The relationship between Sjögren's syndrome and recurrent pregnancy loss: a bioinformatics analysis.

RESEARCH QUESTION: As Sjögren's syndrome is an autoimmune disease and an essential factor in recurrent pregnancy loss (RPL), are there gene-related relationships between the pathogenesis of Sjögren's syndrome and RPL? DESIGN: The gene datasets for Sjögren's syndrome and RPL were obtained from the Gene Expression Omnibus database, and the co-expression modules and shared differentially expressed genes were identified through weighted gene co-expression network analysis (WGCNA) and limma analysis based on sample size. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses were applied to reveal the hidden biological pathways. Additionally, shared hub gene identification, gene set enrichment analysis, association of the hub gene with ferroptosis and immunity, drug sensitivity analysis, single-cell RNA sequencing analysis, and construction of the competing endogenous RNA (ceRNA) network were conducted. RESULTS: By intersecting the genes from WGCNA and limma analysis, one shared hub gene (KCNN3) was derived, exhibiting up-regulation in Sjögren's syndrome and RPL. There was a positive relationship between KCNN3 and the immune-related gene TLR2. The ceRNA network revealed that XIST was the most shared long non-coding RNA, which may bind competitively with eight microRNA to regulate the expression of KCNN3. Forty-eight drugs were found to be strongly associated with KCNN3 expression, including estramustine and cyclosporine. Moreover, KCNN3 exhibited high expression in RPL endothelial cells of villous tissue. CONCLUSIONS: This is one of the first studies to reveal that Sjögren's syndrome shares common biological pathways with RPL. KCNN3 was identified as the hub gene associated with Sjögren's syndrome and RPL, and may be a new target for mechanistic studies on Sjögren's syndrome and RPL.

Impact of omega-3 fatty acids supplementation on lipid levels in pregnant women with previous pregnancy losses: a retrospective longitudinal study.

Objective: This research aims to investigate the impact of omega-3 fatty acids supplementation on the lipid levels of pregnant women who have experienced pregnancy losses. Methods: This retrospective study analyzed data from pregnant women with previous pregnancy losses from two medical centers. Their lipid profiles were measured at least twice during pregnancy. According to the use of omega-3 soft gel capsules, participants were divided into the omega-3 group and the control group. We assessed the relationship between omega-3 fatty acids supplementation and longitudinal lipid levels during pregnancy using generalized estimating equations (GEE). Subsequently, we conducted subgroup analyses to delineate the profile of beneficiaries who received omega-3 fatty acids based on body mass index (BMI), age, menstrual regularity, number of previous pregnancy losses, number of previous live births, and educational level. Results: The omega-3 group included 105 participants, while the control group comprised 274 participants. Women in the omega-3 group started supplementation between 3.43 and 17.14 weeks of gestation. According to GEE analysis, supplementing omega-3 fatty acids significantly reduced triglyceride (TG) levels during pregnancy (adjusted ß = -0.300, 95% CI -0.445 to -0.154, p < 0.001). No associations between omega-3 fatty acids supplementation and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) levels were observed. Subgroup analyses revealed that omega-3 fatty acids supplementation was related to a reduction in TG levels among pregnant women with age of ≤35 years, a normal BMI (18.5-24.9 kg/m2), 1-2 previous pregnancy losses, no previous live births, or an educational level above high school. Conclusion: Supplementation with omega-3 fatty acids may significantly reduce TG levels, yet it does not seem to improve TC, LDL-C, or HDL-C levels in pregnant women with previous pregnancy losses.

Intravenous immunoglobulin improves live birth rates in patients with unexplained recurrent pregnancy loss.

