ICSI media buffers: is there room for improvement?

Maintaining physiological extracellular pH (pHe) is essential for oocyte viability and embryonic development, particularly during ICSI, when metaphase II oocytes have their intracellular pH (pHi) regulation mechanisms temporarily inactivated. HEPES- and MOPS-buffered handling media are routinely used in IVF laboratories, with decades of clinical use supporting their effectiveness and safety. Although concerns regarding their biological effects beyond pH buffering have occasionally emerged, most are derived from experimental settings and are not representative of clinical IVF procedures, more likely influenced by experimental conditions and media composition rather than by the zwitterions themselves. Nevertheless, while evidence from human oocytes remains extremely limited and preliminary, the improved embryological outcomes and transcriptomic profiles recently reported from bicarbonate-buffered handling media have renewed interest in exploring more physiological ICSI media formulations. While current evidence remains far from conclusive and insufficient to support immediate changes in clinical practice, emerging findings suggest that routine systems may not yet be fully optimized and could represent an opportunity for further improvement. Future evaluation of bicarbonate-buffered media for ICSI should include robust standardization of pH measurement methodologies together with optimization of handling conditions, including oil and dish characteristics, that influence pHe stability.