Search Results (27)

Bacterial vaginosis is more than a mild inconvenience for women and has been shown to be an important cause of morbidity and mortality in women through sexually transmitted infections, and in babies due to late miscarriage and preterm birth. The aetiology of bacterial vaginosis remains unclear but there is increasing evidence to support sexual transmission as a cause. Preterm birth is a major cause of neonatal and perinatal mortality and morbidity worldwide and a huge cost on healthcare. The earlier bacterial vaginosis is detected in pregnancy, the greater the risk of an adverse outcome like preterm birth. Bacteriophages influence the vaginal microbiome, resulting in a eubiotic or dysbiotic state that may have implications on the prediction and prevention of preterm birth. We have provided the evidence to link vaginal dysbiosis in the form of bacterial vaginosis with the prediction and prevention of preterm birth. We have also explored the role of bacteriophages in bacterial vaginosis and the possibility of therapeutic interventions. Bacteriophages play an important role in the aetiology of vaginal dysbiosis and novel therapeutic interventions may help in the prediction and prevention of preterm birth through achieving vaginal eubiosis. Full article

Background/Objectives: Miscarriage is an increasingly common event worldwide arising from various factors, and identifying its etiology is important for planning and managing any future pregnancies. It is estimated that about half of early pregnancy loss cases are caused by genetic abnormalities, while a significantly lower rate is found in late pregnancy loss. Multiplex ligation-dependent probe amplification (MLPA) can detect small changes within a gene with precise breakpoints at the level of a single exon. The aim of our study was to identify the rate of copy number variations (CNVs) in spontaneous pregnancy loss samples after having previously tested them via quantitative fluorescence PCR (QF-PCR), with no abnormal findings. Methods: DNA was extracted from product-of-conception tissue samples, followed by the use of an MLPA kit for the detection of 31 microdeletion/microduplication syndromes (SALSA^® MLPA^® Probemix P245 Microdeletion Syndromes-1A, MRC-Holland, Amsterdam, The Netherlands). Results: A total of 11 (13.1%) out of the 84 successfully tested samples showed CNVs. Duplications accounted for 9.5% of the analyzed samples (eight cases), while heterozygous or hemizygous deletions were present in three cases (3.6%). Among all the detected CNVs, only three were certainly pathogenic (3.6%), with two deletions associated with DiGeorge-2 syndrome and Rett syndrome, respectively, and a 2q23.1 microduplication syndrome, all detected in early pregnancy loss samples. For the remaining cases, additional genetic tests (e.g., aCGH/SNP microarray) are required to establish CNV size and gene content and therefore their pathogenicity. Conclusions: MLPA assays seem to have limited value in detecting supplementary chromosomal abnormalities in miscarriages. Full article

Women exhibit marked physiological transformations in pregnancy, mandating regular and holistic assessment. Maternal and fetal vitality is governed by a spectrum of clinical, demographic, and lifestyle factors throughout this critical period. The existing maternal health monitoring techniques lack precision in assessing pregnancy-related risks, often leading to late interventions and adverse outcomes. Accurate and timely risk prediction is crucial to avoid miscarriages. This research proposes a deep learning framework for personalized pregnancy risk prediction using the NFHS-5 dataset, and class imbalance is addressed through a hybrid NearMiss-SMOTE approach. Fifty-one primary features are selected via the LASSO to refine the dataset and enhance model interpretability and efficiency. The framework integrates a multimodal model (NFHS-5, fetal plane images, and EHG time series) along with two core architectures. ResRNN-Net further combines Bi-LSTM, CNNs, and attention mechanisms to capture sequential dependencies. MultiScaleFusion-Net leverages GRU and multiscale convolutions for effective feature extraction. Additionally, TabNet and MLP models are explored to compare interpretability and computational efficiency. SHAP and Grad-CAM are used to ensure transparency and explainability, offering both feature importance and visual explanations of predictions. The proposed models are trained using 5-fold stratified cross-validation and evaluated with metrics including accuracy, precision, recall, F1-score, and ROC–AUC. The results demonstrate that MultiScaleFusion-Net balances accuracy and computational efficiency, making it suitable for real-time clinical deployment, while ResRNN-Net achieves higher precision at a slight computational cost. Performance comparisons with baseline machine learning models confirm the superiority of deep learning approaches, achieving over 80% accuracy in pregnancy complication prediction. Full article

