Luteal phase support in assisted reproduction

The first report of the combined use of pituitary suppression and ovarian hyperstimulation in invitro fertilization (IVF) and embryo transfer programmes was published in 1984 (1). Since then, the advantages of gonadotrophin hormonereleasing hormone analogues (GnRHa) have been well documented; the cancellation rate has been decreased through the prevention of premature luteinizing hormone (LH) surge, follicular recruitment has improved, and the ovarian response to hyperstimulation has been better synchronized, thus facilitating the scheduling of oocyte retrieval (OR). This pituitary suppression however, results in an impaired gonadotrophin production later on, and the output of LH remains blocked for at least 10 days after cessation of GnRHa administration (2, 3). As gonadotrophins are necessary to maintain progesterone output by the corpus luteum, exogenous luteal support is mandatory. However several reports have shown that corpus luteum function and luteal phase duration are shortened in IVF cycles regardless of the protocol used for multifollicular induction. In comparing HMG either alone or with the addition of GnRH antagonist cetorolix, Tavaniotuo et al. 2001, have shown that LH concentration declines at the mid luteal phase and without luteal supplementation the corpus luteum function will be disturbed which results in a very low implantation rate (4). The induction of multiple follicle development per se could either directly or indirectly influence the duration of the luteal phase (5); the removal of large quantities of granulosa cells at oocyte retrieval may diminish the most important source of progesterone synthesis by the corpus luteum, thus disrupting the luteal phase (6). supraphysiological levels of steroids [related to the larger number of corpora lutea] during the early luteal phase could directly inhibit LH release via negative feedback actions at the hypothalamic-pituitary axis (7). A metaanalysis comparing placebo with any form of luteal support favored the addition of luteal support (8). Vlaisavljevic (2007) compared natural IVF cycles with and without luteal support and concluded that even in a natural cycle IVF a higher pregnancy rate was observed if HCG was administered after embryo transfer (9).