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Problem: Pregnancy complications such as spontaneous abortion, preeclampsia, and preterm birth persist, despite current interventions aimed at their prevention and treatment largely proving unsuccessful. Interleukin‐27 (IL‐27), composed of p28 and EBI3 subunits, binds to IL‐27R, which consists of gp130 and IL‐27Rα (also known as WSX‐1 or TCCR), and plays a pivotal role in tumor development and inflammation regulation. At the maternal‐fetal interface, IL‐27 expression has been detected in trophoblasts, endometrial stromal cells, and decidual cells. Abnormal levels of IL‐27/IL‐27R have been linked to adverse pregnancy outcomes, including spontaneous miscarriage, preeclampsia, and preterm birth. This review aims to explore the expression of IL‐27 at the maternal‐fetal interface and its signaling pathway, uncovering the complex role of IL‐27 in pregnancy complications. Method of Study: A comprehensive literature review was conducted using PubMed/Medline, Scopus, and Embase databases, analyzing studies on IL‐27 expression and its signaling pathways at the maternal‐fetal interface. The review focused on identifying the presence of IL‐27 in various cell types and linking abnormal IL‐27/IL‐27R expression to pregnancy complications such as spontaneous miscarriage, preeclampsia, and preterm birth. Discussion and Conclusion: IL‐27 plays a complex role at the maternal‐fetal interface, with abnormal expression linked to several pregnancy complications. These findings highlight the need for further research to elucidate IL‐27's mechanisms and develop targeted interventions. Future studies should aim to develop targeted interventions and improve therapeutic strategies for managing pregnancy complications. [ABSTRACT FROM AUTHOR]

Spontaneous miscarriage is a common complication of early pregnancy. Previous studies have shown that mitochondrial function plays an important role in establishment of a successful pregnancy. Cytochrome c oxidase subunit 4 isoform 1 (COX4I1), a component of electron transport chain complex Ⅳ, is required for coupling the rate of ATP production to energetic requirements. However, there is very limited research on its role in trophoblast biology and how its dysfunction may contribute to spontaneous miscarriage. Placental villi (7–10 weeks gestational age) collected from either induced termination of pregnancy or after spontaneous miscarriage were examined for expression of COX4I1. COX4I1 was knocked down by siRNA transfection of primary isolates of EVT cells. Real-time cell analysis (RTCA) and 5-Ethynyl-2′-deoxyuridine (EdU) were used to detect changes in proliferation ability after COX4I1 knockdown of EVT cells. Migration and invasion indices were determined by RTCA. Mitochondrial morphology was observed via MitoTracker staining. Oxidative phosphorylation, ATP production, and glycolysis in COX4I1-deficient cells and controls were assessed by a cellular energy metabolism analyzer (Seahorse). In placental villous tissue, COX4I1 expression was significantly decreased in the spontaneous miscarriage group. Knockdown of COX4I1 inhibited EVT cell proliferation, increased the migration and invasion ability and mitochondrial fusion of EVT cells. Mitochondrial respiration and glycolysis were impaired in COX4I1-deficient EVT cells. Knockdown of MMP1 could rescue the increased migration and invasion induced by COX4I1 silencing. Low expression of COX4I1 leads to mitochondrial dysfunction in EVT, resulting in altered trophoblast function, and ultimately to pregnancy loss. • COX4I1 expression is decreased in spontaneous miscarriage anchoring villi. • COX4I1 deficient EVT have reduced proliferation, increased migration/invasion. • COX4I1 deficient EVT contain dysfunctional mitochondria. [ABSTRACT FROM AUTHOR]

Transvaginal (TVUS) and transabdominal ultrasound (TAUS) are both utilized in the evaluation of early pregnancy patients. While many practitioners using point of care ultrasound (POCUS) will generally not pursue TVUS in cases where an intrauterine pregnancy (IUP) is visualized on TAUS, this may not be true in Radiology performed ultrasound. To evaluate for differences in transvaginal ultrasound (TVUS) utilization between Radiology performed (RP) ultrasound and point of care ultrasound (POCUS) by Emergency Department (ED) physicians in early pregnancy patients. Secondarily, to assess length of stay (LOS) differences and the impact of specialized emergency ultrasound training on TVUS utilization. This was a retrospective study at a single academic ED. Study population was all ED patients who underwent first trimester ultrasound during the one year period of March 1, 2021 to February 28, 2022. Variables evaluated were chief complaint, gestational age, LOS, TAUS and TVUS utilization, ultrasound findings, and ultrasound specialty training of the ED physician. There were 133 cases of POCUS ultrasound and 254 cases of RP ultrasound. All cases had TAUS imaging performed. Median LOS for patients when POCUS was utilized was 207 min (IQR 151–294) and 258 min (IQR 208–328) for those only using RP ultrasound, p ≤ 0.001. In the POCUS cohort, 38% (95% CI 30%–46%) received TVUS, while 94% received TVUS in the RP cohort (95% CI 90%–96%), p ≤ 0.001. Patients seen by ED faculty with ultrasound specialty training had TVUS 53% of the time (95% CI 41%–65%), while those seen by other ED faculty had TVUS 79% (95% CI 74%–83%) of the time, p = 0.035. POCUS in early pregnancy is associated with a significant reduction in TVUS usage. We suspect that POCUS users elect not to pursue TVUS after an IUP is identified on TAUS, while technicians perform protocol-based TVUS irrespective of TAUS findings. Patients seen by ultrasound trained ED physicians are less likely to receive TVUS. [ABSTRACT FROM AUTHOR]

Abstract Background Macrophages phenotypic deviation and immune imbalance play vital roles in pregnancy-associated diseases such as spontaneous miscarriage. Trophoblasts regulate phenotypic changes in macrophages, however, their underlying mechanism during pregnancy remains unclear. Therefore, this study aimed to elucidate the potential function of trophoblast-derived miRNAs (miR-410-5p) in macrophage polarization during pregnancy. Methods Patient decidual macrophage tissue samples in spontaneous abortion group and normal pregnancy group (those who had induced abortion for non-medical reasons) were collected at the Reproductive Medicine Center of Renmin Hospital of Wuhan University from April to December 2021. Furthermore, placental villi and decidua tissue samples were collected from patients who had experienced a spontaneous miscarriage and normal pregnant women for validation and subsequent experiments at the Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital), from March 2021 to September 2022. As an animal model, 36 female mice were randomly divided into six groups as follows: naive-control, lipopolysaccharide-model, agomir-negative control prevention, agomir-410-5p prevention, agomir-negative control treatment, and agomir-410-5p treatment groups. We analyzed the miR-410-5p expression in abortion tissue and plasma samples; and supplemented miR-410-5p to evaluate embryonic absorption in vivo. The main source of miR-410-5p at the maternal–fetal interface was analyzed, and the possible target gene, signal transducer and activator of transcription (STAT) 1, of miR-410-5p was predicted. The effect of miR-410-5p and STAT1 regulation on macrophage phenotype, oxidative metabolism, and mitochondrial membrane potential was analyzed in vitro. Results MiR-410-5p levels were lower in the spontaneous abortion group compared with the normal pregnancy group, and plasma miR-410-5p levels could predict pregnancy and spontaneous abortion. Prophylactic supplementation of miR-410-5p in pregnant mice reduced lipopolysaccharide-mediated embryonic absorption and downregulated the decidual macrophage pro-inflammatory phenotype. MiR-410-5p were mainly distributed in villi, and trophoblasts secreted exosomes-miR-410-5p at the maternal–fetal interface. After macrophages captured exosomes, the cells shifted to the tolerance phenotype. STAT1 was a potential target gene of miR-410-5p. MiR-410-5p bound to STAT1 mRNA, and inhibited the expression of STAT1 protein. STAT1 can drive macrophages to mature to a pro-inflammatory phenotype. MiR-410-5p competitive silencing of STAT1 can avoid macrophage immune disorders. Conclusion MiR-410-5p promotes M2 macrophage polarization by inhibiting STAT1, thus ensuring a healthy pregnancy. These findings are of great significance for diagnosing and preventing spontaneous miscarriage, providing a new perspective for further research in this field.