This real-world study aimed to assess the clinical efficacy and safety of intravenous immunoglobulin (IVIG) in treating unexplained recurrent pregnancy loss (uRPL) patients. A total of 238 patients with uRPL were enrolled in this retrospective study. According to the treatment, patients were assigned into treatment group (n=184, receiving IVIG+low molecular weight heparin [LMWH]) and control group (n=54, only LMWH). The primary outcome was the live birth rates (LBR) after 24 weeks of gestation. In addition, we performed subgroup analyses to assess the LBR in uRPL patients with age (≥30 years or <30 years), body mass index (BMI, 18-24 kg/m2 or ≥24 kg/m2), number of previous pregnancy losses (2 or ≥3), gestational week of first medication, and IVIG medication regimen during pregnancy. The LBR showed a significant increase after IVIG treatment compared to the control group (77.7 % vs. 53.7 %, P=0.001). Multivariable logistic regression indicated that IVIG was associated with increased LBR (aOR=4.383, 95 %CI 2.024-9.489). Besides, we observed a significantly lower incidence of decreased platelet count (1.6 % vs. 7.4 %, P=0.049) in the treatment group. Subgroup analyses showed that IVIG treatment was associated with improved LBR in uRPL patients with age of <30 years (aOR=4.012, 95 %CI 1.428-11.266), previous pregnancy losses ≥3 times (aOR=17.327, 95 %CI 2.525-118.921), and BMI of 18-24 kg/m2 (aOR=8.914, 95 %CI 2.985-26.618). IVIG treatment significantly improves the LBR in uRPL patients. These findings from real-world data provide evidence for the safety and efficacy of IVIG as a viable treatment for uRPL patients in clinical practice.

Corrigendum: A new prognostic model for recurrent pregnancy loss: assessment of thyroid and thromboelastograph parameters.

[This corrects the article DOI: 10.3389/fendo.2024.1415786.].

A predictive model of pregnancy loss using pre-pregnancy endocrine and immunological parameters in women with abnormal glucose/lipid metabolism and previous pregnancy loss.

OBJECTIVE: To investigate the clinical and endocrine risk factors for pregnancy loss in women with abnormal glucose/lipid metabolism and a history of pregnancy loss, and to develop a predictive model to assess the risk of pregnancy loss in these women's subsequent pregnancies. METHODS: Patients with a history of pregnancy loss who had abnormal glucose/lipid metabolism were retrospectively included in this study, and their pre-pregnancy baseline and clinical characteristics were collected. A predictive nomogram was constructed based on the results of the multivariable logistic regression model analysis, and its calibration and discriminatory capabilities were evaluated. The internal validation was then performed and the net benefits were assessed by the clinical decision curve. RESULTS: The predictive model was eventually incorporated eight variables, including maternal age, previous pregnancy losses, anticardiolipin antibody (aCL) IgG, aCL IgM, thyroid peroxidase antibody, complement 4, free thyroxine and total cholesterol. The area under the curve (AUC) of the nomogram was 0.709, and Chi-square value and P value of the Hosmer-Lemeshow test were 12.786 and 0.119, respectively, indicating that the nomogram had a satisfactory calibration and discriminatory performance. The validation cohort showed a similar result for the discrimination of the nomogram (AUC = 0.715). The clinical decision curve demonstrated the nomogram had good positive net benefits. CONCLUSIONS: This is the first study to predict the risks of subsequent pregnancy loss in women with abnormal glucose/lipid metabolism and history of pregnancy loss using pre-pregnancy clinical and endocrine parameters. This predictive nomogram may provide clinicians assistance to personalize the management of subsequent pregnancies in these patients.

A new prognostic model for recurrent pregnancy loss: assessment of thyroid and thromboelastograph parameters.

Objective: This study aimed to identify predictors associated with thyroid function and thromboelastograph (TEG) examination parameters and establish a nomogram for predicting the risk of subsequent pregnancy loss in recurrent pregnancy loss (RPL). Methods: In this retrospective study, we analyzed the medical records of 575 RPL patients treated at Lanzhou University Second Hospital, China, between September 2020 and December 2022, as a training cohort. We also included 272 RPL patients from Ruian People's Hospital between January 2020 and July 2022 as external validation cohort. Predictors included pre-pregnancy thyroid function and TEG examination parameters. The study outcome was pregnancy loss before 24 weeks of gestation. Variable selection was performed using least absolute shrinkage and selection operator regression and stepwise regression analyses, and the prediction model was developed using multivariable logistic regression. The study evaluated the model's performance using the area under the curve (AUC), calibration curve, and decision curve analysis. Additionally, dynamic and static nomograms were constructed to provide a visual representation of the models. Results: The predictors used to develop the model were body mass index, previous pregnancy losses, triiodothyronine, free thyroxine, thyroid stimulating hormone, lysis at 30 minutes, and estimated percent lysis which were determined by the multivariable logistic regression with the minimum Akaike information criterion of 605.1. The model demonstrated good discrimination with an AUC of 0.767 (95%CI 0.725-0.808), and the Hosmer-Lemeshow test indicated good fitness of the predicting variables with a P value of 0.491. Identically, external validation confirmed that the model exhibited good performance with an AUC of 0.738. Moreover, the clinical decision curve showed a positive net benefit in the prediction model. Meanwhile, the web version we created was easy to use. The risk stratification indicated that high-risk patients with a risk score >147.9 had a higher chance of pregnancy loss (OR=6.05, 95%CI 4.09-8.97). Conclusions: This nomogram well-predicted the risk of future pregnancy loss in RPL and can be used by clinicians to identify high-risk patients and provide a reference for pregnancy management of RPL.

