Clinical use of cytokines in ovulation induction

Ovarian dysfunction, which is resistant to normal ovulation induction therapies and known to the clinician as "poor response", is a heterogenic syndrome. Although most causes of ovarian dysfunction are unclear, recent molecular techniques have clarified the subtle defects in function of the cells surrounding the oocyte. Macrophages have been identified in growing follicles of humans and rats and they promote the proliferation of granulosa cells as local mediators. A hematopoietic growth factor, colony-stimulating factor-1 (CSF-1), is produced by granulosa cells and stimulates the follicular macrophages to enhance cytokine production. In CSF-1 null mice, characterized by severely depleted macrophage populations in many tissues, the numbers of both antral and mature follicles are significantly lower, but are recovered by administration of CSF-1. We have reported that gonadotropins lead to increased human ovarian CSF-1 production and that this augmentation of CSF-1 in response to human menopausal gonadotropins (hMG) administration is lost in poor responders. By concomitant administration of CSF-1 with hMG, follicle development is improved in poor responders who show low serum CSF-1 levels in the follicular phase. These women show normal responses to the examination of the growth hormone (GH) reserve. Thus, CSF-1 may be a useful therapeutic tool for selected poor responders. (C) 2004 Published by Elsevier B.V.