Miscarriage Group Research Articles

Immune cell profiling of vaginal blood from patients with early pregnancy bleeding.

Vaginal bleeding during early pregnancy is estimated to occur in 20% of all pregnancies and it is often difficult to predict who will ultimately miscarry. The role of immune cells in early pregnancy loss is poorly understood. In this prospective cohort study, 28 pregnant women presenting with first-trimester vaginal bleeding donated vaginal blood, peripheral venous blood, and saliva during their initial emergency room visit, and at a follow-up. The composition, frequency, and phenotype of immune cells in the vaginal blood were determined using flow cytometry. The proteome of serum and saliva was analyzed with OLINK proximity extension assay and correlated to vaginal immune cell phenotype and outcome of pregnancy. The course and outcome of pregnancies were followed and recorded. Vaginal blood contained all main immune cell lineages including B cells, NK cells, T cells, and monocytes/macrophages. Notably, vaginal blood immune cells expressed tissue residency markers including CD49a. Women who subsequently miscarried had a higher frequency of vaginal blood CD49a+ NK cells compared to those who did not miscarry, and this correlated with serum levels of granzyme A and H, as well as CSF1, CAIX, and TWEAK. Women in the miscarriage group also had a higher frequency of peripheral blood T cells expressing CD49a. Our study provides novel insight into human reproductive immunology in relation to miscarriage. Tissue-resident NK cells in vaginal blood alone or in combination with serological biomarkers hold potential as prognostic factors in the prediction of pregnancy outcome in women with early pregnancy bleedings.

Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology.

Miscarriage is a major concern in early pregnancy among women having conceived with assisted reproductive treatments. This study aimed to examine potential miscarriage-related biophysical and biochemical markers at 6 weeks' gestation among women with confirmed clinical pregnancy following in vitro fertilization (IVF)/embryo transfer (ET) and evaluate the performance of a model combining maternal factors, biophysical and biochemical markers at 6 weeks' gestation in the prediction of first trimester miscarriage among singleton pregnancies following IVF/ET. A prospective cohort study was conducted in a teaching hospital between December 2017 and January 2020 including women who conceived through IVF/ET. Maternal mean arterial pressure, ultrasound markers including mean gestational sac diameter, fetal heart activity, crown rump length and mean uterine artery pulsatility index (mUTPI) and biochemical biomarkers including maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), kisspeptin and glycodelin-A were measured at 6 weeks' gestation. Logistic regression analysis was carried out to determine significant predictors of miscarriage prior to 13 weeks' gestation and performance of screening was estimated by receiver-operating characteristics curve analysis. Among 169 included pregnancies, 145 (85.8%) pregnancies progressed to beyond 13 weeks' gestation and had live births whereas 24 (14.2%) pregnancies resulted in a miscarriage during the first trimester. In the miscarriage group, compared to the live birth group, maternal age, body mass index, and mean arterial pressure were significantly increased; mean gestational sac diameter, crown rump length, mUTPI, serum sFlt-1, glycodelin-A, and the rate of positive fetal heart activity were significantly decreased, while no significant differences were detected in PlGF and kisspeptin. Significant prediction for miscarriage before 13 weeks' gestation was provided by maternal age, fetal heart activity, mUTPI, and serum glycodelin-A. The combination of maternal age, ultrasound (fetal heart activity and mUTPI), and biochemical (glycodelin-A) markers achieved the highest area under the curve (AUC: 0.918, 95% CI 0.866-0.955), with estimated detection rates of 54.2% and 70.8% for miscarriage before 13 weeks' gestation, at fixed false positive rates of 5% and 10%, respectively. A combination of maternal age, fetal heart activity, mUTPI, and serum glycodelin-A at 6 weeks' gestation could effectively identify IVF/ET pregnancies at risk of first trimester miscarriage.

Immunohistochemical study of MMP-2, MMP-9, EGFR and IL-8 in decidual and trophoblastic specimens of recurrent pregnancy loss cases

Background and Aim: Unexplained recurrent pregnancy loss has been a a challenging research task to experts since there is no explicit pathophysiological mechanism and therefore, the treatment remains elusive. Immunological imbalance and morphological abnormalities are under investigation. This study aims to evaluate the implication of MMP-2, MMP-9, EGFR, and IL-8 in recurrent pregnancy loss cases. Materials & Methods: The study was carried out through comparison among two groups; the unexplained miscarriage group which consisted of 22 women, and the control group consisted of 18 women, who had electively terminated their pregnancies. Both groups were in the first trimester of gestation. The specimens included the trophoblast, decidua basalis, and decidua parietalis. The study was conducted via immunohistochemical methods. Antibodies were used against MMP-2, MMP-9, EGFR, and IL-8. The results were presented at a contingency table and were statistically analyzed with the Chi-Square Test (X2). Results: There were remarkable disparities in some cases in the comparison of the two groups. MMP-9 was detected significantly high in recurrent pregnancy loss (RPL) cases, both on trophoblastic and decidual specimens (p-value < .00001), MMP-2 displayed no difference among the two groups (mild to moderate detection on trophoblast and almost negative on decidual tissues). EGFR was highly detected in trophoblastic tissue (p-value = .014). IL-8 detection was particularly different in both trophoblast and decidua parietalis of the two groups (p-value < .01). Conclusion: The study revealed both morphological and immunological dysregulations that might participate in the RPL pathogenesis.