The safety and efficacy of tumor necrosis factor-alpha inhibitor on pregnancy outcomes in patients with unexplained recurrent miscarriage.

OBJECTIVES: Although tumor necrosis factor-alpha inhibitor (TNFi) treatment may improve pregnancy outcomes in unexplained recurrent miscarriage (URM) patients, evidence for its efficacy and safety is still insufficient. The goal of this study was to evaluate the efficacy and safety of TNFi on pregnancy outcomes in patients with URM. METHODS: This retrospective study was conducted at a single institution in China, involving 121 patients treated with TNFi for URM from 2019 to 2022. Patients enrolled were divided into treatment group (receiving TNFi and heparin therapy) and control group (receiving heparin therapy). The outcome variables were the 24-week live birth rate, miscarriage rate, ectopic pregnancy rate, neonatal outcomes, and adverse events. RESULTS: In our study, patients receiving TNFi treatment exhibited a significant increase in live birth rates, achieving 71.2 % compared to the 50.9 % observed in the control group (OR 2.507, 95 % CI: 1.127-5.579). Concurrently, there was a discernible reduction in the miscarriage rate within the TNFi-treated group, marking 24.2 %, in contrast to 43.6 % in the control group (OR 0.387, 95 % CI: 0.170-0.884). Subgroup analyses further illuminated that those under the age of 35 benefitted remarkably from TNFi treatment, with live birth rates soaring to 62.5 % (OR 2.525, 95 % CI: 1.041-6.125). For patients with a history of two miscarriages, the TNFi regimen significantly augmented the live birth rate to 58.9 % (OR 3.044, 95 % CI: 1.039-8.921). Patients with a normal weight range registered a 58.4 % live birth rate post-TNFi treatment (OR 4.261, 95 % CI: 1.539-11.397). Notably, an evident interaction between BMI and TNFi treatment was identified, suggesting a potential modulatory role of BMI on the therapeutic efficacy of TNFi. About safety assessments, neither the TNFi-treated group nor the control manifested any significant disparities in liver function abnormalities, platelet count anomalies, or other pregnancy-related complications. CONCLUSIONS: TNFi, alongside basic therapy, notably enhances the live birth rate in URM patients under 35, with two prior miscarriages or a normal BMI, without increasing adverse event risk. Further prospective studies are essential to validate these observations.

The Relationship Between the Average Decreased Times of Estradiol and Early Miscarriage: An Observational Study.

Decreased estradiol (E2) levels are associated with early miscarriage (EM), but the relationship between decreased times of E2 and EM has not been reported. We aimed to investigate the relationship between the average decreased times of E2 (ADTE) and EM. Women with a history of miscarriage were retrospectively recruited from the Reproductive Center of Lanzhou University Second Hospital (Lanzhou, China) between September 2019 and February 2022. Based on pregnancy outcome, they were divided into ongoing pregnancy group (n = 359) and EM group (n = 104). In addition, subgroup analyses were performed for the number of previous miscarriages and whether E2 levels decreased continuously. The exposure and outcome variables were ADTE and miscarriage before 12 weeks of gestation, respectively. Totally, 1171 patients were recruited and 463 patients were finally analyzed. ADTE was associated with EM (odds ratio [OR] = 1.346, 95% confidence interval [CI]1.154-1.571, P < 0.001). When ADTE ≥ 2.5, the EM risk increased 1.17-fold compared to patients with 0-1.249 times (OR = 2.170, 95% CI 1.144-4.117, P = 0.018). Moreover, a threshold effect existed in the ADTE and the risk of EM with a value of 4.9 times. When exceeding 4.9 times, the EM risk increased 4.713-fold for each increased unit (OR = 5.713, 95% CI 1.255-23.170, P = 0.024). Subgroup analysis showed that ADTE had a greater effect on the occurrence of EM in women with a history of 1-2 miscarriages than in women with 3 miscarriages. Decreased E2 was a risk factor for EM regardless of whether it dropped continuously or not. In conclusion, our study identifies a potential link between ADTE and early miscarriage risk in women with prior miscarriages, yet cautious interpretation is necessary due to inherent design limitations. Further research with prospective designs and large population samples is essential to validate ADTE's utility as a predictive indicator for early miscarriage in clinical settings.

