Search

The adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA), are strongly correlated with water-soluble vitamins, but how to predict RSA occurrence using them remains unsatisfactory. This study aims to investigate the possibility of predicting RSA based on the baseline levels of water-soluble vitamins tested by ultra-liquid chromatography-tandem mass spectrometry. A total of 918 pregnant women was consecutively enrolled in this cross-sectional study. According to the miscarriage numbers, they were divided into normal first pregnancy (NFP, n = 608), once spontaneous abortion (OSA, n = 167), and continuous spontaneous abortion (CSA, n = 143) groups. The Cox proportional-hazards regression model was employed to establish a risk model for predicting RSA. The RSA occurrence was 6.54% in overall pregnant women, with a prevalence of 12.57% in the OSA group and 27.27% in the CSA group. Significant differences were observed in baseline deficiencies of vitamin B3, B5, B6, and B9 among NFP, OSA, and CSA groups (χ2 = 12.191 ~ 37.561, all P < 0.001). Among these vitamins, B9 (HR = 0.89 and 0.88, all P < 0.001) and B6 (HR = 0.83 and 0.78, all P < 0.05) were identified as independent factors in both the OSA and CSA groups; whereas B5 was identified as an additional independent factor only in the CSA group (HR = 0.93, P = 0.005). The Cox proportional-hazards model established using these three vitamins exhibited poor or satisfactory predictive performance in the OSA (Sen = 95.2%, Spe = 39.0%) and CSA (Sen = 92.3%, Spe = 60.6%) groups, respectively. However, B5, B6, and B9 compensatory levels were not associated with RSA occurrence (all P > 0.05). Our study presents a highly sensitive model based on mass spectrometry assay of baseline levels in B vitamins to predict the RSA occurrence as possible. [ABSTRACT FROM AUTHOR]

Purpose: To assess the risk of adverse obstetric and perinatal outcomes in subsequent pregnancies among women with a history of recurrent pregnancy loss (RPL). Methods: Relevant studies were identified by searching the PubMed, Web of Science, and Embase databases. The pooled effect sizes were reported as odds ratios (OR) with their respective 95% confidence intervals (95% CI), and data analysis was performed using the random effects model. Results: A total of 26 studies involving 4,730,728 women were included in this meta-analysis. The results reveal a significant increase in the prevalence of placenta accreta cases after RPL compared to women without RPL (pooled OR 4.04; 95% CI 1.16–14.15; 2 studies; I2 = 94%; P = 0.03). However, no elevated risk of aneuploidies (pooled OR 1.69, 95% CI 0.73–3.90; 5 studies; I2 = 48%; P = 0.22) or congenital anomalies (pooled OR 1.12, 95% CI 0.97–1.30; 7 studies; I2 = 13%; P = 0.12) in subsequent pregnancies of women with RPL was observed. Additionally, a moderate increase in the risk of various other obstetric and perinatal outcomes was found. The magnitude of the elevated risk of these adverse outcomes varied depending on the region. Conclusions: Women with a history of RPL exhibit a significantly elevated risk of placenta accreta in subsequent pregnancies, along with a moderate increase in the risk of various other adverse obstetric and perinatal outcomes. However, RPL does not signify an increased risk of aneuploidies or congenital anomalies in a consecutive pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: Studies have investigated miR‐125a for its predictable role in recurrent pregnancy loss (RPL) cases to regulate many biological events required for the maintenance of pregnancy by regulating its confirmed target genes LIFR, ERBB2 and STAT3. Methods: The present study included 40 cases of women with at least two RPLs in ≤20 weeks of gestation against 40 healthy multiparous women without a previous history of abortion. Expression analysis of ERBB2, LIFR, STAT3 and miR‐125a was conducted by quantitative real‐time PCR (qPCR). Results: The expression of miR‐125a was significantly lower in the plasma of RPL cases (P = 0.0001) and showed a significantly increased mean expression level in product of conception (2.56‐fold, P < 0.0001). Among the target gene of miR‐125a, ERBB2 and STAT3 gene expression level was significantly increased (2.58‐fold, P = 0.04; 1.87‐fold, P = 0.025), respectively in RPL cases while the LIFR gene revealed comparable expression (P = 0.64). Furthermore, expression analysis of ERBB2 gene with respect to its regulatory miR‐125a cases depicted a significant association (P = 0.0005). Kaplan–Meier survival analysis revealed cases with low miR‐125a expression had significantly shorter time to miscarriages, (log‐rank P = 0.02). Also, decreased expression of miR‐125a significantly conferred >2‐fold increased risk for RPL (HR = 2.34: P < 0.05). Conclusion: The overall conclusion of the study was that altered miR‐125a expression may cause deregulation in target genes LIFR, ERBB2 and STAT3 resulting in adverse consequence in the outcome of pregnancy. Synopsis: The impact of altered miR‐125a expression causes deregulation in target genes LIFR, ERBB2 and STAT3 that result in deleterious effect in the outcome of the pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Clinical practice guidelines provide inconsistent recommendations regarding progestogen supplementation for threatened and recurrent miscarriage. We conducted a systematic review and meta‐analysis to assess the effectiveness and safety of progestogens for these patients. Material and methods: We searched Medline, Embase, and Cochrane Central Registry of Controlled Trials up to October 6, 2023 for randomized control trials (RCTs) comparing progestogen supplementation to placebo or no treatment for pregnant women with threatened or recurrent miscarriage. We assessed the risk of bias using a modified version of the Cochrane risk‐of‐bias tool and the certainty of evidence using the GRADE approach. Results: Of 15 RCTs (6616 pregnancies) reporting on threatened or recurrent miscarriage, 12 (5610 pregnancies) reported on threatened miscarriage with or without a prior history of miscarriage. Results indicated that progesterone probably increases live births (relative risk (RR) 1.04, 95% confidence interval (CI) 0.99–1.10, absolute increase 3.1%, moderate certainty). Of these RCTs, three (1973 pregnancies) reporting on threatened miscarriage with a prior history of miscarriage indicated that progesterone possibly increases live births (RR 1.06, 95% CI: 0.97–1.16, absolute increase 4.4%; low certainty), while four (2540 pregnancies) reporting on threatened miscarriage and no prior miscarriage left the effect very uncertain (RR 1.02, 95% CI: 0.96–1.10, absolute increase 1.7%; very low certainty). Three trials reporting on 1006 patients with a history of two or more prior miscarriages indicated progesterone probably increases live births (RR 1.08, 95% CI: 0.98–1.19, absolute increase 5.7%, moderate certainty). Six RCTs that reported on 2979 patients with at least one prior miscarriage indicated that progesterone probably increases live births (RR 1.07, 95% CI: 1.01–1.13, absolute increase 5.0%; moderate certainty). Progesterone probably has little or no effect on congenital anomalies (RR 1.06, 95% CI: 0.76–1.48, absolute increase 0.1%; moderate certainty), and other serious adverse pregnancy events (RR 1.07, 95% CI: 0.83–1.40, absolute increase 0.2%, moderate certainty). Conclusions: In women at increased risk of pregnancy loss, progestogens probably increase live births without increasing adverse maternal and neonatal events. It remains possible that the benefit is restricted to those with prior miscarriages. [ABSTRACT FROM AUTHOR]

• Adverse psychological conditions are present in women who experience recurrent spontaneous abortions; depression was the most prevalent. • In this meta -analysis, women with recurrent spontaneous abortions (RSA) were associated with a significantly increased risk of depression when compared with women without RSA. • Women who had been married for longer than three years, three spontaneous abortions, and induced abortions had a higher prevalence of depression. Nonetheless, the risk of depression was significantly lower in women who had previously given birth to living children. It is widely recognized that depression is highly prevalent among women experiencing recurrent spontaneous abortion (RSA), exerting detrimental effects on both the individual and the family. To assess the depression risk and associated factors among women with RSA. Data sources. Our search strategy encompassed PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), and WANFANG. The research was conducted in May 2022. We included both randomized and nonrandomized studies that reported the prevalence of depression among women with RSA. Data extraction and synthesis. Two independent evaluators reviewed the titles and abstracts, assessed the full-text papers, extracted data from the included studies, and evaluated their quality using the Newcastle-Ottawa Scale (NOS). We performed random-effects meta -analyses to pool the data. Odds ratios (ORs) and standardized mean differences (SMDs) were combined based on effect sizes for binary and continuous outcomes. Main outcomes. To conduct a meta-analysis to understand the risk of depression in women with RSA who were not treated with psychiatric medications, as well as an analysis of potential factors for depressive symptoms. Out of the initially identified 527 papers, a total of 20 studies (N = 13087) that fulfilled the inclusion criteria were selected. Compared to healthy controls, patients with RSA had a significantly higher risk of depression (OR: 4.26, 95 % confidence interval [CI]: 2.44–7.41; SMD: 0.89, 95 % CI: 0.51–1.26). The occurrence of depression among RSA patients was found to be significantly associated with several factors including the severity of depressive symptoms (OR: 3.82, 95 % CI: 2.22–6.59), number of spontaneous miscarriages (SMD: 0.59, 95 % CI: 0.01–1.18), history of therapeutic termination of pregnancy (SMD: 0.20, 95 % CI: 0.09–0.32), history of live birth (SMD: −0.32, 95 % CI: −0.49-−0.15), and duration of marriage (SMD: 0.15, 95 % CI: 0.02–0.27). In clinical practice, it is crucial to provide appropriate psychological interventions for women undergoing RSA. These individuals face a significantly heightened risk of depression, which exhibits strong correlations with various demographic factors such as the severity of depressive symptoms, history of both spontaneous miscarriages and therapeutic termination of pregnancy, number of live births, and duration of marriage. Consequently, women who are suffering RSA deserves more assistance and emotional support. [ABSTRACT FROM AUTHOR]

