Lipocalin-2 (LCN2) has been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). Our previous work demonstrated a significant increase in astrocyte-derived LCN2 in the hippocampal region during SAE. Notably, this elevated expression strongly correlates with neuronal loss and cognitive impairment, although the underlying mechanisms remain elusive. In our study, we demonstrate that increased secretion of LCN2 from hippocampal astrocytes in SAE mice binds to the neuronal receptor 24p3R, thereby inducing neuronal damage. Notably, the downregulation of neuronal 24p3R effectively abolished the detrimental effects of LCN2. In both lipopolysaccharide (LPS)- and cecal ligation and puncture (CLP)-induced sepsis models in C57 mice, neuronal 24p3R knockdown similarly alleviated sepsis-induced synaptic dysfunction and cognitive deficits. Moreover, elevated brain LCN2 levels during sepsis coincided with suppressed autophagy. Mechanistic studies revealed that LCN2-24p3R axis activated the neuronal mTOR-ULK1 pathway, leading to inhibition of autophagy. Importantly, the inhibition of neuronal mTOR activity restored autophagy and ameliorated mitochondrial damage and neuronal loss caused by astrocyte-derived LCN2. These findings suggest an etiopathogenic mechanism of SAE, which is initiated by the increased astrocytic secretion of LCN2, acting on neuronal 24p3R to activate the mTOR-ULK1 pathway, suppress autophagy, and promote mitochondrial dysfunction and neuronal loss, ultimately driving SAE progression. This study provides novel insights into the molecular mechanisms of astrocyte-neuron communication in SAE and identifies potential therapeutic targets for effective intervention.

Mitophagy is a conserved cellular process that removes dysfunctional or excess mitochondria. Increasing evidence suggests that impaired mitophagy plays a crucial role in AD development. Promoting mitophagy has been shown to be protective in models of AD, representing an important target of Alzheimer's disease (AD). However, the molecular mechanisms underlying impaired mitophagy in AD are still elusive. Here, we provide evidence that highly expressed acylglycerol kinase (AGK), a mitochondrial lipid kinase associated with mitochondrial protein transport, glycolysis, and platelet formation, is a key mediator of mitophagy in AD. We found that AGK promoted the binding of ATPase family AAA domain containing 3A to translocase of the inner mitochondrial membrane 23 and sequentially increased mitochondrial import of PTEN-induced putative kinase 1, leading to the decrease of mitophagy. Further investigations revealed that the AGK downregulation in neuronal cells and APP/PS1 mice enhanced mitophagy, increased mitochondrial membrane potential, decreased pathological Tau/Aβ and neuroinflammation, and alleviated cognitive dysfunctions in the mice. Altogether our findings indicate that AGK plays a critical role in mediating mitophagy defects in AD; furthermore, downregulation of AGK promotes mitophagy and the decrease of Aβ and pathological Tau, providing an encouraging therapeutic treatment for AD.

Assisted reproductive technology (ART) increasingly relies on the selection of high-quality embryos to improve implantation success, yet non-invasive and reliable methods for assessing embryo implantation potential remain limited. Here, we present a biosensing strategy that integrates surface-enhanced Raman spectroscopy (SERS) with a feature-engineered artificial neural network (ANN) to predict embryo implantation outcomes through molecular spectral profile of embryo-derived small extracellular vesicles (Embryo-sEVs). Embryo-sEVs were isolated from day-5 blastocyst culture media, and characterized by SERS. Multivariate analysis revealed group-level differences in spectral signatures between implanted and non-implanted embryos, showing differential contributions from protein secondary structures, aromatic amino acids, lipid components, and nucleic acid backbones. To translate these biochemical features into a clinically relevant predictive tool, a hybrid ANN model was constructed using variable importance-weighted spectral features. The resulting model achieved an accuracy of 87.07%, an F1-score of 0.87, and an AUC of 0.91 on an independent test set, outperforming conventional machine learning classifiers. This fully label-free, non-invasive, and rapid method demonstrates strong potential for objective embryo quality assessment and highlights the broader applicability of SERS-deep learning biosensors for extracellular vesicle-based diagnostics.