Symptoms of anxiety and depression in women with gestational trophoblastic disease compared to women who had a miscarriage: a cross-sectional study

This study was conducted between March 2020 and February 2021 to analyze anxiety and depression symptoms in 64 women with gestational trophoblastic disease (GTD) and 99 women who had miscarried. The Hospital Anxiety and Depression Scale (HADS) was applied by telephone three months after pregnancy loss. Multivariate analysis was performed using hierarchical logistic regression to evaluate associations between variables. Probable anxiety (HADS-A ≥ 8) and depression (HADS-D ≥ 8) were found in 53.1% and 43.8% of the GTD group and 49.5% and 39.4% of the miscarriage group, with no difference between the groups. Severe symptoms of anxiety (HADS-A 15-21) and depression (HADS-D 15-21) were found, respectively, in 12.5% and 4.7% of the GTD group and in 9.1% and 4.0% of the miscarriage group, also with no difference between the groups. Lack of partner support proved a risk factor for anxiety and depression, while poor education increased the risk of depression symptoms 3.43-fold following pregnancy loss. In conclusion, three months after pregnancy loss the frequency of anxiety and depression symptoms was similarly high in both groups, with poor education and lack of partner support being significant risk factors for the subsequent development of psychiatric morbidity.

Papillomavirus Infection as Potential Cause of Miscarriage in the Early Gestational Age: A Prospective Study.

The possible association between human papillomavirus (HPV) infection and negative pregnancy outcomes has been debated in the literature, with conflicting results from clinical trials. While some authors support a link between HPV and miscarriage, others argue that the mere detection of the virus does not necessarily indicate a causal relationship with negative pregnancy outcomes. In this study, we conducted a prospective, controlled investigation of the potential association between HPV infection and miscarriage. Our study included 59 women who had experienced a miscarriage and 57 women who had undergone voluntary termination of pregnancy (TOP) within the 12th week of gestation. We assessed HPV prevalence, maternal age, and HPV genotype in both groups and evaluated the relationship between these factors and pregnancy outcome. Unlike previous studies that only identified HPV in cases of abortion, we also correlated the positivity of chorionic villi with gestational age in both groups. We found a close correlation between positive chorionic villi and very early gestational age, with all 13 cases of virus-positive chorionic villi in the miscarriage group occurring in gestational periods of less than 8 + 5 weeks (<60 days) (RR = 28.6). Our analysis showed no correlation between HPV infection and maternal age or viral genotypes. The results suggest that the presence of HPV alone is not enough to cause spontaneous abortion, but a high viral load in early pregnancy may increase the risk of negative outcomes. These findings have important implications for the management of HPV infection during pregnancy and may provide a rationale for the use of HPV vaccines to reduce the incidence of spontaneous abortion and infertility due to preclinical spontaneous abortions.

Efficacy of Gonadotropin-Releasing Hormone Agonist (GnRH-a) in Ovarian Preservation in Females With Systemic Lupus Erythematosus (SLE) Receiving Cyclophosphamide (CYC) [ID: 1375370

INTRODUCTION: Systemic lupus erythematosus (SLE) female patients with severe disease manifestations are treated with cyclophosphamide (CYC), which causes ovarian cytotoxicity. Gonadotropin-releasing hormone agonist (GnRH-a) is often co-administered with CYC to preserve ovarian function and reproductive potential. However, there is a lack of evidence to support this use of GnRH-a. We conducted a retrospective study and questionnaire of SLE patients who received CYC with or without GnRH-a to evaluate its efficacy in preserving ovarian function. METHODS: This study was approved by the IRB of the National Institutes of Health (IRB#:001011). Review of medical records resulted in 50 female SLE patients treated with CYC who were less than 40 year old at the time of treatment: CYC only (n=20, group 1), CYC and GnRH-a (n=30, group 2). These patients were age/gender-matched with 50 SLE patients not treated with CYC (group 3). Data about demographics, SLE disease activity, damage accrual, cumulative CYC exposure, and pregnancy outcomes were collected by chart review. Self-reported questionnaires were used to collect data assessing menses cycles, pregnancies and their outcome, or infertility. RESULTS: There was no significant difference in SLE disease activity, baseline demographics, total damage accrual, or other clinical parameters between groups 1 and 2. The mean cumulative CYC dose was 1.2 g (group 1) and 1.5 g (group 2) (P=.16). Number of pregnancies were similar: mean (SD) group 1=2 (1.6); group 2=1.2 (1.4); group 3=1.3 (1.4) (P=.18). There were more miscarriages in group 1 compared to groups 2 and 3 (P=.015). CONCLUSION: Our data suggest use of GnRH-a improves pregnancy outcomes in SLE patients on CYC, but prospective studies are needed to establish its safety and efficacy.

