The use of gonadotrophin releasing-hormone analogues (GnRHa), in in-vitro fertilization: some clinical and experimental investigations of a direct effect on the human ovary.

Several lines of investigation suggest a direct modulatory role for gonadotrophin-releasing hormone (GnRH) on granulosa cell functions. Also, GnRH and its analogues (GnRHa) have been implicated in the resumption of meiosis, both in vivo and in vitro. Despite the presence of specific receptors for GnRH on human granulosa and luteal cells, very little is known about the possible effects of this hormone on the ovary. The use of GnRHa for long periods of time in patients undergoing in vitro fertilization (IVF) may influence granulosa cell function and/or oocyte maturation. We describe our clinical and experimental data in which we have searched for evidence of a direct action of GnRHa on the ovary. We have found that the retrieval of higher numbers of oocytes in women treated with GnRHa is correlated with oocytes of lower quality, manifested by a decreased fertilization and implantation rate. This impairment seems to be the consequence of oocyte immaturity, as ascertained by cytogenetic analysis of unfertilized oocytes in which an increase in diploidy, as well as prematurely condensed sperm chromosomes of the G1 phase, was observed in women with an excessive response to the stimulating drugs. Follicular atresia was not increased in women treated with GnRHa. Thus, there was no evidence for a direct effect of GnRHa on the human oocyte. Rather, the observations reflect the harmful effect of pushing follicles in early stages of development using this stimulation protocol. We have also searched for possible effects of GnRHa on granulosa-luteal cells obtained at ovum collection. In vitro culture of these cells has shown that the steroidogenic pathway is affected.(ABSTRACT TRUNCATED AT 250 WORDS)