Hepatitis E, caused by the hepatitis E virus (HEV), is a zoonotic disease that extends beyond hepatocellular necrosis to replicate in multiple organs. While most infections are self-limiting, HEV infection during pregnancy is associated with severe outcomes, including acute liver failure, preterm delivery, and miscarriage, with the mechanisms underlying this high pathogenicity remaining poorly understood. This study established a pregnant tree shrew model with a late-stage HEV infection and a cellular model using zoonotic HEV genotypes GT3 and GT4 to investigate the effects of estrogen on HEV replication. Results showed that negative-strand RNA detection revealed replicative intermediates in feces and tissues during the acute phase, with peak viral loads occurring within one week and the highest titers in bile. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels rose at 3 days post-inoculation (DPI), peaking at 7 DPI. Elevated estrogen levels post-miscarriage correlated with increased viral loads, a trend mirrored in cell culture models showing linear relationships between estrogen and viral replication. Histopathology demonstrated viral hepatitis lesions in liver tissues and abnormalities in the uterus, ovaries, and brain, including hydropic degeneration, neuronal disruption, and granulosa cell necrosis. This study developed a pregnant tree shrew model for HEV infection, providing a robust tool for exploring pathogenic mechanisms during pregnancy and genotype-specific differences in zoonotic HEV pathogenicity. These findings offer new insights into the role of estrogen in HEV replication and its contribution to adverse pregnancy outcomes. Full article

Background/Objectives: The objective of the study was to explore the combined effect of polymorphisms in the platelet glycoproteins Ia (GpIa) and IIIa (GpIIIa), along with the platelet-endothelial cell adhesion molecule-1 (PECAM-1) and P-Selectin genes, on the risk of recurrent pregnancy loss. Methods: This study involved 162 women with primary unexplained recurrent miscarriages and 60 fertile controls who had at least one uncomplicated full-term pregnancy without experiencing fetal loss. All participants were of Greek origin and were genotyped for four single nucleotide polymorphisms (SNPs), GpIa-C807T, GpIIIa-PlA1/PlA2, PECAM-1-C373G, and P-Selectin-A37674C, using pyrosequencing. A genetic risk score (GRS) was calculated in two forms: one based on the number of SNPs (dominant model) and the other based on the number of polymorphic alleles (additive model), utilizing logistic regression and receiver operator characteristic (ROC) analyses. Results: A statistically significant increase in the risk of miscarriage was observed with the number of polymorphic genes, with an odds ratio (OR) of 2.2 (95% confidence interval [CI]: 1.5 to 3.2, p < 0.001) for each additional SNP. The ROC analysis revealed an area under the curve (AUC) of 0.689 (95% CI: 0.614 to 0.763, p < 0.001). The presence of two or more polymorphic genes demonstrated a sensitivity of 69.8% and specificity of 65%, with an OR = 4.3 (95% CI: 2.3 to 8.0, p < 0.001). The performance of the GRS improved in younger patients and those experiencing late miscarriages. An AUC = 0.839 (95% CI: 0.749 to 0.930, p < 0.001) and an OR = 7.0 (95% CI: 2.8 to 17.8, p < 0.001) per SNP were achieved for the age group < 30 years. For subjects with second trimester fetal loss, the GRS yielded an AUC = 0.742 (95% CI: 0.610 to 0.874, p = 0.002) and an OR = 3.6 (95%OR = 7.0, 95% CI: 2.8 to 17.8) per SNP. The allelic GRS produced similar or slightly diminished results. Conclusions: This study highlights the promising potential of a genetic risk score based on four SNPs in predicting unexplained recurrent miscarriages, particularly in younger individuals and in cases of late miscarriage. These findings contribute to a deeper understanding of the epidemiology of unexplained recurrent miscarriage, emphasizing the role of platelet thrombophilia. Full article