Serum Cu, Zn and IL-1β Levels May Predict Fetal Miscarriage Risk After IVF Cycles: A NestedCase-Control Study.

To explore the association between serum-related indicators (levels of inflammatory cytokines and essential trace elements) and miscarriage risk among infertile women undergoing assisted reproductive techniques (ART) on the 14th day after embryo transfer, and to develop and establish a multivariable algorithm model that might predict pregnancy outcome. According to a nestedcase-control study design, a total of 100 miscarriage cases and 100 live birth controls were included in this study, and women in both groups were infertile and have underwent in vitro fertilization (IVF). Pregnancy tests were performed and serum levels of five essential trace elements (vanadium (V), copper (Cu), zinc (Zn), selenium (Se) and molybdenum (Mo)) and five inflammatory cytokines (interleukin-1β (IL-1β), IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α)) of the participants were measured on the 14th day after embryo transfer. The serum levels of five inflammatory cytokines were determined by multiple magnetic bead enzyme immunity analyzer; and the serum concentrations of five elements were determined simultaneously by inductively coupled plasma‒mass spectrometry (ICP ‒ MS). The logistic regression was used to evaluate the relationship between these serum indices and miscarriage risk among women undergoing ART, and a predictive model of pregnancy outcome based on these indices was established. The levels of IL-10, IL-1β and TNF-α of infertile women in the live birth group were significantly higher than those in the miscarriage group (p = 0.009, p < 0.001, p = 0.006), and the levels of V, Cu, Zn and Se of infertile women in the live birth group were also significantly higher than those in the miscarriage group (all p < 0.001). Through logistic regression analyses, we found that serum levels of IL-1β, TNF-α, V, Cu, Zn and Se were significantly and negatively associated with miscarriage risk. Different combination prediction models were generated according to the results of logistic regression analyses, and the combination of IL-1β, Cu and Zn had the best prediction performance. The area under the curve (AUC) was 0.776, the sensitivity of the model was 60% and the specificity was 84%. In conclusion,the serum-related indicators of women undergoing ART on the 14th day after embryo transfer, including the inflammatory cytokines such as IL-1β and TNF-α and the essential trace metal elements such as V, Cu, Zn and Se, were negatively correlated with miscarriage risk. A multivariate algorithm model to predict pregnancy outcome among women undergoing ART was established, which showed that IL-1β, Cu and Zn might synergistically predict pregnancy outcome.

Human Leukocyte Antigen Alleles Compatibility and Immunophenotypic Profile Associations in Infertile Couples.

The maternal immune system has a major role in the successful embryo implantation and maintenance of the pregnancy. This study aimed to investigate the maternal immunophenotyping profile (percentage of Natural Killer [NK] cellsand the CD4/CD8 [cluster designation] ratio in peripheral blood lymphocytes)and the HLA (Human Leukocyte Antigen)-DQA1 alleles sharing in infertile couples. This cross-sectional study included 78 women who had experienced at least two spontaneous miscarriages and 110 women with a history of recurrent implantation failures after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) (IVF-ET failures). The NK cell percentage and the CD4/CD8 ratio were determined by flow cytometry. Genotyping of the HLA-DQA1alleles was carried out for all women and their partners, and couple HLA-DQA1 compatibility was expressed as the percentage of commonHLA-DQA1 alleles (totaling 35 alleles)shared between spouses to the sum of the unique alleles observed. In women with recurrent miscarriages, high values (%) of the NK population with a median (interquartile range [IQR]) of 10.3% (7.7% to 12.5%) and CD4/CD8 ratio (1.7) (1.5 to 2.1) were found. In women with IVF-ET failures, the (%) NK population (10.5%) (8.6% to 12.5%) and CD4/CD8 ratio (1.8) (1.5 to 2.1) were similarly increased (p=0.390, and p=0.490, respectively). The proportion of women with >10% NK cells was 53.8% and 58.2% in women with miscarriages and IVF-ET failures, respectively (p=0.554). The prevalence of HLA-DQA1*5 allele carriage was elevated in women with miscarriages as well as those with IVF-ET failures (52.6% and 61.8%, respectively; p=0.206). The proportion of couples with high (>50%) HLA-DQA1 sharing was 65.4% in the group with miscarriages and 73.6% in the group with IVF-ET failures, respectively (p=0.222). The CD4/CD8 ratio was statistically significantly positively correlated with the (%) NK population in women with IVF-ET failures (rho = 0.297, p=0.002) and with the (%) HLA-DQA1 sharing in the group with miscarriages (rho = 0.266, p=0.019). The couples in which both spouses were carriers of the HLA-DQA1*5 allele had an increased probability of high (>50%) HLA-DQA1 compatibilitycompared with the couples in which neither of the spouses carried the allelein the miscarriage group (OR = 24.3, 95% CI: 3.0 to 198.9, p<0.001), and the IVF-ET failure group (OR = 10.5, 95% CI: 2.2 to 49.8, p<0.001). The peripheral NK (%) population and CD4/CD8 ratio, as well as the prevalence of the HLA-DQA1*5 allele, were elevated in women with recurrent miscarriages and IVF-ET failures. Furthermore, these couples with negative reproductive outcomes had a high percentage of HLA-DQA1 allele similarity. The presence of the HLA-DQA1*5 allele in spouses was strongly associated with overall couple HLA-DQA1 compatibility, implying that it could be used as a surrogate marker for assessing overall immunological compatibility in infertile couples.

