Low-dose aspirin and heparin treatment improves pregnancy outcome in recurrent pregnancy loss women with anti-ß2-glycoprotein I/HLA-DR autoantibodies: a prospective, multicenter, observational study.

Introduction: Anti-ß2-glycoprotein I (ß2GPI)/human leukocyte antigen (HLA)-DR antibodies may be a risk factor for recurrent pregnancy loss (RPL). The therapeutic modality for women with RPL and anti-ß2GPI/HLA-DR antibody positivity has not been evaluated. This prospective, multicenter, observational study aimed to assess whether low-dose aspirin (LDA) and/or heparin therapies improve pregnancy outcomes in women with RPL who tested positive for anti-ß2GPI/HLA-DR antibodies. Methods: Between August 2019 and December 2021, 462 women with RPL underwent anti-ß2GPI/HLA-DR antibody measurements and risk assessments for RPL. Each attending physician decided the treatment modality for women with RPL who tested positive for anti-ß2GPI/HLA-DR antibodies, and their pregnancy outcomes were followed up until December 2023. Finally, 47 pregnancies in 47 women with RPL and anti-ß2GPI/HLA-DR antibody positivity were included in the analysis and were divided into two groups regarding whether they were treated with LDA and/or unfractionated heparin (UFH) (LDA/UFH group, n = 39) or with neither of them (non-LDA/non-UFH group, n = 8). The rates of live birth and pregnancy complications (i.e., preeclampsia and preterm delivery before 34 gestational weeks due to placental insufficiency) were compared between the two groups. Results: The live birth rate in the LDA/UFH group was higher than that in the non-LDA/non-UFH group (87.2% vs 50.0%, p = 0.03). The pregnancy complication rate in the LDA/UFH group was significantly lower than that in the non-LDA/non-UFH group (5.9% vs 50.0%, p = 0.048). Among 21 women who tested positive for anti-ß2GPI/HLA-DR antibodies and had no other risk factors for RPL, the live birth rate in the LDA/UFH group (n = 14) was much higher than that in the non-LDA/non-UFH group (n = 7) (92.9% vs 42.9%, p = 0.03). Discussion: This study, for the first time, demonstrated that LDA and/or UFH therapies are effective in improving pregnancy outcomes in women with RPL and aß2GPI/HLA-DR antibody positivity.

Management of early pregnancy loss by reproductive endocrinologists: does access to mifepristone matter?

Objective: To describe patterns and variations in the medical and procedural management of early pregnancy loss (EPL) among reproductive endocrinology and infertility specialists, with attention to mifepristone use. Design: Cross-sectional. Setting: Online survey. Patients: Society for Reproductive Endocrinology and Infertility members. Intervention: Not applicable. Main Outcome Measure: Preferred management for EPL. Results: Of 101 completed surveys (response rate: 12.2%), 70.3% of respondents reported diagnosing EPL at least once per week. Half (50.5%) of respondents preferred medical management compared with 27.7% who preferred procedural management and 21.8% who preferred expectant management. Approximately one-quarter (26.7%) of respondents offer mifepristone for medical management of EPL. The most common reason cited for not prescribing mifepristone was a lack of access to the medication. Mifepristone prescribers were more likely to work in a hospital or university setting than private practice. Increasing years in practice was also associated with mifepristone use. The use of mifepristone for EPL did not vary by the respondent's age, gender, prior abortion training, or practice region. Conclusion: The most effective method of medical management uses both mifepristone and misoprostol. However, nearly three-quarters of reproductive endocrinology and infertility physicians do not offer mifepristone, which may be linked to access issues.

Is lifestyle different in male partners experiencing recurrent pregnancy loss compared to men fathering a live birth?