Background and Aims: Emerging evidence suggests adverse pregnancy outcomes (APOs) may increase future cardiovascular risk. This study aimed to assess in a Spanish cohort the long-term risk of cardiovascular disease in women with APOs compared to those without such complications. Methods: A retrospective longitudinal cohort study was conducted at Hospital Vall d’Hebron (Barcelona, Spain), including pregnant women delivering between January 2010 and December 2015. Women with pre-existing medical conditions were excluded. APOs included preeclampsia, gestational diabetes, preterm birth, late miscarriage, and stillbirth. Cardiovascular events were defined as acute myocardial infarction or stroke. Both APO and non-APO groups were compared for their risk of cardiovascular events in the years following delivery, using unadjusted and adjusted models. Results: Out of 12,071 pregnant women delivered at Hospital Vall d’Hebron during the study period. 10,734 met the inclusion criteria (8234 in the non-APO group and 2500 in the APO group). The adjusted model revealed a significant association between APOs and cardiovascular events post-delivery (HR 2.5; 95% CI 1.4–4.4). Furthermore, an increased number of APOs (≥2) correlated with a higher risk of post-delivery cardiovascular events (HR 8.6; 95% CI 2.8–26.8). Conclusions: Women with adverse pregnancy outcomes (APOs), particularly those experiencing preeclampsia, preterm birth, and late miscarriage, exhibit an elevated long-term risk of cardiovascular events. Our findings highlight that these associations persist even after adjusting for traditional cardiovascular risk factors, indicating that APOs may independently influence long-term cardiovascular health. This underscores the importance of recognizing pregnancy as a critical window for early cardiovascular health interventions and counseling. Addressing these risks proactively could improve long-term health outcomes for women with a history of APOs. Full article

Chlamydia are obligate intracellular bacterial pathogens affecting humans and animals, causing miscarriage, stillbirth, or weak fetuses in the late stages of pregnancy of goats and sheep. Because there is no commercial vaccine for chlamydia in animals, drug treatment has become the most effective curative method. Natural products, also known as secondary metabolites, are becoming one of the main sources used in new drug development because of their structural diversity and biodiversity. In natural products, plant sources play a major role in the development process of new drugs. In this study, five undescribed highly oxygenated bisabolane sesquiterpenes (Pararubin W, Pararubin X, Pararubin Y., Pararubin Z, and Pararubin AA) were isolated from whole plants of Ligularia narynensis. Their chemical structures were determined via analyses of HRESIMS, IR, 1D, and 2D NMR data, along with the assignment of their relative configurations. These compounds were tested for their anti-chlamydial activity. The results show that compounds 1 and 5 inhibited the growth of Chlamydia abortus in host cells in a dose-dependent manner. Full article