Profiling of Immunomodulatory Genes and Quantification of CD25+ Cells in Different Types of Early Pregnancy Loss.

Maternal regulatory T (Treg) cells play a pivotal role in establishing general immune homeostasis in the decidua for maintenance of pregnancy. We aimed in this study to investigate the relationship between mRNA expression of immunomodulatory genes and CD25+ Treg cells with early pregnancy losses. Our study included 3 groups of early pregnancy losses including sporadic spontaneous abortions, recurrent spontaneous abortions, sporadic spontaneous abortions post IVF treatment and the control group. We performed RT-PCR for analyzing mRNA expression levels of 6 immunomodulatory genes and CD25 immunohistochemistry for quantification of Treg cells. Only FOXP3, CD274 (PDL1), and TGFβ1 mRNA expression levels were significantly decreased in the miscarriage groups in comparison to the control group, whereas there was no significant mRNA expression change of CD4, IL2RA, and IL10. We also found significantly lower number of CD25+ cells in the miscarriages. We conclude that decreased expression of FOXP3 and PD-L1 may play a significant role in the pathogenesis of spontaneous abortion cases whereas decreased expression of TGFβ1 gene may be associated with the occurrence of early loss in IVF-treated pregnancies. Additional immunoprofiling of Treg cell population is needed to quantify Treg cells in early pregnancy losses.

Dysregulated low-density granulocyte contributes to early spontaneous abortion.

Spontaneous abortion (SA) is a common adverse pregnancy event with unclarified pathogenesis and limited therapeutic efficiency. Although most SA cases with the euploid embryo(s) are associated with immunological factors, the contribution of low-density granulocyte (LDG) in SA pathogenesis is rarely reported. This study aimed to investigate the serial characteristics and possible contribution of LDG and their subpopulations in early pregnancy, especially in early SA. Unpregnant (UP), normally pregnant (NP), and SA women were recruited, and the peripheral blood and endometrium/decidua were collected for LDG isolation and histological observation. The percentage, phenotype, and subpopulations of LDG were analyzed via flow cytometric analysis, and the ability of Nets formation was assessed by immunofluorescent and immunohistochemical assays. As a result, 43 participants were enrolled, including 10 UP, 15 NP, and 18 SA women. Compared with the UP group, the LDG percentage in peripheral blood mononuclear cells (PBMCs) and decidual immune cells (DICs) increased in the NP group, while the loss of this increase was observed in the SA group. Meanwhile, CD16int/- cell percentage in peripheral blood LDG (PB-LDG) increased in the NP and SA groups, and insufficient activation of CD16hi PB-LDG characterized by reduced CD11b expression was discovered in the SA group. Moreover, the LDG percentage in DICs was higher than that in PBMCs, and the decidual LDG (D-LDG) showed a surface marker expression profile that is easier to be activated in the pregnant cohort (NP + SA women). Finally, increased decidual Nets formation was observed in the SA group compared with the NP group, and more Nets formation was detected in D-LDG of NP and SA women following PMA stimulation. Overall, LDG participates in the maintenance of early pregnancy, while dysregulated LDG is responsible for early SA, providing novel potential targets for further exploration of SA pathogenesis and therapeutics.