BACKGROUND: Recurrent pregnancy loss is characterized by three or more consecutive pregnancy losses. Although the causes of recurrent pregnancy loss are often unknown, chromosomal defects and fetal anomalies account for a significant proportion of cases. Previous research has primarily focused on maternal factors, but recent attention has shifted to the role of male lifestyle factors. OBJECTIVES: This study examined how male lifestyle factors and chronic illnesses affect recurrent pregnancy loss in a Danish cohort. Objectives included analyzing demographic and clinical features, as well as assessing lifestyle factors and pregnancy outcomes. MATERIALS AND METHODS: We included 741 males referred to the Danish recurrent pregnancy loss unit between 2009 and 2021, alongside a control group of 1173 males from the PREGCO study. Data on demography, clinical features, lifestyle factors, and pregnancy outcomes were collected and analyzed. RESULTS: The recurrent pregnancy loss group had a higher mean age compared to the controls. Although there was a trend suggesting a higher prevalence of obesity in the recurrent pregnancy loss group, statistical significance was not reached. The prevalence of chronic illnesses was similar in both groups. In the recurrent pregnancy loss group, a higher body mass index and history of previous or current smoking were associated with a lower pregnancy rate, and men who never smoked had an increased likelihood of achieving pregnancy. However, these associations lost significance after adjusting for potential confounders. DISCUSSION: The study suggests an association between male obesity and smoking, and decreased pregnancy rates after referral for recurrent pregnancy loss. However, further research is needed to understand the underlying mechanisms and establish causality in this association. CONCLUSION: The study reveals potential associations between male smoking, male obesity, and reduced pregnancy rates in individuals referred for recurrent pregnancy loss. These findings emphasize the importance of considering male lifestyle factors in the evaluation and management of recurrent pregnancy loss.

Is pregnancy loss (that) disenfranchised? Evidence from a vignette study.

Background: Perceiving that society disregards grief after pregnancy loss (disenfranchised grief) elevates bereaved parents' psychological burden.Objective: In this research, we aimed to compare the disenfranchisement of pregnancy loss with four other loss types considering the bereaved's gender.Method: We collected data from Turkish participants (N = 1,280) using a 5 (loss type) x 2 (gender) between-subjects design with randomly assigned vignettes. Participants reported their expected grief and behavioural tendencies toward the bereaved. We conducted MANOVA and ANOVA analyses.Results: Results revealed that participants expected higher grief for pregnancy loss than two other disenfranchised grief types (former colleague's death, grandfather's diagnosis with Alzheimer's). Expected grief for pregnancy loss was higher than or similar to the level for the best friend's loss across examinations but lower than the level for the one-year-old child's loss. Behaviour tendencies were alike across vignettes, and their results did not paint a coherent picture. Findings did not differ by the bereaved's gender.Conclusion: Pregnancy loss might be less disenfranchised than bereaved parents perceive it, and parents' perceptions could be targeted in therapeutic interventions.

We investigated whether pregnancy loss is more disenfranchised by society than four other loss types considering the bereaved's gender.We collected data from a large sample in Turkey.Pregnancy loss might be less disenfranchised than argued in the literature.

High Prevalence of Anti-Prothrombin IgM and IgG Autoantibodies in Women With Unexplained Recurrent Pregnancy Loss.

To investigate the association between anti-prothrombin IgM and IgG antibodies and recurrent pregnancy loss (RPL) in a cohort of Lebanese women, and their impact on pregnancy outcomes. This was a retrospective case-control study involving 207 women with RPL and 179 age-matched multiparous controls. Quantitative sandwich ELISA assayed anti-prothrombin IgM and IgG antibodies. Univariate and multivariate logistic regression were employed to assess the risk imparted by anti-prothrombin antibodies, while ROC analysis was used to determine their sensitivity and specificity. Our study revealed that women with RPL had significantly higher serum levels of anti-prothrombin IgM and IgG than controls. Univariate regression analysis demonstrated that elevated anti-prothrombin IgM (OR = 1.13; 95% CI = 1.07, 1.19; P < 0.001) and IgG (OR = 1.05; 95% CI = 1.03, 1.08; P < 0.001) were associated with increased RPL risk. Multivariate analysis confirmed these findings, indicating that anti-prothrombin IgM (aOR = 1.13; 95% CI = 1.05, 1.20; P < 0.001) and IgG (aOR = 1.08; 95% CI = 1.05, 1.11; P < 0.001) are independent risk factors. ROC analysis yielded an AUC of 0.720 for IgM and 0.649 for IgG, underscoring their predictive value and offering hope for improved risk assessment and management of RPL. Elevated levels of anti-prothrombin IgM and IgG are significantly associated with RPL, suggesting an autoimmune component to pregnancy loss. These findings highlight the importance of screening for these antibodies in women with unexplained RPL to guide management and therapeutic strategies.