Background/Objectives: The aim of this study is to assess the inter- and intra-observer reproducibility of the identification of direct and indirect ultrasonographic features of adenomyosis as defined by the revised Morphological Uterus Sonographic Assessment (MUSA) consensus (2022). Methods: A cohort of 74 women, aged 18 to 45, were recruited from the recurrent miscarriage and general gynaecology clinic at a university-based fertility centre. All the participants underwent 2D and 3D transvaginal Ultrasound scan (TVS) examination in the late follicular and early luteal phase. Conventional grey scale and power Doppler image volumes were acquired and stored. Subsequently, the stored 3D ultrasound images were independently re-evaluated offline by the two observers for the direct and indirect features of adenomyosis as outlined by the revised MUSA group. The intra- and the inter-observer reproducibility was estimated using Cohen’s Kappa coefficient. Results: The intra- and interobserver reproducibility (K −0.27, 95% CI 0.06–0.48 and K 0.13, 95% CI −0.10–0.37, respectively) for at least one direct feature of adenomyosis was only modest. Amongst the individual direct features, the interobserver variability of identifying myometrial cysts was fair (K 0.21, 95% CI −0.00–0.42), whereas the intra-observer variability was moderate (K 0.44, 95% CI 0.26–0.63). While hyperechogenic islands identification achieved a fair level of intra- (K 0.31, 95% CI 0.09–0.53) and interobserver (K 0.24, 95% CI 0.01–0.47) agreement, the reproducibility of reporting sub-endometrial lines/buds was fair for the intra-observer (K 0.22, 95% CI −0.02 0.47) and poor for the interobserver (K 0.00, 95% CI −0.20–0.19). The interobserver agreement for indirect features varied from poor to moderate, while the intra-observer agreement ranged between poor to good. Conclusions: The reporting of adenomyosis using direct features suggested by the revised MUSA group consensus showed only modest interobserver and intra-observer agreement. The definitions of ultrasound features for adenomyosis need further refining to enhance the reliability of diagnosis criteria of adenomyosis. Full article

Viruses are the most common congenital infections in humans and an important cause of foetal malformations, neonatal morbidity, and mortality. The effects of these infections, which are transmitted in utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (when the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, herpes simplex type-2, parvovirus B19, rubella, varicella zoster and zika viruses. There are currently very few efficacious antiviral agents licensed for use in pregnancy. For most of these infections, therefore, prevention is mainly by vaccination (where there is a vaccine). The administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss some of the congenital and perinatal infections and their consequences on both the mother and fetus and their management focusing mainly on prevention. Full article

Background: Retained products of conception after childbirth or miscarriage are associated with an increased rate of maternal complications, such as abnormal vaginal bleeding and infections. Late complications may also include intrauterine adhesions, causing infertility. Surgical interventions carry a certain risk. Thus, conservative management is often discussed as an alternative. The aim of this study was to assess the clinical outcomes of patients with retained products of conception, comparing a primary surgical approach to conservative management. Methods: We conducted a retrospective cohort study of 88 patients diagnosed with retained products of conception after 23+0 weeks of gestation at the Medical University Vienna between 2014 and 2022. Results: Forty-seven (53.4%) patients underwent primary surgical management and 41 (46.6%) primary conservative management. After primary conservative treatment, a complication could be observed in 10 (24.4%) women. In contrast, complications occurred in 32 (68.1%) women in the group with primary surgical treatment (p < 0.001). The most common complication in both groups was the ongoing suspicion of retained products of conception. Patients after primary surgical treatment were significantly more likely to require a secondary change in treatment (p < 0.001). Ultimately, secondary conservative management was applied in 30 (63.8%) patients. In contrast, only nine (21.95%) patients with primary conservative management required secondary surgical management. Conclusions: Due to the high risk of complications and persistent retained products of conception, primary surgical management should only be prioritized in hemodynamically instable or septic patients. Full article