Psychological disorders associated with women after abortion

The researcher's aimed in their current research to identify the levels and the significant of the difference of psychological disorders of women after abortion for (150) participants in Erbil city. Taking into consideration variables such as ages among (5) groups {(21 - 25), (26 - 30), (31 - 35), (36 - 40), (41 &amp; more)}, then number of miscarriages among (3) groups {(1 -2), (3 - 4), (5 &amp; more)} and academic achievement among (4) groups {(Illiterate), (Middle school &amp; less), (Secondary), (Diploma &amp; higher)}. To measuring the Variable's in current researcher's prepared the items of psychological disorders and its (5) dimensions (anxiety, depression, phobia , guilt, OCD) depended on Mental Health Literature after translating the scale according to the need of the research, the validity and reliability of scale were verified. The, (% 90.90 ) of experts agreed on all items of the scale, and the researcher's relied on the Split-half and Cronbach's Alpha methods to record the scales reliability, the results showed that the reliability value of psychological disorders is (0.83) (0.80) respectively. After that the scale were applied on the research samples through individual interviews, and then data processing by using (Spss) the results showed: 1. The prevalence rate of psychological disorders and all dimensions (anxiety, depression, phobia , guilt, OCD) are high and significant among participant's women after abortion in Erbil city. 2. There are significant differences in the prevalence rate of psychological disorders and all dimensions (anxiety, depression, phobia, OCD) according to the variable of age groups among participant's women after abortion , except for the dimensions of guilt it is not significant. 3. There are significant differences in the prevalence rate of psychological disorders and all dimensions (anxiety, depression, phobia, guilt, OCD) according to the variable of number of miscarriage's groups among participant's women after abortion. 4. There are no significant differences in the prevalence rate of psychological disorders and all dimensions (anxiety, depression, phobia, guilt, OCD) according to the variable of academic achievement groups among participant's women after abortion. Depending on these results, the researchers has presented some recommendations and suggestions.

Determination of the Predictive Roles and Potentially Pathogenic Antigen Epitopes of α-Enolase Related to the Development of Miscarriage in Females with Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) is a common endocrine disease which causes a significantly increased risk of miscarriage. Our recent study has shown that the increased ENO1 autoantibody (ENO1Ab) expression in an experimental AIT mouse model was induced by thyroglobulin (Tg) immunization only. In this study, we explored the potential roles of ENO1Ab in miscarriage occurrence among AIT women, and the specific epitopes of ENO1 targeted by ENO1Ab. A total of 432 euthyroid pregnant participants were selected from the project of Subclinical Hypothyroid during Early Pregnancy, including 48 women with AIT and miscarriage, 96 with miscarriage but no AIT, 96 with AIT but no miscarriage, and 192 without either AIT or miscarriage. The enzyme-linked immunosorbent assay was used to determine the serum levels of total IgG against ENO1 and 18 predicted antigen epitopes of ENO1. The results showed that women with AIT and miscarriage had the highest serum levels of ENO1Ab compared to the other groups. Logistic regression analysis showed that the serum ENO1Ab was an independent risk factor for miscarriage, especially among AIT females. The serum level of total IgG against the predicted epitope peptide 6 (i.e., P6 and aa168-183) of ENO1 was significantly increased in women with AIT and miscarriage when compared with those of both the AIT non-miscarriage group and non-AIT miscarriage group. This pilot study suggests that serum ENO1Ab may have a fair predictive value for AIT-related miscarriage, and the autoantibody specific to P6 epitope may especially be more specifically related to this disorder.

Association of MTHFR gene C677T polymorphism with pregnancy outcome.

The two objectives of the present study were to analyze the correlation between pregnancy outcomes and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism, and to provide evidence for clinical improvement of adverse pregnancy outcomes. 1,995 cases of pregnant women were selected as objects of the study, and underwent MTHFR gene C677T polymorphism detection in the Second Affiliated Hospital of Guangxi Medical University from October 2020 to September 2021, in which 919 cases whose pregnancy outcomes could be tracked. According to the result of MTHFR gene C677T polymorphism detection, 1,995 cases of pregnant women were classified into a wild-type (CC) group, heterozygous (CT) group, or homozygous (TT) group, and the distributions of MTHFR gene C677T polymorphism in pregnant women were analyzed. In addition, according to complications, 919 cases of pregnant women whose pregnancy outcomes could be tracked were divided into the normal pregnancy group (676 cases), GDM group (146 cases), HDP group (47 cases), abnormal fetus group (13 cases), and spontaneous abortion group (37 cases), and the genotype distributions of MTHFR gene C677T in each group were analyzed. Besides, according to genotype, 919 cases of pregnant women whose pregnancy outcome could be tracked were divided into CC group (515 cases), CT group (289 cases), and TT group (115 cases), and the correlation between genotype and pregnancy outcomes, such as fetal distress, postpartum hemorrhage, premature birth, and full-term delivery, was then analyzed. For the C677T locus of MTHFR gene in the 1,995 cases of pregnant women, there are 1,162 (58.25%) cases of CC genotype, 649 (32.53%) cases of CT genotype, 184 (9.22%) cases of TT genotype. The proportion of TT genotype in GDM, HDP, abnormal fetus, and spontaneous abortion groups were respectively 19.86% (29/148), 25.53% (12/47), 46.15% (6/13), 40.54% (15/37), which were significantly higher than that in normal pregnancy group (7.84%, 53/676), and there were statistically significant differences (p < 0.05). The full-term birth rate in TT group (75.65%, 87/115) was lower than those of CC group (91.26%, 470/515) and CT group (89.27%, 258/289), and there were statistically significant differences (p < 0.05). The TT type gene mutation at the C677T site ofMTHFR gene is closely related to conditions that contribute to a decrease in the number of full-term births and increase the risk of adverse pregnancy outcomes, including GDM, HDP, spontaneous abortion, and fetal abnormalities.