Objectives: This study aims to comprehensively investigate the potential genetic link between periodontitis and adverse pregnancy outcomes using a two-sample Mendelian Randomization approach. Materials and methods: We employed robust genetic instruments for chronic periodontitis as exposure data from the FinnGen database. Data encompassing various pregnancy stage outcomes, including pre-pregnancy conditions (irregular menstruation, endometriosis, abnormal reproductive bleeding, and female infertility), pregnancy complications (hemorrhage, spontaneous miscarriage, and abnormalities in products), and post-pregnancy factors (single spontaneous delivery, labor duration, and birth weight of the child), were obtained from the UK Biobank. The random-effects inverse-variance weighted (IVW) method was utilized to compute primary estimates while diligently assessing potential directional pleiotropy and heterogeneity. Results: Our findings indicate a negative association between periodontitis and labor duration (odds ratio [OR] = 0.999; 95% confidence interval [CI]: 0.999 to 1.000; P = 0.017). Individuals with periodontitis are more likely to deliver lower-weight infants (OR = 0.983; 95% CI: 0.972 to 0.995; P = 0.005). We found no evidence of pleiotropy or heterogeneity in aforementioned two associations. We did not observe casual links with pre-pregnancy conditions and pregnancy complications. Conclusions: This Mendelian Randomization study underscores the genetic influence of periodontitis on specific adverse pregnancy outcomes, particularly concerning labor duration and lower birth weight deliveries. Clinical relevance: Our study emphasizes the critical importance of maintaining periodontal health during pregnancy and offers genetic evidence supporting these associations. Further investigation is required to delve deeper into the specific underlying mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Objective Association between a genetic polymorphism and disease, either positively or negatively, within a population may not necessarily predict association in other race-ethnic populations. The aim of this study was to genotype well recognized thrombophilia associated polymorphisms as common risk factors for miscarriage and investigate their benefit to use as risk factors in southwest region of Iran females (Khuzestan) in the Arabs ethnic minority group with spontaneous miscarriage. We developed a Reverse Dot Blot Assay for the genotyping of four polymorphisms. Results There were significant differences in the genotype distribution and allelic frequencies of the MTHFR 1298 A > C, MTHFR 677 C > T, Factor V Leiden 1691 G > A, PAI-1-844G > A polymorphisms between the case and control groups. The MTHFR 1298 A > C, MTHFR 677 C > T and Factor V Leiden 1691 G > A polymorphisms were significantly associated with spontaneous miscarriage risk. Unlike some other race-ethnic populations, PAI-1-844G > A polymorphism was associated with risk of developing unplanned miscarriage in Iranian Arabs ethnic minority group females.

Objective: Association between a genetic polymorphism and disease, either positively or negatively, within a population may not necessarily predict association in other race-ethnic populations. The aim of this study was to genotype well recognized thrombophilia associated polymorphisms as common risk factors for miscarriage and investigate their benefit to use as risk factors in southwest region of Iran females (Khuzestan) in the Arabs ethnic minority group with spontaneous miscarriage. We developed a Reverse Dot Blot Assay for the genotyping of four polymorphisms. Results: There were significant differences in the genotype distribution and allelic frequencies of the MTHFR 1298 A > C, MTHFR 677 C > T, Factor V Leiden 1691 G > A, PAI-1-844G > A polymorphisms between the case and control groups. The MTHFR 1298 A > C, MTHFR 677 C > T and Factor V Leiden 1691 G > A polymorphisms were significantly associated with spontaneous miscarriage risk. Unlike some other race-ethnic populations, PAI-1-844G > A polymorphism was associated with risk of developing unplanned miscarriage in Iranian Arabs ethnic minority group females. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can potential mechanisms involved in the likely concurrence of diminished ovarian reserve (DOR) and miscarriage be identified using genetic data? SUMMARY ANSWER Concurrence between ovarian reserve and spontaneous miscarriage was observed, and may be attributed to shared genetic risk loci enriched in antigen processing and presentation and autoimmune disease pathways. WHAT IS KNOWN ALREADY Previous studies have shown that lower serum anti-Müllerian hormone (AMH) levels are associated with increased risk of embryo aneuploidy and spontaneous miscarriage, although findings have not been consistent across all studies. A recent meta-analysis suggested that the association between DOR and miscarriage may not be causal, but rather a result of shared underlying causes such as clinical conditions or past exposure. Motivated by this hypothesis, we conducted the present analysis to explore the concurrence between DOR and miscarriage, and to investigate potential mechanisms using genetic data. STUDY DESIGN, SIZE, DURATION Three data sources were used in the study: the clinical IVF data were retrospectively collected from an academically affiliated Reproductive Medicine Center (17 786 cycles included); the epidemiological data from the UK Biobank (UKB), which is a large-scale, population-based, prospective cohort study (35 316 white women included), were analyzed; and individual-level genotype data from the UKB were extracted for further analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS There were three modules of analysis. First, clinical IVF data were used to test the association between ovarian reserve biomarkers and the subsequent early spontaneous miscarriage risk. Second, the UKB data were used to test the association of spontaneous miscarriage history and early menopause. Third, individual-level genotype data from the UKB were analyzed to identify specific pleiotropic genes which affect the development of miscarriage and menopause. MAIN RESULTS AND THE ROLE OF CHANCE In the analysis of clinical IVF data, the risk of early spontaneous miscarriage was 1.57 times higher in the group with AMH < 1.1 ng/ml group (P  < 0.001), 1.62 times for antral follicular count <5 (P  < 0.001), and 1.39 times for FSH ≥10 mIU/ml (P  < 0.001) in comparison with normal ovarian reserve groups. In the analysis of UKB data, participants with a history of three or more miscarriages had a one-third higher risk of experiencing early menopause (odds ratio: 1.30, 95% CI 1.13–1.49, P  < 0.001), compared with participants without spontaneous miscarriage history. We identified 158 shared genetic risk loci that affect both miscarriage and menopause, which enrichment analysis showed were involved in antigen processing and presentation and autoimmune disease pathways. LIMITATIONS, REASONS FOR CAUTION The analyses of the UKB data were restricted to participants of European ancestry, as 94.6% of the cohort were of white ethnicity. Further studies are needed in non-white populations. Additionally, maternal age at the time of spontaneous miscarriage was not available in the UKB cohort, therefore we adjusted for age at baseline assessment in the models instead. It is known that miscarriage rate in IVF is higher compared to natural conception, highlighting a need for caution when generalizing our findings from the IVF cohort to the general population. WIDER IMPLICATIONS OF THE FINDINGS Our findings have implications for IVF clinicians in terms of patient counseling on the prognosis of IVF treatment, as well as for genetic counseling regarding miscarriage. Our results highlight the importance of further research on the shared genetic architecture and common pathophysiological basis of DOR and miscarriage, which may lead to new therapeutic opportunities. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Hunan Youth Science and Technology Innovation Talent Project (2020RC3060), the International Postdoctoral Exchange Fellowship Program (Talent-Introduction Program, YJ20220220), the fellowship of China Postdoctoral Science Foundation (2022M723564), and the Natural Science Foundation of Hunan Province, China (2023JJ41016). This work has been accepted for poster presentation at the 39th Annual Meeting of ESHRE, Copenhagen, Denmark, 25–28 June 2023 (Poster number: P-477). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Christopher Thom, Matthew Kongkatong, James Moak Emergency Medicine, University of Virginia Health System, Charlottesville, VA, USACorrespondence: Christopher Thom, Email ct9k@hscmail.mcc.virginia.eduIntroduction: Ultrasonography has an important role in the evaluation of Emergency Department (ED) patients presenting with early pregnancy complaints. Both transabdominal (TAUS) and transvaginal ultrasound (TVUS) can be utilized. While TVUS generally allows for greater detail, it is unclear how much added benefit exists in performing TVUS once an intrauterine pregnancy (IUP) has been identified on TAUS.Methods: This was a retrospective study utilizing Radiology Department ultrasound examinations obtained in first trimester pregnancy ED patients during a consecutive four month period in 2019. Studies wherein both TAUS and TVUS were both performed were included. Two ED physicians with specialized training in point of care ultrasound reviewed only the TAUS images from these studies. Their findings were compared to the Radiologist interpretation, which was inclusive of both TAUS and TVUS components of the study.Results: 108 studies met inclusion criteria. Amongst these, 82 had IUP’s identified on the radiologist report. 69 studies had an IUP identified by ED physician review of the TAUS images, with 1 false positive. Each case of intrauterine fetal demise (IUFD) was identified on ED physician review of TAUS. Two ectopic pregnancies were present, neither of which was mistaken for IUP on ED physician TAUS review. There were 15 studies with subchorionic hemorrhage and 3 studies with an ovarian cyst noted on the radiologist report.Conclusion: Following the identification of an IUP on TAUS, the added diagnostic value of TVUS amongst this cohort of ED patients was low. Given the added time and cost of TVUS, selective instead of routine usage should be encouraged.Keywords: ectopic pregnancy, ultrasound, threatened miscarriage, spontaneous miscarriage, yolk sac, subchorionic hemorrhage