The paradigm shift of lactate from a mere metabolic byproduct to a pleiotropic signaling molecule, coupled with the discovery of lactylation, provides a crucial framework for understanding how metabolic reprogramming drives systemic pathology. In this review, we systematically delineate the dynamic equilibrium of lactate homeostasis and the evolution of the lactate shuttle theory, exploring its multidimensional roles as a metabolic substrate, signal transducer, and immunomodulator. Furthermore, we summarize how lactylation orchestrates diverse pathophysiological processes across major organ systems, including metabolic dysfunction and fibrosis in the cardiovascular system, neuroinflammation and apoptosis in the central nervous system, and microenvironment-driven injury across the respiratory, digestive, and urinary tracts. Notably, we highlight the female reproductive system as a unique physiological model for investigating metabolic-epigenetic crosstalk, detailing how histone and non-histone lactylation contribute to the progression of various gynecological pathologies and critical reproductive processes. Finally, we evaluate the clinical translational potential of lactate-related biomarkers and lactylation-targeted therapeutics. Ultimately, this comprehensive framework underscores lactate and its mediated modifications as fundamental epigenetic regulators of cellular function and promising pharmacological targets for precision medicine.

Endometriosis is characterized by progressive fibrosis and limited therapeutic options. Cuproptosis, a copper-dependent form of regulated cell death, has been implicated in multiple pathological conditions, but its relevance to fibroblast-mediated fibrotic progression in endometriosis remains unclear. Single-cell RNA sequencing data from normal, eutopic, and ectopic endometrial tissues were analyzed to assess cuproptosis-related gene (CRG) activity and fibroblast heterogeneity. Pseudotime analysis, cell–cell communication analysis and high-dimensional weighted gene co-expression network analysis were performed to identify disease-associated fibroblast states and candidate fibrosis-related genes. Machine learning approaches were applied to prioritize candidate hub genes. Functional validation was conducted in endometrial stromal cells, and a mouse model of endometriosis was used to assess the effects of tetrathiomolybdate (TTM), a copper chelator. Elevated CRG activity was enriched in a distinct fibroblast subpopulation with profibrotic transcriptional features. Network and machine learning analyses consistently prioritized AEBP1 as a candidate fibroblast-associated hub gene linked to cuproptosis-related signatures. In vitro, CuCl2 plus elesclomol treatment was associated with increased AEBP1 and fibrosis-related marker expression, accompanied by changes in β-catenin pathway-related proteins, whereas FDX1 or AEBP1 knockdown attenuated these effects. In vivo, TTM treatment reduced lesion burden, fibrotic marker expression and collagen deposition in ectopic lesions. Cuproptosis-related molecular alterations are associated with fibroblast activation and fibrotic progression in endometriosis. Targeting copper metabolism may have therapeutic potential in limiting lesion fibrosis.

AIM:Endometriosis is an estrogen-dependent disease with unclear pathogenesis. Recent evidence suggests that ferroptosis plays an important role in the development of endometriosis. In this study, we aimed to explore whether membrane-bound O-acyltransferase domain-containing 1 (MBOAT1) is a key factor by which estradiol (E2) regulates ferroptosis in endometriosis. METHODS:The expression of estrogen receptors (ESR1 and ESR2) and MBOAT1 was examined by western blotting in endometrium and primary endometrial stromal cells (ESCs). We measured iron content, MDA, and GSH levels using corresponding assay kits and assessed the level of ROS by flow cytometry to evaluate ferroptosis. We treated primary ESCs and human ESCs (T HESCs) with or without RSL3, E2, and an estrogen receptor inhibitor, fulvestrant (Ful), to verify the regulatory relationship between E2 and ferroptosis. In addition, endometriosis model mice were constructed and treated with an intraperitoneal injection of 5 mg/kg Ful once a day for 2 weeks. RESULTS:Ectopic ESCs (EESCs) showed increased expression of ESR1, ESR2, and MBOAT1. Meanwhile, EESCs demonstrated resistance to ferroptosis compared with normal ESCs (NESCs). Compared with NESCs, EESCs showed significant resistance to RSL3-induced ferroptosis. E2 could up-regulate the expression of MBOAT1 and alleviate RSL3-induced ferroptosis in NESCs, while Ful could down-regulate the expression of MBOAT1 and accelerate RSL3-induced ferroptosis in EESCs. Furthermore, Ful treatment significantly decreased the number and size of ectopic lesions in endometriosis mice by promoting ferroptosis. CONCLUSION:E2 affected ferroptosis by regulating the expression of MBOAT1 and further participated in the progression of endometriosis.