Analysis of the guidance and predictive value of uterine artery flow parameters in patients with recurrent spontaneous abortion.

To analyze the uterine artery blood flow parameters of patients with recurrent spontaneous abortion (RSA) at different gestational ages and to investigate the effects of aspirin and low molecular weight heparin (LMWH) on uterine artery blood flow parameters and pregnancy outcomes. This was a retrospective cohort study involving analysis of clinical data for 140 patients: 47 in an aspirin group, 49 in a combination group, and 44 in a control group. The uterine artery blood flow parameters of the three groups in the middle luteal period and 10th, 12th, 16th, and 20th gestational weeks were compared. Trends in uterine artery flow parameters were predicted by function fitting, and the uterine artery flow parameters and pregnancy outcomes between different drug administration regimens were compared. With increasing gestational age, the uterine artery blood flow parameters of the three groups gradually decreased. In the middle luteal phase, the uterine artery blood flow parameters (mRI, mPI, mS/D) of the recurrent spontaneous abortion group, that is, the aspirin and combination groups, were significantly higher than those of the control group. Uterine artery blood flow parameters from 10 to 20 weeks of gestation were as follows: combined group < aspirin group < normal pregnancy group. The mean resistance index (mRI) in the combination group decreased most rapidly compared with the aspirin group between 10 and 20 weeks of gestation. The live birth rate was higher in the combination group than in the aspirin group. Both aspirin and aspirin combined with LMWH can reduce uterine artery blood flow parameters, and combination therapy is superior to aspirin alone. In the RSA group, the rate of mRI decline may predict pregnancy outcome to some extent. Combination therapy can improve the live birth rate and reduce the miscarriage rate.

Assessment of Some Biochemical Parameters in Iraqi Women with Recurrent Miscarriage

Miscarriage a is pregnancy loss that occurs within the first 23 weeks. The risk factors that increase miscarriage is multivariate. Spontaneous loss of a conception before the 20th week of pregnancy is known as a miscarriage. There are two types of miscarriage: spontaneous and recurrent, one or more sporadic miscarriages affects approximately 25 – 50 percent of all women. Recurrent miscarriage, on the other hand, affects about 1% of couples trying to conceive. There are a number of things that can cause a miscarriage, such as inflammatory and immune system diseases. This study aims to compare the levels of calcium, Zinc, lipid peroxidation (Malondialdehyde), and superoxide dismutase (SOD) in the serum of women who have experienced a miscarriage with those of women who are pregnant and healthy. The study included 140 blood samples of women who suffered from a miscarriage and a healthy pregnant group. Calcium and Zinc were evaluated in serum of miscarriage and healthy control group, serum Malondialdehyde MDA, an indicator of lipid peroxidation, serum SOD, antioxidant enzyme, and superoxide dismutase. The calcium concentration was low in aborted women compared with the healthy pregnant control group. Serum zinc levels were lower in women who had an abortion compared to those who were pregnant and healthy. The level of serum SOD and MDA in aborted women raveled differences significantly compared with the healthy pregnant group, a decrease in the mean level of SOD was noticed in aborted women in contrast to the healthy pregnant group. At the same time, MDA showed it enhanced among the aborted group compared with healthy delivered women.

Reproductive outcomes after uterine septum resection in patients with recurrent miscarriage or infertility: a retrospective study in Chinese women.