Pregnancy loss and risk of cardiometabolic multimorbidity in Chinese women: the China Kadoorie Biobank study.

BACKGROUND: While the association between pregnancy loss and individual cardiometabolic diseases (CMDs) is well-established, its impact on the risk of coexisting CMDs remains unclear. Therefore, the aim of this study is to investigate the association between pregnancy loss with the risk of cardiometabolic multimorbidity in Chinese women. METHOD: We analyzed the cross-sectional data of 299,582 female participants aged 30-79 years old from the China Kadoorie biobank. Cardiometabolic multimorbidity was defined as the coexistence of two or more CMDs, including coronary heart disease, stroke, hypertension, and diabetes. Multivariable logistic regression was used to evaluate the odds ratios (ORs) between the number and type of pregnancy loss with the risk of cardiometabolic multimorbidity, characterized by the number and type of CMD. RESULTS: After adjusting for confounding factors, pregnancy loss was found to be significantly associated with increased cardiometabolic multimorbidity risk (OR, 1.13 95% CI 1.08-1.19). Specifically, pregnancy loss due to spontaneous and induced abortion (OR 1.10, 95% CI 1.03-1.18 and OR 1.13, 95% CI 1.08-1.19, respectively). In contrast, no significant association was found between stillbirth and cardiometabolic multimorbidity (OR 1.03, 95% CI 0.95-1.11). The risk of cardiometabolic multimorbidity increases as the number of pregnancy loss increases (one pregnancy loss: OR 1.10, 95% CI 1.05-1.16, two or more pregnancy loss: OR 1.16, 95% CI 1.10-1.22). Similarly, the diagnosis of multiple CMDs increases with increasing number of pregnancy loss. Pregnancy loss was related to higher risk of cardiometabolic multimorbidity across most CMD combinations of CMDs. CONCLUSION: Pregnancy loss, in particular, spontaneous and induced abortion was significantly associated with greater risk of cardiometabolic multimorbidity. The associations were stronger among those with recurrent pregnancy loss.

Social consequences of recurrent pregnancy loss and maternal myths, past, present, and future in Japan.

In Japan, the myth of motherhood, the idea that every woman harbours maternal love and that a woman only becomes a full-fledged woman after giving birth, has existed for a long time. However, there has been a limited number of studies concerning this motherhood myth in patients with recurrent pregnancy loss (RPL). The present study aimed to examine the experiences of maternal myths in patients with RPL and to determine whether maternal myths affect depression. Participants in the study included 61 patients in 1995, 71 patients in 2002, 503 patients from 2008 to 2012, and 318 patients and 1210 pregnant women from 2017 to 2020. Patients who sought an examination of their RPL visited Nagoya City University Hospital, while pregnant women requiring a prenatal checkup visited Nagoya City West Medical Center. Both groups completed a questionnaire concerning seven maternal myths and how they rated their level of depression (K6). It was found that not only patients with RPL but also pregnant women with no pregnancy loss had encountered maternal myths and many of them felt some discomfort. It has become clear that exposure to such myths has decreased over the 25 years from 1995 to 2020 (p < 0.05). Additionally, opportunities for exposure to maternal myths clearly had an impact on depression (p < 0.05). It is imperative that we recognize the distress caused by these myths. One potential solution to this problem is to improve education on gender issues.

Exploration of the Relationship between Polycystic Ovary Syndrome and Recurrent Pregnancy Loss Based on Bioinformatics.

BACKGROUND: Recurrent Pregnancy Loss (RPL) and Polycystic Ovary Syndrome (PCOS) are both common diseases involving women of childbearing age, and their pathogenesis is still not sufficiently known. OBJECTIVE: This study aimed to explore the relationship between RPL and PCOS in bioinformatics. METHODS: Two expression chips, GSE86241 (obtained from 8 PCOS patients and 9 healthy controls) and GSE73025 (obtained from 5 RPL patients and 5 healthy controls), were downloaded from the Gene Expression Omnibus (GEO) database. We used the GEO database to analyze the gene expression profiles of PCOS and RPL to identify the intersection of abnormal miRNA expression, predicted the target genes of the intersecting miRNAs from miRDB, miRTarBase, and TargetScan databases, and then incorporated the miRNA-mRNA modulation network. By using the string database, the PPI network was built, which could screen the Hub genes and enrich them for analysis. Ultimately, the critical miRNA-mRNA regulatory network was set on the basis of the relationship between hub genes and miRNA. RESULTS: A total of 39 significantly altered miRNAs of PCOS and 137 significantly altered miRNAs of RPL were obtained, three miRNAs (miR-767-5p, miR-3196, and miR-187-3p), five signaling pathways (PI3K-Akt, p53, Toll-like receptor, C-type lectin receptor, and TNF signaling pathways), and six Hub genes (CASP8, PIK3R1, ADAMTS2, ADAMTS3, COL3A1, and MDM2) were found to be related to the development and progression of two diseases. More importantly, all Hub genes were regulated by miR-767-5p. CONCLUSION: This research clarifies the possible relationship between miRNA and mRNA with PCOS and RPL for the first time. It provides a basis for illustrating the pathogenic mechanism and a target of therapies for these two diseases.

