BACKGROUND:Female infertility is multifactorial, with adiposity and regional fat distribution hypothesized as contributors, though evidence using detailed fat measures is limited. This study aims to examine the association between fat distribution indicators and female infertility in a nationally representative sample. METHODS:This retrospective cross-sectional study analyzed NHANES 2013-2018 data from 2,531 women aged 20-45. Infertility was defined by self-reported difficulty conceiving ≥ 12 months or seeking fertility care. Exposures included body mass index (BMI) and DXA-based measures: total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android fat/gynoid fat ratio (AGR), visceral fat/total fat (VPF), subcutaneous fat/total fat (SPF), and visceral fat/subcutaneous fat ratio (VSR). Multivariable logistic regression was used to assess associations, and sensitivity analyses were performed to evaluate robustness. RESULTS:In multivariable-adjusted models, TPF, APF, AGR, and BMI were modestly associated with higher odds of infertility (TPF: OR = 1.02, 95%CI: 1.00-1.05; APF: OR = 1.03, 95%CI: 1.01-1.04; AGR: OR = 1.02, 95%CI: 1.01-1.03; BMI: OR = 1.02, 95%CI: 1.01-1.04). Smooth curve fitting suggested a generally monotonic positive pattern for these associations. Associations were broadly similar across subgroups, although some subgroup interactions were observed. CONCLUSION:In this analysis, TPF, APF, AGR, and BMI showed modest associations with infertility, which should not be interpreted causally. Although associations were generally consistent across subgroups, subgroup-specific heterogeneity cannot be excluded.

Per- and polyfluoroalkyl substances (PFAS) are persistent pollutants with widespread human exposure and increasing concern for female reproductive health. This review synthesizes epidemiological and mechanistic evidence published between 2023 and 2026 using a lifecourse framework spanning preconception through pregnancy and early life. Biomonitoring studies indicate that PFAS can cross key physiological barriers and are repeatedly detected in reproductive-relevant matrices, including follicular fluid, placental tissue, cord blood, and breast milk. Across cohorts, PFAS exposure is associated with indicators of impaired ovarian function (including diminished ovarian reserve and altered reproductive hormones) and poorer assisted reproductive technology (ART) performance, with reports of reduced normal fertilization (2PN) and blastocyst formation. During pregnancy, exposure has been linked to hypertensive disorders of pregnancy (particularly preeclampsia), fetal growth restriction (e.g., SGA/LBW), and preterm birth. Mechanistic studies converge on placental dysfunction—characterized by impaired trophoblast differentiation/invasion, disrupted angiogenic balance, mitochondrial bioenergetic deficits, and placental senescence—together with oxidative stress, mitochondrial injury, and epigenetic alterations. Evidence on replacement PFAS (e.g., GenX, PFBS, 6:2 Cl-PFESA) does not consistently support hazard reduction relative to legacy PFAS, and co-exposure scenarios (including mixtures with microplastics) may amplify toxicity. Future work should prioritize mixture-oriented risk assessment, longitudinal evaluation of replacement PFAS, integration of paternal exposure metrics, and high-fidelity human models to support prevention and policy.