Septate uterus is the most common structural uterine anomaly, which is related to the adverse pregnancy outcomes in women of childbearing age. This article provides a retrospective review of hysteroscopic uterine septum resection performed in our hospital during recent years, focusing on the patients with recurrent miscarriage and primary infertility, and also to identify which patients are more likely to benefit from the surgery. This is a single-center retrospective study. Cases of women who underwent hysteroscopic septum resection at West China Second Hospital of Sichuan University from January 2014 to December 2019, retrieved through the medical record system, were divided into three groups: Group A was the recurrent miscarriage group, Group B had a history of pregnancy with spontaneous abortion once at most, and Group C was the primary infertility group. Each patient was followed up by telephone about further pregnancy, miscarriage and live birth for at least 1year. A total of 176 surgical patients were included in this study. Group A, B, and C include 42, 74, and 60 cases, respectively. The postoperative pregnancy rates of the three groups were 71.4, 82.4, and 75.0%; live births rates were 50.0, 74.3, and 71.7%; and spontaneous abortion rates were 21.4, 17.6, and 13.3%. 62 patients had a complete uterine septum and 114 had a partial uterine septum. For patients with complete septate uterus, the preoperative pregnancy rate was 54.84% and the pregnancy rate increased to 85.48% after surgery; and yet the preoperative and postoperative pregnancy rates in patients with partial septate uterus were close (from 71.9 to 72.8%). After uterine septum resection, the pregnancy rate and spontaneous abortion rate in RSA patients were not significantly different from the other two groups, but the live birth rate was still significantly lower. Patients with complete uterine septum may benefit more from surgery. The surgical indications should be carefully and strictly evaluated.

Systematic analysis of microbiota in pregnant Chinese women and its association with miscarriage.

Miscarriage is the most common adverse pregnancy outcome and more than 50% of its incidence remains unexplained. Earlier studies have suggested that maternal microbiota might be associated with miscarriage, but the association is insufficiently understood. We used 16S ribosomal RNA (rRNA) amplicon sequencing and metagenomic sequencing technology to characterize the bacterial composition of three sites including the rectum, vagina, and cervix of a case group of 63 pregnant women who had miscarried compared to a control group of 24 pregnant women who underwent voluntary elective abortion. The alpha-diversity from the rectum and cervix was significantly decreased in the case group relative to the control group. However, we did not find significant differences in microbial diversity of vaginal samples between the two groups. Lactobacillus was the most predominant genus in the cervix and vaginal samples. Gestational age at the time of surgery was positively associated with the rectum microbiota diversity, with an effect size of 10% (P=0.004). Host factors including gestational age and red blood count (RBC) were associated with the rectal microbiota diversity. We detected a significantly lower rectal microbiota diversity and a pro-inflammatory tendency in the miscarriage group. This is the first study to investigate the association of microbiota from samples collected from three sites and miscarriage. Further studies are warranted to explore further the role of microbiota in miscarriage.

Construction of machine learning tools to predict threatened miscarriage in the first trimester based on AEA, progesterone and β-hCG in China: a multicentre, observational, case-control study

BackgroundEndocannabinoid anandamide (AEA), progesterone (P4) and β-human chorionic gonadotrophin (β-hCG) are associated with the threatened miscarriage in the early stage. However, no study has investigated whether combing these three hormones could predict threatened miscarriage. Thus, we aim to establish machine learning models utilizing these three hormones to predict threatened miscarriage risk.MethodsThis is a multicentre, observational, case-control study involving 215 pregnant women. We recruited 119 normal pregnant women and 96 threatened miscarriage pregnant women including 58 women with ongoing pregnancy and 38 women with inevitable miscarriage. P4 and β-hCG levels were detected by chemiluminescence immunoassay assay. The level of AEA was tested by ultra-high-performance liquid chromatography-tandem mass spectrometry. Six predictive machine learning models were established and evaluated by the confusion matrix, area under the receiver operating characteristic (ROC) curve (AUC), accuracy and precision.ResultsThe median concentration of AEA was significantly lower in the healthy pregnant women group than that in the threatened miscarriage group, while the median concentration of P4 was significantly higher in the normal pregnancy group than that in the threatened miscarriage group. Only the median level of P4 was significantly lower in the inevitable miscarriage group than that in the ongoing pregnancy group. Moreover, AEA is strongly positively correlated with threatened miscarriage, while P4 is negatively correlated with both threatened miscarriage and inevitable miscarriage. Interestingly, AEA and P4 are negatively correlated with each other. Among six models, logistic regression (LR), support vector machine (SVM) and multilayer perceptron (MLP) models obtained the AUC values of 0.75, 0.70 and 0.70, respectively; and their accuracy and precision were all above 0.60. Among these three models, the LR model showed the highest accuracy (0.65) and precision (0.70) to predict threatened miscarriage.ConclusionsThe LR model showed the highest overall predictive power, thus machine learning combined with the level of AEA, P4 and β-hCG might be a new approach to predict the threatened miscarriage risk in the near feature.

