VITAL: A Five-Domain Classification of Host-Tissue Regenerative Reserve in Regenerative Gynecology

ABSTRACT Background: Regenerative gynecology has been organised around technologies (laser, radiofrequency, platelet-rich plasma, autologous fat, exosomes) and, more recently, around clinical phenotype and evidence maturity. A variable that precedes both is missing: the biological capacity of the host tissue to respond to a regenerative stimulus. Energy-based and growth-factor interventions do not regenerate tissue by themselves; they ask the tissue to perform the regeneration. When that tissue is oestrogen-deprived, poorly perfused, fibrotic or inflamed, the same stimulus may be inert or harmful. Purpose. To propose VITAL, to our knowledge the first classification designed to grade the regenerative reserve of vulvovaginal tissue and to link it to the mechanism of action of the intervention. Development. VITAL was derived by conceptual reasoning from Paget’s “seed and soil” principle, the oestrogen-dependent physiology of wound healing, the biology of radiation injury and pelvic senescence, and the inconsistencies observed in sham-controlled trials in regenerative gynecology. It was built to complement, not replace, the VAGINA-R phenotype model and the GRACE evidence classification previously proposed by the authors. The framework. Five domains form the mnemonic VITAL: Vascular perfusion, Inflammatory activity, Trophic-hormonal status, Architecture of the extracellular matrix and Lactobacillary ecology. The mnemonic is deliberate: it asks whether the tissue is still vital enough to regenerate. Each domain is scored from 0 (preserved) to 2 (exhausted), giving a total of 0–10 and four reserve grades: R0 preserved, R1 reduced, R2 compromised and R3 depleted, with a mandatory override rule for the ischaemic-fibrotic pattern. Three modifiers record iatrogenic exposure (x), senescence and duration of deprivation (s), and systemic metabolic-vascular load (m). In parallel, interventions are re-classified by their dependence on the host into four mechanistic classes: C (Condition the terrain), T (Trigger a host response), S (Signal) and R (Replenish cells and matrix). The terrain–mechanism compatibility principle predicts that the efficacy of classes T and S declines as reserve falls, and that R2–R3 terrains must be conditioned (class C) or replenished (class R) before any stimulus. Application. Re-reading published trials through VITAL shows that null results of laser in breast cancer survivors receiving aromatase inhibitors, and of platelet-rich plasma in active lichen sclerosus, are compatible with terrain–mechanism mismatch — a hypothesis that cannot be confirmed retrospectively and requires prospective testing. Conclusion. VITAL shifts the clinical question from “which technology should be used?” to “can this tissue respond to this technology now?”. Four testable hypotheses and a four-phase validation programme are proposed before any routine clinical use. Keywords: regenerative gynecology; regenerative reserve; genitourinary syndrome of menopause; vaginal laser; platelet-rich plasma; fat grafting; radiation injury; classification; precision medicine. Abbreviations: BV, bacterial vaginosis; CST, community state type; FSFI, Female Sexual Function Index; GSM, genitourinary syndrome of menopause; GVHD, graft-versus-host disease; HSCT, haematopoietic stem cell transplantation; PRP, platelet-rich plasma; SASP, senescence-associated secretory phenotype; UTI, urinary tract infection; VHI, Vaginal Health Index; VMI, vaginal maturation index.