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

Background: Unexplained recurrent pregnancy loss (URPL) is a clinical dilemma in reproductive fields. Its diagnosis is mainly exclusionary after extensive clinical examination, and some of the patients may still face the risk of miscarriage. Methods: We analyzed follicular fluid (FF) from in vitro fertilization (IVF) in eight patients with URPL without endocrine abnormalities or verifiable causes of abortion and eight secondary infertility controls with no history of pregnancy loss who had experienced at least one normal pregnancy and delivery by direct data-independent acquisition (dDIA) quantitative proteomics to identify differentially expressed proteins (DEPs). In this study, bioinformatics analysis was performed using online software including g:profiler, String, and ToppGene. Cytoscape was used to construct the protein-protein interaction (PPI) network, and ELISA was used for validation. Results: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEPs are involved in the biological processes (BP) of complement and coagulation cascades. Apolipoproteins (APOs) are key proteins in the PPI network. ELISA confirmed that APOB was low-expressed in both the FF and peripheral blood of URPL patients Conclusion: Dysregulation of the immune network intersecting coagulation and inflammatory response is an essential feature of URPL, and this disequilibrium exists as early as the oogenesis stage. Therefore, earlier intervention is necessary to prevent the development of URPL. Moreover, aberrant lipoprotein regulation appears to be a key factor contributing to URPL. The mechanism by which these factors are involved in the complement and coagulation cascade pathways remains to be further investigated, which also provides new candidate targets for URPL treatment. [ABSTRACT FROM AUTHOR]

This article discusses a case where the Taqman system, commonly used for genotyping, failed to accurately identify a specific genetic mutation. The study found that a rare mutation at the MTHFR 679 locus resulted in the failure of genotyping for a different mutation. The authors highlight the importance of adaptability and alternative approaches in genetic testing. They also explore the relationship between this mutation and enzyme activity and susceptibility to recurrent spontaneous abortion. The article provides valuable information on a specific genetic variant and its clinical significance, making it a useful resource for those researching genetics and its connection to specific health conditions. [Extracted from the article]

Objective Study Design Results Conclusion Recurrent pregnancy loss (RPL) has a multifactorial etiology, with a majority of cases remaining unexplained. To account for these unexplained cases, possible male factors are being explored. Conventional semen analysis lacks a qualitative assessment of sperms and information regarding sperm DNA integrity. Sperm DNA fragmentation (SDF) has diagnostic value in unexplained RPL, and it may account for a number of unexplained cases. Hence, we planned a study to explore and evaluate the impact of sperm DNA fragmentation in couples with unexplained recurrent pregnancy losses.Analytical cross‐sectional study was conducted at a tertiary‐level referral facility in India between August 2021 and July 2023. Participants (n = 70) were divided into two groups—male partners of couples with unexplained RPL (following spontaneous conceptions) (n = 35) and men with at least one previous live birth (spontaneous or following fertility treatments for female factor infertility such as ovulation induction or intrauterine insemination) as controls (n = 35). Neither of the two groups of couples recruited for this study had undergone ART as fertility treatment. Primary outcome assessed was mean DNA fragmentation index (DFI). Secondary outcomes included differences in semen parameters such as sperm concentration, progressive sperm motility and morphology, proportion of men with high (≥30%) and low DFI in the two groups, and the association between various semen parameters and DFI.Univariate logistic regression revealed that sperm DNA fragmentation was higher in men with unexplained RPL (30.0; IQR (interquartile range) 19.0, 46.0) as compared to controls (22.0; IQR 14.0, 30.0) although it was not statistically significant (OR, odds ratio, 1.02; 95% CI 1.0–1.1, p = 0.08). A higher proportion of men with unexplained RPL had DFI ≥30% compared to controls (54.2% vs. 25.7%; OR 3.43 (95% CI 1.2–9.4); p = 0.02). No statistically significant differences were observed in semen volume, sperm concentration, progressive motility, and morphology between the two groups. Sperm DNA fragmentation index also showed a weak but significant inverse relationship with sperm morphology (r = −0.336, p = 0.004).The current study did not show any significant difference in the mean sperm DNA fragmentation levels in male partners of couples with unexplained RPL compared to controls. However, a higher proportion of men with DFI ≥30% were observed in unexplained RPL population when compared to controls. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether IL-6 using in early pregnancy can improve the pregnancy outcome of recurrent spontaneous abortion （RSA） mice and its relevant mechanism, providing new ideas for RSA clinical treatment. Methods: CBA/J×DBA/2 RSA model mice were constructed, and randomly divided the pregnant mice into five groups: control group, 0.1 ng/ml IL-6 group, 1 ng/ml IL-6 group, 10 ng/ml IL-6 group and 100 ng/ml IL-6 group. IL-6 was not injected in control group, while different concentrations of IL-6 were respectively injected into other groups on the 0.5 day of pregnancy. Pregnant rats were killed at 13.5 d and the embryo loss rate was calculated, the placental tissue was taked out, and expressions of IL-6 and indoleamine 2, 3-dioxygenase （IDO） in tissues were detected by Western blot. Results: Embryo absorption rates of 0.1 ng/ml IL-6 group, 1 ng/ml IL-6 group, 10 ng/ml IL-6 group and 100 ng/ml IL-6 group were obviously lower than that in control group （P=0.002 4, P=0.007 0, P=0.027 0, P=0.031 0）. IL-6 of exogenous injection was positive correlated with that expressed in mice placental tissue（r=0.791, P=0.000 052）. IL-6 concentration of exogenous injection was between 0~1 ng/ml, which was positively correlated with IDO expression in placental tissue（r=0.868, P<0.000 1）, IL-6 was positively correlated with IDO expressed in placental tissue （r=0.982, P<0.000 1）. IL-6 concentration of exogenous injection was between 1~100 ng/ml, which was inversely correlated with IDO expression（r=-0.725, P=0.002）, and IL-6 was inversely correlated with IDO expressed in placental tissue（r=-0.972, P<0.000 1）. Conclusion: A single intraperitoneal injection of specific concentration of exogenous IL-6 to RSA mice can reduce embryo absorption rate of mice and modify their pregnancy outcome, which possible mechanism is the exogenous IL-6 induces expressions of IL-6 and IDO for a long term. Whether the IDO expression in placental tissue increase or not can be regarded as a mark for whether the specific concentration IL-6 can protect the pregnancy or not. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to assess the comparative efficacy of low-molecular-weight heparin (LMWH) in combination with low-dose aspirin for the management of recurrent miscarriage and scrutinize alterations in coagulation function following such treatment. A retrospective analysis was conducted on clinical data obtained from 97 patients with recurrent miscarriage treated at our institution from January 2019 to June 2020. Patients were categorized into either the study or control groups based on the administration of LMWH. The control group comprised 48 patients treated solely with aspirin, while the study group included 49 patients treated with both LMWH and aspirin. Comparative evaluations between the two groups encompassed pregnancy outcomes, coagulation function, adverse reactions, and blood loss during delivery. Results revealed a higher term birth rate in the study group (83.67%) compared to the control group (50%). Post-treatment, the study group exhibited lower prothrombin time, plasminogen activator inhibitor, and D-dimer levels than the control group. Moreover, the study group experienced fewer adverse reactions and reduced blood loss during delivery in comparison to the control group, demonstrating statistical significance (P < 0.05). The combination of LMWH and low-dose aspirin exhibited noteworthy application in the management of recurrent miscarriage. This therapeutic approach not only fostered the enhancement of coagulation function conducive to pregnancy but also diminished the incidence of adverse reactions observed with aspirin alone. [ABSTRACT FROM AUTHOR]