To optimize ovulation induction protocols for infertile women with PCOS, ovulation effect and adverse reactions of different doses of letrozole (2.5 vs 5.0 mg) combined sequentially HMG therapy were compared in infertility PCOS patients. This open-label randomized controlled trial (RCT) included 174 infertile women aged 18–40 who met the Rotterdam criteria for PCOS at the Wuhan Union Hospital of China from May 2021 to January 2022. They were randomly assigned at a 1:1 ratio to 2.5 mg LE or 5.0 mg LE on cycle days 3–7 with sequential HMG injections (n = 87 for each). There is no difference in ovulation rate between LE (2.5 mg) + HMG group and LE (5.0 mg) + HMG group in infertile women with PCOS (85.1 vs 85.1

BACKGROUND:endometriosis as a common gynecologic finding significantly affects the quality of life of many women. An accurate understanding of the epidemiological characteristics of endometriosis is essential for disease control and prevention. We aimed to use the latest data from the Global Burden of Disease (GBD) 2021 to comprehensively analyze the various epidemiological indicators of surgically confirmed endometriosis and their changing trends to better measure the disease burden and help improve health management. METHODS:We delineated incidence, prevalence, and years lived with disability (YLDs) of surgically confirmed endometriosis at the global, regional, and national levels. The estimated annual percentage change (EAPC) was calculated to assess temporal trends in the age-standardized rate (ASR). In addition, we used joinpoint regression models to describe local trends in these indicators, assessed the correlation between disease burden and Socio-demographic index (SDI) levels, and used decomposition analysis to quantitatively analyze the driving factors leading to changes in disease burden. RESULTS:Globally, the age-standardized rate of incidence, prevalence, and YLDs of surgically confirmed endometriosis all showed a decreasing trend from 1990 to 2021. The burden of surgically confirmed endometriosis is mainly concentrated in women aged 20-30 years and declines with increasing SDI levels. The results of the decomposition analysis indicated that population growth is the main driving factor for the upward in the number of incidence, prevalence, and YLDs cases of endometriosis worldwide. CONCLUSIONS:The overall burden of endometriosis has decreased globally from 1990 to 2021, but there are regional disparities. Managing this condition remains a major challenge, and more refined policies and interventions are needed to effectively address the burden of endometriosis.