Objective and design: To investigate the balancing mechanisms between decidualization-associated inflammation and pregnancy-related immunotolerance. Material or subjects: Decidual samples from women with normal pregnancy (n = 58) or unexplained spontaneous miscarriage (n = 13), peripheral blood from normal pregnancy and endometria from non-pregnancy (n = 10) were collected. Primary endometrial stromal cells (ESCs), decidual stromal cells (DSCs), decidual immune cells (DICs) and peripheral blood mononuclear cells (PBMCs) were isolated. Treatment: The plasmid carrying neuropilin-1 (NRP1) gene was transfected into ESC for overexpression. To induce decidualization in vitro, ESCs were treated with a combination of 10 nM estradiol, 100 nM progesterone and 0.5 mM cAMP. Anti-Sema3a and anti-NRP1 neutralizing antibodies were applied to block the ligand–receptor interactions. Methods: RNA-seq analysis was performed to identify differentially expressed genes in DSCs and DICs, and NRP1 expression was verified by Western blotting and flow cytometry. The secretion of inflammatory mediators was measured using a multifactor cytometric bead array. The effects of Sema3a-NRP1 pathway on DICs were determined by flow cytometry. Statistical differences between groups were compared using the T test and one way or two-way ANOVA. Results: Combined with five RNA-seq datasets, NRP1 was the only immune checkpoint changing oppositely between DSCs and DICs. The decreased expression of NRP1 in DSCs allowed intrinsic inflammatory responses required for decidualization, while its increased expression in DICs enhanced tolerant phenotypes beneficial to pregnancy maintenance. DSC-secreted Sema3a promoted immunosuppression in DICs via NRP1 binding. In women with miscarriage, NRP1 was abnormally elevated in DSCs but diminished in decidual macrophages and NK cells. Conclusion: NRP1 is a multifunctional controller that balances the inflammatory states of DSCs and DICs in gravid uterus. Abnormal expression of NRP1 is implicated in miscarriage. [ABSTRACT FROM AUTHOR]

Background: Rubella or German measles is a viral disease transmitted via aerosol droplets affecting mainly children, Mostly, rubella is a simple and self-limiting disease with no chronic consequences, except in infected pregnant women which may result in devastating outcomes depending on the trimester of pregnancy. Materials and methods: the study enrolled 1004 women suffering from spontaneous miscarriage tested for rubella IgM antibodies using ELISA. The sampling was conducted in two different seasons, summer and winter. Results: Test reading showed that 15.23% of all tested women were positive for rubella IgM antibodies i.e. 153 out of 1004 women. Seasonal change showed no significant variation in the percentage of the infection, where 15.8% of all participants were positive in summer versus 14.35% seropositive in the winter season (p˃ 0.05). Conclusion: Rubella infection is affecting a relatively high number of women suffering from a spontaneous miscarriage in Mosul city, and there was no seasonal variation in the rate of infection.

Objectives. To define the factors that determine spontaneous miscarriage and preterm birth in pregnant women with isthmic-cervical insufficiency (ICI), to develop recommendations for providing medical care depending on the individual risk. Material and methods. The object of the study was 300 pregnant women with ICI (main group) and their newborns: subgroup 1 – 91 patients with spontaneous miscarriage and ICI, subgroup 2 – 106 patients with preterm labor and ICI, subgroup 3 – 103 patients with term labor and ICI. The control group (subgroup 4) consisted of 100 women with term labor without ICI. All patients received treatment in Vitebsk region hospitals in 2016-2022. Results. The anamnestic data, the features of the current pregnancy course, the results of laboratory and instrumental diagnostic methods, the effectiveness of a vaginal cerclage, an obstetric pessary, and a hormonal method of treating ICI were studied. An assessment of the influence of the studied factors on the timing of the completion of pregnancy, the morbidity of newborns and the need for the second stage of nursing was made. Risk factors for ICI and factors influencing pregnancy outcomes in ICI in the 2nd and the 3rd trimesters have been established, which will enable the prediction of gestational complications, timely performing of primary and secondary prevention of miscarriage, and improvement of perinatal morbidity rates. Conclusions. A high risk of spontaneous miscarriage in patients with ICI is determined by the following risk factors: ≥ 3 deliveries; history of premature birth; ICI in the anamnesis; severe undifferentiated connective tissue dysplasia (UCTD); hyperprolactinemia; cervical dysplasia during the current pregnancy; asymptomatic bacteriuria during the current pregnancy; cervical length ≤25 mm at 16 weeks of gestation. Risk factors for preterm delivery against the background of ICI during the current pregnancy are: severe UCTD; cervical length ≤25 mm at 22 weeks of gestation. To reduce the likelihood of spontaneous miscarriage in patients with ICI the use of prophylactic progesterone; dynamic ultrasonic cervicometry; diagnosis and treatment of asymptomatic bacteriuria; prophylactic vaginal cerclage when the cervical length is 25-30 mm at 14-16 weeks of pregnancy may be useful. To reduce the rate of preterm birth in patients with ICI prophylactic administration of progesterone; dynamic ultrasonic cervicometry; prophylactic vaginal cerclage when the cervical length is 25-30 mm at 20-22 weeks of pregnancy may be recommended.

(1) Background: The aim of our study is to evaluate whether cell-free DNA testing can overlap the genetic testing of miscarriage tissue in women with early pregnancy loss (EPL) and length of recurrent pregnancy loss (RPL); (2) Methods: We conducted a prospective cohort study at the Pregnancy Loss Unit of the Fondazione Policlinico Universitario A. Gemelli (IRCCS), Rome, Italy between May 2021 and March 2022. We included women with EPL and length of RPL. Gestational age was >9 weeks + 2 days and <12 weeks + 0 days of gestation corresponding to a crown rump length measurement of >25 and <54 mm. Women underwent both dilation and curettage for the collection of miscarriage tissue and for blood sample collection. Chromosomal microarray analysis (CMA) on miscarriage tissues was performed by oligo-nucleotide- and single nucleotide polymorphisms (SNP)-based comparative genomic hybridization (CGH+SNP). Maternal blood samples were analyzed by Illumina VeriSeq non-invasive prenatal testing (NIPT) to evaluate the cell-free fetal DNA (cfDNA) and the corresponding fetal fraction and the presence of genetic abnormalities; (3) Results: CMA on miscarriage tissues revealed chromosome aneuploidies in 6/10 cases (60%), consisting of trisomy 21 (5 cases) and monosomy X (one case). cfDNA analysis was able to identify all cases of trisomy 21. It failed to detect monosomy X. A large 7p14.1p12.2 deletion concomitant to trisomy 21 was, in one case, detected by cfDNA analysis but it was not confirmed by CMA on miscarriage tissue. (4) Conclusions: cfDNA largely reproduces the chromosomal abnormalities underlying spontaneous miscarriages. However, diagnostic sensitivity of cfDNA analysis is lower with respect to the CMA of miscarriage tissues. In considering the limitations when obtaining biological samples from aborted fetuses suitable for CMA or standard chromosome analysis, cfDNA analysis is a useful, although not exhaustive, tool for the chromosome diagnosis of both early and recurrent pregnancy loss. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a heterogeneous entity comprising broad spectra of ovarian disorders with trademark features of metabolic syndrome like insulin resistance, obesity, and dyslipidaemia to name a few. Hyperhomocysteinemia, an independent risk factor of metabolic syndrome, has been suggested as a causative factor in spontaneous miscarriage in PCOS. However, it is yet to be resolved whether hyperhomocysteinemia has a contributory role in the pathogenesis or could direct long-term sequences of the syndrome. A total of 2355 women with history of one or more first trimester abortions were screened and 1539 were selected for the study. Selected patients were initially divided by the presence or absence of PCOS, while subsequent stratification was based on hyperhomocysteinemia, insulin resistance, and/or obesity. The miscarriage population/s was mostly represented by hyperhomocysteinemia in both the cohorts (PCOS: 69.08% vs. non-PCOS: 56.68%). ROC-AUC values suggest increased predisposition of hyperhomocysteinemia-mediated miscarriage (hyperhomocysteinemia: 0.778; insulin resistance: 0.601; BMI: 0.548). A probabilistic causal model was designed using dynamic Bayesian network to evaluate the time-series data points before, during, and after pregnancy which revealed a possibility of 32.24% (n = 79) of PCOS cohort developing hypertension, 26.94% (n = 66) of onset of diabetes and 4.49% cardiovascular disease 3 years following pregnancy. We conclude hyperhomocysteinemia may possibly contribute to spontaneous miscarriage and related to metabolic derailments later in life. [ABSTRACT FROM AUTHOR]