Background & Objective: Miscarriage, a common complication of early pregnancy before 12 completed weeks of gestation, is typically managed medically. We aimed to estimate the success and complication rate of medical management in women with first-trimester missed miscarriages. Our objective was to calculate the rate of complete uterine evacuation within three weeks of treatment, rate of infection, significant blood loss, re-admission, or surgical evacuation. Methods: It was a retrospective cross-sectional study that included women diagnosed with miscarriage at less than 13 weeks’ gestation in Latifa Hospital’s Gynecology Department from January 2019 to December 2019 in Dubai. These patients were given vaginal misoprostol, 400-800 mcg every 6-8 hours until expulsion of pregnancy. Results: There were 294 women included in the study. The success rate was 60.5% (178/294). Twenty women developed significant blood loss (6.8%), four women developed infection (1.4%), 76 required readmission (25.9%), 12 women received blood transfusion (4.1%), and 74 women required a surgical evacuation (25.2%). Nulliparity, unscarred uterus, and the presence of abdominal pain with vaginal bleeding before treatment were significantly associated with the successful medical treatment (p<0.05). Conclusion: The success rate of the medical regimen studied lies on the lower end of what is quoted in the literature. The difference in the success rate could be attributed to the different definitions of success in other studies. Nulliparity, unscarred uterus and presence of abdominal pain with vaginal bleeding were associated with higher success. [ABSTRACT FROM AUTHOR]

Introduction: Distinguishing paracentric inversions (PAIs) from chromosomal insertions has traditionally relied on fluorescent in situ hybridization (FISH) techniques, but recent advancements in high‐throughput sequencing have enabled the use of genome sequencing for such differentiation. In this study, we present a 38‐year‐old male carrier of a paracentric inversion on chromosome 2q, inv (2)(q31.2q34), whose partner experienced recurrent miscarriages. Material and Methods: FISH analysis confirmed the inversion, and genome sequencing was employed for detailed characterization. Results: Preimplantation genetic testing (PGT) revealed that all assessed embryos were balanced, consistent with the low risk of unbalanced offspring associated with PAIs. While PAI carriers traditionally exhibit low risk of producing unbalanced offspring, exceptions exist due to crossover events within the inversion loop. Although the sample size was limited, the findings align with existing sperm study data, supporting the rare occurrence of unbalanced progeny in PAI carriers. Conclusions: This study highlights the possibility of characterizing PAIs using genome sequencing to enable correct reproductive counseling and PGT decisions. Detailed characterization of a PAI is crucial for understanding potential outcomes and guiding PGT strategies, as accurate knowledge of the inversion size is essential for appropriate method selection in PGT. Given the very low risk of unbalanced offspring in PAI carriers, routine PGT may not be warranted but should be considered in specific cases with a history of unbalanced progeny or recurrent miscarriages. This study contributes to our understanding of PAI segregation and its implications for reproductive outcomes. [ABSTRACT FROM AUTHOR]

Background: Conjoined twins (CT), which used to be historically defined as "monstrous human" and previously so-called Siamese twins in the early eighteenth century, are one of the very rare congenital malformations with an uncertain etiology and complex yet remain inconclusively debatable regarding its pathophysiological mechanisms of fusion and fission theories. Among all types of CT, parasitic CT, especially the pygopagus sub-type, is exceedingly rarer. To the best of the authors' knowledge, no parasitic CT had been reported in Papua, and this is the first finding in South Papua. Case Report: Herein, a 30-year-old multigravida female with 37th-week gestation, previous twice spontaneous miscarriage, and non-adequate antenatal care history is presented with a chief complaint of painful construction and greenish fluid leakage from the vagina, with an examination that showed a cephalic presentation with a "peculiar" big mass at the upper uterus and complete cervical dilation toward second-stage inpartu. Vaginal delivery was performed with a complication of obstructed labor due to uncommon dystocia with a suspected "big mass" below the fetal buttocks and intrapartum dead. Intrapartum transabdominal ultrasound demonstrates a gross anatomically like an organ inside a fluid-filled mass with unidentified parts, leading to a suspected type of congenital malformation at the baby's sacral region. Emergency C-section was done with findings of parasitic pygopagus CT, showing an attachment of a large irregular fluid-filled mass-like incomplete twin (parasite) with palpable soft tissue and bony structure inside to the buttocks of a male autosite twin, and an additional third leg which happened to be an under-developed lower extremity with a sacrum-like structure. Conclusions: An obstetrician's routine ANC and critical radiological evaluation will increase the odds of identifying CT or other congenital malformations to provide better delivery planning or further management. Increasing maternal health knowledge in society, improving medical skills and knowledge levels for health providers, and advancing supporting facilities and specialists are future strategies for managing and preventing such cases in low-middle-income countries. [ABSTRACT FROM AUTHOR]

To propose a new gene expression signature that identifies endometrial disruptions independent of endometrial luteal phase timing and predicts if patients are at risk of endometrial failure. Multicentric, prospective study. Reproductive medicine research department in a public hospital affiliated with private fertility clinics and a reproductive genetics laboratory. Caucasian women (n = 281; 39.4 ± 4.8 years old with a body mass index of 22.9 ± 3.5 kg/m2) undergoing hormone replacement therapy between July 2018 and July 2021. Endometrial samples from 217 patients met RNA quality criteria for signature discovery and analysis. Endometrial biopsies collected in the mid-secretory phase. Endometrial luteal phase timing-corrected expression of 404 genes and reproductive outcomes of the first single embryo transfer (SET) after biopsy collection to identify prognostic biomarkers of endometrial failure. Removal of endometrial timing variation from gene expression data allowed patients to be stratified into poor (n = 137) or good (n = 49) endometrial prognosis groups on the basis of their clinical and transcriptomic profiles. Significant differences were found between endometrial prognosis groups in terms of reproductive rates: pregnancy (44.6% vs. 79.6%), live birth (25.6% vs. 77.6%), clinical miscarriage (22.2% vs. 2.6%), and biochemical miscarriage (20.4% vs. 0%). The relative risk of endometrial failure for patients predicted as a poor endometrial prognosis was 3.3 times higher than those with a good prognosis. The differences in gene expression between both profiles were proposed as a biomarker, coined the endometrial failure risk (EFR) signature. Poor prognosis profiles were characterized by 59 upregulated and 63 downregulated genes mainly involved in regulation (17.0%), metabolism (8.4%), immune response, and inflammation (7.8%). This EFR signature had a median accuracy of 0.92 (min = 0.88, max = 0.94), median sensitivity of 0.96 (min = 0.91, max = 0.98), and median specificity of 0.84 (min = 0.77, max = 0.88), positioning itself as a promising biomarker for endometrial evaluation. The EFR signature revealed a novel endometrial disruption, independent of endometrial luteal phase timing, present in 73.7% of patients. This EFR signature stratified patients into 2 significantly distinct and clinically relevant prognosis profiles providing opportunities for personalized therapy. Nevertheless, further validations are needed before implementing this gene signature as an artificial intelligence (AI)-based tool to reduce the risk of patients experiencing endometrial failure. [ABSTRACT FROM AUTHOR]

To provide evidence-based recommendations regarding the diagnosis and effectiveness of surgical treatment of a uterine septum. This guideline provides evidence-based recommendations regarding the diagnosis and effectiveness of surgical treatment of a uterine septum. This replaces the last version of the same name (Fertil Steril. 2016 Sep 1;106(3):530-40). Outcomes of interest included the impact of a septum on underlying fertility, live birth, clinical pregnancy, and obstetrical outcomes. The literature search identified relevant studies to inform the evidence for this guideline. The treatment of uterine septa and subsequent outcomes associated with infertility, recurrent pregnancy loss, and adverse obstetrical outcomes are summarized. Resection of a septum has been shown to improve outcomes in patients with recurrent pregnancy loss and to decrease the likelihood of malpresentation. In the setting of infertility, it is recommended to use a shared decision-making model after appropriate counseling to determine whether or not to proceed with septum resection. [ABSTRACT FROM AUTHOR]