BackgroundMiscarriage affects 15%–20% of clinically recognized pregnancies, yet reliable biomarkers for risk stratification remain elusive. While systemic inflammatory markers derived from routine complete blood count have shown promise in identifying associations with adverse pregnancy outcomes, their association with miscarriage has not been systematically evaluated.MethodsIn this retrospective cohort study of 347 pregnant women with a history of at least one prior pregnancy loss, we calculated neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) from routine complete blood count tests. Associations with miscarriage were evaluated using four progressively adjusted logistic regression models accounting for demographic, reproductive, and metabolic confounders. Dose-response relationships were assessed through quartile analysis, threshold effects through piecewise linear regression, and non-linear associations through generalized additive models.ResultsAfter comprehensive adjustment, higher NLR was independently associated with reduced miscarriage risk (OR = 0.67 per doubling, 95%CI: 0.49–0.91, P = 0.012), with women in the highest quartile showing 60% lower risk than those in the lowest quartile (Q4 vs. Q1: OR = 0.398, P = 0.006). This protective effect was most pronounced at NLR values <4.16 (OR = 0.64, P = 0.001), plateauing at higher levels. Conversely, elevated LMR significantly increased miscarriage risk (OR = 1.839 per doubling, 95%CI: 1.12–3.01, P = 0.015), with risk more than doubling in the highest quartile (OR = 2.236, P = 0.017) and accelerating above LMR values of 6.46 (OR = 1.62, P = 0.049). No significant association was observed between PLR and pregnancy outcomes in our study.ConclusionsAmong women with a history of prior pregnancy loss, NLR and LMR were independently associated with miscarriage in opposing directions, consistent with a “Goldilocks” conceptual framework of immune balance in early pregnancy. No significant association was observed between PLR and pregnancy outcomes in our study. These readily available CBC-derived inflammatory indices may provide useful insight into immune-related changes associated with miscarriage risk, but require prospective validation in independent cohorts.

Background Multiple omics studies on patients with recurrent pregnancy loss (RPL) have deepened the understanding of its pathogenesis. However, few studies have combined multi-omics techniques to provide a more accurate characterization of RPL. This study aims to identify biomarkers with RPL through proteomic and transcriptomic analyses, providing new insights for its diagnosis and treatment.Methods Endometrial tissue samples were collected from RPL patients (n = 34) and normal controls (n = 22) for proteomic analysis to identify differentially expressed proteins (DEPs). Protein-protein interaction network analysis and functional enrichment analysis were performed to explore the biological functions of the DEPs. LASSO regression was used to screen for hub proteins, which were further validated using transcriptomic data from the GSE165004 dataset (24 RPL patients and 24 controls). An artificial neural network (ANN) model was constructed to assess the classification performance of the key DEPs.Results A total of 275 DEPs were identified between the RPL group and the normal groups. Function enrichment analyses revealed significant involvement of these DEPs in immune and inflammatory responses. LASSO analysis identified 23 hub proteins. By combining transcriptomic data, five proteins, FOSB, HPS4, MRPL34, LCAT, and TMSB10 were ultimately identified as key DEPs. The ANN model demonstrated high accuracy in distinguishing between RPL patients and normal controls, with an accuracy rate of 81.25%.Conclusion Our study identified five key DEPs closely associated with RPL and revealed their promising diagnostic potential. Future validation in independent cohorts and functional studies is warranted to confirm their value as diagnostic biomarkers.Clinical Trials Registry Not applicable

Elevated homocysteine (HCY) levels have been implicated in early pregnancy loss (EPL) but evidence remains inconclusive. The aim of this study was to investigate the association between preconception serum HCY levels and EPL in women who have experienced recurrent pregnancy loss (RPL). Using data from a prospective dynamic pregnancy loss cohort established by our group, we screened 812 eligible patients with RPL, collected their medical records, and followed them for subsequent pregnancy outcomes. Multivariable logistic regression was used to assess the relationship between preconception serum HCY levels and the risk of subsequent EPL. Generalized additive models were also used to examine nonlinear associations between serum HCY levels and EPL. Subgroup analyses were further performed according to age, body mass index (BMI), and the number of previous pregnancy losses. The proportion of subsequent EPL was 22.66