Background and Objectives: This retrospective cohort study investigates the role of genetic thrombophilia in pregnant women experiencing early pregnancy loss compared to those with late pregnancy loss. Materials and Methods: Participants were categorized into early and late pregnancy loss groups based on gestational age. A total of 156 patients were included, out of which 103 had early-trimester pregnancy losses and 96 had multiple miscarriages. Results: The study revealed a synergistic effect of Factor V Leiden (FVL G1691A) and Methylenetetrahydrofolate Reductase (MTHFR C677T) mutations (coefficient 3.42). Prothrombin (PT) G20210A and β-Fibrinogen 455 G>A mutations exhibited a significant interaction (coefficient 1.98). Additionally, MTHFR A1298C and Plasminogen Activator Inhibitor-1 (PAI-1 4G/5G) mutations showed a significant interaction (coefficient 1.65). FVL G1691A and Endothelial Protein C Receptor (EPCR) allele A1/A2 mutations also demonstrated a significant association (coefficient 2.10). Lastly, MTHFR C677T and Glycoprotein IIb/IIIa T1565C mutations interacted significantly (coefficient 1.77). Risk factor analysis identified several mutations associated with early pregnancy loss, including PAI-1 4G/5G homozygous (OR 3.01), FVL G1691A heterozygous (OR 1.85), and MTHFR A1298C heterozygous (OR 1.55). Both homozygous and heterozygous MTHFR C677T mutations were significant risk factors (OR 2.38; OR 2.06), as was PT G20210A homozygous mutation (OR 1.92). The PAI-1 4G/4G homozygous variant posed a risk (OR 1.36). Late pregnancy loss was associated with MTHFR A1298C homozygous mutation (OR 3.79), β-Fibrinogen 455 G>A heterozygous mutation (OR 2.20), and MTHFR A1298C heterozygous mutation (OR 2.65). Factor XIII G1002T heterozygous mutation (OR 1.18) and PAI-1 4G/5G homozygous mutation (OR 2.85) were also significant risk factors. EPCR allele A1/A2 (OR 1.60) and A2/A3 (OR 1.73) mutations were identified as significant risk factors for late pregnancy loss. Furthermore, FVL G1691A homozygous mutation, PT G20210A homozygous mutation, MTHFR C677T heterozygous mutation, MTHFR A1298C heterozygous mutation, and EPCR allele A1/A2 were identified as significant risk factors for multiple miscarriage. Conclusions: This study highlights significant interactions and risk factors related to genetic thrombophilia mutations in different types of pregnancy loss, contributing valuable insights for miscarriage management guidelines. Full article

Background: COVID-19 is a modern worldwide pandemic that affected and continues to affect millions of people around the world. Since the discovery that angiotensin-converting enzyme 2 (ACE2) is the binding site for COVID-19 to achieve cell entry, there has been a continuous debate about the effect of COVID-19 infection in first and second trimester abortions. The aim of this review is to investigate the impact of COVID-19 infection on the incidence of miscarriage. Furthermore, we seek to identify potential pathophysiological mechanisms of early pregnancy loss present in infected women. Methods: A literature review was conducted on different databases, including PubMed, Google Scholar, Ovid, Science Direct, Scopus, and Cochrane library, between 1 January 2020 and 31 August 2023. A total of 364 articles were identified and 32 articles were ultimately included in the review. Results: There are several case studies that provide evidence that early pregnancy loss is associated with COVID-19 infection. These findings are not further confirmed by the majority of systematic reviews and meta-analyses, which demonstrate that the total number of miscarriages do not differ significantly between infected and non-infected groups. Furthermore, there are also case reports that associate COVID-19 infection with late second trimester abortions. Conclusions: Given that the virus persists globally, it is important to gain a better understanding of its associated risks in the reproductive process, and larger, more homogeneous, and controlled studies are required to obtain more robust data that can be meta-analyzed to obtain an overview of this potential relationship. Full article

Background: The reproductive tract microbiota that evolved as an integrative component has been studied intensively in the last decade. As a result, novel research, clinical opportunities, and perspectives have been derived following the close investigation of this microecological environment. This has paved the way for an update to and improvement of the management strategies and therapeutic approaches. However, obscurities, contradictions, and controversies arise regarding the ascension route from the vagina to the endometrium via the cervix, with finality in adverse obstetric outcomes. Methods: Starting from these considerations, we aimed to gather all existing data and information from four major academic databases (PubMed, ISI Web of Knowledge, Scopus, and ScienceDirect) published in the last 13 years (2010–2023) using a controlled vocabulary and dedicated terminology to enhance the coverage, identification, and sorting of potentially eligible studies. Results: Despite the high number of returned entries (n = 804), only a slight percentage (2.73%) of all manuscripts were deemed eligible following two rounds of evaluation. Cumulatively, a low level of Lactobacillus spp. and of other core microbiota members is mandatory, with a possible eubiosis-to-dysbiosis transition leading to an impairment of metabolic and endocrine network homeostasis. This transposes into a change in the pro-inflammatory landscape and activation of signaling pathways due to activity exerted by the bacterial lipopolysaccharides (LPSs)/endotoxins that further reflect a high risk of miscarriage in various stages. While the presence of some pathogenic entities may be suggestive of an adverse obstetric predisposition, there are still pros and cons of the role of specific strains, as only the vagina and cervix have been targeted as opposed to the endometrium, which recently started to be viewed as the key player in the vagina–cervix–endometrium route. Consequently, based on an individual’s profile, diet, and regime, antibiotics and probiotics might be practical or not. Conclusions: Resident bacteria have a dual facet and are beneficial for women’s health, but, at the same time, relaying on the abundance, richness, and evenness that are definitory indexes standing as intermediaries of a miscarriage. Full article

