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Background： Genetic factors are the main cause of early miscarriage. This study aimed to investigate aneuploidy in spontaneous abortion by fluorescence in situ hybridization （FISH） using probes for 13, 16, 18, 21, 22, X and Y chromosomes. Methods： A total of 840 chorionic samples from spontaneous abortion were collected and examined by FISH. We analyzed the incidence and type of abnormal cases and sex ratio in the samples. We also analyzed the relationship between the rate of aneuploidy and parental age, the rate of aneuploidy between recurrent abortion and sporadic abortion, the difference in incidence of aneuploidy between samples from previous artificial abortion and those from no previous induced abortion. Results： A total of 832 samples were finally analyzed. 368 （44.23%） were abnormal, in which 84.24% （310/368） were aneuploidies and 15.76% （58/368） were polyploidies. The first was trisomyl6 （121/310）, followed by trisomy 22, and X monosomy. There was no significant difference in the rate ofaneuploidy in the advanced maternal age group （≥35 years old） and young maternal age group （〈35 years old）. However, the rate oftrisomy 22 and the total rate of trisomies 21, 13, and 18 （the number oftrisomy 21 plus trisomy 13 and trisomy 18 together） showed significantly different in two groups. We found no skewed sex ratio. There was no significant difference in the rate of aneuploidy between recurrent miscarriage and sporadic abortion or between the samples fi＇om previous artificial abortion and those from no previous artificial abortion. Conclusions： Aneuploidy is a principal factor of miscarriage and total parental age is a risk factor. There is no skewed sex ratio in spontaneous abortion. There is also no difference in the rate of aneuploidy between recurrent abortion and sporadic abortion or between previous artificial abortion and no previous induced abortion.

Background: One of the reproductive medicine challenges is to determine the role of hyperhomocysteinemia in the pathogenesis of polycystic ovary syndrome (PCOS), especially in women with recurrent pregnancy loss (RPL). Objective: Determine the correlation between hyperhomocysteinemia and pregnancy outcome in women with PCOS. Materials and Methods: This case-control study involved 245 women (20-30 yr) and was conducted in Georgia, Tbilisi from 2019-2022. Of these, 175 were women with PCOS (study group) and 70 were healthy women (control group). Women with PCOS were divided into group I with RPL (n = 90), and group II with live births (n = 85). Group I was divided into subgroups A and B with and without insulin resistance. The investigation measured homocysteine (Hcy), follicle-stimulating, luteinizing, anti-Mullerian hormones, total and free testosterone were determined. To determine the ovarian volume and antral follicle count, participants also underwent an ultrasound examination. Results: In women with PCOS, the average Hcy level was significantly higher than in the controls, p < 0.05. In group I, the average Hcy level was significantly higher than in group II and controls, p < 0.05. There was no significant difference in average Hcy level between group II and controls. The average Hcy level in group I, subgroup A was significantly higher than in subgroup B, p < 0.05. The average total, free testosterone levels, and homeostatic model assessment-insulin resistance levels (HOMA-IR) in group I was significantly higher than in group II and controls. HOMA-IR in group II and controls did not differ significantly. The average anti-Mullerian hormone levels in women with PCOS were significantly higher than controls, p < 0.05. No significant difference was observed in average anti-Mullerian hormone level, ovarian volume, antral follicle count, and body mass index between the comparison groups of PCOS. In group I, a positive correlation between Hcy with HOMA-IR was detected. Conclusion: Serum Hcy levels are elevated in women with PCOS and RPL, which correlates with their insulin resistance status. Key words: Polycystic ovary syndrome, Hyperhomocysteinemia, Recurrent abortion, Insulin resistance.