In this study, we aimed to explore the effect of the timing of surgical management of hydrosalpinx on in vitro fertilization/intracytoplasmic single-sperm injection (IVF/ICSI) pregnancy outcomes in patients with tubal factor infertility. This retrospective study included 377 patients who underwent laparoscopic (LAP) unilateral or bilateral salpingectomy due to hydrosalpinx, IVF/ICSI-embryo transfer (ET), or frozen ET (FET) at the Department of Reproductive Medical Center, Guangdong Women and Children Hospital, between June 2013 and April 2023. Patients were divided into two groups: those who underwent oocyte retrieval first, followed by LAP, and FET (Group A, n = 190) and those who underwent LAP first, followed by oocyte retrieval, and ET/FET (Group B, n = 187). According to age, patients were divided into groups A1 ( < 35 years, n = 136), A2 (≥35 years, n = 54), B1 ( < 35 years, n = 153), and B2 (≥35 years, n = 34). According to the different ET times after LAP, patients were further divided into two groups: those who underwent ET ≤ 3 months after LAP (n = 193), and > 3 months after LAP (n = 184). According to the different oocyte retrieval times after LAP, the patients in group B (n = 187) were further divided into two groups: those who underwent oocyte retrieval ≤ 3 months after LAP (n = 83) and > 3 months after LAP (n = 104). We compared the pregnancy outcomes, complications after oocyte retrieval, oocyte contamination, and time and economic costs between the groups. The differences in clinical pregnancy, live birth rates (57.9

This study aims to explore the potential mechanisms contributing to recurrent pregnancy loss (RPL) and identify potential biomarkers. We analyzed endometrial samples from 39 RPL and 22 healthy controls using proteomics, identifying differentially expressed proteins (DEPs) with DEqMS and quantifying immune cell infiltration with CIBERSORT. We also examined a decidual scRNA-seq dataset (CRA002181) to identify macrophage marker genes, performed WGCNA to correlate macrophage infiltration with protein expression, and conducted functional enrichment analysis. Immunofluorescence staining was conducted to quantify the proportions of CD3+, CD8a+, CD68+, and CD206+ cells, and Western blot analysis was performed to determine MMP9 expression in endometrial tissues from RPL and controls. M2 macrophages and CD8+ T cells were enriched in the endometrium of RPL. Proteomic analysis of endometrial tissues from RPL identified 310 DEPs associated with immune response, cell adhesion, and secretory granule processes. From the scRNA-seq dataset, 295 macrophage marker genes were identified. WGCNA revealed that the brown module exhibited the highest correlation with macrophage infiltration. MMP9 emerged as the sole intersecting candidate, showing marked downregulation in RPL. Mendelian randomization analysis showed that genetically predicted higher circulating MMP9 levels decrease RPL risk (OR 0.75, 95% CI 0.57-0.98; p=0.036). Additionally, RPL patients showed significantly higher proportions of CD3+CD8a+ cells (p<0.05) and CD68+CD206+ cells (p=0.265), and decreased MMP9 protein expression (p<0.05), compared with controls. In conclusion, this study indicates that an imbalance in endometrial M2 macrophage and CD8+ T cell immune infiltration is associated with RPL. MMP9 may represent a potential predictive biomarker for RPL.

Aims:This study investigated the associations of four insulin resistance (IR) indicators-the triglyceride-glucose (TyG) index, the TyG-body mass index (TyG-BMI), the metabolic score for IR (METS-IR), and the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio-with subsequent pregnancy outcomes in women with recurrent pregnancy loss (RPL) and assessed their predictive value. Methods:This cohort study recruited RPL participants from the Chinese Pregnancy Loss Cohort. Enrollment occurred between September 2019 and December 2022. All participants were followed up every 6 months, with a minimum follow-up duration of 18 months, to document pregnancy outcomes (live birth or subsequent pregnancy loss). Univariate and multivariate logistic regression analyses were performed to assess the associations between four IR indicators (TG/HDL-C, TyG, TyG-BMI, METS-IR) and pregnancy outcomes. Receiver operating characteristic (ROC) analysis was conducted to determine the predictive efficacy of each indicator. Results:Among 2,454 screened participants, 897 RPL women were analyzed (638 live births, 71.1%; 259 pregnancy losses, 28.9%). In the fully adjusted model, the highest tertiles of TyG-BMI and METS-IR were associated with significantly elevated odds of pregnancy loss (OR = 1.52, 95% CI: 1.01-2.27, P = 0.044; OR = 1.49, 95% CI: 1.05-2.29, P = 0.045, respectively). METS-IR demonstrated the highest predictive efficacy for pregnancy outcomes (AUC = 0.710), followed by TyG-BMI, TG/HDL-C, and the TyG index. Conclusions:Among women with RPL, TyG-BMI and METS-IR are independently associated with increased pregnancy loss risk, with METS-IR demonstrating superior predictive performance.

