Long-term pituitary down-regulation pretreatment for endometriosis - chronicles of guidelines and recommendations

It was suggested in the 1980s that long-term pituitary down-regulation by a gonadotrophin-releasing hormone agonist, termed the ultra-long protocol, inducing a hypo-oestrogenic state, might improve reproductive outcomes in women with endometriosis. Subsequently, international guidelines strongly supported the long-term pituitary down-regulation protocol in women with endometriosis based on a Cochrane review from 2006. The recently published European Society for Human Reproduction and Embryology guideline, based on the updated Cochrane review from 2019 and newer evidence, has reversed this recommendation. This paper explores the past and current evidence that led to these recommendations and calls for a consideration of refinement of the international guidelines to include additional factors and evaluate whether a paradigm shift is needed in the approach to endometriosis-related infertility. We believe that this can optimize evidence-based patient-centred care and benefit women worldwide and improve the design of future studies.