Abstract:The effectiveness of the GnRH antagonist protocol remains controversial due to inconsistent conclusions and inadequate subgroup analyses. The aim of this study was to provide some references for clinicians when choosing the GnRH antagonist protocol for patients. A retrospective cohort study analyzed 1,845 infertility patients aged 20-50 years who underwent IVF/ICSI treatment. They used the GnRH agonist or GnRH antagonist protocol at the Assisted Reproduction Center of Wuhan Union Hospital from June 2023 to June 2024. One-to-one PSM was used to match the population characteristics. The difference of cumulative live birthrates (CLBR) was analyzed by multivariate logistic regression. Endometrial tissues were obtained, and the endometrial receptivity was determined by detecting the expression of mesenchymal-epithelial transition (MET), decidualization markers, and cell implantation in vitro. There was a significantly higher CLBR in the GnRH agonist compared with the GnRH antagonist protocol (81.54 versus 73.07%, P < 0.05). The GnRH agonist also had a significantly higher clinical pregnancy rate and live birth rate (LBR) per fresh ET cycle compared to the GnRH antagonist. Multivariate logistic regression analysis showed that the ovarian stimulation protocol was an independent risk factor for CLBR. Age and endometrial thickness were significantly correlated with CLBR. Furthermore, the GnRH antagonist reduces endometrial receptivity mainly by hindering the formation of MET in stromal cells and affecting endometrial decidualization. The GnRH antagonist protocol may be associated with inferior LBR per fresh ET cycle and CLBR per cycle compared with the GnRH agonist protocol, likely due to its negative impact on endometrial receptivity. Lay summary:Doctors are not sure how well one of the methods used for IVF treatment - the GnRH antagonist method - works. It uses drugs to temporarily block brain signals to the ovaries, controlling egg maturation and preventing early egg release (critical for IVF success). It is not known how effective this method is at achieving pregnancy or live birth. We analyzed previous data and lab tests to guide doctors using this method. Results showed that another common method - the GnRH agonist method (using drugs that first boost then lower brain signals to ovaries to control eggs) - had much higher pregnancy rates and LBRs per fresh embryo transfer cycle than the GnRH antagonist one. Data showed three key factors affected the cumulative LBR: the ovarian stimulation plan used, the patient's age, and the thickness of their womb lining (where embryos attach). Overall, the GnRH antagonist method may lead to lower LBRs (per transfer and per cycle) than the agonist one - most likely because it makes the womb lining less able to support embryos.

Organochlorine pesticides (OCPs) are extensively dispersed throughout the environment, which potentially have harmful impacts on the female reproductive system. Therefore, the purpose of this study was to clarify the association between exposure to OCPs and the history of uterine fibroids in American women. The present study comprised female individuals who were over 20 years old and were selected from the National Health and Nutrition Examination Survey (NHANES). The logistic regression models were used to investigate the associations between eight primary serum OCP compounds and uterine fibroids. The collective impact of OCP compounds on the overall association with uterine fibroids was assessed using three statistical approaches: weighted quantile sum regression (WQS), quantile g-computation model (Qgcomp), and Bayesian kernel machine regression (BKMR) model. In the end, a total of 931 individuals were included in the analysis. Out of the total, 126 participants were identified as patients with uterine fibroids. Upon accounting for covariables, the logistic regression analysis revealed a positive association between the highest tertiles of OCP compounds and ln-transformed OCP compounds and the history of uterine fibroids. The analysis of WQS and Qgcomp showed that a 25

High-salt (HS) diet is an established risk factor for cognitive impairment, but the underlying mechanisms remain unclear. This study reveals that HS diet reduces SHANK1, a key postsynaptic scaffolding protein, via downregulation of the PKA/CREB pathway, leading to synaptic dysfunction and cognitive deficits in rats. RNA sequencing of HS-fed rat hippocampi showed downregulation of cAMP signaling and SHANK1 expression. Pharmacological inhibition of PKA/CREB reduced SHANK1 levels and impaired dendritic structure and synaptic function, while PKA activation restored CREB activity and SHANK1 expression, reversing HS-induced deficits. Notably, CREB activation is essential for SHANK1 regulation, as a CREB mutant (S133A) blocked the effects of PKA activation, and a constitutively active CREB (S133D) prevented SHANK1 downregulation. These findings highlight the PKA/CREB/SHANK1 pathway as a potential therapeutic target for HS-induced cognitive dysfunction.