Association of coexposure to perfluoroalkyl and polyfluoroalkyl compounds and heavy metals with pregnancy loss and reproductive lifespan: The mediating role of cholesterol.

Previous studies have demonstrated the toxic effects of per- and polyfluoroalkyl substances (PFASs) and heavy metals on the reproductive system. However, the interactions and combined effects of these substances remain unexplored. This study utilizes data from the National Health and Nutrition Examination Survey to investigate the associations between coexposure to four types of PFASs, lead (Pb), mercury (Hg) and self-reported pregnancy loss and reproductive lifespan in females. Genes associated with these substances and abortion were identified via the Comparative Toxicogenomics Database. The results revealed that Ln-PFOA (IRR=1.88, 95 % CI=1.42-2.50, Ln--: log transformed), Ln-PFOS (IRR=1.58, 95 % CI=1.12-2.22), Ln-PFHxS (IRR=1.99, 95 % CI=1.57-2.52), and Ln-Hg (IRR=1.92, 95 % CI=1.41-2.43) were positively associated with the risk of pregnancy loss. Ln-PFOA (ß=1.27, 95 % CI=0.28-2.27), Ln-PFOS (ß=1.01, 95 % CI=0.39-1.63), Ln-PFHxS (ß=0.71, 95 % CI=0.12-1.63), Ln-PFNA (ß=1.15, 95 % CI=0.23-2.08), Ln-Pb (ß=3.87, 95 % CI=2.58-5.15), and Ln-Hg (ß=1.01, 95 % CI=0.39-1.64) exposures were positively associated with reproductive lifespan. The mixed and overall effects of coexposure to PFASs and heavy metals were positively correlated with the risk of pregnancy loss and reproductive lifespan. Cholesterol partially mediated the association with the risk of pregnancy loss, whereas delay in menopause fully mediated the association with reproductive lifespan. Significant additive interactions were observed between PFOA and Pb and between PFOS, PFHxS, PFNA and Hg at high levels of coexposure. Thirty-nine overlapping genes associated with abortion were identified for these substances, and further analyses revealed that these genes significantly interact and may contribute to abortion through oxidative stress.

Unexplained Recurrent Pregnancy Loss: Clinical Application of Immunophenotyping.

PROBLEM: Recurrent pregnancy loss (RPL) is defined as the failure of two or more pregnancies and affects approximately 5% of couples, often without a clear cause. The etiologies of RPL include factors such as maternal age, endocrine dysfunction, uterine abnormalities, chromosomal abnormalities, thrombophilias, infections, and autoimmune disorders. However, these conditions account for only 50%-60% of RPL cases. Research has explored whether an altered immune system, compared to the physiological state, may be linked to RPL. This review aims to determine whether specific immunophenotypes are associated with unexplained Recurrent Pregnancy Loss (uRPL) and whether targeted therapies addressing specific immunophenotypic alterations can improve pregnancy outcomes. METHODS: A literature review was conducted using Pubmed/Medline, Scopus, and Embase databases, analyzing data from 95 articles published between 2001 and 2023. The roles of various cells of the immune system (B lymphocytes, T lymphocytes, natural killer cells, macrophages) in different tissues (peripheral blood, menstrual blood) were specifically investigated in women with uRPL. DISCUSSION AND CONCLUSION: Specific immunophenotypes have been demonstrated to be associated with this condition. However, there is a need to standardize immunophenotyping assays and conduct more trials to stratify RPL risk and improve potential therapeutic strategies.