The high incidence of idiopathic recurrent pregnancy loss (iRPL) may stem from the limited research on male contributory factors. Many studies suggest that sperm DNA fragmentation and oxidative stress contribute to iRPL, but their roles are still debated. MicroRNAs (miRNAs) are short non-coding RNAs that regulate various biological processes by modulating gene expression. While differential expression of specific miRNAs has been observed in women suffering from recurrent miscarriages, paternal miRNAs remain unexplored. We hypothesize that analyzing sperm miRNAs can provide crucial insights into the pathophysiology of iRPL. Therefore, this study aims to identify dysregulated miRNAs in the spermatozoa of male partners of iRPL patients. Total mRNA was extracted from sperm samples of iRPL and control groups, followed by miRNA library preparation and high-output miRNA sequencing. Subsequently, raw sequence reads were processed for differential expression analysis, target prediction, and bioinformatics analysis. Twelve differentially expressed miRNAs were identified in the iRPL group, with eight miRNAs upregulated (hsa-miR-4454, hsa-miR-142-3p, hsa-miR-145-5p, hsa-miR-1290, hsa-miR-1246, hsa-miR-7977, hsa-miR-449c-5p, and hsa-miR-92b-3p) and four downregulated (hsa-miR-29c-3p, hsa-miR-30b-5p, hsa-miR-519a-2-5p, and hsa-miR-520b-5p). Functional enrichment analysis revealed that gene targets of the upregulated miRNAs are involved in various biological processes closely associated with sperm quality and embryonic development. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the prevalence of congenital and acquired anomalies of the uterus in women with recurrent pregnancy loss (RPL) of unknown etiology examined using 3D transvaginal ultrasound (US)? SUMMARY ANSWER Depending on the adopted diagnostic criteria, the prevalence of partial septate uterus varies between 7% and 14% and a T-shaped uterus is 3% or 4%, while adenomyosis is 23%, at least one of type 0, type 1 or type 2 myoma is 4%, and at least one endometrial polyp is 4%. WHAT IS KNOWN ALREADY ESHRE and the Royal College of Obstetricians and Gynaecologists guidelines on RPL recommend the adoption of the 3D transvaginal US to evaluate the 'uterine factor'. Nevertheless, there are no published studies reporting the prevalence of both congenital and acquired uterine anomalies as assessed by 3D transvaginal US and diagnosed according to the criteria proposed by the most authoritative panels of experts in a cohort of women with RPL. STUDY DESIGN, SIZE, DURATION This was a retrospective cohort study including 442 women with at least two previous first-trimester spontaneous pregnancy losses (i.e. non-viable intrauterine pregnancies), who referred to the obstetrics and gynecology unit of two university hospitals between July 2020 and July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS Records of eligible women were reviewed. Women could be included in the study if: they were between 25 and 42 years old; they had no relevant comorbidities; they were not affected by infertility, and they had never undergone ART; they and their partner tested negative to a comprehensive RPL diagnostic work-up; and they had never undergone metroplasty, myomectomy, minimally invasive treatments for uterine fibroids or adenomyomectomy. Expert sonographers independently re-analyzed the stored 2- and 3D transvaginal US images of all included patients. Congenital uterine anomalies (CUAs) were reported according to the American Society for Reproductive Medicine (ASRM) 2021, the ESHRE/European Society for Gynaecological Endoscopy (ESGE) and the Congenital Uterine Malformation by Experts (CUME) criteria. Acquired uterine anomalies were reported according to the International Federation of Gynecology and Obstetrics (FIGO) and the Morphological Uterus Sonographic Assessment (MUSA) criteria. MAIN RESULTS AND THE ROLE OF CHANCE The partial septate uterus was diagnosed in 60 (14%; 95% CI: 11–17%), 29 (7%; 95% CI: 5–9%), and 47 (11%; 95% CI: 8–14%) subjects, according to the ESHRE/ESGE, the ASRM 2021, and the CUME criteria, respectively. The T-shaped uterus was diagnosed in 19 women (4%; 95% CI: 3–7%) according to the ESHRE/ESGE criteria and in 13 women (3%; 95% CI: 2–5%) according to the CUME criteria. The borderline T-shaped uterus (diagnosed when two out of three CUME criteria for T-shaped uterus were met) was observed in 16 women (4%; 95% CI: 2–6%). At least one of FIGO type 0, type 1, or type 2 myoma was detected in 4% of included subjects (95% CI: 3–6%). Adenomyosis was detected in 100 women (23%; 95% CI: 19–27%) and was significantly more prevalent in women with primary RPL and in those with three or more pregnancy losses. At least one endometrial polyp was detected in 4% of enrolled women (95% CI: 3–7%). LIMITATIONS, REASONS FOR CAUTION The absence of a control group prevented us from investigating the presence of an association between both congenital and acquired uterine anomalies and RPL. Second, the presence as well as the absence of both congenital and acquired uterine anomalies detected by 3D US was not confirmed by hysteroscopy. Finally, the results of the present study inevitably suffer from the intrinsic limitations of the adopted classification systems. WIDER IMPLICATIONS OF THE FINDINGS The prevalence of CUAs in women with RPL varies depending on the classification system used. For reasons of clarity, the US reports should always state the name of the uterine anomaly as well as the adopted classification and diagnostic criteria. Adenomyosis seems to be associated with more severe forms of RPL. The prevalence rates estimated by our study as well as the replicability of the adopted diagnostic criteria provide a basis for the design and sample size calculation of prospective studies. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was used. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

• A meta -analysis address the impact of insulin resistance on IVF/ICSI in PCOS women. • Insulin resistance reduces MII oocytes, total embryo and clinical pregnancy rate. • Insulin resistance leads to a higher rate of miscarriage. • In women with PCOS, insulin resistance had a negative impact on IVF/ICSI outcomes. To evaluate the effect of insulin resistance (IR) on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes in patients with polycystic ovary syndrome (PCOS). PubMed, Google Scholar,Web of Science, Embase, Scopus and the Cochrane Library were searched to identify relevant studies. A total of 6,137 PCOS women undergoing IVF/ICSI with or without IR were included in the systematic review and meta -analysis. The systematic review and meta -analysis included twelve observational studies that were free from inherent bias. When comparing PCOS women undergoing IVF/ICSI, the IR and non-IR groups did not show significant differences in oocytes retrieved (WMD = -0.63, 95 % CI: −2.37 to 1.12, P = 0. 483), fertilization rate (WMD = 1.01, 95 % CI: −0.66 to 2.67, P = 0.236; OR = 0.97, 95 % CI: 0.79 to 1.19, P = 0.783), and live birth rate (OR = 1.02, 95 % CI: 0.78 to 1.33, P = 0.892). However, the group with IR had a lower number of MII oocytes (WMD = -1.07, 95 % CI: −1.54 to −0.59, P < 0.001), total embryos (WMD = -1.37, 95 % CI: −1. 78 to −0.95, P < 0.001), and clinical pregnancy rate (OR = 0.77, 95 % CI: 0.59 to 0.99, P = 0.042), as well as a higher miscarriage rate (OR = 1.11, 95 % CI: 1.02 to 1.22, P = 0.017) compared to the non-IR group. In women with PCOS, IR had a negative impact on IVF/ICSI outcomes. To obtain more favourable empirical support, larger studies are necessary. [ABSTRACT FROM AUTHOR]

Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, traditional Chinese medicine has become a feasible alternative for certain diseases, including recurrent spontaneous abortion. However, because of the complex composition of the traditional Chinese medicine formula, its action mechanism remains unclear. Methods: We selected two isolated active ingredients (RAMP and baicalin) from the traditional Chinese medicine formula and used an abortion-prone CBA/J × DBA/2 model to simulate human RSA and compared the changes in fetal resorption rate, Treg cell percentage, and relevant cytokines before and after combination therapy. In addition, The mechanisms were preliminarily discussed using in vitro differentiation models. Results: In CBA/J × DBA/2 abortion-prone mice, the combination therapy resulted in a lower embryo resorption rate compared to that obtained with individual delivery of either RAMP or baicalin, thereby playing an embryo-protective role through the increase in Treg cells for the maintenance of maternal-fetal immune tolerance. In in vitro primary cell differentiation experiments, the concentration of Treg cells significantly increased from 11% to 17.9% after the combination therapy compared to that of the single administration group. Conclusion: the synergistic effects of RAMP and baicalin were responsible for Treg differentiation. The present study provides a solid basis for improving the applicability of traditional Chinese herbs in the treatment of recurrent spontaneous abortion. [ABSTRACT FROM AUTHOR]

Background and Aims: One of the causes of preterm labor and recurrent abortion is progesterone deficiency in the luteal phase. The aim of the study was a comparison of the effect of oral dydrogesterone and vaginal progesterone for luteal‐phase support (LPS) in assisted reproductive technology cycles (ART). Methods: This randomized clinical control trial study was conducted on 207 infertile women. Samples were randomly divided into two groups. The first group received a natural micronized vaginal progesterone (MVP) of 400 mg once daily and the second group received dydrogesterone (Duphestone) 20 mg twice daily. Then chemical pregnancy, abortion, and live births were compared in two groups. Results: The results of the study showed that the vaginal form of the drug could increase the chance of pregnancy (positive β‐human chorionic gonadotropin) versus the oral form. According to the results of multiple logistic regression analysis after adjusting for other variables, the live birth rate in the vaginal group was more than five times that of the oral group (odds ratio = 5.07; 95% confidence interval = 1.24–20.65; p = 0.023). Conclusion: The vaginal form of the progesterone could increase the chance of pregnancy and the outcome of fertility (live birth). Thus, vaginal progesterone is effective for LPS in women undergoing fresh embryo transfer. [ABSTRACT FROM AUTHOR]

The article reviews the effectiveness of surrogate endpoints, specifically preterm birth (PTB) and time to delivery from spontaneous preterm labor (sPTL), in predicting neonatal outcomes. Topics discussed include the strength of surrogacy for these endpoints, the variability in trial results, and the need for better empirical measures and reporting guidelines.