Background： Antiphospholipid syndrome （APS）-related immune factors are considered as an important cause of recurrent spontaneous abortion （RSA）. Anticoagulant and anti-inflammatory treatments are believed to effectively improve adverse pregnancy outcomes by affecting the abnormal autoimmune response of the maternal-fetal interface. The aim of this study was to observe the clinical characteristics and treatment outcomes of anticoagulant regimens and anti-inflammatory plus anticoagulation regimens for APS-related RSA. Methods： APS-related RSA cases from September 2011 to September 2016 at Peking University Third Hospital were retrospectively analyzed. The patients were assigned to study group （anti-inflammation plus anticoagulation） and control group （simple anticoagulation）, The incidence of repeat abortion, the incidence of placental dysfunction, the gestational weeks of pregnancy, and the mean weight of the fetus were observed. Results： The pregnancy and neonatal outcome indicators of the repeat pregnancy loss rate （ 11. 11% vs. 22.70%）, placental dysfunction-related diseases （6.35% vs. 15.60%）, the mean birth weight of infants born after 24 weeks gestation （3152.4 ± 844.67 g vs. 2765.76 ± 816.40 g）, full-ternl delivery weight （3456.28 ±419.79 g vs. 3076.18±518.79 g）, the proportions of low birth weight infants （ 12.70% vs. 21.98%）, and small for gestational age （6.35% vs. 14.18%） differed significantly between the study and control groups （all P 〈 0.05）. The incidence of preterm delivery, term delivery, and stillbirth was not significantly different between the two groups, and there was no significant difference between the study and control groups in gestational age at birth （37.6 ± 3.3 weeks vs. 36.9 ± 3.2 weeks： P 〉 0.05）. Conclusion： The anti-inflammatory and anticoagulation regimen is more effective than the simple anticoagulation regimen in the treatlnent of APS recurrent abortion.

Tumor necrosis factor-α (TNF-α) is a central regulator of inflammation, and TNF-α antagonists may be effective in treating inflammatory disorders in which TNF-α plays a major pathogenic role. TNF-α has also been associated with inflammatory mechanisms related to implantation, placentation, and pregnancy outcome. TNF-α is secreted by immune cells and works by binding to TNFR1 and TNFR2 cell receptors. TNF-α is also related to JAK/STAT pathways, which opens up hypothetical new targets for modifying. The accurate balance between Th1 cytokines, mainly TNF-α, Th17, and Th2, particularly IL-10 is essential to achieve good obstetric outcomes. TNF-α targeted therapy could be rational in treating women with obstetric complication related to overproduction of TNF-α, such as recurrent pregnancy loss, early and severe pre-eclampsia, and recurrent implantation failure syndrome, all “idiopathic” or related to aPL positivity. Along the same lines, Th1 cytokines, mainly TNF- α, play a leading pathogenic role in rheumatic and systemic autoimmune diseases occurring in women and, to a lesser extent, in men of reproductive age. These disorders have to be clinically silent before pregnancy can be recommended, which is usually only possible to achieve after intensive anti-inflammatory and immunosuppressive treatment, TNF-α blockers included. Physicians should be aware of the theoretic potential but low embryo-fetal toxicity risk of these drugs during pregnancy. From an updated review in May 2016, we can conclude that TNF-α blockers are useful in certain “refractory” cases of inflammatory disorders related to poor obstetric outcomes and infertility. Furthermore, TNF-α blockers can be safely used during the implantation period and pregnancy. Breastfeeding is also permitted with all TNF-α inhibitors. Since data on the actual mechanism of action of JAK-STAT in inflammatory obstetric disorders including embryo implantation are scarce, for the time being, therapeutic interventions in this setting should be discouraged. Finally, adverse effects on sperm quality, or causing embryo-fetal anomalies, in men treated with TNF inhibitors have not been described.