This case–control study was designed to examine the association between different types of miscarriage history and autism spectrum disorder (ASD), and determine whether the number of miscarriage history affects the risk of ASD. All of 2274 children with ASD and 1086 healthy controls were recruited. Sociodemographic and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Multivariable logistic regression analyses were applied to investigate association between miscarriage history and ASD. Stratified analyses based on sex and types of miscarriages were similarly performed. History of miscarriage was potential risk factors for ASD ([aOR] = 2.919; 95% [CI] = 2.327–3.517). Stratified analyses revealed that induced ([aOR] = 2.763, 95% [CI] = 2.259–3.379) and spontaneous miscarriage history ([aOR] = 3.341, 95% [CI] = 1.939–4.820) were associated with high risk of ASD, respectively. A sex-biased ratio in the risk of ASD was observed between females ([aOR] = 3.049, 95% [CI] = 2.153–4.137) and males ([aOR] = 2.538, 95% [CI] = 1.978–3.251). Stratified analysis of induced miscarriage history revealed that only iatrogenic miscarriage history was associated with an increased risk ASD ([aOR] = 2.843, 95% [CI] = 1.534–4.268). Also, multiple spontaneous miscarriage histories ([aOR] = 1.836, 95% [CI] = 1.252–2.693) were associated with higher autism risk than one spontaneous miscarriages history ([aOR] = 3.016, 95% [CI] = 1.894–4.174). In conclusion, miscarriage history is related to an increased risk for ASD in offspring, which is affected by the types of miscarriage and sex of the fetus. [ABSTRACT FROM AUTHOR]

Background: Spontaneous miscarriage (SM) is the most common complication of pregnancy. Its psychological repercussions are widely documented but few studies have investigated its effect on women’s experience of a subsequent pregnancy. Aim: To evaluate the impact of prior SM on the level of stress experienced by pregnant women during the first trimester of pregnancy. Design and setting: Cross-sectional, observational study, which was conducted between June and October 2021 in France. Method: A self-report questionnaire was distributed to women in the first trimester of pregnancy. Stress was assessed using the Antenatal Perceived Stress Inventory to yield an overall score and a score for three dimensions ('medical and obstetric risks or fetal health'; 'psychosocial changes during pregnancy'; and the ‘prospect of childbirth'). Women with a history of prior SM and those without were compared. Results: In total, 93 women were included; 63 without and 30 with a history of prior SM. Prior SM was not associated with the overall score. The score for the dimension 'medical and obstetric risks or fetal health' was significantly higher in women with prior SM (3.00±0.86 versus 2.34±0.80; β = 0.61 [95% confidence interval {CI} = 0.25 to 0.96]; P = 0.001). Prior SM was significantly associated with the items 'the baby’s health' (P = 0.048) and 'the echography' (P = 0.002). Conclusion: This study shows a significant impact of prior SM on the level of stress of pregnant women during the first trimester, particularly relating to the medical and obstetric risks or fetal health, underlining the need for appropriate psychological support to be provided to women who experience SM. [ABSTRACT FROM AUTHOR]

Background: Spontaneous miscarriage (SM) is the most common complication of pregnancy. Its psychological repercussions are widely documented but few studies have investigated its effect on women’s experience of a subsequent pregnancy. Aim: To evaluate the impact of prior SM on the level of stress experienced by pregnant women during the first trimester of pregnancy. Design and setting: Cross-sectional, observational study, which was conducted between June and October 2021 in France. Method: A self-report questionnaire was distributed to women in the first trimester of pregnancy. Stress was assessed using the Antenatal Perceived Stress Inventory to yield an overall score and a score for three dimensions ('medical and obstetric risks or fetal health'; 'psychosocial changes during pregnancy'; and the ‘prospect of childbirth'). Women with a history of prior SM and those without were compared. Results: In total, 93 women were included; 63 without and 30 with a history of prior SM. Prior SM was not associated with the overall score. The score for the dimension 'medical and obstetric risks or fetal health' was significantly higher in women with prior SM (3.00±0.86 versus 2.34±0.80; β = 0.61 [95% confidence interval {CI} = 0.25 to 0.96]; P = 0.001). Prior SM was significantly associated with the items 'the baby’s health' (P = 0.048) and 'the echography' (P = 0.002). Conclusion: This study shows a significant impact of prior SM on the level of stress of pregnant women during the first trimester, particularly relating to the medical and obstetric risks or fetal health, underlining the need for appropriate psychological support to be provided to women who experience SM.

Aims: Repeated pregnancy loss (RPL) is commonly considered as ≥3 fetal losses previously 20 weeks of gestation. Vitamin D has an important role on immune inflection at the maternal-fetal part. Though, vitamin D can be utilized as a useful approach to treat patients with repeated pregnancy loss. There was lack of consensus on prescribing Vitamin D during pregnancy to prevent pregnancy complications. However, the present study was conducted to compare the effect of low and high dose of Vitamin D on to prevent pregnancy complications. Materials & Methods: We conducted a single-blinded, randomized controlled trial in Yasuj, Iran, to assess the influence of different doses of vitamin D supplement through pregnancy in women on pregnancy and birth outcomes (preterm births and stillbirths, pre-eclampsia, gestational diabetes and low birth weight. Findings: Patients (n=150) in their first trimester were enrolled and randomized to two groups of vitamin D supplementation; 500IU/day (group A; n=70) and 2000IU/day (group B; n=70). 131 patients completed the intervention. Maternal vitamin D supplementation 2000IU/day had a positive effect only on gestational diabetes mellitus, spontaneous miscarriage and preeclampsia and preterm births but there was no statistically significant difference between two groups (p>0.05). Conclusion: Increasing dose from 500 units to 2000 units per day does not increase the effectiveness of vitamin D to decrease pregnancy complications. Vitamin D supplementation (500 IU/day) appeared sufficient to reduce the risk of pregnancy complications as well as the higher dose. [ABSTRACT FROM AUTHOR]