Increased miscarriage rate is associated with at least four components of metabolic syndrome in women with polycystic ovary syndrome undergoing in vitro fertilization or intracytoplasmic sperm injection embryo transfer cycle.

AIM: This study aimed to investigate the association between the components of metabolic syndrome (MetS) and reproductive outcomes in women with polycystic ovary syndrome (PCOS) undergoing their first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) embryo transfer cycle. METHODS: This is a retrospective study that included 720 women with PCOS from January 2018 to December 2021. Anthropometric, biochemical, and reproductive data of the study subjects were collected from electronic medical record. Women with PCOS met <3, 3, and >3 criteria of MetS were classified in group 1, 2, and 3, respectively. RESULTS: The miscarriage rate in women with MetS was significantly higher than that in non-MetS group (23.2% vs. 14.2%, p = 0.03). There was a significant increasing trend in miscarriage rate from group 1 to group 3 (p for trend <0.05). The miscarriage rate in group 3 was significantly higher than that in group 1 (29.3% vs. 14.2%, p < 0.05). Logistic regression analyses showed that women with at least four components of MetS (group 3) were independently associated with a high risk of miscarriage, with the odds ratios and 95% confidence intervals for group 2 and 3 versus group 1 were 1.38 (0.67-2.82) and 2.46 (1.06-5.74), respectively (p for trend = 0.04). CONCLUSIONS: PCOS women accompanied with at least four diagnostic criteria of MetS is independently associated with increased miscarriage rate when undergoing their first IVF or ICSI cycle.

Comparison of the predictive value of four insulin resistance surrogates and hyperuricemia in women with recurrent pregnancy loss: A cross-sectional study.

BACKGROUND: Insulin resistance (IR), hyperuricemia (HUA), and recurrent pregnancy loss (RPL) elevate the risk of cardiovascular disease and metabolic disorders, while also impacting reproductive health. The relationship between IR, HUA, and RPL has not been thoroughly investigated. This study investigates the relationship between four IR surrogates and the risk of HUA in RPL patients. METHODS: Data from a real-world study on RPL in China were analyzed using multivariable regression to determine the relationship between HUA and triglyceride and glucose (TyG) index, triglyceride glucose-body mass index (TyG-BMI), triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and metabolic score for insulin resistance (METS-IR). The predictive ability of these surrogates for detecting HUA in RPL patients was evaluated using the area under the curve and receiver operating characteristic analysis. Sensitivity analysis was performed using bootstrapping resampling. RESULTS: The study included 769 patients with a mean age of 30 ± 4 years old, 8.32% of whom had HUA. Four IR surrogates were closely related to HUA in patients of RPL after adjusting for age, menstrual cycle, creatinine, alanine transaminase, aspartate transaminase, total cholesterol, homocysteine, and low-density lipoprotein, with area under the curve values of TyG index (OR = 0.693, 95% confidence interval [CI]: 0.626, 0.759), TyG-BMI (OR = 0.731 95% CI: 0.657, 0.805), TG/HDL-C (OR = 0.703, 95% CI: 0.641, 0.764), and METS-IR (OR = 0.728, 95% CI: 0.655, 0.799). Bootstrap resampling yielded similar results. CONCLUSIONS: The TyG index, TyG-BMI, TG/HDL-c, and METS-IR significantly correlated with HUA in patients with RPL. The TyG-BMI had the highest predictive value of the four IR surrogates.

Attitudes and preferences towards erectile dysfunction treatment among men with fertility needs: insights from a clinical study.

Erectile dysfunction (ED) is prevalent among males experiencing fertility challenges, yet attitudes towards actively treating ED in this group are under-researched. From a cohort of 1256 men with reproductive needs, 303 were identified with ED. The survey encompassed 296 respondents who correctly completed the second questionnaire, revealing that 50.3% sought ED treatment, with higher ED severity increasing the likelihood of seeking treatment. Infertile men were more likely to seek treatment than those with pregnancy loss (OR 3.18, 95% CI 1.74-5.83). Men with normal semen parameters were more open to ED therapy (OR 3.02, 95% CI 1.69-5.36), whereas those undergoing Assisted Reproduction Treatment were less inclined (OR 0.32, 95% CI 0.18-0.58). PDE-5 inhibitors (PDE-5Is) were preferred by 51.0% of those seeking treatment, with 29.7% of men with pregnancy loss and 60.1% of infertile men choosing PDE-5Is as their first option. Concerns included potential adverse effects of PDE-5Is on fetal health (78.7% of men with pregnancy loss) and on sperm quality (44.2% of infertile men). In conclusion, the different fertility requirements, semen parameters, and whether received ART are significant factors influencing the acceptance of treatment, PDE-5Is utilization among individuals in men with couple pregnancy loss is notably limited.