Predicting risk of subsequent pregnancy loss among women with recurrent pregnancy loss: An immunological factor-based multivariable model.

PROBLEM: Studies on subsequent pregnancy loss prediction models specific for recurrent pregnancy loss (RPL) patients are very limited. This study aims to develop a risk predictive model based on the immunological parameters for the subsequent pregnancy loss risk in northwest Chinese RPL patients. METHOD OF STUDY: Totally of 357 RPL patients recruited from Lanzhou University Second Hospital were included in this retrospective study. Univariate analysis was performed on RPL patients with outcomes of live birth or pregnancy loss. Subsequently, the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables among baseline and clinical characteristics and to develop a pregnancy loss risk prediction model with all 357 RPL patients. The area under the curve (AUC), calibration curve and decision curve analyses were used to evaluate the performance of the prediction model; moreover, 10-fold cross-validation was used for internal validation. RESULTS: Ten factors of maternal age, age of menarche, previous pregnancy loss, IL-10, complement 4, IgA, antiprothrombin antibody IgG/IgM, rheumatoid factor IgA, and lupus anticoagulant (LA) 1/LA2 ratio were finally selected as variables for the prediction model of pregnancy loss risk. The AUC value and Hosmer-Lemeshow test p-value of the model were .707 and .599, respectively, indicating a satisfactory discrimination and calibration performance. Moreover, the clinical decision curve suggested this prediction model have a good positive net benefit. CONCLUSIONS: This is the first prediction model for the risk of subsequent pregnancy loss in northwest Chinese women with RPL, providing a user-friendly tool to clinicians for the early prediction and timely management of RPL patients.

Reproductive factors and subsequent pregnancy outcomes in patients with prior pregnancy loss.

BACKGROUND: At present, individualized interventions can be given to patients with a clear etiology of pregnancy loss to improve the subsequent pregnancy outcomes, but the current reproductive status of the patient cannot be changed. The aim of this study was to investigate the association between female reproductive status and subsequence pregnancy outcome in patients with prior pregnancy loss (PL). METHODS: A prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to February 2022, a total of 1955 women with at least one previous PL were enrolled. Maternal reproductive status and subsequent reproductive outcomes were recorded through an electronic medical record system and follow-up. Logistic regression was used to evaluate the association between reproductive status and the risk of subsequent reproductive outcomes. RESULTS: Among all patients, the rates of subsequent infertility, early PL, late PL, and live birth were 20.82%, 24.33%, 1.69% and 50.77% respectively. In logistic regression, we found that age (OR 1.08, 95% CI 1.04-1.13) and previous cesarean delivery history (OR 2.46, 95% CI 1.27-4.76) were risk factors for subsequent infertility in patients with PL. Age (OR 1.06, 95% CI 1.03-1.10), age at first pregnancy (OR 1.06, 95% CI 1.03-1.10), BMI (OR 1.06, 95% CI 1.02-1.11), previous PL numbers (OR 1.18, 95% CI 1.04-1.57) and without pre-pregnancy intervention (OR 1.77, 95% CI 1.35-2.24) were risk factors for non-live birth. Age (OR 1.06, 95% CI 1.03-1.09), age at first pregnancy (OR 1.06, 95% CI 1.02-1.09), BMI (OR 1.07, 95% CI 1.02-1.11), previous PL numbers (OR 1.15, 95% CI 1.02-1.31) and without pre-pregnancy intervention (OR 2.16, 95% CI 1.65-2.84) were risk factors for PL. CONCLUSIONS: The reproductive status of people with PL is strongly correlated with the outcome of subsequent pregnancies. Active pre-pregnancy intervention can improve the subsequent pregnancy outcome. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).

