of five evolutive phases and six climatic factors on pregnancy and sterility in 《huang di nei jing》.

Medical Termination of Pregnancy (MToP) in the 1st trimester - the role of human chorionic gonadotropin and ultrasound in pregnancy diagnosis and MToP follow-up.

OBJECTIVE: In the Czech Republic, it is possible, to carry out Medical Termination of Pregnancy (MToP) in the 1st trimester up until the 49th day of secondary amenorrhea. The aim of the study is to analyse the significance of serum/urine human chorionic gonadotropin (hCG) assessment and ultrasound (US) examination in pregnancy diagnosis and MToP follow-up. METHODS: In 2017-2018, MToP was carried out in a total of 109 women by administering a combination of mifepristone (600 mg orally) and misoprostol (400 mcg orally). Serum/urine (LSUP - low sensitivity urine pregnancy test) hCG assessment and US examination were performed at pregnancy diagnosis and MToP follow-up. RESULTS: At pregnancy diagnosis, there was a positive and medium strong correlation between serum hCG and size of the gestational sac - GS (R = 0.711; P  1,000 IU/L and LSUP test was always positive). In 5.5% of women (6/109), a subsequent surgical intervention was carried out including those with ongoing pregnancy (N = 5); missed abortion (N = 1) was treated by additional misoprostol, where surgical intervention was not necessary. CONCLUSION: At pregnancy diagnosis, there is a positive and medium strong correlation between serum hCG and CRL. In MToP follow-up, a negative LSUP test enables reliable exclusion of ongoing pregnancy and missed abortion. In case of a positive LSUP test, US examination should be performed; however, surgical intervention should not be indicated solely on the basis of uterine cavity dilatation.