Follicular fluid (FF) constitutes the microenvironment of the developing oocyte. We recently characterized its lipid composition and found lipid signatures of positive pregnancy outcome after in vitro fertilization (IVF). In the current study, we aimed to test the hypothesis that unexplained female infertility is related to lipid metabolism, given the lipid signature of positive-outcome IVF patients we previously found. Assuming that FF samples from IVF patients with male factor infertility can represent a non-hindered metabolic microenvironment, we compared them to FF taken from women with unexplained infertility. FF from patients undergoing IVF was examined for its lipid composition. We found highly increased triacylglycerol levels, with a lower abundance of monoacylglycerols, phospholipids and sphingolipids in the FF of patients with unexplained infertility. The alterations in the lipid class accumulation were independent of the body mass index (BMI) and were altogether kept across the age groups. Potential lipid biomarkers for pregnancy outcomes showed a highly discriminative abundance in the FF of unexplained infertility patients. Lipid abundance distinguished IVF patients with unrecognized infertility and provided a potential means for the evaluation of female fertility.
Chimeric antigen receptor T (CAR-T) cell therapy has become a standard of care for many hematological malignancies, and has significantly transformed treatment outcomes. However, CAR-T therapy is associated with specific toxicities, including infections. Although the anti-CD19 CAR-T risks are well-characterized, infectious complications following B-cell maturation antigen (BCMA)-directed CAR-T in multiple myeloma (MM) remain under-researched. In this study, we evaluated the incidence and clinical impact of cytomegalovirus (CMV), Epstein–Barr virus (EBV), and adenovirus (ADV) reactivations in 75 patients receiving anti-BCMA CAR-T for MM, and compared them to 60 patients receiving commercial anti-CD19 CAR-T for B-cell lymphoma (BCL). The viral reactivation rates were 20% for CMV and 8% for EBV in the MM group, vs. 31.7% and 3%, respectively, in the BCL group. No ADV reactivations were seen in either cohort. Most of the CMV reactivations (87% in the MM cohort and 68.5% in the BCL cohort) were asymptomatic and clinically insignificant, and had no impact on progression-free survival (PFS) or overall mortality. Overall, these findings suggest that although CMV and EBV reactivations are relatively common after anti-BCMA CAR-T, they are rarely associated with meaningful disease, and the risks do not exceed those of CD19-directed therapy. Thus, routine pre-emptive screening for these viruses may be unwarranted in asymptomatic patients.