Chronic endometritis and recurrent reproductive failure: a systematic review and meta-analysis.

Background: The endometrium holds a crucial role in reproduction by supporting blastocyst adhesion, cytotrophoblast invasion and fetal development. Among the various uterine disorders, endometritis, particularly chronic endometritis (CE), has gained attention due to its association with adverse reproductive outcomes (recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), and infertility). The association between CE and adverse reproductive outcomes stresses the necessity for comprehensive diagnostic and therapeutic strategies to optimize fertility outcomes and support individuals in their journey towards parenthood. Aim: To explore the relationship between CE and reproductive disorders. Methods: Following PRISMA guidelines, a systematic review and meta-analysis using published data from 1990 to 2024 were carried out. Results: A population of 1,038 women was included. Regarding CE-infertility association, a positive correlation was found, with 19.46% CE rate in infertile women compared to 7.7% in controls (OR: 2.96, 95% CI 1.53-5.72, p 0.001). No significant association was observed between RIF and CE (OR: 1.10, 95% CI 0.26-4.61, p 0.90), CE rates in both groups were relatively comparable, with 6.35% in women with RIF and 5.8% in controls. On the opposite, a strong association between CE and RPL was found, reporting a CE rate of 37.6% in RPL cases compared to 16.4% in controls (OR: 3.59, 95% CI 2.46-5.24, p < 0.00001). Conclusions: CE appears to be associated to infertility and RPL, while no significant association was noted in cases of RIF. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails PROSPERO, identifier CRD42024541879.

The Impact of Human Papillomavirus Infections on Recurrent Pregnancy Loss: A Review of the Literature.

Human papillomavirus (HPV) infections are significantly associated with multiple adverse reproductive outcomes such as miscarriages. Pregnant women are more susceptible to an HPV infection and its prevalence increases as pregnancy progresses. In this present review, we summarize the existing evidence indicating the potential impact of an HPV infection on the occurrence of recurrent pregnancy loss (RPL). Comprehensive research of the literature was performed in the Medline/PubMed and Scopus databases. A total of 185 articles were identified and 40 full-text articles were assessed. Four studies were eligible to be included in this literature review. To our knowledge, this is the first review aiming to summarize the current state of evidence regarding the possible association of HPV infections and RPL. Recurrent pregnancy loss constitutes a distressing reproductive event and scientific research has made significant efforts to determine the causes and mechanisms that could lead to RPL. It is still unclear whether the papillomavirus infection is associated with an increased risk for recurrent miscarriages. Research in the field revealed conflicting results and their deductions are limited by methodological limitations. Given the high prevalence of HPV infections and their potential role in the occurrence of adverse outcomes during pregnancy, further research is required to clarify the possibility of an HPV infection being a potential risk factor for recurrent miscarriages.

Surface Immune Checkpoints as Potential Biomarkers in Physiological Pregnancy and Recurrent Pregnancy Loss.