Preconception anti-annexin A5 antibodies are associated with subsequent live birth in women with recurrent miscarriage: A retrospective study from China.

PROBLEM: To evaluate the correlation between the antiannexin A5 antibodies (aAnxA5) multiples of median (MOM) and subsequent pregnancy outcomes in women with recurrent miscarriage (RM). METHODS: Totally, 310 RM women were included in this study and grouped into tertiles according to their MOM of preconception aAnxA5 circulating levels determined by ELISA. The effect of aAnxA5 on the pregnancy outcomes was performed using multiple logistic regression. The outcomes included early miscarriage (before 10 weeks of gestation), late miscarriage (between 10 and 24 weeks), ongoing pregnancy (beyond 10 weeks), and live birth (after 24 weeks) characterized by pregnancy with fetal heartbeat. RESULTS: For each unit increase in aAnxA5 MOM, the odds of live birth after 24 weeks and ongoing pregnancy were reduced by 40.2% (OR = .598; 95%CI 0.406-0.882, P = .010) and 38.1% (OR = .619; 95%CI 0.424-0.904, P = .013), respectively, after adjusting for demographic and clinical characteristics. The rise in aAnxA5 MOM was associated with an increased risk of early miscarriage (OR = 1.616; 95%CI 1.106-2.361, P = .013) and miscarriage (early + late miscarriage) (OR = 1.671; 95%CI 1.134-2.464, P = .010). Further subgroup analyses showed a decreased risk of live birth rates after 24 weeks of gestation in the two subgroups: maternal age ≥35 years (OR = .131; 95%CI 0.026-0.652), and previous pregnancy loss ≥ 3 (OR = .381; 95%CI 0.173-0.837). CONCLUSIONS: Higher preconception aAnxA5 MOM levels in women with RM may be linked with a decreased risk of live birth after 24 weeks and an increased risk of early miscarriage, especially in individuals aged ≥35 years or with previous pregnancy losses ≥3.

Preconception Non-criteria Antiphospholipid Antibodies and Risk of Subsequent Early Pregnancy Loss: a Retrospective Study.

The aim of this study was to investigate the subsequent early pregnancy outcomes in women positive for non-criteria antiphospholipid antibodies (NC-aPLs) before pregnancy. A total of 273 patients who had experienced sporadic or recurrent pregnancy loss and had been screened for 13 NC-aPLs at preconception were recruited in this study from September 2019 to February 2022. Serum levels of NC-aPLs were measured by ELISA using specific kits. The primary outcome was early pregnancy loss, and the secondary outcomes were biochemical pregnancy, clinically confirmed pregnancy loss, and ongoing pregnancy. Among these subjects, 56 patients had one previous pregnancy loss, and 217 had recurrent pregnancy loss (RPL). The NC-aPLs (+) and NC-aPLs (-) groups had similar rates of early pregnancy loss (EPL) after adjustment, regardless of the number of positive NC-aPLs (aOR = 1.054, 95% CI 0.602-1.846). Other outcomes were comparable in both groups, including the rates of biochemical pregnancy (aOR = 1.344, 95% CI 0.427-4.236), clinically confirmed pregnancy loss (aOR = 0.744, 95% CI 0.236-2.344), and ongoing pregnancy (aOR = 0.949, 95% CI 0.542-1.660). Based on sensitivity analysis, the NC-aPLs (+) were not associated with adverse early pregnancy outcomes in women with RPL. Furthermore, the difference in gestational weeks of pregnancy loss between the two groups was also insignificant. This study found no evidence linking preconception NC-aPL positivity to early pregnancy outcomes but offers a reference for future research to clarify NC-aPLs' potential clinical impact.

Chromosome analysis of foetal tissue from 1903 spontaneous abortion patients in 5 regions of China: a retrospective multicentre study.

