Recent evidence suggests that human chorionic gonadotropin (hCG), in addition to its well-known endocrine effects on the corpus luteum, may act as a growth and differentiation factor during pregnancy. According to experimental results, its mode of action may be divided into three sequential phases. During the first phase, which begins at the blastocyst stage and lasts until the occurrence in the serum, hCG acts preferentially in a juxtacrine manner. We have used an intrauterine microdialysis system developed in our laboratory to administer low concentrations of hCG to the endometrium of women in the luteal phase of the menstrual cycle. HCG administration provoked profound effects on paracrine parameters of differentiation (IGFBP-1, prolactin) and implantation (LIF, M-CSF). VEGF, a cytokine important for neoangiogenesis, was significantly stimulated by hCG (P < .01), suggesting a role for hCG in the control of endometrial vascularization and placentation. The investigation of endometrial parameters of tissue remodeling revealed a significant increase of MMP-9 (P