Recurrent Pregnancy Loss (RPL) affects 1–2% of women, and its triggering factors are unclear. Several studies have shown that the vaginal, endometrial, and gut microbiota may play a role in RPL. A decrease in the quantity of Lactobacillus crispatus in local microbiota has been associated with an increase in local (vaginal and endometrial) inflammatory response and immune cell activation that leads to pregnancy loss. The inflammatory response may be triggered by gram-negative bacteria, lipopolysaccharides (LPS), viral infections, mycosis, or atypia (tumor growth). Bacterial structures and metabolites produced by microbiota could be involved in immune cell modulation and may be responsible for immune cell activation and molecular mimicry. Gut microbiota metabolic products may increase the amount of circulating pro-inflammatory lymphocytes, which, in turn, will migrate into vaginal or endometrial tissues. Local pro-inflammatory Th1 and Th17 subpopulations and a decrease in local Treg and tolerogenic NK cells are accountable for the increase in pregnancy loss. Local microbiota may modulate the local inflammatory response, increasing pregnancy success. Analyzing local and gut microbiota may be necessary to characterize some RPL patients. Although oral supplementation of probiotics has not been shown to modify vaginal or endometrial microbiota, the metabolites produced by it may benefit patients. Lactobacillus crispatus transplantation into the vagina may enhance the required immune tolerogenic response to achieve a normal pregnancy. The effect of hormone stimulation and progesterone to maintain early pregnancy on microbiota has not been adequately studied, and more research is needed in this area. Well-designed clinical trials are required to ascertain the benefit of microbiota modulation in RPL. [ABSTRACT FROM AUTHOR]

Background: Recurrent spontaneous abortion (RSA) is a challenging condition that affects the health of women both physically and mentally, but its pathogenesis and treatment have yet to be studied in detail. In recent years, Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been shown to be effective in treating various diseases. Current understanding of RSA treatment using WJ-MSCs is limited, and the exact mechanisms of WJ-MSCs action in RSA remains largely unclear. In this study, we explored the decidual deficiencies in RSA and the therapeutic potential of WJ-MSCs at single-cell resolution. Methods: Three mouse models were established: a normal pregnancy group, an RSA group, and a WJ-MSC treatment group. Decidual tissue samples were collected for single-cell RNA sequencing (scRNA-seq) and functional verification, including single-cell resolution in situ hybridization on tissues (SCRINSHOT) and immunofluorescence. Results: We generated a single-cell atlas of decidual tissues from normal pregnant, RSA, and WJ-MSC-treated mice and identified 14 cell clusters in the decidua on day 14. Among these cell populations, stromal cells were the most abundant cell clusters in the decidua, and we further identified three novel subclusters (Str_0, Str_1, and Str_2). We also demonstrated that the IL17 and TNF signaling pathways were enriched for upregulated DEGs of stromal cells in RSA mice. Intriguingly, cell–cell communication analysis revealed that Str_1 cell-related gene expression was greatly reduced in the RSA group and rescued in the WJ-MSC treatment group. Notably, the interaction between NK cells and other cells in the RSA group was attenuated, and the expression of Spp1 (identified as an endometrial toleration-related marker) was significantly reduced in the NK cells of the RSA group but could be restored by WJ-MSC treatment. Conclusion: Herein, we implemented scRNA-seq to systematically evaluate the cellular heterogeneity and transcriptional regulatory networks associated with RSA and its treatment with WJ-MSCs. These data revealed potential therapeutic targets of WJ-MSCs to remodel the decidual subpopulations in RSA and provided new insights into decidua-derived developmental defects at the maternal–foetal interface. [ABSTRACT FROM AUTHOR]

Background: Lipopolysaccharides (LPS) is well known to manifest a miscarriage-inducing effector during early pregnancy and activate macrophage to induce M1 macrophage polarization. However, the role of macrophage polarization in LPS-related miscarriage-inducing effect is not apparent. Methods: In this work, gene expression changes and the percentage of M1/M2 macrophages and monocytes in LPS-induced miscarried uterus were firstly analyzed by RNA sequencing (RNA-seq) and Flow Cytometry. To explore the origin that contributes to M1/M2 macrophage differentiation, the expression of monocyte chemotactic protein (MCP-1), CCL3, and CCL4, chemokines related to monocyte/macrophage migration, was tested by quantitative real time PCR (qRT-PCR). Results: We found that percentage of M1 macrophages rose, while the percentage of M2 macrophages declined down in the injected mice uterus. Meanwhile, the percentage of M1 and M2 macrophages showed no significant difference in the spleens of LPS injected mice compared to PBS injected control mice. Expression of Mcp-1, Ccl3, and Ccl4 and numbers of monocytes were remarkably up-regulated in LPS-induced miscarried mice uterus. Conclusion: These results indicated that polarization and proportion changes of macrophage in the uterus may contribute to miscarriage. Our work provides new evidence correlating the aberrant regulation of M1/M2 macrophage polarization with deleterious miscarriage-inducing effects. This will help us understand the roles of critical immune cell differentiation in maintaining normal pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Vitamin D deficiency and variations in the vitamin D binding protein (VDBP) gene may play a role in the development of Polycystic ovary syndrome (PCOS). This study aims to investigate the association of the rs4588 polymorphism with PCOS in Iranian women, as well as its association with infertility and recurrent pregnancy loss (RPL) in these patients. Results: The analysis revealed statistically significant differences in the distributions of genotypes and alleles of the rs4588 polymorphism among the three groups (p < 0.0001). The AC genotype and A allele showed an association with an elevated risk of PCOS and infertility. In this study, no association was found between genotypes and alleles of the rs4588 polymorphism and the risk of RPL in women with PCOS. Subjects with the AA or AC genotype exhibited significantly higher levels of LDL compared to those with the CC genotype. [ABSTRACT FROM AUTHOR]

Maternally-loaded factors in the egg accumulate during oogenesis and are essential for the acquisition of oocyte and egg developmental competence to ensure the production of viable embryos. However, their molecular nature and functional importance remain poorly understood. Here, we present a collection of 9 recessive maternal-effect mutants identified in a zebrafish forward genetic screen that reveal unique molecular insights into the mechanisms controlling the vertebrate oocyte-to-embryo transition. Three genes, over easy, p33bjta, poached and black caviar, were found to control initial steps in yolk globule sizing and protein cleavage during oocyte maturation that act independently of nuclear maturation. The krang, kazukuram, p28tabj, and spotty genes play distinct roles in egg activation, including cortical granule biology, cytoplasmic segregation, the regulation of microtubule organizing center assembly and microtubule nucleation, and establishing the basic body plan. Furthermore, we cloned two of the mutant genes, identifying the over easy gene as a subunit of the Adaptor Protein complex 5, Ap5m1, which implicates it in regulating intracellular trafficking and yolk vesicle formation. The novel maternal protein Krang/Kiaa0513, highly conserved in metazoans, was discovered and linked to the function of cortical granules during egg activation. These mutant genes represent novel genetic entry points to decipher the molecular mechanisms functioning in the oocyte-to-embryo transition, fertility, and human disease. Additionally, our genetic adult screen not only contributes to the existing knowledge in the field but also sets the basis for future investigations. Thus, the identified maternal genes represent key players in the coordination and execution of events prior to fertilization. Author summary: The oocyte-to-embryo transition consists of the coordinated regulation of multiple molecular processes acting in the late oocyte, egg and early zygote. This transcriptionally silent period requires the precisely timed function of maternally-supplied gene products during oogenesis. However, knowledge of their molecular nature and in vivo function remains incomplete. Importantly, defects associated with the oocyte-to-embryo transition in humans cause reduced female reproductive success, in addition to a possible increased incidence of miscarriage. The mutants reported here provide access to maternal factors regulating the processes that prepare an oocyte for reproductive competence and embryogenesis. We have identified essential regulators of yolk granule formation, cortical granule biology, and microtubule organizing assembly control. Specifically, we found that the highly conserved maternal Ap5m1 protein regulates yolk granule maturation, which generate essential nutrients and immunity for growth and development in oviparous animals. We characterized the Krang factor, which regulates aspects of egg activation likely by modulating the secretory pathway. The mutants presented here represent attractive genetic models to investigate the molecular and cell biological mechanisms that control the oocyte-to-embryo transition, as well as reveal a collection of genetic factors indispensable for reproduction and survival. Importantly, knowledge of their genetic underpinnings and biological importance in reproduction will also pave the way to investigate the evolution of maternal genes during vertebrate development. [ABSTRACT FROM AUTHOR]