BACKGROUND: Abnormal foetal tissue chromosome karyotypes are one of the important pathogenic factors for spontaneous abortion (SA). To investigate the age and abnormal foetal karyotypes of 1903 couples who experienced SA. METHODS: A retrospective multicentre study collected age and foetal tissue karyotypes CNV-seq data of 1903 SA couples from 6 hospitals in 5 regions from January 2017 to March 2022. The distribution and correlation of abnormal foetal tissue karyotypes were evaluated by using regions and age. RESULTS: In our study, 1140 couples (60.5% of the total) had abnormal foetal tissue chromosome karyotypes in all regions. We found that there were differences in the number of abnormal foetal tissue chromosome karyotypes, of which the incidence of trisomy was higher. At the same time, the populations situated in the eastern region had a more triploid (15.5%) distribution, trisomy (58.1%) in the southern region, mosaicism (14.8%) and microduplication (31.7%) in the southwestern region, microdeletion (16.7%) in the northern region. There are variances across areas, and it is more common in the north. The incidence risk of prenatal chromosomal abnormalities varied according to age group. CONCLUSION: The findings of this study suggest that the karyotypes of patients with abnormal foetal tissue chromosome abortion in different regions were different. Meanwhile, patients ≥ 35 years old had a higher risk of abnormal foetal tissue chromosome abortion.

Omega-3 fatty acid supplements and recurrent miscarriage: A perspective on potential mechanisms and clinical evidence.

Recurrent miscarriage (RM) affects approximately 1%-5% of couples worldwide. Due to its complicated etiologies, the treatments for RM also vary greatly, including surgery for anatomic factors such as septate uterus and uterine adhesions, thyroid modulation drugs for hyperthyroidism and hypothyroidism, and aspirin and low molecular weight heparin for antiphospholipid syndrome. However, these treatment modalities are still insufficient to solve RM. Omega-3 fatty acids are reported to modulate the dysregulation of immune cells, oxidative stress, endocrine disorders, inflammation, etc., which are closely associated with the pathogenesis of RM. However, there is a lack of a systematic description of the involvement of omega-3 fatty acids in treating RM, and the underlying mechanisms are also not clear. In this review, we sought to determine the potential mechanisms that are highly associated with the pathogenesis of RM and the regulation of omega-3 fatty acids on these mechanisms. In addition, we also highlighted the direct and indirect clinical evidence of omega-3 fatty acid supplements to treat RM, which might encourage the application of omega-3 fatty acids to treat RM, thus improving pregnancy outcomes.

Pregnancy outcomes and adverse events in patients with recurrent miscarriage receiving fondaparinux versus low molecular-weight heparin: A meta-analysis.

OBJECTIVE: Current opinion on the superiority of fondaparinux versus low molecular-weight heparin (LMWH) in treating recurrent miscarriage is controversial. This meta-analysis aimed to comprehensively compare the pregnancy outcomes and adverse events in patients with recurrent miscarriage receiving fondaparinux versus LMWH. METHODS: EMBASE, PubMed, Cochrane, China National Knowledge Internet (CNKI), Wanfang Database, and China Science and Technology Journal Database (CQVIP) databases were searched for articles reporting fondaparinux versus LMWH in treating recurrent miscarriage till June 10, 2022. Inclusion criteria for study screening were: (i) randomized, controlled trials (RCT), non-randomized controlled studies, or observational studies; (ii) patients aged over 18 years; (iii) patients with recurrent miscarriage during gestation period; (iv) patients in the experimental/observational group who received FD, and patients in the control group who received LMWH; (v) studies involving at least one outcome of interest for the current analysis. Exclusion criteria were: (i) systematic reviews, meta-analyses, case reports, or animal studies; (ii) duplicated studies; (iii) incomplete or inconsistent data. Quality assessment was conducted with Newcastle-Ottawa Scale criteria or Cochrane Collaboration. Data of live birth, abortion, birth weight, fetal growth restriction (FGR), and adverse events were extracted and synthesized. RESULTS: Six eligible studies (4 observational studies and 2 RCTs) with 321 patients receiving fondaparinux and 546 patients receiving LMWH were enrolled. Live birth (relative risks (RR) = 1.05, 95% confidence interval (CI) = 0.97 âˆ¼ 1.14, P = 0.217), abortion (RR = 0.73, 95% CI = 0.50 âˆ¼ 1.08, P = 0.113), birth weight (weighted mean difference = 167.20, 95% CI = -236.89 âˆ¼ 571.30, P = 0.417), and FGR (RR = 0.95, 95% CI = 0.25 âˆ¼ 3.59, P = 0.942) were of no difference between patients receiving fondaparinux and LMWH. Regarding adverse events, the incidence of ecchymosis (RR = 0.11, 95% CI = 0.03 âˆ¼ 0.46, P = 0.002) and skin reaction at injection site (RR = 0.15 95% CI = 0.05 âˆ¼ 0.44, P = 0.001) were lower in patients receiving fondaparinux compared with those receiving LMWH, while that of thrombocytopenia (RR = 0.45, 95% CI = 0.09 âˆ¼ 2.14, P = 0.315), vagina bleeding (RR = 1.03, 95% CI = 0.62 âˆ¼ 1.71, P = 0.646), and oral mucosa hemorrhage (RR = 1.08, 95% CI = 0.33 âˆ¼ 3.51, P = 0.899) did not vary between these patients receiving these two treatments. However, most studies were conducted in China, which could induce regional and ethnic bias. CONCLUSION: Fondaparinux is attributable to fewer adverse events and similar pregnancy outcomes compared with LMWH in patients with recurrent miscarriage.

