Clinical assessment of human gonadotrophins produced by recombinant DNA technology

Abstract

Human gonadotrophins are follicle stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotrophin (HCG). All three gonadotrophins are now produced in vitro by recombinant DNA technology. Being complex heterodimeric proteins, an eukaryotic cell line, has been selected for expression and large scale production (Chinese hamster ovary cells). The advantages of producing the gonadotrophins in vitro rather than extracting them from human fluids are: (i) a fully controlled production process from bulk to finished product; (ii) high purity and specific activity; (iii) batch-to-batch consistency; and (iv) complete absence of contamination by the other gonadotrophins. Pharmacokinetic characterization of recombinant human gonadotrophins has shown that this first generation have pharmacokinetic characteristics very similar to the extractive gonadotrophins with an apparent terminal half-life after s.c. administration of ~ 37 h, 12 h and 32 h for recombinant FSH (rhFSH), recombinant LH (rhLH) and recombinant HCG (rhHCG) respectively. Clinical efficacy and safety have been demonstrated in several randomized, well-controlled studies, comparing rhFSH administered s.c. with uhFSH administered i.m. for stimulating follicular development prior to assisted reproductive technology and in WHO Group II anovulation. To date, ~ 1300 patients have been treated with rhFSH. Moreover, rhLH has recently been successfully used in association with rhFSH for inducing ovulation and pregnancy in WHO I anovulatory patients and rhCG has been successfully used for triggering final follicular maturation prior to assisted reproductive technology.