Background: Recurrent aphthous stomatitis (RAS) is a common chronic inflammatory oral disease that negatively impacts the quality of life. Current therapies aim to reduce pain and healing process yet challenges such as rapid loss due to salivary flushing in topical drugs and adverse effects due to prolonged use of systemic medications require further notice. Low-level laser therapy is reported with immediate pain relief and faster healing thus preserving the potential for optimal treatment modalities. This review critically analyses and summarizes the effectiveness of LLLT in reducing pain scores and healing time of RAS. Methods: A systematic search was conducted in ScienceDirect, PubMed, and Scopus using keywords of low-level laser therapy, photo-biomodulation therapy, and recurrent aphthous stomatitis. RCTs between 1967 to June 2022, presenting characteristics of the laser and reporting pain score and/or healing time of RAS after irradiation were included. Animal studies and recurrent aphthous ulcers with a history of systemic conditions were excluded. Studies were critically appraised using the RoB 2 tool. A meta-analysis was performed using inverse variance random effects. Results: Fourteen trials with a total of 664 patients were included. Reduced pain was reported in 13 studies, while shortened healing time was presented in 4. The pooling of two studies after CO2 irradiation demonstrated faster healing time compared to placebo (MD − 3.72; 95% CI − 4.18, − 3.25). Conclusion: Pain score and healing time of RAS were reduced after irradiation with LLLT. RoB resulted in "some concerns" urging well-designed RCTs with larger samples to further assess each laser application for comparison. Systematic review registration: PROSPERO CRD42022355737. [ABSTRACT FROM AUTHOR]

c-FLIP functions as a dual regulator of apoptosis and inflammation, yet its implications in Zika virus (ZIKV) infection remain partially understood, especially in the context of ZIKV-induced congenital Zika syndrome (CZS) where both apoptosis and inflammation play pivotal roles. Our findings demonstrate that c-FLIP promotes ZIKV infection in placental cells and myeloid-derived macrophages, involving inflammation and caspase-8/3-mediated apoptosis. Moreover, our observations reveal that c-FLIP augments ZIKV infection in multiple tissues, including blood cell, spleen, uterus, testis, and the brain of mice. Notably, the partial deficiency of c-FLIP provides protection to embryos against ZIKV-induced CZS, accompanied by a reduction in caspase-3-mediated apoptosis. Additionally, we have found a distinctive parental effect of c-FLIP influencing ZIKV replication in fetal heads. In summary, our study reveals the critical role of c-FLIP as a positive regulator in caspase-8/3-mediated apoptosis during ZIKV infection, significantly contributing to the development of CZS. Author summary: Zika virus (ZIKV) infection in pregnant women can lead to the development of Congenital Zika Syndrome (CZS) in infants, resulting in complications such as microcephaly, intrauterine growth restriction (IUGR), and miscarriages. Although the mechanisms of apoptosis and inflammatory responses in ZIKV-induced CZS are not fully understood, our study investigated the role of c-FLIP, a critical regulator of apoptosis and inflammation during ZIKV infection and its associated CZS. In both human trophoblast cells and murine-derived macrophages, we observed that c-FLIP facilitated ZIKV infection by modulating caspase-8/3-mediated apoptosis. Mice deficient in c-FLIP exhibited reduced ZIKV replication and a decrease in inflammatory cytokine production. Importantly, c-FLIP deficiency demonstrated an inhibitory effect on CZS in ZIKV-infected pregnant mice. Additionally, c-FLIP displayed a parental influence on ZIKV replication in the fetal head by triggering caspase-3 activation. This research emphasizes the significance of c-FLIP in regulating caspase-8/3 and its profound impact on ZIKV-induced CZS, providing valuable insights into the role of apoptosis in ZIKV vertical transmission and fetal development. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The purpose of this study was to determine the etiologies of recurrent miscarriage in our hospital and whether its diagnostic approach followed the recommendations of the American Society of Reproductive Medicine (ASRM) guidelines published in 2012 and the National Institute for Health and Care Excellence (NICE) guidelines published in 2011.This was a retrospective study. The medical records of 158 patients diagnosed with recurrent miscarriage between 2013 and 2018 at Santander University Hospital were reviewed. The Institutional Review Board of HUS approved the study in May 2020.The most common etiologies identified were protein S deficiency, thrombophilia, and cervical insufficiency, with incidence rates of 25.9%, 10.7%, and 3.8%, respectively. Moreover, the most frequently requested diagnostic tests were for protein S, protein C, and anti‐phospholipid IgG. Abnormal results for protein S were obtained in 49% of the patients, whereas lupus anticoagulant was abnormal in 12.8%, and Factor V Leiden gene mutations in 8.5% of the patients. Three substantial deviations from the recommended diagnostic approach for recurrent miscarriage by international guidelines were identified in our population: the lack of request for cytogenetic analysis of pregnancy tissue, request for cytogenetic analysis for the parents in only 0.6% of the study sample, and the request for imaging tests to assess uterine anatomy in only 6.3% of the studied population. Both the ASRM and NICE guidelines were only partially followed with a combined adherence rate of 66.5%.The diagnostic approach for recurrent miscarriage poses important clinical challenges when compared to the recommendations of international guidelines. Therefore, the development of a local recurrent miscarriage assessment protocol is proposed in our institution. [ABSTRACT FROM AUTHOR]

Background: Depression is a common mental disorder with a much higher prevalence in women than in men. Although there has been a gradual increase in research on the association between reproductive health and depression, there is still some inconsistency in the evidence of the relationship between pregnancy loss and depression. This study aimed to investigate the relationship between pregnancy loss and depressive symptoms. Methods: We analyzed data from the 2007–2020 National Health and Nutrition Examination Survey (NHANES), which included female participants aged 20 to 80 years. Pregnancy loss was determined based on participants' self-reported number of pregnancies and pregnancy outcomes. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9, score ≥ 10). Multivariate logistic regression, smoothed curve fitting, and generalized additive modeling were used to examine the association between pregnancy loss and depression. We also performed sensitivity analyses and subgroup analyses to verify the robustness and specificity of the findings. Results: A total of 12,873 female participants were included in our study, of which 1,595 (12.39%) were categorized as depressed. Multivariate logistic regression results indicated that experiencing a pregnancy loss increased the risk of prevalence of depression in women (for 1 loss: OR = 1.31, 95% CI 1.15,1.50; for 2 or more losses: OR = 1.58, 95% CI 1.38, 1.81). When sensitivity analyses were performed, an association between pregnancy loss and depression was found in both multivariate linear regressions with PHQ-9 scores as a continuous variable and multivariate logistic regressions with a threshold of 5 PHQ-9 scores. The association between pregnancy loss and depression remained stable across subgroups. Conclusion: Pregnancy loss correlated with elevated PHQ-9 scores and a heightened risk of depression in adult women across the United States. Focusing on the incidence of adverse pregnancy events in the female population may help prevent or early recognize the onset of depression. Highlights: We analyzed the relationship between pregnancy loss and depression in American adult women. The sample size was large and nationally representative. Pregnancy loss was associated with higher PHQ-9 scores and an increased likelihood of depression among adult women. Our study is expected to provide more effective strategies to mitigate the impact of adverse pregnancy events on women's mental health. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is an autoimmune disease with arteriovenous thrombosis and recurrent miscarriages as the main clinical manifestations. Due to the complexity of its mechanisms and the diversity of its manifestations, its diagnosis and treatment remain challenging issues. Antiphospholipid antibodies (aPL) not only serve as crucial "biomarkers" in diagnosing APS but also act as the "culprits" of the disease. Endothelial cells (ECs), as one of the core target cells of aPL, bridge the gap between the molecular level of these antibodies and the tissue and organ level of pathological changes. A more in-depth exploration of the relationship between ECs and the pathogenesis of APS holds the potential for significant advancements in the precise diagnosis, classification, and therapy of APS. Many researchers have highlighted the vital involvement of ECs in APS and the underlying mechanisms governing their functionality. Through extensive in vitro and in vivo experiments, they have identified multiple aPL receptors on the EC membrane and various intracellular pathways. This article furnishes a comprehensive overview and summary of these receptors and signaling pathways, offering prospective targets for APS therapy. [ABSTRACT FROM AUTHOR]

