ABSTRACT
The success of assisted reproduction technologies during the last two decades is intimately connected with the use of exogenous gonadotrophins. Administration of surplus gonadotropins results in multi-follicular development and maximise the number of oocytes for fertilisation in vitro. Historically, follicular stimulation protocols attempted to mimic the normal physiology of folliculogenesis by including both FSH and LH. The classical, urine-derived hMG preparations contain equal amounts of FSH and LH-like activity (i.e. 75IU per ampoule) and were originally founded in the 2-cell twogonadotropin concept. In the late 1980’s it became clear, that increased tonic levels of LH during the follicular phase of the cycle was associated with reduced rates of fertilisation and implantation, but also increased miscarriage rate.1-4 These observations in combination with studies, which questioned the role and necessity of LH in folliculogenesis5 pawed the way for the introduction of ovarian stimulation regimes, which aimed at reducing the concentration of LH as much as possible. One important measure in this endeavour was the development of gonadotropin preparations with reduced or very low levels of LH (e.g. Normegon®, Organon, Metrodin®, Serono, Metrodin-HP®, Serono). The ultimate goal has been achieved with the introduction of recombinant FSH preparations, which are “pure” and without concomitant activity of LH (e.g. Puregon®, Organon; Gonal F®, Serono). This bouquet of gonadotropin preparations in combination with the recently developed recombinant preparations of LH and hCG (i.e. Luveris® and Ovitrelle® both Serono) allow us to control for the specific contribution of either FSH and LH during folliculogenesis and provide us with the unique opportunity to study the precise gonadotropin requirements of the developing follicle. Indeed, recent research has demonstrated, that LH cannot be neglected in connection with preovulatory follicular development and several studies indicate that very low levels of LH may reduce treatment outcome in connection with ART.6-9 It therefore appears, that LH should neither be too high nor too low. However, the level and range of LH required during the follicular phase in order to secure an optimal maturation of oocytes, fertilisation, pre-embryo development, and conception of a child is still an open question. The present review focuses on the importance of LH for normal folliculogenesis and evaluates the potential negative effects of a profound reduction of LH in connection with ovarian stimulation protocols.
