PURPOSE: To develop a pharmacodynamic model that can describe the time course of follicular growth and to investigate the influence, if any, of covariates on the parameters of the model. METHODS: A population pharmacodynamic analysis was performed on total follicular volume data obtained after in vitro fertilisation and embryo transfer with urinary or recombinant human follicle stimulating hormone (FSH) treatment. A growth model in which the increase in total follicular volume with time is a function of several possible components was chosen. RESULTS: In the final population pharmacodynamic model, increase in total follicular volume (TFV) was described by the equation: dTFV/dt = Emax.TFV/(TFV + TFV50) + constant, in which Emax, TFV50, and constant were 508 mm3/hr (interindividual variability 72%), 12,900 mm3 (66%), and 1.43 mm3/hr (91%), respectively. Growth was positively correlated to baseline estradiol levels, so that Emax and TFV50 changed 0.52% for every picomolar change from the median baseline estradiol value of 100 pmol/L. Growth was negatively correlated to pretreatment FSH levels, so that individuals with a median FSH (6.7 IU/L) were expected to have a fivefold higher total follicular volume at day 10 after the start of treatment, compared to individuals at the high end of the pretreatment FSH range (12 IU/L). No relationship between FSH concentration and follicular growth was found. The urinary versus recombinant origin of the drug did not influence the ovarian response. CONCLUSION: Women with high endogenous levels of FSH respond less to standard doses of exogenous FSH. Women with higher baseline levels of estradiol have larger expected follicular growth rates.
RCT Entities:
PURPOSE: To develop a pharmacodynamic model that can describe the time course of follicular growth and to investigate the influence, if any, of covariates on the parameters of the model. METHODS: A population pharmacodynamic analysis was performed on total follicular volume data obtained after in vitro fertilisation and embryo transfer with urinary or recombinant human follicle stimulating hormone (FSH) treatment. A growth model in which the increase in total follicular volume with time is a function of several possible components was chosen. RESULTS: In the final population pharmacodynamic model, increase in total follicular volume (TFV) was described by the equation: dTFV/dt = Emax.TFV/(TFV + TFV50) + constant, in which Emax, TFV50, and constant were 508 mm3/hr (interindividual variability 72%), 12,900 mm3 (66%), and 1.43 mm3/hr (91%), respectively. Growth was positively correlated to baseline estradiol levels, so that Emax and TFV50 changed 0.52% for every picomolar change from the median baseline estradiol value of 100 pmol/L. Growth was negatively correlated to pretreatment FSH levels, so that individuals with a median FSH (6.7 IU/L) were expected to have a fivefold higher total follicular volume at day 10 after the start of treatment, compared to individuals at the high end of the pretreatment FSH range (12 IU/L). No relationship between FSH concentration and follicular growth was found. The urinary versus recombinant origin of the drug did not influence the ovarian response. CONCLUSION:Women with high endogenous levels of FSH respond less to standard doses of exogenous FSH. Women with higher baseline levels of estradiol have larger expected follicular growth rates.