Recurrent pregnancy loss (RPL) is a common reproductive disorder with unclear etiology in a substantial proportion of patients. Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental pollutants with potential reproductive toxicity, but their association with RPL and underlying mechanisms remain elusive. This study aimed to explore whether PFAS exposure is an independent risk factor for RPL, and to clarify the role of oxidative stress and the HIF1α‑GLUT1/VEGFA signaling axis in PFAS-induced reproductive injury. We conducted a case-control study including 50 RPL patients and 100 healthy controls, combined with mouse experiments and in vitro cell assays. Serum PFAS levels were measured by LC-MS/MS, and multi-omics analyses were performed to screen key pathways. Pregnant mice were exposed to PFOA or PFPeA, and reproductive function, histology, and pathway expression were evaluated. Human reproductive cell lines were treated with PFAS, and N-acetylcysteine (NAC) rescue experiments were conducted to verify the mechanism. Clinical results showed that serum PFOA and PFPeA concentrations were significantly higher in RPL patients, and PFAS exposure was independently associated with increased RPL risk. Multi-omics identified the HIF1α‑GLUT1/VEGFA axis as a core pathological pathway. Animal experiments demonstrated that PFAS disrupted estrous cycles, reduced pregnancy rates, increased embryo resorption, and downregulated GLUT1 and VEGFA while upregulating HIF1α in reproductive tissues. In vitro assays showed PFAS inhibited cell viability, induced ROS overproduction, impaired trophoblast migration and endothelial angiogenesis, and dysregulated the HIF1α‑GLUT1/VEGFA axis. NAC pretreatment reversed oxidative stress, pathway disorder, and functional damage. In conclusion, PFAS exposure is an independent risk factor for RPL. Oxidative stress-mediated HIF1α‑GLUT1/VEGFA axis disorder serves as a key mechanism underlying PFAS-induced reproductive toxicity and adverse pregnancy outcomes. Our findings highlight the potential reproductive health risks of ubiquitous PFAS exposure and provide mechanistic insights for environmental health governance.

Objective:This study aimed to evaluate the association between intravenous immunoglobulin (IVIG) treatment and pregnancy outcomes among women with recurrent pregnancy loss (RPL) in China. Methods:We conducted a retrospective cohort study involving RPL pregnant women who delivered at the Lanzhou University Second Hospital between April 2023 and August 2024. Participants were categorized into a treatment group (received IVIG during pregnancy) and a control group (not received). The pregnancy outcomes were live birth rate (LBR), preterm birth, birth weight, and neonatal unit admission. RPL pregnant women exposed to IVIG were matched to unexposed in a 1:1 ratio with propensity score matching (PSM), using the nearest neighbor matching. Multivariable logistics regression was used to assess the association between IVIG use during pregnancy and pregnancy outcomes. We further conducted a stratified analysis based on the mean daily dose and the gestational age at the initiation of IVIG administration. Results:A total of 504 RPL pregnant women were included, of whom 173 received IVIG during pregnancy and 331 did not. After PSM, 276 patients were analyzed with balanced baseline characteristics. The primary analysis showed that IVIG treatment during pregnancy was associated with a significantly higher LBR compared to controls (60.1% vs. 44.9%; adjusted OR [aOR]=1.960). This association remained significant after excluding cases with embryonic abnormal karyotypes (64.3% vs. 46.3%; aOR=2.187). Stratified analyses indicated that a mean daily IVIG dose <20 g was associated with improved LBR (aOR=2.484), and the benefit persisted after excluding abnormal karyotypes (aOR=3.000). Additionally, initiation of IVIG between 6-12 weeks' gestation yielded higher LBR (72.8% vs. 44.9%; aOR=3.253), especially among participants without abnormal karyotypes (76.6% vs. 46.3%; aOR=3.757). No significant associations were observed between IVIG use and preterm birth rate, birth weight, or neonatal unit admission rate. Conclusions:IVIG use during pregnancy was associated with a significantly higher LBR among RPL women, particularly when initiated between 6-12 weeks of gestation and administered at a dose <20 g/d; these associations remained robust after excluding cases with abnormal karyotypes. These findings suggest that IVIG may be an effective immunological intervention for improving pregnancy outcomes in selected RPL patients.