Background: It is still unclear whether social support can moderate the high risk of depression and anxiety due to spontaneous miscarriage., Objective: This study prospectively investigated the associations of spontaneous miscarriage with risks of depression and anxiety, and evaluated the interactions between spontaneous miscarriage and the degree of social support in relation to depression and anxiety risks., Study Design: A total of 179,000 participants from the UK Biobank with pregnancy experience and without depression or anxiety at baseline were included. Spontaneous miscarriage was defined by self-report from participants at enrollment or by International Classification of Diseases codes. The degree of social support was defined as the number of social support factors including living with a spouse or partner, participation in social activities, and confiding. Cox proportional hazards models were used to evaluate the joint association of spontaneous miscarriage and social support with the risks of depression and anxiety., Results: During a median follow-up of 12.3 years, 4939 depression incidents and 5742 anxiety incidents were documented. For participants with 1, 2, and ≥3 spontaneous miscarriages, hazard ratios (95% confidence intervals) for depression were 1.10 (1.02-1.19), 1.31 (1.14-1.50), and 1.40 (1.18-1.67), respectively (P trend <.001), compared with participants without a history of spontaneous miscarriage, after adjustment for covariates. For anxiety, the hazard ratios (95% confidence intervals) were 1.07 (1.00-1.15), 1.04 (0.90-1.19), and 1.21 (1.02-1.44), respectively (P trend=.01). Moreover, we found that the risk of depression associated with a combination of spontaneous miscarriage and low degree of social support in later life was greater than the sum of the risks associated with each individual factor, indicating significant interactions on an additive scale (P interaction=.03)., Conclusion: Spontaneous miscarriage is associated with higher risks of depression and anxiety, and the risk of depression is further increased when there is also low degree of social support., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Relevance. Miscarriage is one of the most common obstetric pathologies that determine the spontaneous death of the fetus. The role of changes in the microbiome of various biotopes is considered as a risk factor of this disease.Aim of the research is to assess the microbiocenoses structure of the reproductive system and the intestine associated with the development of spontaneous miscarriages in early pregnancy.Materials and methods. A case-control study was conducted and organized. The group of «cases» included 23 women with spontaneous miscarriage at 5–14 weeks of pregnancy and the control group included 23 women with normal pregnancies Based on the data of metagenomic sequencing of V3–V4 regions of the 16S rRNA gene, a comparative assessment of the structure of the vaginal and intestinal microbiome in these groups was carried out.Results. As a result of the study, a number of taxonomic groups of microorganisms in the vagina and intestines associated with miscarriage. It was found that the decrease in the proportion of Lactobacillus spp. in the structure of the vaginal microbiome, less than 90% of the total number of identified taxa is associated with this pathology (OR = 5.28 (95% CI = 1.2-23.2)). The gut microbiocenoses of women with spontaneous miscarriage are characterized by less taxonomic diversity than the gut microbiome of women with advanced pregnancy. At the same time, some representatives of the intestinal microbiome (Akkermansia sp., Faecalibacterium sp., Bifidobacterium sp., Methanobrevibacter sp., Lactococcus sp.) predominate in women with a normal pregnancy.Conclusion. The study demonstrated a significant role of changes in microbiocinosis of the reproductive tract and intestines in miscarriage. There is a potentially protective function of lactobacilli. The obtained data substantiates the need for active use of molecular genetic methods focused on the assessing the structure of the vaginal and intestinal microbiota in assessing the risks of reproductive failures.

Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications. [ABSTRACT FROM AUTHOR]

Spontaneous miscarriage is a common pregnancy complication. Multiple etiologies have been proposed such as genetic aberrations, endocrinology disorder, and immunologic derangement; however, the relevance of circulating lipidomes to the specific condition remains unclear. In the present study, lipidomics profiling was examined on serum of women with spontaneous miscarriage after in vitro fertilization and embryo transfer (IVF-ET). Screening and analysis of differential lipid levels were conducted using a machine learning approach to verify the stability and validity of potential serum biomarkers. Seven lipid species presented significant differences between the abortion and term birth patients, including three types of sphingomyelins (SMs), two types of diglycerides (DGs), one phosphatidylcholine (PC), and one lysophosphatidylethanolamine (LPE). All the SMs presented with a fold change of > 1, while both the PC and LPE had a fold change of < 1. The DG containing two saturated fatty acyl chains was decreased, but that containing two unsaturated fatty acyl chains was increased in the miscarriage group compared to the control group. This study reveals the relevance of lipid profiles to spontaneous abortion after IVF-ET, providing potential biomarkers and therapeutic targets for the specific clinical scenario. [ABSTRACT FROM AUTHOR]

Objective: To study the relationship between history of miscarriage (induced or spontaneous) and current use of modern contraceptive method among women in Pakistan. Study Design: Cross Sectional study. Setting: OPD of MCH, PIMS. Period: July 2019 to December 2019. Material & Methods: A total of 80 married women were enrolled, 40 women who had induced miscarriage (group A) and 40 from spontaneous miscarriage (group B). Data is obtained on predesigned questionnaire. Primary outcome was acceptance of contraception (LARC) after induced versus spontaneous miscarriage. Results: About 51% of women were in the age group of 30-35 years and out of total 80 women, 67 (83%) women had parity of three or above (27 % had parity of three). Out of 66 women who used contraception, 35 (53%) had induced miscarriage (group A) and 31 (46%) had spontaneous miscarriage (group B). Women who belonged to induced miscarriage (group A) faced menstrual irregularity, as the reason of leaving contraception, followed by chronic PID and husband opposition. While in the group B, fertility desire was main reason of discontinuation of contraception. In Group A, 20 (50%) women were willing to use LARC (long acting reversible contraception) after induced abortion to reduce the chances of unwanted pregnancy while in other group B, 15 (37.5%) women were wanted to use LARC and 18 (45%) women were not ready to use contraception due to fertility. Conclusion: High rate of induced abortion due to failed contraception and dis-continuation of contraceptives needs to be addressed by encouraging women to manage the side effects to ensure continuity of contraceptives. [ABSTRACT FROM AUTHOR]

Background. Spontaneous miscarriage is the most common complication of pregnancy. Obesity increases the risk of adverse pregnancy outcomes. Aim of the study. To assess the cytokine profile as a marker of spontaneous miscarriage in women with metabolic disorders in the past medical history. Materials and methods. A prospective study of 170 adolescent girls with metabolic disorders was conducted between 2000 and 2013. Assessment of menstrual and reproductive function was carried out in 86, pregnancy outcomes – in 72 women. The average age of women in reproductive age was 21.95 ± 0.2 years, BMI – 24.7 ± 3.9 kg/m2. Results. In women with early pregnancy losses and metabolic disorders in past medical history, the predictor of an early pregnancy loss is an increase in the ratio of pro- and anti-inflammatory cytokines TNF-a/IL-10 in serum at 7–8 weeks of gestation (OR = 2.29). It was determined a significant correlation between the levels of pro- and anti-inflammatory cytokines of the same name in serum and chorion (IL-10 (p = 0.000) and TNF-α/IL-10 (p = 0.001), which indicates similar changes in chorion. The activity of NF-kB in chorion was 5.75 ± 0.51 pg/ml. Conclusions. The findings suggest that the cytokine balance of pro- and anti-inflammatory cytokines in women with metabolic disorders in past medical history is an important component in the development of early pregnancy losses.

Abstract LINE1 retrotransposons are mobile DNA elements that copy and paste themselves into new sites in the genome. To ensure their evolutionary success, heritable new LINE-1 insertions accumulate in cells that can transmit genetic information to the next generation (i.e., germ cells and embryonic stem cells). It is our hypothesis that LINE1 retrotransposons, insertional mutagens that affect expression of genes, may be causal agents of early miscarriage in humans. The cell has evolved various defenses restricting retrotransposition-caused mutation, but these are occasionally relaxed in certain somatic cell types, including those of the early embryo. We predict that reduced suppression of L1s in germ cells or early-stage embryos may lead to excessive genome mutation by retrotransposon insertion, or to the induction of an inflammatory response or apoptosis due to increased expression of L1-derived nucleic acids and proteins, and so disrupt gene function important for embryogenesis. If correct, a novel threat to normal human development is revealed, and reverse transcriptase therapy could be one future strategy for controlling this cause of embryonic damage in patients with recurrent miscarriages.

