Žilvinas Survila

Unexplained infertility (UI) continues to pose a diagnostic challenge, affecting a considerable proportion of reproductive-aged women. Increasing evidence suggests that oxidative stress (OS) may contribute to impaired female reproductive function. Malondialdehyde (MDA) is a lipid peroxidation marker, while total antioxidant capacity (T-AOC) reflects overall antioxidant defense. Evaluating these biomarkers may help to better understand the role of OS in UI and the potential benefit of antioxidant therapy. A prospective observational study included 30 women diagnosed with primary unexplained infertility. Serum levels of MDA and T-AOC were measured at baseline and after a period of antioxidant supplementation lasting 1–7 months (duration mode: 3 months). All participants received standardized antioxidant therapy consisting of vitamin E (50 mg/day), zinc (15 mg/day), coenzyme Q10 (15 mg/day), and selenium (70 µg/day). Participants with known causes of infertility were excluded. Nonparametric statistical tests were used to evaluate changes in oxidative stress markers before and after supplementation and to compare subgroups with and without comorbidities. Median baseline MDA concentration was 228.2 ng/mL and decreased significantly after antioxidant supplementation to 173.9 ng/mL (p < 0.001), with a reduction observed in 90% of participants. Median T-AOC increased slightly from 23.9 U/mL to 26.2 U/mL, but the change was not statistically significant (p = 0.735). No significant differences in oxidative stress markers were found between women with and without comorbidities, although higher baseline MDA levels were observed in participants with endometriosis (stage I–II). A significant decrease in MDA after supplementation was seen both in women with endometriosis (p = 0.005) and without it (p < 0.001). Women with unexplained infertility demonstrate biochemical evidence of oxidative stress, reflected by elevated MDA levels. Antioxidant supplementation was associated with a significant reduction in lipid peroxidation, suggesting a potential therapeutic role of antioxidants in UI. Combined assessment of MDA and T-AOC may provide useful insight into oxidative imbalance in infertility, although larger controlled studies are needed.

Unexplained infertility (UI) remains a diagnostic challenge affecting a significant proportion of women of reproductive age. Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis and inflammation, has been implicated in reproductive and immune processes. This prospective observational study evaluated serum VEGF levels and allergen sensitization (via ALEX² macroarray) in 70 women—51 with UI and 19 fertile controls—to assess VEGF’s potential as a biomarker in UI. Median VEGF concentrations were higher in women with UI compared to fertile controls (128.6 pg/mL vs. 82.5 pg/mL), though not statistically significantly. However, sensitized women showed significantly elevated VEGF levels compared to non-sensitized peers (115.9 pg/mL vs. 85.7 pg/mL, p = 0.028), and a stepwise increase in VEGF was observed with rising allergy severity (p = 0.045). Sensitization to pet allergens, particularly cat allergen Fel d 1, was associated with the highest VEGF levels. A literature review confirmed wide variability in VEGF concentrations and the lack of standardized norms. While VEGF alone may not serve as a definitive biomarker for infertility, elevated levels may reflect an underlying inflammatory state. Our findings suggest VEGF testing could support broader clinical evaluation in women with UI, especially in the presence of allergic sensitization.

Unexplained infertility (UI) remains a diagnostic challenge affecting a significant proportion of women of reproductive age. Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis and inflammation, has been implicated in reproductive and immune processes. This prospective observational study evaluated serum VEGF levels and allergen sensitization (via ALEX² macroarray) in 70 women—51 with UI and 19 fertile controls—to assess VEGF’s potential as a biomarker in UI. Median VEGF concentrations were higher in women with UI compared to fertile controls (128.6 pg/mL vs 82.5 pg/mL), though not statistically significant. However, sensitized women showed significantly elevated VEGF levels compared to non-sensitized peers (115.9 pg/mL vs 85.7 pg/mL, p = 0.028), and a stepwise increase in VEGF was observed with rising allergy severity (p = 0.045). Sensitization to pet allergens, particularly cat allergen Fel d 1, was associated with the highest VEGF levels. Literature review confirmed wide variability in VEGF concentrations and the lack of standardized norms. While VEGF alone may not serve as a definitive biomarker for infertility, elevated levels may reflect an underlying inflammatory state. Our findings suggest VEGF testing could support broader clinical evaluation in women with UI, especially in the presence of allergic sensitization.

This study aimed to evaluate the diagnostic potential of soluble Programmed Death Ligand 1 (sPD-L1) and Programmed Death 1 (sPD-1) molecules in plasma, along with urinary mRNA biomarkers—Prostate-Specific Membrane Antigen (PSMA), Prostate Cancer Antigen 3 (PCA3), and androgen receptor (AR) genes—for identifying clinically significant prostate cancer (PCa), defined as pathological stage 3. In a cohort of 68 PCa patients, sPD-L1 and sPD-1 levels were quantified using ELISA, while mRNA transcripts were measured by RT-qPCR. Results highlight the potential of integrating these liquid-based biomarkers. In particular, the combination of sPD-L1, sPD-1, and AR demonstrated the most significant improvement in diagnostic performance, increasing the area under the curve (AUC) from 0.65 to 0.81 and sensitivity from 60% to 88%, compared to AR alone. PSMA demonstrated an AUC of 0.82 and a specificity of 52.8%, which improved to an AUC of 0.85 and a specificity of 94.4% with the inclusion of sPD-L1 and sPD-1. Similarly, PCA3 achieved an AUC of 0.75 and a specificity of 53.8%, increasing to an AUC of 0.78 and a specificity of 76.9% when combined with these biomarkers. Incorporating sPD-L1 into a three-gene panel further elevated the AUC from 0.74 to 0.94. These findings underscore the value of multimodal liquid-based diagnostic panels in improving the management of clinically significant PCa.

Objectives: To assess the role of soluble PD-L1 and PD-1 in combination with mRNA transcripts of PCA3, PSMA, AR genes in diagnostics of clinically significant prostate cancer (PCa). Methods: For 68 PCa patients, plasma sPD-L1 and sPD-1 were measured by ELISA method and the urinary PSMA, PCA3 and AR were tested using RT-qPCR. Results: PSMA and AR were iden-tified as the most reliable biomarkers for predicting clinically significant prostate cancer, with AUCs of 0.81 and 0.78, respectively. Additionally, the expression levels of PSMA and PCA3 were associated with the pT3 stage. Despite the diagnostic potential of mRNA transcripts alone, the ad-dition of sPD-L1 and sPD-1 significantly enhanced diagnostic accuracy. Combination doubled the specificity of PCA3 from 44.1% to 88.0%, compared to PCA3 alone. sPD-L1, sPD-1 and AR resulted in the best distinction between clinically significant and insignificant prostate cancer, achieving an AUC of 0.97, an accuracy of 0.95, a sensitivity of 100%, a specificity of 95%, revealing the potential of AR in distinguishing clinically significant PCa, more effectively than PSMA and PCA3. Our find-ings highlight the significant potential of sPD-1 in enhancing diagnostic accuracy when added to a triple gene panel, achieving an AUC of 0.90 compared to an AUC of 0.78 without sPD-1. This un-derscores the value of sPD-1, which has been less explored than sPD-L1 in cancer diagnostics. Con-clusions: sPD-L1 and sPD-1 has a potential to significantly enhance the accuracy of PCa diagnostics when added to the diagnostic panel, alongside PSMA, PCA3, and AR mRNA transcripts.