Aberrant gene expression of superoxide dismutases in Chlamydia trachomatis-infected recurrent spontaneous aborters

Study aimed to characterize the expression of antioxidant genes SOD1 and SOD2 in Chlamydia trachomatis-induced recurrent spontaneous aborters and further determine their role by in silico analysis. First void urine was collected from 130 non-pregnant women with history of recurrent spontaneous abortion (RSA) (Group I) and 130 non-pregnant women (Group II; control) attending Obstetrics and Gynecology Department, SJH, New Delhi, India. C. trachomatis detection was performed by conventional PCR in urine. Gene expression of SOD1 and SOD2 was performed by quantitative real-time PCR. Further, its interacting partners were studied by in silico analysis. 22 patients were positive for C. trachomatis in Group I. Significant upregulation was observed for SOD2 gene in C. trachomatis-infected RSA patients while SOD1 was found to be downregulated. Increased concentration of oxidative stress biomarkers 8-hydroxyguanosine and 8-isoprostane was found in C. trachomatis-infected RSA patients. Protein–protein interaction (PPI) of SOD proteins and its interacting partners viz.; CCS, GPX1, GPX2, GPX3, GPX4, GPX5, GPX7, GPX8, CAT, PRDX1, TXN, SIRT3, FOXO3, and AKT1 were found to be involved in MAPK, p53 and foxo signaling pathways. Molecular pathways involved in association with SODs indicate reactive oxygen species (ROS) detoxification, apoptotic pathways and cell cycle regulation. Overall data revealed alleviated levels of SOD2 gene and decreased expression of SOD1 gene in response to C. trachomatis-infection leading to production of oxidative stress and RSA.

P-544 CNV is a genetic factor underlying risk of neurodevelopmental disorder in a child of a woman with miscarriage in anamnesis

Abstract Study question What underlies an increased risk of having children with neurodevelopmental disorders in women with miscarriage? Summary answer Women with miscarriage have a statistically significant increase in the frequency of giving birth to children with intellectual disabilities due to CNV. What is known already A link between woman’s history of miscarriage and neurodevelopmental disorders (NDD) in her children was shown recently (PMID:30058166, PMID:33580539). In women with sporadic and recurrent miscarriage, the risk of having a child with NDD is increased by 13% and 30%, respectively (PMID:33580539). About half of miscarriage cases can be due to genetic causes. Genetic abnormalities also underlie NDD. It is likely that CNV may be a common etiological factor for both pathologies. Our aim was to assess the frequency and characteristics of CNV in groups of mothers having a child with NDD and presence or absence of miscarriages in anamnesis. Study design, size, duration Families with children with NDD and maternal obstetric history were investigated (n = 405). They were divided into groups based on the presence (n = 190) or absence (n = 215) of pathogenic CNV in a child. Further each group was divided into subgroups with the presence (n = 37, n = 21) or absence (n = 153, n = 194) of miscarriage to determine the association of CNV with pregnancy loss and NDD. Genes involved in CNVs were obtained to identify pathogenetically significant molecular pathways. Participants/materials, setting, methods The DNA of patients and their parents was isolated from blood lymphocytes. Probands with NDD were studied using aCGH on SurePrint G3 Human CGH Microarray Kit, 8 × 60K (Agilent Technologies). Validation of CNVs and determination of their origin was carried out using qPCR. Enrichment analysis was performed by the Enrichr resource and the Mammalian Phenotype ontology. The results of the analysis were considered significant at p ≤ 0.05. The chi-squared test was used for statistical analysis. Main results and the role of chance For the first time we showed that pathogenic CNVs were statistically significantly more common in families with miscarriage having a child with NDD (p = 0.006). In the groups with or without miscarriage, respectively, 16 and 66 deletions and 21 and 87 duplications were found. Thus, no predominance of a certain type of CNV was found (p = 0.991). The origin was established for 49 CNVs out of 190 (26%). The group with miscarriage included 8 maternally inherited and 2 de novo CNVs, while the non-miscarriage group included 33 inherited (mat-18, pat-15) and 6 de novo variants (p = 0.899). Enrichment analysis revealed 26 and 36 categories, respectively, in miscarriage and non-miscarriage groups. Common categories between the groups were maternal imprinting, abnormal cochlear innervation pattern, abnormal GABA-mediated receptor currents, increased skeletal muscle fiber size. Separately, the miscarriage group included one category associated with abnormal head morphology. The group without miscarriage included categories associated with development, functioning and anomalies of different organs. Although the enrichment analysis identified categories that may be associated with the pathologies included in this study, at this stage of data collection it was not possible to explain why some CNV can lead to either miscarriage or child with NDD in the same family. Limitations, reasons for caution There is no data on the causes of miscarriage, at least on the presence or absence of maternally inherited CNV in abortions. A small sample size does not allow us to identify differences in the structure of CNVs between groups with and without miscarriage. Wider implications of the findings Accumulating data potentially can be used for predicting the risk of having a child with NDD in families with miscarriage. If one of the parents carries pathogenic CNV with pleiotropic effect prenatal diagnosis or PGT-SR should be recommended. This study was supported by the Russian Science Foundation № 21-65-00017, https://rscf.ru/project/21-65-00017/. Trial registration number not applicable