Introduction: Approximately half of miscarriages are of an unknown aetiology and are likely characterized by aberrant inflammation at the uteroplacental interface. High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that participates in the pathological inflammatory response. The present study investigated the role of HMGB1 in inflammation-induced damage in trophoblasts and elucidated the underlying mechanism.Methods: Immunohistochemistry, qRT-PCR and Western blotting were used to detect the expression of HMGB1 in early unexplained miscarriage and normal placentas. Lipopolysaccharide (LPS)-induced HTR8/SVneo cells were used as an in vitro model to mimic the aberrant inflammation at the uteroplacental interface of miscarriage. The expression of HMGB1 and the autophagy-related proteins LC3 and Beclin1 was detected using Western blotting. Autophagy was studied in villous tissues using immunofluorescence and Western blotting. Cell proliferation and migration were analysed.Results: The expression level of HMGB1 in villous tissues with early unexplained miscarriage was significantly higher than the normal pregnancy group. The inhibition of HMGB1 in LPS-treated HTR8/SVneo cells decreased the expression of Beclin 1 and LC3, which promoted cell proliferation and migration. We found a high level of autophagy in miscarriage placentas. HMGB1 and autophagy inhibition reversed the proliferation and migration of LPS-induced HTR-8/SVneo cells.Discussion: Our results demonstrated that HMGB1 participated in LPS-induced inflammation via autophagy and regulated trophoblast functions, such as cell proliferation and migration, to potentially participate in the pathogenesis of miscarriage. [ABSTRACT FROM AUTHOR]

• Even in samples with MCC, CNV-seq can still detect abnormalities in some samples that can explain the cause of miscarriage. • Initial CNV-seq followed by QF-PCR if needed was an efficient and cost-effective strategy for the genetic analysis of POCs. Copy number variation sequencing (CNV-seq) is crucial in prenatal diagnosis, but its limitations in detecting polyploidy, maternal cell contamination (MCC), and uniparental disomy (UPD) restrict its application in the analysis of products of conception (POCs). This study aimed to investigate an optimal genetic testing strategy for POCs in the era of CNV-seq. CNV-seq and quantitative fluorescent polymerase chain reaction (QF-PCR) were performed in all 4,211 spontaneous miscarriage cases. Different testing strategies were compared and the optimal testing strategies were proposed. Of the 4,211 cases, 2561 (60.82%) exhibited clinically significant chromosomal abnormalities. CNV-seq alone, without QF-PCR, might misdiagnose 311 (7.39%) cases, including 278 polyploidy, 13 UPD, and 20 MCC. In 20 MCC cases identified by QF-PCR, CNV-seq successfully pinpointed the cause of miscarriage in 13 cases. Furthermore, in cases where QF-PCR suggested polyploidy, CNV-seq improved the diagnostic accuracy in 54 (1.28%) hypo/hypertriploidy cases. After comparing four different strategies, the sequential approach (initiating with CNV-seq followed by QF-PCR if necessary) emerged as advantageous, reducing approximately 70% of the cost associated with QF-PCR while maintaining result accuracy. We propose an initial CNV-seq followed by QF-PCR if needed—an efficient and cost-effective strategy for the genetic analysis of POCs. [ABSTRACT FROM AUTHOR]

The article presents a discussion of the issue of management of patients after spontaneous abortion to prevent inflammatory complications. The condition of 165 patients distributed randomly in two groups is analyzed. Attention was paid to a full-fledged microbiological examination, including bacterioscopy and modern methods of PCR-diagnostics: «Inbioflor(4+MHC)» and «Femoflor-16». Patients of the first group (85 people) were prescribed antibacterial therapy (doxycycline, metronidazole, povidoniodine), as well as modern methods of physiotherapy: magnetoinfrared laser and ozone therapy. The second group (80 people) received similar antibacterial therapy, without physiotherapy. The study showed that the best effect can be achieved with complex therapy, including antibacterial drugs and modern methods of physiotherapy.

Obesity is prevalent among women of reproductive age and is associated with increased risk of developing multiple pregnancy disorders. Pregnancy must induce immune tolerance to avoid fetal rejection, while obesity can cause chronic inflammation through activating the immune system. Impaired maternal immuno-tolerance leads to pregnancy failure, such as recurrent spontaneous abortion (RSA), one of the most common complications during early pregnancy. How does maternal immune response change under obesity stress in normal pregnancy and RSA? In turn, is obesity affected by different gestational statuses? Limited information is presently available now. Our study investigated pregnancy outcomes and maternal immune responses in two murine models (normal pregnancy and spontaneous abortion models) after obesity challenge with a high-fat diet (HFD). Abortion-prone mice fed HFD had significantly higher weight gains during pregnancy than normal pregnant mice with HFD feeding. Nonetheless, the embryo implantation and resorption rates were comparable between HFD and normal chow diet (NCD)-fed mice in each model. Evaluation of immune cell subsets showed HFD-induced obesity drove the upregulation of activated NK cell-activating receptor (NKp46)+ NK cells and pro-inflammatory macrophages (MHCIIhigh Mφ) as well as CD4+ and CD8+ T cells in the normal pregnancy group. However, in the abortion-prone group, relative more immature NK cells with decreased activity phenotypes were found in obese mice. Moreover, there were increased DCreg (CD11bhigh DC) cells and decreased CD4+ and CD8+ T cells detected in the HFD abortion-prone mice relative to those fed the NCD diet. Our findings reveal how pregnancy obesity and maternal immune regulation are mutually influenced. It is worth noting that the abortion-prone model where active maternal immune status was intensified by obesity, in turn stimulated an overcompensation response, leading to an over-tolerized immune status, and predisposing to potential risks of perinatal complications.

Obesity is prevalent among women of reproductive age and is associated with increased risk of developing multiple pregnancy disorders. Pregnancy must induce immune tolerance to avoid fetal rejection, while obesity can cause chronic inflammation through activating the immune system. Impaired maternal immuno-tolerance leads to pregnancy failure, such as recurrent spontaneous abortion (RSA), one of the most common complications during early pregnancy. How does maternal immune response change under obesity stress in normal pregnancy and RSA? In turn, is obesity affected by different gestational statuses? Limited information is presently available now. Our study investigated pregnancy outcomes and maternal immune responses in two murine models (normal pregnancy and spontaneous abortion models) after obesity challenge with a high-fat diet (HFD). Abortion-prone mice fed HFD had significantly higher weight gains during pregnancy than normal pregnant mice with HFD feeding. Nonetheless, the embryo implantation and resorption rates were comparable between HFD and normal chow diet (NCD)-fed mice in each model. Evaluation of immune cell subsets showed HFD-induced obesity drove the upregulation of activated NK cell-activating receptor (NKp46)+ NK cells and pro-inflammatory macrophages (MHCIIhigh M φ) as well as CD4+ and CD8+ T cells in the normal pregnancy group. However, in the abortion-prone group, relative more immature NK cells with decreased activity phenotypes were found in obese mice. Moreover, there were increased DCreg (CD11bhigh DC) cells and decreased CD4+ and CD8+ T cells detected in the HFD abortion-prone mice relative to those fed the NCD diet. Our findings reveal how pregnancy obesity and maternal immune regulation are mutually influenced. It is worth noting that the abortion-prone model where active maternal immune status was intensified by obesity, in turn stimulated an overcompensation response, leading to an over-tolerized immune status, and predisposing to potential risks of perinatal complications. [ABSTRACT FROM AUTHOR]

Miscarriage is one of the fundamental complications occurring in pregnant women. Many fastidious and uncultivated bacterial species are related to miscarriage and have a significant role in the infection. The association between inverse pregnancy outcomes and infections of abnormal bacteria has been rarely investigated. Therefore, this study aimed to determine Leptotrichia amnionii and Atopobium vaginae as a risk factor for miscarriage states. A total of 80 cervical swabs and blood samples were obtained from females (34 non-pregnant with recurrent spontaneous miscarriage, 11 pregnant who had previous miscarriage, and 35 without miscarriage as control) who were referred to a hospital in Baghdad city. The relationship between demographic characteristics and miscarriage groups indicates a positive association between the age of 30 years and >45 years and miscarriage states, while no significant association (p>0.05) was found for the other parameters compared with the control. Also, no association was observed between the levels of TORCH IgM, antiphospholipid (APL) IgM, and anticardiolipidin (ACL) IgM antibodies and spontaneous miscarriage. The findings of RT-PCR detection revealed that, out of 45 samples of recurrent spontaneous miscarriage, 17 were detected with high-risk of L. aminonia compared with two samples from the control group. Also, 7 samples of recurrent spontaneous miscarriage were shown to be infected with A. vaginae compared with five samples from the control group. The adjusted odd ratios (ORs) of L. anmionii for spontaneous miscarriage and pregnancy states were 7.89 (CI 95%, 1.60 - 39.00) and 9.43 (CI 95%, 1.43 - 61.9), respectively, with highly significant difference between the study groups compared with the control. While no significant result was recorded between the adjusted ORs of A. vaginae for spontaneous miscarriage and pregnancy states, which were 1.23 (CI 95%, 0.416 - 3.67) and 0.636 (CI 95%, 0.083 - 4.88), respectively, compared with the control. [ABSTRACT FROM AUTHOR]