Background: While some studies have suggested a link between gut microbiota (GM) and abortion, the causal relationship remains unclear. Methods: To explore the causal relationship between GM and abortion, including spontaneous abortion (SA) and habitual abortion (HA), we performed a twosample Mendelian randomization (MR) analysis. We used summary statistics data from MiBioGen and FinnGen for genome-wide association studies (GWAS), with GM data as the exposure variable and abortion data as the outcome variable. Results: In the absence of heterogeneity and horizontal pleiotropy, the inversevariance weighted (IVW) method identified five genetically predicted GM genera linked to the risk of abortions. Lactococcus was negatively correlated with the risk of SA, whereas the Eubacterium fissicatena group was positively correlated with the risk of SA. Genetic predictions of Coprococcus3 and Odoribacter were linked to a reduced risk of HA, while the Eubacterium ruminantium group was associated with an increased risk of HA. Conclusion: Our study suggests a genetic causal relationship between specific GM and two types of abortions, improving our understanding of the pathological relationship between GM and abortion. [ABSTRACT FROM AUTHOR]

Establishing prediction models of pregnancy outcomes for recurrent pregnancy loss women at specific gestational weeks will provide patients and physicians with more precise information, ultimately leading to time and cost savings associated with unnecessary revisits. Therefore, our aim was to develop a prediction model for first trimester pregnancy loss in RPL patients. We used ultrasound indices during the first trimester of pregnancy in combination with demographic characteristics and commonly used serum markers. The independent risk factors for each week were as follows: age and P in the fifth week; age, mGSD and CRL in the sixth week; age, hCG and CRL in the seventh week; CRL in the eighth week; mGSD and CRL in ninth week. The corresponding AUC was 0.671, 0.796, 0.872, 0.871, 0.813, respectively. There is a linear relationship between age and first trimester pregnancy loss. hCG < 69,636.6 mIU/ml was associated with a higher risk of pregnancy loss in the seventh gestation week. An mGSD < 18.3 mm, adjusted for age, BMI, and previous pregnancy loss in the sixth week, was linked to an increased risk of first trimester pregnancy loss. A small CRL measurement (less than 2.4 mm, 9.9 mm, 16.9 mm, and 18.6 mm) in the sixth, seventh, eighth and ninth week was closely correlated with higher risk of first trimester pregnancy loss. Furthermore, an mGSD < 33.3 mm and > 48.3 mm in ninth gestational week was associated with a higher risk of pregnancy loss. These models and thresholds may help physicians and patients make more informed decisions together. Further studies are needed to confirm the results. [ABSTRACT FROM AUTHOR]

Recurrent pregnancy loss (RPL) is a major reproductive health issue with multifactorial causes, affecting 2.6% of all pregnancies worldwide. Nearly half of the RPL cases lack clinically identifiable causes (e.g., antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities), referred to as unexplained RPL (uRPL). Here, we perform a genome-wide association study focusing on uRPL in 1,728 cases and 24,315 female controls of Japanese ancestry. We detect significant associations in the major histocompatibility complex (MHC) region at 6p21 (lead variant=rs9263738; P = 1.4 × 10−10; odds ratio [OR] = 1.51 [95% CI: 1.33–1.72]; risk allele frequency = 0.871). The MHC associations are fine-mapped to the classical HLA alleles, HLA-C*12:02, HLA-B*52:01, and HLA-DRB1*15:02 (P = 1.1 × 10−10, 1.5 × 10−10, and 1.2 × 10−9, respectively), which constitute a population-specific common long-range haplotype with a protective effect (P = 2.8 × 10−10; OR = 0.65 [95% CI: 0.57–0.75]; haplotype frequency=0.108). Genome-wide copy-number variation (CNV) calling demonstrates rare predicted loss-of-function (pLoF) variants of the cadherin-11 gene (CDH11) conferring the risk of uRPL (P = 1.3 × 10−4; OR = 3.29 [95% CI: 1.78–5.76]). Our study highlights the importance of reproductive immunology and rare variants in the uRPL etiology. Here, the authors perform a genome-wide association study for recurrent pregnancy loss without apparent clinical causes and identify a protective HLA haplotype. They also show that rare predicted loss-of-function variants in CDH11 are associated with risk of recurrent pregnancy loss. [ABSTRACT FROM AUTHOR]

Background: Episodes of recurrent or severe hypoglycemia can occur in patients with diabetes mellitus, insulinoma, neonatal hypoglycemia, and medication errors. However, little is known about the short-term and long-term effects of repeated episodes of acute severe hypoglycemia on the brain, particularly in relation to hippocampal damage and cognitive dysfunction. Methods: Thirty-six wistar rats were randomly assigned to either the experimental or control group. The rats were exposed to severe hypoglycemia, and assessments were conducted to evaluate oxidative stress in brain tissue, cognitive function using the Morris water maze test, as well as histopathology and immunohistochemistry studies. The clinical and histopathological evaluations were conducted in the short-term and long-term. Results: The mortality rate attributed to hypoglycemia was 34%, occurring either during hypoglycemia or within 24 h after induction. Out of the 14 rats monitored for 7 to 90 days following severe/recurrent hypoglycemia, all exhibited clinical symptoms, which mostly resolved within three days after the last hypoglycemic episode, except for three rats. Despite the decrease in catalase activity in the brain, the total antioxidant capacity following severe insulin-induced hypoglycemia increased. The histopathology findings revealed that the severity of the hippocampal damage was higher compared to the brain cortex 90 days after hypoglycemia. Memory impairments with neuron loss particularly pronounced in the dentate gyrus region of the hippocampus were observed in the rats with severe hypoglycemia. Additionally, there was an increase in reactive astrocytes indicated by GFAP immunoreactivity in the brain cortex and hippocampus. Conclusion: Recurrent episodes of severe hypoglycemia can lead to high mortality rates, memory impairments, and severe histopathological changes in the brain. While many histopathological and clinical changes improved after three months, it seems that the vulnerability of the hippocampus and the development of sustained changes in the hippocampus were greater and more severe compared to the brain cortex following severe and recurrent hypoglycemia. Furthermore, it does not appear that oxidative stress plays a central role in neuronal damage following severe insulin-induced hypoglycemia. Further research is necessary to assess the consequences of repeated hypoglycemic episodes on sustained damage across various brain regions. [ABSTRACT FROM AUTHOR]

Successful human pregnancy needs several highly controlled steps to guarantee an oocyte's fertilization, the embryo's pre-implantation development, and its subsequent implantation into the uterine wall. The subsequent placenta development ensures adequate fetal nutrition and oxygenation, with the trophoblast being the first cell lineage to differentiate during this process. The placenta sustains the growth of the fetus by providing it with oxygen and nutrients and removing waste products. It is not surprising that issues with the early development of the placenta can lead to common pregnancy disorders, such as recurrent miscarriage, fetal growth restriction, pre-eclampsia, and stillbirth. Understanding the normal development of the human placenta is essential for recognizing and contextualizing any pathological aberrations that may occur. The effects of these issues may not become apparent until later in pregnancy, during the mid or advanced stages. This review discusses the process of the embryo implantation phase, the molecular mechanisms involved, and the abnormalities in those mechanisms that are thought to contribute to the development of pre-eclampsia. The review also covers the histological hallmarks of pre-eclampsia as found during the examination of placental tissue from pre-eclampsia patients. [ABSTRACT FROM AUTHOR]

