A population model for the follicular growth in women treated with follicle stimulating hormone.
OBJECTIVE
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.


CONCLUSIONS
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.
Karlsson
M O
MO
Department of Pharmacy, Uppsala University, Sweden. mats.karlsson@biof.uu.se
Wade
J R
JR
Loumaye
E
E
Munafo
A
A
D000328:Adult; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology* / Q000627:therapeutic use; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D043373:Follicle Stimulating Hormone, Human; D006801:Humans; D008596:Menotropins / Q000494:pharmacology* / Q000627:therapeutic use; D008954:Models, Biological; D006080:Ovarian Follicle / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D014463:Ultrasonography
D005300:Fertility Agents, Female; D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; D008596:Menotropins; D005640:Follicle Stimulating Hormone