Vaginal bleeding in the first trimester is a common occurrence, but the majority of the pregnancies have a normal outcome. The careful assessment is yet important, given the possibility of complications. The patients with a threatened abortion should be monitored for progression to pregnancy failure. The most common type of spontaneous abortion is early pregnancy loss, defined as death of an embryo or fetus within the first 13 weeks of pregnancy. The clinical manifestations have low specificity, neither the duration of bleeding, nor the presence of lower abdominal cramping in the first trimester being reliable indicators of pregnancy outcome, thus the special attention has turned to ultrasonography for the evaluation of early pregnancy complications. The therapeutic approach (expectant management, medication or surgical interventions) should be tailored based on the gestational age, clinical and ultrasound findings. Severe hemorrhage requires urgent treatment, the surgical evacuation of the products of conception being often necessary. In this paper, we present the incidence and prevalence of early pregnancy loss and threat of abortion in the Department of Obstetrics and Gynecology of the Bucharest University Emergency Hospital, for a two-year period, discussing the impact of the advanced maternal age as a risk factor for spontaneous abortion. [ABSTRACT FROM AUTHOR]

Chromosomal abnormalities (CAs) can cause spontaneous miscarriage and increase the incidence of subsequent pregnancy loss and other complications. Presently, CAs are detected mainly by array comparative genomic hybridization (CGH) and single nucleotide polymorphism microarrays. The present study developed a low-coverage next-generation sequencing method to detect CAs in spontaneous miscarriage and assess its clinical performance. In total, 1,401 patients who had experienced an abortion were enrolled in the present study and divided into two groups. In group I, 437 samples that had been previously validated by array CGH were used to establish a method to detect CAs using a semiconductor sequencing platform. In group II, 964 samples, which were not verified, were assessed using established methods with respect to clinical significance. Copy number variant (CNV)-positive and euploidy samples were verified by array CGH and short tandem repeat profiling, respectively, based on quantitative fluorescent PCR. The low-coverage sequencing method detected CNVs >1 Mb in length and a total of 3.5 million unique reads. Similar results to array CGH were obtained in group I, except for six CNVs <1 Mb long. In group II, there were 341 aneuploidies, 195 CNVs, 25 mosaicisms and 403 euploidies. Overall, among the 1,401 abortion samples, there were 536 aneuploidies, 263 CNVs, 34 mosaicisms, and 568 euploidies. Trisomies were present in all autosomal chromosomes. The most common aneuploidies were T16, monosomy X, T22, T15, T21 and T13. Furthermore, one tetrasomy 21, one CNV associated with Wolf-Hirschhorn syndrome, one associated with DiGeorge syndrome and one associated with both Prader-Willi and Angelman syndromes were identified. These four cases were confirmed by short tandem repeat profiling and array CGH. Quantitative fluorescent PCR revealed nine polyploidy samples. The present method demonstrated equivalent efficacy to that of array CGH in detecting CNVs >1 Mb, with advantages of requiring less input DNA and lower cost. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review and meta-analysis of observational studies were conducted to assess the association between antibiotics use during pregnancy and spontaneous miscarriage.Methods: A systematic search of online databases as well as reference lists of retrieved studies were performed up to September 2018 to identify observational studies that investigated the association between antibiotics use and spontaneous miscarriage. The retrieved studies were assessed for methodological quality. Pooled relative risk (RR) and 95% confidence intervals were calculated using DerSimonian and Laird method. Random-effects meta-analysis was used to account for conceptual heterogeneity. Sensitivity analysis was performed to assess the robustness of pooled estimates using Stata software.Results: Of 1435 retrieved studies, 89 were reviewed in depth and 12 (8 prospective cohort and 4 population-based case-control studies) met the criteria for inclusion in a systematic review with 1,084,792 participants and 7015 cases of spontaneous miscarriage. Finally, 11 studies were included in the meta-analysis (one study was not included in the meta-analysis owing to methodological issues and low-quality score). Overall percentage of miscarriage in women who received antibiotics was 2.6%. After adjusting for important potential confounders, use of macrolides (RR: 1.42; 95% CI 1.04, 1.93), quinolones (RR: 2.48; 95% CI 1.46, 4.20), and tetracyclines (RR: 2.57; 95% CI 1.95, 3.38) during pregnancy were significantly associated with spontaneous miscarriage. In macrolides class, a significant positive association was found between clarithromycin and spontaneous miscarriage (RR: 1.98; 95% CI 1.46, 2.70). Sensitivity analysis demonstrated the consistency of the results, indicating that the meta-analysis model was robust.Conclusion: Findings support a significant positive association between use of macrolides (especially clarithromycin), quinolones, and tetracyclines during pregnancy and spontaneous miscarriage, although it should be interpreted with caution in the context of limitations of the available data.Review Registration: International register for systematic reviews; PROSPEROCRD42018093465. [ABSTRACT FROM AUTHOR]

Background: The yolk sac is essential in early life of the embryo because it is the first route of exchange between the embryo and the mother. Aim of the study: To determine the association of the spontaneous miscarriage with the abnormal morphology and size of the yolk sac. Methods: A cohort study was conducted among 85 pregnant women with gestational age ranged between 7-12 weeks, transvaginal ultrasonography was done for all patients at first time. The gestational age was calculated according to the last menstrual period (LMP), crown-rump lengths (CRL), mean gestational sac diameters (MGSD). We divided the sample into two groups, 27 women had abnormal yolk sac represented the 1st group (study) and 53 women had normal sonographic appearance of the yolk sac represented the 2nd group (control). We followed the women until the 20th weeks of pregnancy and compared the spontaneous miscarriage rate between the two groups. Results: Most of the embryos had a yolk sac with a regular shape (80%), whereas the remaining embryos had a yolk sac with an irregular shape (15%), calcified 2.5%. and 2.5% echogenic. about one third of the women with abnormal yolk sac (cohort group) had miscarriage in front of 10.9% of the control group and the association was significant (p value = 0.013). Significant association between spontaneous miscarriage and abnormal large diameter yolk sac. Conclusion: Abnormal yolk sac increases significantly the risk of spontaneous miscarriage. [ABSTRACT FROM AUTHOR]

