Luteal Phase Support in In Vitro Fertilization

It has been well demonstrated that luteal phase physiology is disrupted in in vitro fertilization (IVF) cycles conducted with either gonadotropin-releasing hormone (GnRH) agonists or antagonists, and that supplementation of the luteal phase with either exogenous progesterone or human chorionic gonadotropin (hCG) is necessary to optimize IVF cycle outcomes. Though both progesterone and hCG supplementation resulted in comparable pregnancy rates, hCG supplementation was associated with increased risk for ovarian hyperstimulation syndrome (OHSS). For that reason progesterone has been used for luteal support by most IVF programs around the world. Vaginal progesterone preparations have been shown definitively to be equally efficacious and better tolerated by patients than intramuscular progesterone injections, but new data on the subcutaneous and oral progesterone are also emerging. New evidence has been accumulating on the benefits of low-dose luteal hCG supplementation in GnRH-antagonist cycles where GnRH agonists are used for the final maturation trigger. New approaches to luteal phase support as well as new formulations of progesterone have been developed since the last comprehensive review was published in 2011. In this article, we examine current evidence for efficacy, dosing, and timing of progesterone preparations as well as the role of hCG for luteal support in IVF cycles triggered with GnRH agonists. We also discuss the data on the role of estrogen supplementation in the luteal phase, optimal duration of progesterone support in early pregnancy, and progesterone replacement in frozen embryo transfer cycles and donor egg recipient cycles.