The Immunological Purity Theory: a testable framework linking peri-menstrual endometrial immune transition to...

The transition from menstruation to endometrial regeneration is a dynamic biological interval involving inflammatory resolution, immune-cell regulation, epithelial repair, vascular remodeling, and endocrine-dependent tissue renewal. Although these processes are individually well established, it remains unclear whether measurable variation in the peri-menstrual endometrial immune transition predicts subsequent endometrial differentiation, receptivity, or implantation within the same cycle. This unresolved question defines the primary focus of the present framework. This article proposes the Immunological Purity Theory, a testable conceptual framework in which immunological purity refers to the transition from menstrual-associated inflammatory and reparative activity toward a regulated endometrial state compatible with subsequent receptivity. The term does not denote sterility, absence of immune activity, complete absence of inflammation, or an established clinical condition. The core hypothesis proposes that interindividual and intraindividual variation in the timing, coordination, or characteristics of this immune-repair transition may prospectively relate to the subsequent trajectory of endometrial regeneration, hormone-dependent differentiation, receptivity, and implantation. The framework does not assume that menstrual inflammation persists until implantation. Rather, it proposes a testable within-cycle relationship between an early endometrial immune-repair phenotype and the later receptive state of the same tissue. This distinction is important because menstruation occurs during the early follicular phase, whereas implantation occurs during the mid-secretory phase. Accordingly, prospective studies are required to determine whether early-cycle immune-repair characteristics provide reproducible information about later endometrial function beyond normal cycle-dependent variation. Placental adaptation, epigenetic programming, and neurodevelopment are presented as sequential downstream extensions of the core reproductive hypothesis rather than established consequences of peri-menstrual immune variation. Current evidence provides biological plausibility for individual components of these pathways but does not validate the complete proposed sequence, and no direct evidence currently links peri-menstrual endometrial immune variation to autism spectrum disorder. The framework therefore prioritizes characterization of reproducible peri-menstrual immune-repair phenotypes and their prospective relationships with receptivity and implantation before investigation of more distal developmental outcomes. The Immunological Purity Theory is presented as a falsifiable research framework requiring direct empirical validation and should not be interpreted as clinical guidance regarding conception timing or neurodevelopmental risk.