Objectives: Our primary aim was to report the incidence of enhanced myometrial vascularity (EMV) in consecutive women attending our early pregnancy assessment unit, following first-trimester miscarriage. We aimed further to evaluate the clinical presentation and complications associated with expectant and surgical management of EMV in these women.Methods: This was a prospective cohort study conducted in a London teaching hospital between June 2015 and June 2018, including consecutive patients with an observation of EMV on transvaginal ultrasonography following first-trimester miscarriage. The diagnosis was made following the subjective identification of EMV using color Doppler ultrasonography and a peak systolic velocity (PSV) ≥ 20 cm/s within the collection of vessels. Women were followed up with repeat scans every 14 days. Management was expectant unless intervention was indicated because of excessive or prolonged bleeding, persistent presence of retained tissue in the endometrial cavity or patient choice. The final clinical outcome was recorded. Time to resolution of EMV was defined as the interval from detection of EMV until resolution.Results: During the study period, there were 2627 first-trimester fetal losses in the department and, of these, 40 patients were diagnosed with EMV, hence the incidence of EMV following miscarriage was 1.52%. All cases were associated with ultrasound evidence of retained products of conception (RPOC) at presentation (mean dimensions, 22 × 20 × 20 mm). Thirty-one patients opted initially for expectant management, of which 18 had successful resolution without intervention, five were lost to follow-up and eight subsequently had surgical evacuation due to patient choice. No expectantly managed case required emergency intervention. Nine patients chose surgical evacuation as primary treatment. No significant correlation was seen between PSV within the EMV at presentation and blood loss at surgery. Median PSV was 47 (range, 20-148) cm/s. The estimated blood loss in all cases managed surgically ranged from 20-300 mL. Presence of RPOC was confirmed in all specimens that were sent for analysis following surgery. For cases successfully managed expectantly, the mean time to resolution was 48 (range, 21-84) days. In the nine cases managed surgically from the beginning, the mean time to resolution of EMV was 10.6 (range, 3-29) days.Conclusions: This study suggests that EMV is an uncommon finding following miscarriage and is associated with the presence of RPOC. Expectant management was a safe option in our cohort, with minimal bleeding, although it was associated with protracted time to resolution. In patients who opted for surgery, the maximum blood loss was 300 mL and no patient required blood transfusion or embolization. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Spontaneous miscarriage is one of the two most common problems encountered in the first trimester of pregnancy. The value of histopathological analysis of products of conception (POC) obtained as a result is a source of controversy. The aim of this study is to evaluate the histopathological characteristics of suspected POC following the first-trimester miscarriage and determine the clinical value of such histopathological analyses. Materials and Methods: This is a retrospective study of the histopathological analysis of POC over a period from January 1st to December 31st of 2016 carried out in the histopathology laboratory of a university teaching hospital. Materials for the study were POC obtained following spontaneous first trimester miscarriage and received in our laboratory. Relevant information about the patients was retrieved from the laboratory database and matched with laboratory request forms and copies of histopathology reports archived in the laboratory. Obtained data were analyzed by simple statistical methods. Results: The most common clinical diagnosis on admission was incomplete abortion (n = 52; 48.6%), followed by complete abortion (n = 31; 29.0%); the lowest was blighted ovum (n = 1; 0.9%). The predominant histopathological type was normal POC which constituted 73 cases (68.2%). Other histopathological diagnoses include hydatidiform mole (9, 8.4%) and no evidence of conception (15, 14%). Clinical and ultrasound evaluation missed 2 (22.2%) of the 9 histopathologically diagnosed hydatidiform moles. Conclusion: Histopathological analysis of POC helps to diagnose molar pregnancies and other conditions which can be missed by clinical and ultrasound evaluation. Therefore, routine histopathological analysis of POC is advocated. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D catabolizing enzymes, along with vitamin D receptor (VDR) and vitamin D binding protein (DBP) are expressed in the decidua and placenta during pregnancy and capable of synthesizing active vitamin D. Vitamin D plays roles in immunoregulation and trophoblast invasion, key features of a successful pregnancy. Epidemiological data suggests that vitamin D deficiency is associated with both spontaneous and recurrent miscarriage but few studies have investigated the expression of the key vitamin D catabolizing enzymes in miscarriage.Methods: Placenta and decidua were collected after termination of apparently normal pregnancies (controls, n = 22) or spontaneous miscarriage (n = 20). Immunohistochemical staining, Western Blot and qRT-PCR were performed for CYP27B1, CYP24A1, CYP2R1, VDR and DBP (not qRT-PCR). HTR-8/SVneo cells were cultured in CoCL2 (hypoxic mimetic) or LPS (bacterial infection mimetic) for 24 h, RNA extracted and qRT-PCR performed for CYP27B1, CYP24A1, CYP2R1 and VDR.Results: In spontaneous miscarriage, placental and decidual expression of CYP27B1 was reduced, while expression of CYP24A1, VDR and DBP was increased. When a trophoblast cell line was treated with CoCL2 expression of CYP27B1 was increased and CYP24A1 was reduced, while LPS induced expression of VDR.Discussion: This is the first report of altered utero-placental vitamin D catabolism in spontaneous miscarriage. It is becoming accepted that women who are undergoing assisted reproductive technologies should ensure they have sufficient vitamin D levels prior to pregnancy, these data support that all women should ensure they are vitamin D replete before planning to get pregnant. [ABSTRACT FROM AUTHOR]

LINE1 retrotransposons are mobile DNA elements that copy and paste themselves into new sites in the genome. To ensure their evolutionary success, heritable new LINE-1 insertions accumulate in cells that can transmit genetic information to the next generation (i.e., germ cells and embryonic stem cells). It is our hypothesis that LINE1 retrotransposons, insertional mutagens that affect expression of genes, may be causal agents of early miscarriage in humans. The cell has evolved various defenses restricting retrotransposition-caused mutation, but these are occasionally relaxed in certain somatic cell types, including those of the early embryo. We predict that reduced suppression of L1s in germ cells or early-stage embryos may lead to excessive genome mutation by retrotransposon insertion, or to the induction of an inflammatory response or apoptosis due to increased expression of L1-derived nucleic acids and proteins, and so disrupt gene function important for embryogenesis. If correct, a novel threat to normal human development is revealed, and reverse transcriptase therapy could be one future strategy for controlling this cause of embryonic damage in patients with recurrent miscarriages. [ABSTRACT FROM AUTHOR]

Spontaneous miscarriage is the spontaneous ending from a pregnancy at a phase where the embryo is incapable of remaining independently, generally defined in humans at prior to 20 weeks from gestation. Overall, reported spontaneous miscarriage rates in recognized pregnancies are 10% to 20%. Pregnant women are exposed to many infectious agents that are potentially harmful to the fetus and an increased risk of miscarriage. The aims of the study were to evaluate the role of many pathogens (Parvovirus B19, Cytomegalovirus, Rubella, and Toxoplasma gondii), and urinary tract infections (UTI) as causes of spontaneous miscarriage. A case-control study conducted in Baghdad Teaching hospital during a period of ten months. A total of 120 women aged between (20 to 25) years were enrolled within the study, 80 with spontaneous miscarriage as a study group and 40 with normal delivery as a control group. A full history was taken, clinical examination was done and various laboratory investigations were carried out for all women in both groups. The study showed a statistically significant correlation between viral infection, Parvovirus (IgM, IgG), Toxoplasmosis (IgM), Rubella (IgM) and Cytomegalovirus (IgM, IgG), with spontaneous miscarriage (P-value 0.001, 0.005, 0.008, 0.014, 0.002). Bacterial, viral and protozoal infection may increase the risk of spontaneous miscarriage in comparison to healthy normal delivery ladies [ABSTRACT FROM AUTHOR]

Miscarriage is one of the main complications occurring in pregnancy. The association between adverse pregnancy outcomes and silent bacterial infections has been poorly investigated. Ureaplasma parvum and urealiticum, Mycoplasma genitalium and hominis and Chlamydia trachomatis DNA sequences have been investigated by polymerase chain reaction (PCR) methods in chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from females with spontaneous abortion (SA, n = 100) and females who underwent voluntary interruption of pregnancy (VI, n = 100). U. parvum DNA was detected in 14% and 15% of SA and VI, respectively, with a mean of bacterial DNA load of 1.3 × 10−1 copy/cell in SA and 2.8 × 10 −3 copy/cell in VI; U. urealiticum DNA was detected in 3% and 2% of SA and VI specimens, respectively, with a mean DNA load of 3.3 × 10−3 copy/cell in SA and 1.6 × 10−3 copy/cell in VI; M. hominis DNA was detected in 5% of SA specimens with a DNA load of 1.3 × 10−4 copy/cell and in 6% of VI specimens with a DNA load of 1.4 × 10−4 copy/cell; C. trachomatis DNA was detected in 3% of SA specimens with a DNA load of 1.5 × 10−4 copy/cell and in 4% of VI specimens with a mean DNA load of 1.4 × 10−4 copy/cell. In PBMCs from the SA and VI groups, Ureaplasma spp, Mycoplasma spp and C. trachomatis DNAs were detected with a prevalence of 1%–3%. Bacteria were investigated, for the first time, by quantitative real‐time PCR (qPCR) in chorionic villi tissues and PBMCs from women affected by SA and VI. These data may help to understand the role and our knowledge of the silent infections in SA. Miscarriage is one of the main complications occurring in pregnancy. Silent bacterial infections in miscarriage have been poorly investigated. Our data may help to understand the role of silent infections in miscarriage. [ABSTRACT FROM AUTHOR]