Background: Estrogen is one of the most important reproductive steroidal hormones and plays a critical role in the maintenance of pregnancy, and its function is mediated by estrogen receptor 1(ESR1). The polymorphisms of ESR1 were involved in recurrent spontaneous abortion (RSA); however, the association between ESR1 polymorphisms and RSA remains controversial. The present meta-analysis was aimed to clarify the association between ESR1 PvuII (-397C/T, rs2234693) and XbaI (-351A/G, rs9340799) polymorphisms and the risk of RSA. Methods: All the included articles were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Med Online Database up to January 3, 2018. Data were processed in the Stata 12.0 software. The odds ratios (OR s) and 95% confidence intervals (95% CI s) were calculated using fixed-effects models (FEM)/random-effects models (REM). Results: Seven case-control studies with 836 cases and 1164 controls were included in the study. Generally, the ESR1 polymorphisms were not associated with RSA in any of the genetic analysis models. However, it was found that as rs9340799 polymorphism was related to increased risk of RSA in non-Asian group in the homozygous genetic model (OR = 2.40, 95% CI = 1.05-5.50, P = 0.039). Moreover, in Asian group, rs9340799 polymorphism was found to be related to decreased RSA risk in both the heterozygous model (OR = 0.53, 95% CI = 0.33-0.85, P = 0.009) and the dominant genetic model (OR = 0.55, 95% CI = 0.30-0.98, P = 0.042). Conclusions: Generally, there was no significant association between the polymorphisms of ESR1 and the risk of RSA. However, subgroup analysis indicated that ESR1 rs9340799 polymorphism was related to increased RSA risk in the non-Asian group while associated with decreased RSA risk in Asian group.

Background: In 4%-8% of couples with recurrent abortion, at least one of the partners has chromosomal abnormality. Most spontaneous miscarriages which happen in the first and second trimesters are caused by chromosomal abnormalities. These chromosomal abnormalities may be either numerical or structural. Material and Methods : Cytogenetic study was done for 73 Egyptian couples who presented with recurrent abortion at Genetic Unit of Children Hospital, Mansoura University. Results : We found that the frequency of chromosomal abnormalities was not significantly different from that reported worldwide. Chromosomal abnormalities were detected in 9 (6.1%) of 73 couples. Seven of chromosomal abnormalities were structural and two of them were numerical. Conclusion : Our results showed that 6.1% of the couples with recurrent abortion had chromosomal abnormalities, with no other abnormalities. We suggest that it is necessary to perform cytogenetic in vestigation for couples who have recurrent abortion.

Background: We aimed to shed light on the risks of elevated levels of IL-18 in aborted women with toxoplasmosis by evaluating the risk or protective function of alleles or genotypes for single nucleotide polymorphism (SNP) of IL-18 (rs 1946519), which might be related to the susceptibility to toxoplasmosis. Methods: IL-18 levels in patient and control blood samples were determined using ELISA, and the SNP IL-18 (ra 1946519) was subjected to the high-resolution method. Results: Compared to healthy pregnant women (HP), the IL-18 serum levels of recurrent abortion with toxoplasmosis (RAWT), recurrent abortion without toxoplasmosis (RAWOT), and healthy non-pregnant (HNP) women decreased with significant differences. Additionally, a strong association between patients and controls was found in the SNP IL-18 data. RAWT and RAWOT with the genotypes AA and AC had significantly lower IL-18 serum levels than women HP, according to the distribution of IL-18 serum levels by SNP. Conclusion: The serum level of IL-18 varied by genotype in patients with substantial differences compared to controls, while the SNP of IL-18 has been linked as a risk factor in toxoplasmosis-infected recurrent abortion women.

Recurrent spontaneous abortion (RSA) is a serious pregnancy complication with an increasing clinical incidence. The various causes of recurrent abortion are complicated. Developments in genetics, immunology, and cell biology have identified important roles of non-coding RNAs (ncRNAs) in the occurrence and progress of recurrent abortion. NcRNAs can affect the growth, migration, and invasion of placental trophoblasts by regulating cell processes such as the cell cycle, apoptosis, and epithelial-mesenchymal transformation. Therefore, their abnormal expression might lead to the occurrence and development of RSA. NcRNAs include small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), ribosomal RNA (rRNA), transfer, RNA (tRNA), circular RNA (cRNA), and Piwi-interacting RNA (piRNA). In this review, we discuss recent research that focused on the function and mechanism of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNA (circRNA) in regulating placental trophoblasts. The use of ncRNAs as potential diagnostic and predictive biomarkers in RSA is also discussed to provide future research insights.