Background and Objectives: The purpose of this study was to describe and evaluate the bleeding that occurs during the first weeks of gestation and its implications throughout pregnancy. Secondarily, we assessed the associated complications in order to identify potential risk factors that could be used to select women at higher risk of adverse outcomes that could benefit from an early diagnosis and improved monitoring. Materials and Methods: We made a selection of all the women who consulted in the Emergency Department of the Hospital QuirónSalud in Malaga on 2015 presenting with first trimester metrorrhagia. We refer to first trimester metrorrhagia as that which occurs until week 12 + 6. Once these pregnant women were identified, we studied several variables not related to the gestation and some others associated with it and its natural course. Results: The average age of the patients assessed was 34.1. Associated gestational complications were metrorrhagia in the second trimester (6.3%), threatened preterm labor (7.4%), preeclampsia (2.5%), gestational diabetes (7.4%), late abortion (1.2%), and early postpartum hemorrhage (1.8%). We sought associations to assess possible risk factors, establishing an increased maternal age as an aggravating factor for the development of complications. We also studied gestational complications, finding a higher prevalence of them in older women, such as prematurity (33.11 vs. 34.48 years), gestational diabetes (33.11 vs. 36.06 years), and preeclampsia (33.25 vs. 35 years). Conclusions: Maternal age is a risk factor for first-trimester spontaneous miscarriage and for the development of complications of pregnancy. It is crucial to perform a correct screening of different pathologies throughout the pregnancy to anticipate potential complications. Full article

We evaluated the potential of cardiovascular-disease-associated microRNAs to predict in the early stages of gestation (from 10 to 13 gestational weeks) the occurrence of a miscarriage or stillbirth. The gene expressions of 29 microRNAs were studied retrospectively in peripheral venous blood samples derived from singleton Caucasian pregnancies diagnosed with miscarriage (n = 77 cases; early onset, n = 43 cases; late onset, n = 34 cases) or stillbirth (n = 24 cases; early onset, n = 13 cases; late onset, n = 8 cases; term onset, n = 3 cases) and 80 selected gestational-age-matched controls (normal term pregnancies) using real-time RT-PCR. Altered expressions of nine microRNAs (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-26a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p, miR-342-3p, and miR-574-3p) were observed in pregnancies with the occurrence of a miscarriage or stillbirth. The screening based on the combination of these nine microRNA biomarkers revealed 99.01% cases at a 10.0% false positive rate (FPR). The predictive model for miscarriage only was based on the altered gene expressions of eight microRNA biomarkers (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-26a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p and miR-195-5p). It was able to identify 80.52% cases at a 10.0% FPR. Highly efficient early identification of later occurrences of stillbirth was achieved via the combination of eleven microRNA biomarkers (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p, miR-145-5p, miR-210-3p, miR-342-3p, and miR-574-3p) or, alternatively, by the combination of just two upregulated microRNA biomarkers (miR-1-3p and miR-181a-5p). The predictive power achieved 95.83% cases at a 10.0% FPR and, alternatively, 91.67% cases at a 10.0% FPR. The models based on the combination of selected cardiovascular-disease-associated microRNAs had very high predictive potential for miscarriages or stillbirths and may be implemented in routine first-trimester screening programs. Full article