Due to the genetic diversity between the mother and the fetus, heightened control over the immune system during pregnancy is crucial. Immunological parameters determined by clinicians in women with idiopathic recurrent spontaneous abortion (RSA) include the quantity and activity of Natural Killer (NK) and Natural Killer T (NKT) cells, the quantity of regulatory T lymphocytes, and the ratio of pro-inflammatory cytokines, which indicate imbalances in Th1 and Th2 cell response. The processes are controlled by immune checkpoint proteins (ICPs) expressed on the surface of immune cells. We aim to investigate differences in the expression of ICPs on T cells, T regulatory lymphocytes, NK cells, and NKT cells in peripheral blood samples collected from RSA women, pregnant women, and healthy multiparous women. We aim to discover new insights into the role of ICPs involved in recurrent pregnancy loss. Peripheral blood mononuclear cells (PBMCs) were isolated by gradient centrifugation from blood samples obtained from 10 multiparous women, 20 pregnant women (11-14th week of pregnancy), and 20 RSA women, at maximum of 72 h after miscarriage. The PBMCs were stained for flow cytometry analysis. Standard flow cytometry immunophenotyping of PBMCs was performed using antibodies against classical lymphocyte markers, including CD3, CD4, CD8, CD56, CD25, and CD127. Additionally, ICPs were investigated using antibodies against Programmed Death Protein-1 (PD-1, CD279), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3, CD366), V-domain Ig suppressor of T cell activation (VISTA), T cell immunoglobulin and ITIM domain (TIGIT), and Lymphocyte activation gene 3 (LAG-3). We observed differences in the surface expression of ICPs in the analyzed subpopulations of lymphocytes between early pregnancy and RSA, after miscarriage, and in women. We noted diminished expression of PD-1 on T lymphocytes (p = 0.0046), T helper cells (CD3CD4 positive cells, p = 0.0165), T cytotoxic cells (CD3CD8 positive cells, p = 0.0046), T regulatory lymphocytes (CD3CD4CD25CD127 low positive cells, p = 0.0106), and NKT cells (CD3CD56/CD16 positive cells, p = 0.0438), as well as LAG-3 on lymphocytes T (p = 0.0225) T helper, p = 0.0426), T cytotoxic cells (p = 0.0458) and Treg (p = 0.0293), and cells from RSA women. Impaired expression of TIM-3 (p = 0.0226) and VISTA (p = 0.0039) on CD8 cytotoxic T and NK (TIM3 p = 0.0482; VISTA p = 0.0118) cells was shown, with an accompanying increased expression of TIGIT (p = 0.0211) on NKT cells. The changes in the expression of surface immune checkpoints indicate their involvement in the regulation of pregnancy. The data might be utilized to develop specific therapies for RSA women based on the modulation of ICP expression.

Correlation Between Serum Markers and Midluteal Phase Doppler Assessment of Uterine Arterial Blood Flow in Unexplained Recurrent Pregnancy Loss.

This study aimed to determine changes in uterine artery Doppler parameters in unexplained recurrent pregnancy loss (URPL) and to explore serum markers possibly associated with them. This retrospective case-control study included 107 URPL women and 107 control women. The mean pulsatility index (PI), resistive index (RI), and systolic-to-diastolic values for uterine arteries in URPL women were significantly higher than those in the controls (P < 0.05). The cutoff values of PI and RI differentiating the women with URPL from the controls were confirmed by ROC and Youden's index. Given a PI cutoff value of 2.6, the prevalence of URPL was significantly elevated in the high-PI group (74.58%) compared with that in the low-PI group (40.65%, P < 0.0001), with sensitivity and specificity of 63% and 69%, respectively. With an RI cutoff value of 0.86, the prevalence of URPL in the high-RI group (65.28%) was significantly elevated compared with that in the low-RI group (42.25%, P = 0.001), with sensitivity and specificity of 66% and 75%, respectively. The levels of serum D-dimers and anticardiolipin antibody (ACA)-IgM in URPL women were significantly higher than those in the controls. A positive correlation existed between the levels of ACA-IgM and uterine artery RI in URPL women (r = 0.43, P < 0.01). These results indicated that URPL women may be at a relatively high risk of a prothrombotic state, and the increased ACA-IgM deserves attention for its role in the elevated uterine artery Doppler parameters in URPL women.

Genetic Insights Into Early Pregnancy Loss: A Case Study of Trisomy 22 and an Enlarged Yolk Sac.

The first trimester of pregnancy is crucial for organ development but also carries a high risk of complications, with early pregnancy loss being the most common. Anomalies in the yolk sac, the first extra-embryonic structure seen by ultrasonography, can indicate severe fetal growth abnormalities and are linked to higher rates of first-trimester loss. This case report details a 38-year-old woman with a history of recurrent pregnancy loss (RPL) who presented with per vaginal bleeding and mild abdominal pain. Transvaginal ultrasonography revealed a yolk sac larger than 10 mm, prompting further genetic investigation. Chromosomal microarray analysis confirmed Trisomy 22. The presence of an enlarged yolk sac, correlated with Trisomy 22, highlights the importance of early detection through sonography and genetic testing. This approach aids in managing RPL by identifying genetic causes, thereby informing pre-conception counseling and future pregnancy management. An abnormal yolk sac size necessitates thorough evaluation, including cytogenetic microarray testing and quantitative fluorescent-polymerase chain reaction analysis, to guide clinical decisions and improve pregnancy outcomes.