OBJECTIVE:This study aims to explore how recombinant human granulocyte colony-stimulating factor (rhG-CSF) impacts pregnancy outcomes among patients with recurrent pregnancy loss (RPL), especially the effects of different rhG-CSF administration types on these outcomes. METHODS:This retrospective cohort study analyzed 504 RPL patients treated at the Lanzhou University Second Hospital, including 291 in the treatment group (receiving rhG-CSF) and 213 in the control group. Potential confounding factors were adjusted by Propensity Score Matching (PSM) and Inverse Probability of Treatment Weighting (IPTW). Logistic regression was employed to assess the association between rhG-CSF and pregnancy outcomes. Additionally, exploratory subgroup analysis was performed based on different rhG-CSF administration types (short-acting, long-acting, and sequential therapy). RESULTS:Overall, rhG-CSF treatment did not significantly improve the rates of live births (OR = 1.259, 95% CI: 0.771-2.062, p = 0.357), preterm births (OR = 1.095, 95% CI: 0.304-6.143, p = 0.917), or neonatal unit admissions (OR = 1.123, 95% CI: 0.205-7.511, p = 0.898). However, exploratory subgroup analysis revealed that short-acting rhG-CSF was linked to a lower live birth rate (LBR) (aOR = 0.476, 95% CI: 0.224-0.971), while sequential therapy significantly increased LBRs (aOR = 2.417, 95% CI: 1.384-4.268). Further analysis showed that there were no significant differences in the rates of preterm birth and neonatal unit admissions among different groups. CONCLUSION:Although rhG-CSF showed no significant overall benefit for pregnancy outcomes in RPL patients, exploratory subgroup analyses revealed divergent effects based on administration types. While a potential negative association was observed with short-acting rhG-CSF and a positive impact with sequential therapy, these subgroup-specific findings should be interpreted with caution and require validation in larger, dedicated prospective cohorts.

ObjectiveThis study aims to develop a machine learning model for predicting early pregnancy outcomes by combining baseline levels and dynamic changes of β-human chorionic gonadotropin (β-hCG), progesterone (P), and estradiol (E2).MethodsThis retrospective study screened out 421 patients treated at the Lanzhou University Second Hospital between March 2023 and August 2024. Feature selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest Recursive Feature Elimination (RF-RFE). Subsequently, we constructed a traditional logistic regression model and five machine learning models: Random Forest (RF), eXtreme Gradient Boosting (XGBoost), k-Nearest Neighbors (KNN), Multilayer Perceptron (MLP) neural network, and Support Vector Machine (SVM). Internal validity was assessed through 5-fold cross-validation. Model performance was measured by the area under the Receiver Operating Characteristic curve (AUC), accuracy, precision, sensitivity, and specificity.ResultsAmong the 421 enrolled patients, 263 had ongoing pregnancies while 158 experienced early pregnancy loss (EPL). LR, RF, XGBoost, KNN, MLP, and SVM achieved AUCs of 0.750, 0.784, 0.750, 0.706, 0.755, and 0.749, respectively, with all accuracy and precision metrics exceeding 0.60. Notably, the RF model yielded optimal performance for EPL prediction, attaining the highest AUC (0.784), accuracy (0.729), and precision (0.724).ConclusionIntegrating dynamic changes in β-hCG, P, and E2 enables effective prediction of early pregnancy outcomes. The RF model exhibited optimal performance, highlighting its potential for clinical implementation as a risk stratification tool based on serial hormone monitoring.

