COMMERCIAL PREPARATION OF GnRH: Are differences of biopotency the causes of variability in patient response?

Moon, Young Jin; Kim, Seung Ryong

Abstract

Ovulation induction in hypothalamic amenorrhea using gonadotropin- releasing hormone(GnRH) pulse therapy is complicated by widely variant patient responses ranging from anovulation to multiple pregnancy. Route of administration(intravenous vs subcutaneous), pulse therapy, GnRH dose, infusion interval, or hormone preparation may contribute. We evaluated the bioactivity of 4 GnRH preparations(Relisorm,Serono; Lutrelef,Ferring; Factrel,Ayerst; GnRH,Sigma) in a rat anterior cell bioassay. Dispersed rat anterior pituitary cells were placed for 48 hrs at 5x105 cells/well, washed and incubated with GnRH. The GnRH was diluted according to the manufacturer's culture medium(10(-12) to 10(-5)M). GnRH stimulated immunoreactive luteinizing hormone(LH) production was assested in culture medium after 4 hrs by radioimmunoassay(RIA). A linear dose-response relationship was exhibited by all preparations from 10(-10) to 10(-7)M. Msximal LH production was 249+/-24 ng/ml/4hrs(mean+/-SEM) and was not different among the preparations tested(ANOVA, p>0.05). The minimal effective dose of GnRH was 10-10M for all preparations(basa1=27+/-4ng/ml/4hrs:mean+/-SEM). No significant differences were noted for MED, or dose-response slope(p<0.05, ANOVA and slope test for parallelism, respectively). In addition, bioactive LH and immuno and bioactive follicular stimulating hormone(FSH) dose responses were confirmed. We concluded that the principal variability of patient response seen with GnRH pulse therapy cannot be attributed to the bioactivity of these commercial GnRH preparations. But rather, most of the variability is due to the inherent individualism in patient response or other factors of the treatment protocol.