Endometriosis-related infertility is a prevalent reproductive health concern of global significance. Functional abnormalities of the endometrium are increasingly recognized as a pivotal contributor to infertility in affected individuals. In the present study, a significant reduction in glycolytic activity was observed in secretory-phase endometrial tissues obtained from patients with endometriosis, and this metabolic defect was attributed to down-regulated expression of lactate dehydrogenase A (LDHA). This impaired glycolysis was found to induce defective endometrial decidualization and contribute to endometriosis-related infertility in a mouse model. Mechanistically, inhibition of LDHA promoted the production of reactive oxygen species and apoptosis of endometrial stromal cells, ultimately resulting in compromised stromal cell decidualization. Furthermore, reduced LDHA expression was confirmed in the eutopic endometrium of patients with endometriosis, which was associated with decreased N6-methyladenosine (m6A) demethylation activity. This attenuation of m6A demethylation was, in turn, attributed to the down-regulated expression of alkB homolog 5-a key enzyme responsible for m6A demethylation modification. Collectively, the findings demonstrate that elevated m6A methylation levels in the eutopic endometrium of patients with endometriosis impair endometrial glycolytic metabolism and decidualization of endometrial stromal cells, thereby contributing to endometriosis-related infertility. This pathologic cascade is mediated by the down-regulation of LDHA expression.

Long noncoding RNA (lncRNA) and N6-methyladenosine (m6A) methylation modification have recently been suggested as potential functional modulators in ovarian endometriosis, however, the function and mechanism of m6A-modified lncRNA in ovarian endometriosis remain poorly understood. In this study, we demonstrated that lncRNA UBOX5-AS1 expression was significantly elevated in ovarian endometriosis tissue and primary ectopic endometrial stromal cells. The expression of lncRNA UBOX5-AS1, which has m6A modifications, was highly positively correlated with demethylase Alk B homologous protein 5 (ALKBH5) expression and autophagy. Functional studies revealed that increased ALKBH5 and lncRNA UBOX5-AS1 expression promoted cell autophagy, proliferation, and invasion in endometriosis in vitro. LncRNA UBOX5-AS1 mediates ALKBH5-regulated autophagy, proliferation, and invasion. ALKBH5-mediated autophagy facilitates cell proliferation, migration, and invasion. In vivo, the knockdown of ALKBH5 inhibited endometriotic lesion growth. Mechanistically, we observed that ALKBH5 mediated the m6A demethylation of lncRNA UBOX5-AS1 and promoted its expression. Thus, our findings highlight that ALKBH5/lncRNA UBOX5-AS1 might serve as potential targets for ovarian endometriosis therapy in the future.NEW & NOTEWORTHY In the present study, we investigated the role and potential molecular mechanism of long noncoding RNA (lncRNA) UBOX5-AS1 in ovarian endometriosis progression. Combined with the aforementioned, we proposed the hypothesis that lncRNA UBOX5-AS1 regulated by Alk B homologous protein 5 (ALKBH5)-mediated N6-methyladenosine (m6A) modification contributes to the progression of ovarian endometriosis progression.

Cystathionine β-synthase (CBS) is a pivotal catalytic enzyme in the transsulfuration pathway, widely expressed in various organs of the female reproductive system. CBS expression affects the contents of sulfur-containing metabolites including cysteine (Cys), glutathione (GSH), and taurine. GSH and taurine act as antioxidants, participating in maintaining the cellular antioxidant defense system. In addition, several reactions catalyzed by CBS are accompanied by the production of hydrogen sulfide (H2S). H2S, as a gaseous transmitter, participates in various biological processes, including angiogenesis, inflammation, and oxidative stress. This review summarizes the structure, the distribution of CBS, factors affecting CBS expression, and CBS-related sulfur-containing metabolites. It also discusses the functions of CBS under normal physiological conditions and pathological circumstances in the female reproductive system and explores the possibility of the CBS/H2S axis as a direction in the treatment of female reproductive system diseases.