Polycystic ovary syndrome (PCOS) is characterized by metabolic and inflammatory heterogeneity, but the relative associations of vitamin D status and insulin resistance with inflammatory activation, uterine perfusion, and reproductive outcomes remain unclear. We analyzed a prospective discovery cohort of 580 affected women and 332 controls, followed by multicenter retrospective external validation in 750 additional affected women. Multivariable linear and logistic regression analyses showed that lower serum 25-hydroxyvitamin D was more broadly and consistently associated than the homeostasis model assessment of insulin resistance (HOMA-IR) with inflammatory markers, uterine artery perfusion indices, recurrent pregnancy loss, and live birth. In contrast, associations of HOMA-IR were narrower, mainly involving C-reactive protein and uterine perfusion, and were less stable after mutual adjustment and external validation. These findings suggest that vitamin D status may be a more informative marker than insulin resistance for inflammatory-vascular and reproductive risk stratification in women with PCOS.

Background Early Pregnancy Loss (EPL) refers to embryonic loss occurring before 10 weeks of gestation, including biochemical pregnancy. Chronic Endometritis is a chronic inflammation of the endometrial lining. The association between chronic endometritis and early pregnancy loss remains controversial, with inconsistent findings and insufficient evidence from existing studies. Therefore, this study was conducted to address this research gap. Methods This prospective cohort study enrolled 1,059 patients with definitive pregnancy outcomes completed the study from December 2020 to December 2024. Using independent samples t-test, analysis of variance (ANOVA), and chi-square test were used to compare differences between groups, while logistic regression analysis was applied to explore the association between CE and EPL. Results The prevalence of CE among patients with pregnancy loss was 39.8% (431/1,059). The incidence of early pregnancy loss was 10.05% in the non-CE group and 28.07% in the CE group. With the increase in CE severity, the incidence of EPL gradually increased: 15.82% in the mild CE group, 22.58% in the moderate CE group, and 33.94% in the severe CE group, with a statistically significant difference between groups (P < 0.001). Multivariate logistic regression analysis showed that CE was an independent risk factor for EPL. After adjustment, patients with CE had a 37% increased risk of EPL (odds ratio OR = 1.37, 95% CI: 1.14–1.67, P = 0.003). Subgroup analysis revealed that the association between CE and EPL was more pronounced in patients aged ≥ 30 years and those with ≥ 3 previous pregnancy losses. Conclusion Chronic endometritis has a high prevalence among patients with pregnancy loss, and its severity is an independent risk factor for subsequent early pregnancy loss. The impact of CE on EPL is more significant in subgroups of older patients and those with multiple previous pregnancy losses. Clinically, screening for CE and assessment of its severity should be performed in patients with pregnancy loss, especially in high-risk subgroups, to optimize pregnancy outcomes. Trial registration This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020)

Recurrent pregnancy loss (RPL), defined as two or more pregnancy failures, affects approximately 1-3% of reproductive-age couples worldwide. Despite advances in clinical evaluation, 50-60% of RPL cases remain unexplained, referred to as unexplained recurrent pregnancy loss (URPL), leaving a substantial proportion of patients without an identifiable etiology or evidence-based preventive strategies. Emerging evidence suggests that environmental exposures may represent an underrecognized yet modifiable contributor to URPL; however, the existing literature remains fragmented and methodologically flawed by the homogenization of pregnancy loss. This narrative review and critical gap analysis evaluates the epidemiological and mechanistic evidence linking a broad spectrum of environmental exposures to pregnancy loss. We systematically map the evidence base across ambient air pollutants, heavy metals, endocrine-disrupting chemicals, pesticides, and lifestyle/occupational hazards, with a strict focus on isolating URPL-specific data from general miscarriage cohorts. We further examine the principal biological mechanisms through which these exposures precipitate pregnancy loss, including oxidative stress, maternal immune dysregulation, epigenetic reprogramming, endocrine disruption, and placental vascular impairment. This critical gap analysis reveals that while environmental pollutants consistently increase the risk of sporadic pregnancy loss, URPL-specific evidence remains profoundly scarce. We highlight the urgent need to address the pervasive conflation of sporadic and recurrent loss in existing cohorts, call for future prospective studies prioritizing mixture-based exposures, and propose a forward-looking, non-judgmental framework for preconception wellness that mitigates the psychological burden on URPL patients.