Efficacy and safety of recombinant human granulocyte colony-stimulating factor in patients with unexplained recurrent spontaneous abortion: A systematic review and meta-analysis.

INTRODUCTION: Published data regarding efficacy of intrauterine perfusion of recombinant human granulocyte colony-stimulating factor for patients with unexplained recurrent spontaneous abortion (URSA) is inconclusive. This study aims at evaluating the efficacy and safety of G-CSF in URSA. MATERIALS AND METHODS: Electronic databases were searched including Cochrane Library, PubMed, Embase, China Biology Medicine disc, China Science and Technology Journal Database, Wanfang Database and China National Knowledge Infrastructure Database (last search was performed on Sep 10th, 2022). A systematic review and meta-analysis was conducted with R-language software. Combined relative risk (RRs), and 95% confidence intervals (CIs) were calculated to estimate efficacy and safety. RESULTS: Compared with placebo, the efficacy of G-CSF in the treatment of URSA patients was significant in conception rate (RR=1.34, 95%CI: 1.03-1.74, P = 0.028), and was none of significance in live birth rate (RR=1.35, 95%CI: 0.99-1.84, P = 0.06). Subgroup analysis showed that the ovulation-period-medication was the protective factor for conception rate, while "Ethnicity Asian" and "ovulation-period medication" were the protective factors for live birth rate. When it comes to the safety of rhG-CSF on URSA, meta-analysis showed that rhG-CSF had no significant effect on the incidence of adverse events (AEs) (RR=1.13, 95% CI: 0.89-1.43, P = 0.322), and subgroup analysis showed that the incidence of AEs in each subgroup did not increase significantly (P > 0.05). CONCLUSION: Based on our meta-analysis, intrauterine perfusion of rhG-CSF in ovulation period is an effective and safe way to improve conception rate in URSA.

Knowledge, attitudes, and practices of patients with recurrent pregnancy loss toward pregnancy loss.

Objective: Self-management is crucial in managing recurrent pregnancy loss (RPL). This study explored the knowledge, attitudes, and practices (KAP) of patients with RPL toward RPL. Methods: This cross-sectional study was conducted among patients with RPL between January 2023 and June 2023 at the Second Hospital of Lanzhou University. Participants' demographic characteristics and KAP were determined using a self-designed questionnaire (Cronbach's α = 0.818). Structural equation modeling (SEM) was used to observe the correlations among KAP and different factors. Results: This study analyzed 497 valid questionnaires. The mean knowledge, attitude, and practice scores were 11.59 ± 4.30 (possible range: 0-20, 57.95%), 44.17 ± 3.18 (possible range: 13-65, 67.95%), and 32.39 ± 5.22 (possible range: 8-40, 80.98%), indicating poor knowledge, moderate attitude, and proactive practice. Age was non-linearly associated with the KAP dimensions, with a positive impact of age on KAP among those aged <32 years old. Knowledge was directly influenced by education (ß = 1.49, p < 0.001) and income (ß = 1.08, p < 0.001). The attitude was directly influenced by knowledge (ß = 0.25, p < 0.001) and indirectly influenced by education (ß = 0.37, p = 0.001) and income (ß = 0.27, p < 0.001). Practice was directly influenced by knowledge (ß = 0.26, p < 0.001), attitude (ß = 0.28, p < 0.001), and income (ß = 0.68, p = 0.012), and indirectly influenced by knowledge (ß = 0.07, p = 0.001), education (ß = 0.59, p = 0.001), and income (ß = 0.42, p < 0.001). Conclusion: Women with RPL in Lanzhou show poor knowledge, moderate attitude, and proactive practice toward RPL. This study identified specific KAP items that would require improvements. The study also identified categories of patients who would need more attention.