OBJECTIVE:To analyse global prevalence data for infertility due to endometriosis from 1990 to 2021, emphasising health inequalities. DESIGN:Population-based study. SETTING:Data from the Global Burden of Disease (GBD) database. POPULATION:Individuals diagnosed with infertility due to endometriosis. METHODS:A statistical method was employed to evaluate changes in disease prevalence over time. We also analysed how disease prevalence varies by age, time period and birth cohort. A model was used to predict future trends. Additionally, we examined the relationship between prevalence and the socio-demographic index (SDI) levels across countries. Finally, we conducted a decomposition analysis to identify key factors driving changes and assessed health inequality. MAIN OUTCOME MEASURES:The burden of infertility due to endometriosis. RESULTS:The global burden of infertility due to endometriosis in 2021 showed a downward trend, and the low SDI region had a notably higher burden. High risk was observed in the 25-29 age group in the age effects analysis. Period risks almost kept decreasing over these years, and for cohort effects, the later born individuals showed an overall lower risk than the earlier born individuals. Cross-country inequality analysis revealed significant disparities, with countries in lower SDI categories bearing a higher burden. CONCLUSIONS:The global burden of infertility due to endometriosis has become a significant public health concern over recent decades. Governments should adapt prevention strategies to fit their specific national contexts.

Sepsis-associated encephalopathy (SAE) is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis. Despite increasing data supporting the hypothesis of neuronal damage, the exact mechanism of sepsis-related cognitive disorders and therapeutic strategies remain unclear and need further investigation. In this study, a sepsis model was established in C57 mice using lipopolysaccharide (LPS). The findings demonstrated that LPS exposure induced neuronal loss, synaptic and cognitive deficits accompanied by mitochondrial damage. Bioinformatics and western blot analyses demonstrated a significant increase in Lipocalin-2 (LCN2) during sepsis as a key hub gene involved in immune and neurological inflammation. Interestingly, the recombinant LCN2 protein exhibited similar effects on synaptic dysfunction and cognitive deficits in C57 mice. Conversely, downregulating LCN2 effectively nullified the impact of LPS, leading to the amelioration of synaptic and cognitive deficits, neuronal loss, and reactive oxygen species (ROS)-associated mitochondrial damage. These findings suggest a novel etiopathogenic mechanism of SAE, which is initiated by the increased LCN2, leading to neuronal loss and cognitive deficit. Inhibition of LCN2 could be therapeutically beneficial in treating sepsis-induced synaptic and cognitive impairments.

Endometriosis is a common gynecological endocrine disease with unclear pathogenesis. Evidence suggests enhanced aerobic glycolysis in ectopic endometrium of endometriosis. The role of N6-methyladenosine (m6A) modification in female reproductive diseases has been revealed in recent years, and it is involved in the regulation of glycolysis in a variety of diseases. Here, we investigated the regulatory effect of m6A modification on glycolysis and its role in endometriosis. RNA sequencing of ectopic endometrium of endometriosis and normal endometrium revealed that hexokinase 2 (HK2) a glycolysis-related gene, was significantly up-regulated in ectopic endometrium of endometriosis. Meanwhile, this result was supported by immunohistochemistry. Subsequently, we found that AlkB homolog 5 (ALKBH5) could upregulate HK2 in human endometrial stromal cells (THESCs). Up-regulation of ALKBH5 promoted glycolysis, invasion, and migration of THESCs, which could be alleviated by 2-Deoxy-d-glucose (2-DG). Furthermore, knockdown of HK2 in THESCs overexpressing ALKBH5 significantly attenuated the promoting effects of ALKBH5 on glycolysis, migration, and invasion of THESCs. Moreover, an ALKBH5 inhibitor, 5-Carboxy-8-hydroxyquinoline (IOX1) was found to inhibit the progression of endometriosis and glycolysis in a mouse model of endometriosis. In conclusion, ALKBH5 promoted glycolysis by up-regulating HK2 and contributed to the progression of endometriosis. ALKBH5 may be a new target for the treatment of endometriosis.