OBJECTIVE:This study aimed to explore psychological distress (PD) patterns in pregnant women with recurrent pregnancy loss (RPL) during early pregnancy and to examine the association between sleep characteristics and these patterns. METHODS:A total of 203 pregnant women with RPL were recruited between October 2022 and April 2023 at the study hospital. The patients' PD was assessed using the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder 7-Item Questionnaire. The Pittsburgh Sleep Quality Index (PSQI) was employed to measure the sleep conditions. Latent profile analysis and multivariable logistic regression were used to identify the patterns of PD in RPL women and connections between their sleep characteristics and these identified patterns. RESULTS:Three PD patterns were identified in participants, including "mild PD" (57.15%), "moderate PD" (36.45%), and "severe PD" (6.40%). Subjective sleep quality, sleep disturbance, sleep efficiency, diurnal dysfunction, and PSQI score in patients varied significantly among the different PD patterns (p < 0.05). Compared with "mild PD," poor subjective sleep quality (Moderate: aOR= 2.76, 95%CI 1.37-5.56; Severe: aOR= 7.19, 95%CI 1.99-25.98) and diurnal dysfunction (Moderate: aOR= 3.1, 95%CI 1.62-5.97; Severe: aOR= 25.16, 95%CI 5.57-113.61) were significantly associated with "moderate" or "severe" PD. Addtionally, low sleep efficiency markedly increased the risk of "severe PD" (aOR= 28.76, 95%CI 1.09-759.02). CONCLUSIONS:This study identified three distinct patterns of PD (mild, moderate, and severe) among women with RPL during early pregnancy. Specific sleep characteristics, including poor subjective sleep quality, diurnal dysfunction, and low sleep efficiency, were significantly associated with moderate/severe PD.

BackgroundThe association between recurrent pregnancy loss (RPL) and environmental exposure has attracted increasing attention. However, associations between RPL and metal exposure in northwestern China remained unclear.MethodsThis case-control study (318 RPL women, 326 controls) investigated associations between serum metal concentrations and RPL. Five machine learning algorithms identified significant variables. Bayesian kernel machine regression (BKMR) and quartile g-computation (Qgcomp) models assessed the combined effects of metal mixtures on RPL risk. Untargeted metabolomics integrated with metal exposure data explored potential mechanisms underlying metal-induced disruption.ResultsCompared to controls, RPL women exhibited higher BMI (P<0.001) and elevated serum Ti, Cu, and Se levels (P<0.05), while controls had higher Li, V, Cr, Sr, Pb, Ni, Zn, and Fe (P<0.05). Machine learning algorithms (AUC = 0.99-1.0) identified V, Li, Cr, Ti, and Ni as top five discriminative metals. Mixture analyses (BKMR/Qgcomp) revealed a significantly increased RPL risk with mixed metals (β=0.37, 95% CI: 0.31–0.42). Ti contributed positively to this risk, whereas V contributed negatively after adjusted for con-founders. Metabolomic analysis in a subset (n=100) linked these metals primarily to perturbations in purine metabolism, pantothenate and CoA biosynthesis, retinol metabolism, and ubiquinone/terpenoid-quinone biosynthesis.ConclusionOur study provides valuable insights into the metabolic and environmental factors associated with RPL.

