N. Macklon Erasmus MC, Centre for Reproduction, Department of Ob/Gyn, 3015 GD Rotterdam, The Netherlands
Since the pioneering days of IVF, it has been evident that ovarian hyperstimulation disrupts the luteal phase, and therefore the process of implantation and establishment of pregnancy. Recently it has been shown that to be high sex-steroid levels at the end of the follicular phase may be the principal cause of the abnormal luteal phase following IVF. Administering luteal phase hormonal support to maintain adequate progesterone levels during the period of implantation following ovarian hyperstimulation and IVF has been shown to improve outcomes. A more contentious issue is the potential value of progesterone supplementation to improve outcomes of early pregnancy in IVF. Classic studies showing removal of the corpus luteum to result in miscarriage highlighted the importance of progesterone in maintaining early pregnancy. More recently, administration of progesterone antagonists has been shown to disrupt implantation and early gestation. Since the 1970s, a therapeutic role for exogenous progesterone supp]ements to prevent miscarriage has been proposed. Despite initial enthusiasm, subsequent studies failed to demonstrate the efficacy and safety of progesterone supplementation in this context. In recent years, increased understanding of the role of the corpus luteum and the importance of progesterone in modulating the immune response to early pregnancy have served to re-ignite discussion over the potential of progesterone supplementation to improve outcomes. When considering the possible value of progesterone intervention in early IVF pregnancy, caution is required when extrapolating data ffom studies of miscarriage following spontaneous conception. Separating fact from fiction requires well designed prospective studies and a better understanding of the factors which determine successful nidation.