Witzenberg Women's experience of health care after a miscarriage: A descriptive qualitative study.

BACKGROUND:  Although some evidence is available from low- and middle-income countries, no South African data are available on how women experience healthcare during treatment for an incomplete miscarriage. AIM:  This study sets out to explore and describe the experiences of healthcare among women who suffered an incomplete spontaneous miscarriage in the Witzenberg subdistrict, a rural area in the Western Cape province of South Africa. SETTING:  Witzenberg subdistrict, Western Cape province, South Africa. METHODS:  This study used a descriptive exploratory qualitative study design. In-person interviews were held with women who experienced a miscarriage. Interviews followed a semi-structured format by a single interviewer to explore the various aspects involving experiences of healthcare. RESULTS:  Eight interviews were conducted and analysed. The five themes that arose from transcribed data were: (1) a need for safety, (2) pain management, (3) moderating behaviours and attitudes, (4) disorienting healthcare systems and (5) abandonment. Several factors contributed to the loss of physical and emotional safety in the emergency centre environment. Timeous emotional and pharmacological pain management were found to be a gap while patients awaited care. Clear communication and staff attitude were found to be integral to the patient's experience and could avoid the perception of abandonment. CONCLUSION:  There is a universal need for basic respectful, supportive and safe care in patients who attend an emergency centre for early pregnancy complications in rural South African. Specific focus should be given to clear communication and appropriate emotional support during and after the miscarriage.Contribution: This study can be used as a guide to improve services by ensuring respectful, transparent, informed, and appropriate continuity of care.

Identification and validation of oxidative stress-related diagnostic markers for recurrent pregnancy loss: insights from machine learning and molecular analysis.

It has been recognized that oxidative stress (OS) is implicated in the etiology of recurrent pregnancy loss (RPL), yet the biomarkers reflecting oxidative stress in association with RPL remain scarce. The dataset GSE165004 was retrieved from the Gene Expression Omnibus (GEO) database. From the GeneCards database, a compendium of 789 genes related to oxidative stress-related genes (OSRGs) was compiled. By intersecting differentially expressed genes (DEGs) in normal and RPL samples with OSRGs, differentially expressed OSRGs (DE-OSRGs) were identified. In addition, four machine learning algorithms were employed for the selection of diagnostic markers for RPL. The Receiver Operating Characteristic (ROC) curves for these genes were generated and a predictive nomogram for the diagnostic markers was established. The functions and pathways associated with the diagnostic markers were elucidated, and the correlations between immune cells and diagnostic markers were examined. Potential therapeutics targeting the diagnostic markers were proposed based on data from the Comparative Toxicogenomics Database and ClinicalTrials.gov. The candidate biomarker genes from the four models were further validated in RPL tissue samples using RT-PCR and immunohistochemistry. A set of 20 DE-OSRGs was identified, with 4 genes (KRAS, C2orf69, CYP17A1, and UCP3) being recognized by machine learning algorithms as diagnostic markers exhibiting robust diagnostic capabilities. The nomogram constructed demonstrated favorable predictive accuracy. Pathways including ribosome, peroxisome, Parkinson's disease, oxidative phosphorylation, Huntington's disease, and Alzheimer's disease were co-enriched by KRAS, C2orf69, and CYP17A1. Cell chemotaxis terms were commonly enriched by all four diagnostic markers. Significant differences in the abundance of five cell types, namely eosinophils, monocytes, natural killer cells, regulatory T cells, and T follicular helper cells, were observed between normal and RPL samples. A total of 180 drugs were predicted to target the diagnostic markers, including C544151, D014635, and CYP17A1. In the validation cohort of RPL patients, the LASSO model demonstrated superiority over other models. The expression levels of KRAS, C2orf69, and CYP17A1 were significantly reduced in RPL, while UCP3 levels were elevated, indicating their suitability as molecular markers for RPL. Four oxidative stress-related diagnostic markers (KRAS, C2orf69, CYP17A1, and UCP3) have been proposed to diagnose and potentially treat RPL.