Background/Objectives: Endometriosis (EM) is a chronic gynecological condition associated with infertility, oxidative stress, and altered metabolic regulation. Follicular fluid (FF) reflects the microenvironment of the developing oocyte, and changes in its amino acid composition may affect reproductive outcomes. This study aimed to characterize alterations in the amino acid composition of the FF in EM and to identify potential reproductive outcomes. Methods: Targeted metabolomic analysis of 20 amino acids was performed on FF samples from 56 women undergoing in vitro fertilization (17 with endometriosis, 39 controls). Amino acid concentrations were quantified and compared between groups, adjusting for age and body mass index. Pathway, biomarker, and multivariate analyses were conducted to explore metabolic alterations and potential diagnostic markers. Results: Asparagine, histidine, and glycine concentrations were significantly higher in the EM group after adjustment for age and BMI. Pathway analysis indicated perturbations in glycine/serine metabolism, glutathione metabolism, and porphyrin metabolism, consistent with oxidative stress and mitochondrial dysfunction. Multivariate modeling demonstrated partial separation between groups, while biomarker analysis identified asparagine (AUC = 0.76), along with glycine and histidine, as potential discriminators. Additional enrichment of bile acid and methylation-related pathways suggested broader systemic metabolic changes in EM. Conclusions: EM is associated with distinct amino acid alterations in the FF, particularly elevated asparagine, histidine, and glycine, reflecting oxidative and mitochondrial imbalance in the follicular environment. These metabolites emerged as candidate biomarkers requiring validation for EM-related oocyte quality changes and may help individualize in vitro fertilization approaches.

Background/Objectives: Endometriosis is a chronic gynecological condition associated with infertility, oxidative stress and altered metabolic regulation. Follicular fluid reflects the microenvironment of the developing oocyte and changes in its amino acid composition may affect reproductive outcomes. This study aimed to characterize alterations in the amino acid composition of the follicular fluid in endometriosis and to identify potential reproductive outcomes. Methods: Targeted metabolomic analysis of 20 amino acids was performed on follicular fluid samples from 56 women undergoing in vitro fertilization (17 with endometriosis, 39 controls). Amino acid concentrations were quantified and compared between groups, adjusting for age and body mass index. Pathway, biomarker and multivariate analyses were conducted to explore metabolic alterations and potential diagnostic markers. Results: Asparagine, histidine and glycine concentrations were significantly higher in the endometriosis group, independent of age and BMI. Pathway analysis indicated perturbations in glycine/serine metabolism, glutathione metabolism and porphyrin metabolism, consistent with oxidative stress and mitochondrial dysfunction. Multivariate modeling demonstrated partial separation between groups while biomarker analysis identified asparagine (AUC=0.76), along with glycine and histidine, as potential discriminators. Additional enrichment of bile acid and methylation-related pathways suggested broader systemic metabolic changes in endometriosis. Conclusions: Endometriosis is associated with distinct amino acid alterations in the follicular fluid, particularly elevated asparagine, histidine, and glycine, which may reflect oxidative stress and impaired mitochondrial function in the follicular environment. These metabolites seem to be potential biomarkers for endometriosis-related oocyte quality changes and may help individualized in vitro fertilization approaches.

Background/Objectives: Dynamic remodeling of the zona pellucida (ZP) is a fundamental biochemical and structural process during human preimplantation development; however, its quantitative characterization and clinical relevance remain incompletely defined. The objective of this study was to evaluate dynamic ZP thinning as a functional marker of embryo developmental competence and to examine its relationship with follicular fluid (FF) biomarkers and clinical pregnancy. Methods: This prospective observational study included 47 IVF cycles performed at a single center, yielding 64 transferred blastocysts with complete time-lapse data. ZP thickness was measured from fertilization to 120 h post-fertilization using time-lapse imaging. Two quantitative parameters were derived: the relative thinning ratio (Δrel) and the linear thinning rate (slope). FF concentrations of growth differentiation factor 9 (GDF-9), hyaluronic acid (HA), and syndecan-4 (Syn4) were quantified by ELISA. Embryo-level associations with spontaneous blastocyst hatching were assessed using logistic regression and multivariate analyses, while patient-level models evaluated predictors of clinical pregnancy. Results: Embryos that underwent spontaneous hatching exhibited significantly greater Δrel than non-hatching embryos (p < 0.001). Δrel remained the strongest predictor of hatching in multivariable models (AUC = 0.91). Among FF biomarkers, only GDF-9 showed a positive association with spontaneous hatching. At the patient level, higher Δrel values of transferred embryos were associated with clinical pregnancy (OR 3.65, p = 0.009), whereas FF biomarkers and assisted hatching showed no significant association. Conclusions: Dynamic ZP thinning quantified by Δrel represents a promising indicator of embryo developmental competence. The concordance between embryo-level hatching behavior and patient-level clinical pregnancy suggests potential clinical relevance of ZP dynamics as an integrative embryological marker, warranting validation in larger cohorts.

Background/Objectives: Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection, commonly accompanied by hypoalbuminemia (<30 g/L serum albumin level), associated with excessive production of reactive oxygen and nitrogen species, leading to oxidative stress, endothelial dysfunction, and organ injury. Low serum albumin reflects increased vascular permeability, reduced hepatic synthesis, and enhanced proteolysis. It also indicates the loss of albumin’s antioxidant and anti-inflammatory functions beyond oncotic regulation. Hypoalbuminemia may exacerbate this by reducing plasma antioxidant capacity and free radical scavenging, supporting interest in albumin supplementation as a potential therapeutic strategy. Methods: This prospective, randomized study investigated the effects of 3-day albumin administration in ICU patients (n = 38) with sepsis and hypoalbuminemia by assessing changes in oxidative stress and inflammatory markers. Results: Albumin supplementation increased serum albumin (p < 0.001) and was associated with higher total antioxidant capacity (Day 3 p = 0.045; Day 5 p = 0.004), glutathione levels (Day 3 p = 0.003; Day 5 p = 0.008), and protein sulfhydryl groups (Day 3–5 p = 0.004). Albumin-treated patients showed increased urinary concentration of the oxidative stress–related tyrosine isomers ortho- and meta-tyrosine (p = 0.004 and p = 0.001, respectively). Catalase activity and myeloperoxidase, procalcitonin, and IL-1β levels did not differ between groups, while IL-6 declined over time (p = 0.029). Conclusions: Based on our results, in septic patients with hypoalbuminemia, short-term albumin supplementation seems to restore serum albumin and improve systemic redox status, as evidenced by increased total antioxidant capacity, glutathione, and protein sulfhydryl levels. However, albumin supplementation did not significantly affect systemic inflammatory markers or cytokine dynamics. Albumin appears to act primarily by modulating oxidative stress, supporting its role as an adjunctive therapy to restore redox homeostasis in sepsis.