CONTEXT:There are various therapeutic approaches available to reduce homocysteine (Hcy) levels. However, it remains unclear which intervention is more effective for healthy adults. OBJECTIVES:A systematic review and network meta-analysis (NMA) were conducted to comprehensively investigate the efficacy of different nutritional supplements in reducing Hcy levels in healthy adults. DATA SOURCES:The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to July 2023. DATA EXTRACTION:The lead author, year of publication, sample size, population characteristics, intervention measures, duration, and mean difference of Hcy levels from baseline to endline were extracted. DATA ANALYSIS:Data were pooled using a random-effects model. Network meta-analysis was conducted by integrating direct and indirect evidence. A total of 16 studies were included in this analysis. The nutritional supplement combination that achieved the highest ranking (surface under the cumulative ranking curve [SUCRA] = 75.8) was superior compared with a single supplement. Among similar or closely dosed folic acid (FA) supplements, 800 μg FA (SUCRA = 93.7) was the most effective option. When comparing various doses of different supplements, 1 mg of FA plus 7.2 mg of vitamin B6 (B6) plus 20 μg of vitamin B12 (B12; SUCRA = 83.9) ranked first and 800 μg of FA (SUCRA = 78.3) ranked second. In comparison with placebo or no-treatment control groups, interventions such as 1 mg of FA plus 7.2 mg of B6 plus 20 μg of B12 (mean difference [MD] = -1.03; 95% CI -1.71 to -0.36), 400 μg of FA plus 400 μg of B12 (MD = -0.87; 95% CI -1.46 to -0.27), and 800 μg of FA (MD =  -0.84; 95% CI -1.12 to -0.56) were more effective in reducing Hcy levels. The random-effects summary MD for all interventions compared with placebo was -0.59 (95% CI -0.71 to -0.48; P < .0001). CONCLUSIONS:The NMA demonstrated that the combination of FA with other vitamins is more effective in reducing Hcy levels, particularly when the dose of FA is close to 800 μg. The combination of 1 mg of FA, 7.2 mg of B6, and 20 μg of B12 is considered the most favorable option. SYSTEMATIC REVIEW REGISTRATION:PROSPERO registration no. CRD42023453123.

BackgroundPolycystic Ovary Syndrome (PCOS) is a common endocrine and metabolic disorder affecting women of reproductive age. Over the past 30 years, significant efforts have been devoted to exploring its various pathogenic mechanisms, physiological and pathological characteristics, and biomarkers. Among these, Anti-Müllerian Hormone (AMH), as a biomarker for PCOS, is a significant biomarker for diagnosing, treating, and monitoring. However, the individual key information extracted from numerous studies is difficult to apply in clinical practice. Therefore, this article employs bibliometric analysis to summarize the current state of knowledge and offer future perspectives.MethodsThe Science Citation Index Expanded (SCI-E) within the Web of Science Core Collection database has been identified as the material source for obtaining articles related to AMH and PCOS. Software such as Origin, Microsoft Excel, Pajek, VOSviewer, and CiteSpace were used for bibliometric analysis and statistical assessment, evaluating countries, institutions, journals, references, and authors, as well as for constructing visual knowledge network maps.ResultsFrom 1994 to 2024, a total of 1,082 articles were included in the bibliometric analysis of research on AMH and PCOS. The number of publications in this field has consistently increased, with contributions from 70 countries, 1,363 institutions, and 5,144 researchers worldwide. Among them, the United States and China are the two countries with the highest number of publications. Zhejiang University, Monash University, and Peking University rank among the top three institutions exhibiting explosive citation bursts. The author with the highest publication volume is Didier Dewailly. The predictive keywords associated with these articles include “consensus,” “morphology,” “criteria,” “prevalence,” and “Müllerian hormone.”ConclusionsThrough bibliometric analysis, this study has identified the primary research hotspots in the field of AMH and PCOS as follows: (1) Refining the diagnostic criteria for PCOS by using AMH as a biomarker; (2) Exploring the molecular role of AMH in the pathophysiological processes of various PCOS phenotypes and its potential as a therapeutic target; (3) Analyzing the impact of baseline AMH levels on female reproductive health and other biomarkers; (4) Investigating the signalling mechanisms of AMH in PCOS and its role in disease progression.