The myocardial infarction-associated transcript 2 inhibits lipid accumulation and promotes cholesterol efflux in oxidized low-density lipoprotein-induced THP-1-derived macrophages via inhibiting mitogen-activated protein kinase signaling and activating the nuclear factor erythroid-related factor 2 signaling pathway.

Dysregulated lipid metabolism of macrophages contributes to thrombosis and antiphospholipid syndrome (APS). The long non-coding RNAs (lncRNA) myocardial infarction-associated transcript 2 (Mirt2) has been reported to inhibit inflammation and lipid accumulation; therefore, this study intended to clarify whether Mirt2 served a role in lipid metabolism. THP-1-derived macrophages with or without Mirt2-knockdown or overexpression, were exposed to oxidized low-density lipoprotein (ox-LDL), then cell migration, lipid accumulation, cholesterol efflux and inflammation were assessed using wound healing, oil red staining, commercial kits and western blot assays. Besides, ML385 was used to treat THP-1-derived macrophages to inhibit nuclear factor erythroid-related factor 2 (NRF2) expression. The expression of proteins involved in the above processes were measured by western blot. Results demonstrated that phorbol 12-myristate 13-acetate (PMA) significantly increased Mirt2 expression in THP-1 cells. Mirt2-knockdown enhanced ox-LDL-induced macrophage migration, lipid accumulation, inflammation, and inhibited cholesterol efflux. By contrast, Mirt2 overexpression displayed the opposite effects. Furthermore, Mirt2-knockdown inhibited NRF2 signaling and enhanced mitogen-activated protein kinase (MAPK) signaling, while Mirt2 overexpression displayed the opposite effects. Finally, the NRF2 inhibitor ML385 significantly reversed the above effects of Mirt2. In summary, Mirt2 served an important role in regulating lipid metabolism in macrophages via inhibiting MAPK signaling and activating the NRF2 signaling pathway.

Tumor necrosis factor inhibitors as therapeutic agents for recurrent spontaneous abortion (Review).

Recurrent spontaneous abortion (RSA) is a troublesome pregnancy disorder that manifests as sequential early pregnancy losses; its causes are diverse and complex. Among the known possible causes of RSA, the development of an immune disorder in response to the embryo appears to be the most pronounced. The imbalance between immune rejection and immune tolerance contributes to pregnancy loss in females with RSA, wherein the abnormal ratio of T helper (Th)1 cell­related cytokines [predominantly tumor necrosis factor (TNF)­α] and Th2 cell­related cytokines is a strong risk factor for RSA. TNF­α is a pro­inflammatory cytokine and TNF inhibitors have been effective in the treatment of various autoimmune diseases, such as ankylosing spondylitis, and inflammatory diseases, such as ulcerative colitis. Based on their immunomodulatory properties, TNF inhibitors have been used in the treatment of RSA to reduce the immune rejection rate and improvement in pregnancy outcomes has been observed in females suffering from RSA who were treated with TNF inhibitors. The aim of the present review was to interpret the involvement of TNF­α in the immunological disorder underlying RSA and summarize the clinical outcomes of TNF inhibitor treatment in patients with RSA.

The role of estrogen receptor-beta gene +1730G/A polymorphisms in recurrent pregnancy loss: A protocol for systematic review and meta-analysis.

OBJECTIVE: To identify the role of estrogen receptor-beta (ER-ß) gene +1730G/A (rs4986938) polymorphisms in recurrent pregnancy loss (RPL). METHODS: All relevant case-control studies will be systematically searched in multiple databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Internet (CNKI), Wanfang and Cqvip. Both pooled odds rations (ORs) and 95% confidence intervals (CIs) will be used to assess the association between ER-ß gene +1730G/A polymorphisms and RPL risk. The publication bias will be evaluated using Egger test. RESULTS: ER-ß gene +1730G/A variation may be associated with a higher risk of RPL in Caucasian population. CONCLUSIONS: The findings of this meta-analysis will provide high-quality evidence for the association between ER-ß gene +1730G/A polymorphisms and RPL, facilitating clinical practice and further scientific studies. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/EW9FB.