Background Hypermobile Ehlers-Danlos syndrome (hEDS), is probably the most common disease among heritable connective tissue disorders. It affects women more than men and causes symptoms in multiple organs. It is associated with chronic pain, skin fragility and abnormal bleeding. These characteristics may hamper reproductive life. We conducted a study to evaluate the gynecologic and obstetric outcomes in women with hEDS. We also explored a possible hormonal modulation of the hEDS symptoms. The gynecologic and obstetric history of 386 consecutive women diagnosed with hEDS was collected by a standardized questionnaire and a medical consultation performed by a senior gynecologist in an expert centre for hEDS between May 2012 and December 2014. Results We observed a high frequency of gynecologic complaints, specifically: menorrhagia (76 %), dysmenorrhea (72 %) and dyspareunia (43 %). Endometriosis was not highly prevalent in this population. The obstetric outcomes were similar to those of the general French population for deliveries by cesarean section (14.6 %) and premature births (6.2 %) but the incidence of multiple spontaneous abortion (13 %) and spontaneous abortion (28 %) were significantly higher. A subset of women were sensitive to hormonal fluctuations with more severe symptoms occurring during puberty, prior to menstruation, during the postpartum period as well as on oral contraception. Conclusions Increased awareness of the gynecological symptomatology in women with hEDS can help discriminate between endometriosis and thus prevent useless, and potentially dangerous, surgery. This study also suggests that hormonal modulation may be an appropriate treatment for a subset of women with hEDS.

This study investigates the therapeutic mechanism of Shoutai Pill in treating unexplained recurrent spontaneous abortion. Clinical samples from affected individuals and healthy pregnant women were analyzed, alongside animal models and primary cell cultures. The results demonstrated that Shoutai Pill reduced pro-inflammatory cytokines such as tumor necrosis factor alpha and interferons alpha and gamma, while enhancing the anti-inflammatory cytokine interleukin-10 and antiviral proteins including interferon-induced protein 44-like, radical S-adenosyl methionine domain-containing protein 2, and bone marrow stromal cell antigen 2. In vitro, serum containing Shoutai Pill increased decidual cell viability and significantly decreased apoptosis. Transcriptome analysis identified key regulatory genes—proline dehydrogenase, serum and glucocorticoid-regulated kinase 2, and neurogenic locus notch homolog protein 4—implicating the PI3K-Akt and Notch signaling pathways. These findings suggest that Shoutai Pill exerts a protective effect by modulating immune responses, enhancing antiviral defense, and maintaining decidual cell stability. This multi-tiered approach provides mechanistic evidence supporting the clinical potential of Shoutai Pill as an adjunct therapy for unexplained recurrent abortion. Cette étude explore le mécanisme thérapeutique de la pilule Shoutai dans le traitement des fausses couches spontanées récurrentes inexpliquées. Des échantillons cliniques provenant de patientes concernées et de femmes enceintes en bonne santé ont été analysé s, parallèlement à des modèles animaux et à des cultures primaires de cellules. Les résultats ont démontré que la pilule Shoutai ré duit les cytokines pro-inflammatoires telles que le facteur de nécrose tumorale alpha et les interférons alpha et gamma, tout en augmentant la cytokine anti-inflammatoire interleukine-10 et des protéines antivirales, notamment la protéine 44-like induite par les interférons, la protéine contenant un domaine radical S-adénosyl méthionine 2, et l'antigène 2 des cellules stromales de la moelle osseuse. In vitro, le sérum contenant la pilule Shoutai a amélioré la viabilité des cellules déciduales et réduit de manière significative l'apoptose. L'analyse du transcriptome a identifié des gènes clés de régulation — la proline déshydrogénase, la kinase 2 régulée par les sérums et les glucocorticoïdes, et la protéine homologue 4 du locus neurogénique Notch — impliquant les voies de signalisation PI3K-Akt et Notch. Ces résultats suggèrent que la pilule Shoutai exerce un effet protecteur en modulant les réponses immunitaires, en renforçant la défense antivirale et en maintenant la stabilité des cellules déciduales. Cette approche multi-niveaux fournit des preuves mécanistiques appuyant le potentiel clinique de la pilule Shoutai en tant que thérapie adjuvante dans le traitement des fausses couches récurrentes inexpliquées.