Molecular and Cellular Endocrinology 161 (2000) 25 – 30 Role of LH and FSH in ovarian function Colin M. Howles * Reproductie Health, Ares -Serono International S.A., 15 Bis, Chemin des Mines, 1202 Genea, Switzerland Abstract Human gonadotrophin preparations have been used in the treatment of infertility for almost four decades. The earliest preparations were derived from urine from postmenopausal women and contained approximately equal amounts of follicle stimulating hormone (FSH) and luteinizing hormone (LH) activities. However, with the recognition that FSH is the principal regulator of follicular growth and maturation, these have been largely superseded by highly purified urinary FSH preparations and, more recently, recombinant human FSH (r-hFSH). Because of its complexity, r-hFSH is expressed in mammalian cells grown in culture and, from a manufacturing stand point, offers superior purity and batch-to-batch consistency, compared with urinary preparations. A number of clinical trials have compared the efficacy of r-hFSH and urinary FSH in women undergoing assisted reproductive technologies (ART). In general, these have shown that fewer FSH ampoules are required to achieve ovarian stimulation with r-hFSH, while the number of oocytes retrieved and embryos produced are higher than with urinary FSH. Additionally, the results of a recent meta-analysis have also shown that the clinical pregnancy rate per cycle started is significantly higher with r-hFSH, compared with urinary FSH. Furthermore, in poor responder patients, higher implantation rates were seen in patients treated with r-hFSH than in those treated with urinary FSH, suggesting that embryo viability is increased following use of the recombinant preparations. The finding that FSH preparations produce effective ovarian stimulation compared to human menopausal gonadotrophins in women undergoing ART raises the question of whether LH is required for ovarian stimulation. This has been investigated in a number of recent studies. For example, results have suggested that implantation rates may actually be lower in women who received exogenous LH. Such studies suggest, therefore, that in normogonadotrophic women, the addition of LH to an r-hFSH regimen does not add any further clinical benefit and may actually be detrimental. Hence, it appears that LH administration is necessary only in women with hypogonadotrophic hypogonadism. In conclusion, r-hFSH is a consistently pure and high quality gonadotrophin preparation and contributes to increasing the successful outcome of an ART cycle. Together with careful auditing of routine clinical practice, and the application of evidence-based medicine to facilitate clinical decision making, this means that a total quality management approach can be applied to optimize the outcome of assisted reproduction. © 2000 Published by Elsevier Science Ireland Ltd. All rights reserved. Keywords: Luteinizing hormone; Follicle stimulating hormone; Gonadotrophins www.elsevier.com/locate/mce 1. Introduction The human gonadotrophin family includes follicle stimulating hormone (FSH), luteinizing hormone (LH) and chorionic gonadotrophin (hCG). Gonadotrophins are complex heterodimeric glycoproteins which consist of two non-covalently linked, non-identical protein components designated as the - and -subunits. The -subunit is common to the three gonadotrophins; the -subunit confers biological activity and specificity. The molecular weight of FSH is around 30 000 Da, of which one-third is from sugar residues. Gonadotrophins are water soluble and highly degradable by enzymes present in the gastrointestinal tract. They must there- fore be administered parenterally (intramuscularly or subcutaneously). Between species, there is sufficient ho- mology for observing biological cross-activity. How- ever, there is also enough heterogeneity for these proteins to be highly immunogenic, resulting in adverse immune reactions and antibody formation; this can cause neutralization of biological activity when the gonadotrophins from one species are administered in another species. * Corresponding author. Tel.: +41-22-7393000; fax: +41-22- 7393043. 0303-7207/00/$ - see front matter © 2000 Published by Elsevier Science Ireland Ltd. All rights reserved. PII:S0303-7207(99)00219-1