Double-Edged Phytochemicals in Endometrial Receptivity: Dietary Exposure, Context Dependence, and the Limits of Directional Claims

Dietary and supplemental phytochemicals are investigated as modulators of endometrial receptivity, yet studies of the same compounds report favorable and unfavorable effects. This critical narrative review examines five compound classes through the lens of pharmacologically relevant exposure. For compounds with paired pharmacokinetic and in vitro data, nominal experimental concentrations exceed plasma concentrations reported after dietary intake, conventional supplementation or a 12 g curcumin probe dose; the comparisons are indirect, and no ratio can be established for some classes. Neither nominal nor plasma concentration indexes the concentration reached in endometrial tissue, which has not been reported for any class; the circulating species may also differ from the molecule tested in culture. We propose five contextual dimensions: receptor context, achieved exposure, exposure window, tissue and cell state, and the measured endpoint. The literature largely evaluates recovery from induced impairment rather than enhancement of normal receptivity. Within the screened records no study directly quantified endometrial perfusion after a defined-compound exposure, and the available endpoints are surrogates of receptivity, not pregnancy outcomes. Because the evidence is heterogeneous and the search was not systematic, the framework is a set of testable propositions, not an established model. We provide an evidence map and a reporting checklist for studies measuring exposure, context and implantation-related outcomes.