Mitochondria produce adenosine triphosphate (ATP), the main source of cellular energy. To maintain normal function, cells rely on a complex mitochondrial quality control (MQC) system that regulates mitochondrial homeostasis, including mitochondrial dynamics, mitochondrial dynamic localization, mitochondrial biogenesis, clearance of damaged mitochondria, oxygen radical scavenging, and mitochondrial protein quality control. The MQC system also involves coordination of other organelles, such as the endoplasmic reticulum, lysosomes, and peroxisomes. In this review, we discuss various ways by which the MQC system maintains mitochondrial homeostasis, highlight the relationships between these pathways, and characterize the life cycle of individual mitochondria under the MQC system.

Aims: The present study aimed to examine the roles of circRNA-circSMAD2 and its regulatory mechanisms in endometriosis (EMs). Background: Evidence has confirmed that circRNAs play multiple roles in regulating the occurrence and development of EMs, but the regulatory mechanisms of circRNAs in EMs remain largely unknown. Objective: The roles and regulatory mechanisms of circSMAD2 in EMs. Method: Eutopic and ectopic endometrium of ovarian EMs as well as normal endometrial tissues, were used to extract circRNA, mRNA, and total proteins. The human endometrial stromal cell lines (ThESCs) and endometrial stromal cells (ESCs) were stimulated with different concentrations or times of 17β-estradiol (E2). The mouse model of EMs was established by implanting uterine horns onto the peritoneum wall using a suture. Result: Compared with normal tissues, the expression of circSMAD2 was significantly decreased in eutopic and ectopic endometrial tissues. Furthermore, the expression of circSMAD2 was downregulated by E2 in a dose- and time-dependent manner in ThESCs and ESCs. Overexpression of circSMAD2 inhibited the invasion and migration of ThESCs, while knockdown of circSMAD2 exerted the opposite effect. The RNA binding protein quaking (QKI), which is involved in circRNA formation, was lower in eutopic and ectopic endometrial tissues compared to normal tissues. conclusion: The E2/ERβ/QKI/circSMAD2 pathway was involved in cellular migration and invasion in EMs Conclusion: Moreover, E2 suppressed the expression of circSMAD2 by inhibiting the expression of QKI. Additionally, E2 enabled the expression of estrogen receptor beta (ERβ) to inhibit the expression of QKI and circSMAD2 in vitro and in vivo. Conclusion: The E2/ERβ/QKI/circSMAD2 pathway was involved in cellular migration and invasion in EMs.

Background:Endometrial thickness measurement (EMT) is not a reliable predictor of clinical pregnancy in Asherman syndrome (AS) patients. The aim of this study is to investigate the impact of endometrial patterns on reproductive outcomes in patients with AS for both fresh and frozen embryo transfers. Additionally, it is essential to determine the preferred endometrial preparation protocol for women in this population who are planning frozen embryo transfer (FET). Methods:Seventy-six patients diagnosed with Asherman syndrome underwent hysteroscopic adhesiolysis followed by in vitro fertilization-embryo transfer (IVF-ET) at Union Hospital of Huazhong University of Science and Technology between February 2019 and July 2021. This study reviewed the endometrial patterns of 134 embryo transfers and the endometrial preparation protocols of 127 frozen embryo transfer (FET) cycles within this cohort of patients. Results:The triple-line endometrial pattern before embryo transfer (ET) was found to be a significant predictor of a positive clinical pregnancy outcome (odds ratio 0.315, P = 0.007) and a successful live birth (odds ratio 0.306, P = 0.009). Moreover, the gonadotropin-releasing hormone agonist (GnRHa) downregulation in conjunction with hormone replacement therapy (HRT) protocol showed improvements in both the clinical pregnancy rate (odds ratio 0.218, P = 0.005) and live birth rate (odds ratio 0.362, P = 0.049) compared to the HRT protocol in FET cycles. Conclusion:A triple-line endometrial pattern before embryo transfer is associated with successful clinical pregnancy and live birth in AS patients undergoing IVF. Additionally, the GnRHa+HRT protocol may increase the clinical pregnancy and live birth rates in AS women undergoing FET cycles.