Simplifying luteal phase support in stimulated assisted reproduction cycles - Fertility and Sterility

The luteal phase is a very popular yet complex and poorly understood topic in the field of in vitro fertilization (IVF). After ovulation, the formation of the corpus luteum occurs under the influence of luteinizing hormone (LH). Studies in humans and primates have demonstrated that the corpus luteum requires a consistent LH stimulus to perform its physiologic function (1x1Jones, G.S. Luteal phase defect: a review of pathophysiology. Curr Opin Obstet Gynecol. 1991; 3: 641–648 Google ScholarSee all References)(1). In 1949, Georgeanna Jones first described luteal phase deficiency as the premature onset of menses resulting from deficient progesterone production, correctable by exogenous progesterone administration. Intriguingly, the luteal phase of almost all stimulated assisted reproductive technology (ART) cycles is defective and requires correction. However, before correcting the luteal phase we first must understand the cause of this luteal phase defect in almost all stimulated ART cycles. Indeed, as Avicenna, the Persian physician and philosopher, correctly stated, “The knowledge of anything, since all things have causes, is not acquired or complete, unless it is known by its causes.” The main etiology of the luteal phase defect observed in stimulated IVF cycles is the supraphysiologic levels of steroids secreted by a high number of corpora lutea during the early luteal phase, which directly inhibits LH release via negative feedback actions at the level of the hypothalamic-pituitary axis (2x2Fatemi, H.M., Popovic-Todorovic, B., Papanikolaou, E., Donoso, P., and Devroey, P. An update of luteal phase support in stimulated IVF cycles. Hum Reprod Update. 2007; 13: 581–590 Google ScholarSee all References)(2). If conception and implantation occur, the developing blastocyst secretes human chorionic gonadotrophin (hCG). The hCG produced by the embryo will maintain the secretory activity of the corpus luteum due to the structural similarity between hCG and LH, thus activating the same receptor (3x3Penzias, A.S. Luteal phase support. Fertil Steril. 2002; 77: 318–323 Google ScholarSee all References)(3). This is the reason why all studies evaluating the continuation or discontinuation of progesterone after a positive hCG test have failed to demonstrate any difference in outcome. A meta-analysis of studies evaluating the duration of progesterone administration after a positive pregnancy test found no influence on the miscarriage or delivery rates when progesterone application was continued or discontinued for 2 weeks after a positive pregnancy test (4x4Liu, X.R.,