Paracrine support of ovarian stimulation

Assisted reproductive technology has evolved on the back of blunderbuss ovarian stimulation regimes designed to maximize the number of oocytes recoverable for treatment purposes. However, oocyte 'quality' is finely programmed by local paracrine and autocrine signalling events during folliculogenesis and can be adversely affected by inappropriate gonadotrophic stimulation. This brief review traces the full follicular lifespan-from initiation to ovulation-to identify gonadotrophin-responsive checkpoints likely to impact oocyte quality. It is argued that these might be targeted during controlled ovarian stimulation therapy to (i) increase responsiveness to FSH through follicular priming with LH or hCG, (ii) improve follicular synchrony and oocyte quality through conditioning with FSH and (iii) promote 'gold standard' pre-ovulatory maturation through follicular coasting with LH or hCG. It is concluded that whereas there can be no one-size-fits-all approach to ovarian stimulation, treatment regimes based on paracrine principles and tailored to personal needs will always be more likely to achieve the desired outcome.