Elevated levels of tumor necrosis factor-alpha (TNF-α) have been associated with adverse pregnancy outcomes, specifically recurrent pregnancy loss (RPL). These elevated levels may be associated with the presence of autoantibodies. Although TNF-α inhibitors have shown promise in improving pregnancy rates, further research is needed to comprehend their impact and mechanisms in RPL patients. This study aims to investigate the association between elevated TNF-α levels and autoantibodies in RPL patients, as well as evaluate the effect of TNF-α inhibition on pregnancy outcomes. A total of 249 RPL patients were included in this study. Serum levels of TNF-α, autoantibodies, and complement were measured and monitored. Among these patients, 138 tested positive for TNF-α, while 111 tested negative. The medical records of these patients were retrospectively evaluated. Additionally, 102 patients with elevated TNF-α levels were treated with TNF-α inhibitors, and their pregnancy outcomes were assessed.TNF-α-positive RPL patients had higher levels of complement C1q, anti-cardiolipin (ACL)-IgA, ACL-IgM ,ACL-IgG, thyroglobulin antibody, and Anti-phosphatidylserine/prothrombin IgM antibody, as well as a higher positive rate of antinuclear antibodies compared to TNF-α-negative patients (23.19% vs. 12.6%, P< 0.05). Conversely, complement C3 were lower in TNF-α-positive patients (t test, P< 0.05). The use of TNF-α inhibitors led to a reduction in the early abortion rate (13.7% vs. 44.4%, P< 0.001) and an improvement in term delivery rate (52.0% vs. 27.8%, P= 0.012). Furthermore, patients who used TNF-α inhibitors before 5 weeks of pregnancy had a lower early abortion rate (7.7% vs. 24.3%, P= 0.033) and a higher term delivery rate (69.2% vs. 48.6%, P= 0.033).TNF-α plays a role in the occurrence and development of RPL, and its expression is closely associated with autoantibodies and complements. TNF-α inhibitors increase the term delivery rate in TNF-α-positive RPL patients, and their use before 5 weeks of pregnancy may more beneficial. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion To evaluate the effect of COVID‐19 during the first trimester on the rate of first‐ and second‐trimester miscarriages. Secondary aims include the effect on stillbirths and the correlation between symptom severity and pregnancy outcomes.A retrospective matched case–control population‐based study extracted data from electronic medical records of a nationwide database of the second largest healthcare organization that provides medical services to over 2 000 000 patients in Israel. Pregnancy outcomes in COVID‐19‐positive pregnant patients in 2020 were compared with an age‐ and gestational‐week‐matched 1:2 case–control cohort of pre‐pandemic pregnant patients that received medical care in 2019.Of 68 485 pregnant women treated in 2020, 2333 were COVID‐19‐positive during pregnancy: 215 during the first trimester, 791 during the second trimester, and 1327 during the third trimester. We compared these data with the control cohort of 4580 pre‐pandemic pregnant patients. The rate of spontaneous miscarriage was significantly higher 146/2187 (6.3%) in COVID‐19‐positive patients versus 214/4580 (4.7%), (P < 0.01, odds ratio 1.34, 95% confidence interval 1.094–1.691). Most miscarriages occurred during the first trimester in both groups, yet the rates were significantly higher in the study group (5.4% vs 3.8%, P < 0.01). There was no association between COVID‐19 severity and miscarriage risk.COVID‐19 diagnosis during early pregnancy increased the rate of spontaneous miscarriage in our cohort compared with an age‐ and gestational‐week‐matched pre‐pandemic control group. [ABSTRACT FROM AUTHOR]

Background: Recurrent miscarriage (RM) is defined as the occurrence of at least two or three subsequent miscarriages within the 20th -24th weeks of pregnancy. The primary objective of this study was to investigate whether histidine-rich glycoprotein C633T single nucleotide polymorphism (HRG C633T SNP) statistically correlates with the occurrence of RM among Iranian women. Methods and results: Blood samples from 200 women were taken at the outset of the study. Then, the blood samples of 100 women who had a record of RM (case group) were compared with the other 100 women's blood samples who had no record of RM (control group). Following DNA extraction, the polymorphism of histidine-rich glycoprotein C633T (HRG C633T) for every case was specified and all women were genotyped by the amplification-refractory mutation system (ARMS) method. The results of the study revealed that there was a statistically significant difference between T/T genotype (OR = 3.5, CI (1.39–8.77), p = 0.007), and C/T genotype (OR = 1.83, CI (0.99–3.37), p = 0.05) in the case and control groups. Also, a statistically significant association was observed in T allelic frequency in the RM participants compared to the control group (OR = 2.01, CI (1.31–3.09), p = 0.01). Conclusions: The present study determined that there was a statistically significant relationship between HRG C633T SNP and increased RM regarding allelic and genotypical aspects. Moreover, it became apparent that women with homozygous T/T genotype were more susceptible to the risk of RM. [ABSTRACT FROM AUTHOR]

Background: There is considerable global discourse on the impact of insufficient vitamin D levels, known for their immunosuppressive properties, on recurrent pregnancy loss. Vitamin D deficiency affects 35% to 80% of the population. Despite advancements in molecular genetics, the study of vitamin D receptor gene (VDR) polymorphisms remains crucial. This study examined the correlation between VDR polymorphisms and idiopathic recurrent pregnancy loss. Methods: A narrative literature review with a meta-analysis of 85 sources from databases such as PubMed, Web of Science, and Scopus was conducted, focusing on studies from 2020 to 2022. The analysis included studies on vitamin D and miscarriage, adhering to ICD-10 criteria, and VDR gene allele analysis through PCR-RFLP. Results: A comprehensive narrative analysis of the available scientific literature verified the link between comorbidities and vitamin D deficiencies, which can lead to recurrent pregnancy loss by hindering adaptive mechanisms and exacerbating complications. Conclusion: The most researched VDR gene polymorphisms, including FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and Cdx2, are linked to various health issues, particularly reproductive outcomes. The FokI (rs2228570) polymorphism in the VDR gene is a critical predictor of vitamin D levels, influencing pregnancy success. These findings are essential for assessing the risk of idiopathic recurrent pregnancy loss and developing new prevention and treatment approaches. [ABSTRACT FROM AUTHOR]

Introduction: Premature ovarian insufficiency (POI) is one of the causes of female infertility. Unexplained POI is increasingly affecting women in their reproductive years. However, the etiology of POI is diverse and remains elusive. We and others have shown that brain-derived neurotrophic factor (BDNF) plays an important role in adult ovarian function. Here, we report on a novel role of BDNF in the Developmental Origins of POI. Methods: Placental BDNF knockout mice were created using CRISPR/CAS9. Homozygous knockout (cKO(HO)) mice didn't survive, while heterozygous knockout (cKO(HE)) mice did. BDNF reduction in cKO(HE) mice was confirmed via immunohistochemistry and Western blots. Ovaries were collected from cKO(HE) mice at various ages, analyzing ovarian metrics, FSH expression, and litter sizes. In one-month-old mice, oocyte numbers were assessed using super-ovulation, and oocyte gene expression was analyzed with smart RNAseq. Ovaries of P7 mice were studied with SEM, and gene expression was confirmed with RT-qPCR. Alkaline phosphatase staining at E11.5 and immunofluorescence for cyclinD1 assessed germ cell number and cell proliferation. Results: cKO(HE) mice had decreased ovarian function and litter size in adulthood. They were insensitive to ovulation induction drugs manifested by lower oocyte release after superovulation in one-month-old cKO(HE) mice. The transcriptome and SEM results indicate that mitochondria-mediated cell death or aging might occur in cKO(HE) ovaries. Decreased placental BDNF led to diminished primordial germ cell proliferation at E11.5 and ovarian reserve which may underlie POI in adulthood. Conclusion: The current results showed decreased placental BDNF diminished primordial germ cell proliferation in female fetuses during pregnancy and POI in adulthood. Our findings can provide insights into understanding the underlying mechanisms of POI. [ABSTRACT FROM AUTHOR]

Purpose: To identify which non-invasive infection indicators could better predict post-cervical cerclage (CC) infections, and on which days after CC infection indicators should be closely monitored. Methods: The retrospective, single-center study included 619 single-pregnancy patients from January 2021 to December 2022. Patients were categorized into infected and uninfected groups based on physicians' judgments of post-CC infections. Registered information included patient characteristics, cervical insufficiency history, gestational age at CC, surgical method (McDonald/Shirodkar), purpose of CC, mid-pregnancy miscarriage/preterm birth, infection history or risk factors, and infection indices on days 1, 3, 5, and 7 after CC. Propensity score matching (PSM) was applied to reduce patient characteristic bias. Statistical analysis of C-reactive protein (CRP), white blood cell (WBC), neutrophil count (NEU), percentage of neutrophil count (NEU_P), interleukin-6 (IL-6), and procalcitonin (PCT) in the infected group compared with the uninfected group was performed using chi-square tests and t-tests. Receiver operating characteristic (ROC) curves were used to further assess the diagnostic value of CRP, PCT, and CRP-PCT in combination. Results: Among the 619 included patients, 206 patients were matched using PSM and subsequently assessed. PCT values on day 1 and day 3 after CC exhibited significant differences between the two groups in two statistical ways (P < 0.01, P < 0.05). The CRP levels on day 1 were significantly higher in the infected group compared to the uninfected group in two statistical ways (P < 0.05). On day 3, the mean CRP value was significantly elevated in the infected group compared to the uninfected group (P < 0.05). Analyses of IL-6, WBC, NEU, and NEU_P did not yield clinically significant results. The area under the ROC curves for CRP, PCT, and CRP-PCT on day 1 and day 3 were all below 0.7. In the preventive CC group, the AUC values of CRP and CRP-PCT obtained on d1 were found to be higher than 0.7, indicating moderate diagnostic accuracy. Conclusion: For women after CC surgery, especially of preventive aim, increased serum CRP and PCT levels from post-CC day 1 to day 3 may signal a potential postoperative infection, warranting close monitoring. [ABSTRACT FROM AUTHOR]