Pulsatile subcutaneous versus bolus intramuscular gonadotrophin administration after pituitary suppression with a long-acting gonadotrophin-releasing hormone analogue: a controlled prospective study.

The potential advantages of pulsatile s.c. administration instead of daily bolus i.m. administration of human urinary gonadotrophin preparations were tested after the administration of a long-acting gonadotrophin-releasing hormone (GnRH) analogue within a programme for in-vitro fertilization (IVF) and embryo transfer. First, the pharmacokinetic properties of human urinary gonadotrophins were analysed with immunological and biological methods, both during bolus i.m. injections and during pulsatile s.c. administration. Second, a prospective randomized controlled study was performed in 75 patients undergoing IVF/embryo transfer in whom the effects of pulsatile s.c. administration were compared with the effects of single daily bolus i.m. injections of the same gonadotrophin preparation. The results showed that neither method of gonadotrophin administration induced measurable changes in the serum concentration of luteinizing hormone (LH). Both oestradiol and androstenedione concentrations were slightly lower during pulsatile s.c. gonadotrophin administration, suggesting that this method of gonadotrophin administration results in less LH occupying the ovarian LH receptors. Pulsatile s.c. gonadotrophin administration resembles a continuous infusion of follicle-stimulating hormone (FSH). Significant fluctuations in the serum concentrations of FSH were observed during single daily bolus i.m. administration of human urinary gonadotrophins, but the pregnancy rate of IVF/embryo transfer per cycle after pulsatile s.c. administration was not significantly better than after the daily bolus i.m. injection of gonadotrophins (42.1 versus 37.2%). It is concluded that pulsatile s.c. administration of gonadotrophins instead of single daily injections does not improve the pregnancy rate in IVF/embryo transfer.