title: Urinary follicle-stimulating hormone for normogonadotropic clomiphene-resistant anovulatory infertility: prospective, randomized comparison between low dose step-up and step-down dose regimens.
abstract: A low dose step-up and step-down regimen for induction of ovulation using urinary FSH was compared in a prospective randomized fashion in 37 normogonadotropic clomiphene-resistant oligo- or amenorrheic infertile women. The objectives was to assess potential differences in duration of treatment, ovarian stimulation (serum FSH levels), and response [serum estradiol (E2) levels and number and size of follicles]. Monitoring (blood sampling and transvaginal sonography) took place on the day of initiation of treatment, the first day of ovarian response as assessed by ultrasound (i.e. the first day a follicle > or = 10 mm could be recognized), the day of hCG administration to induce ovulation, and 3 days thereafter. The median duration of treatment in the low dose step-up group was 18 (range, 7-41) days compared to 9 (range, 4-16) days in the step-down group (P = 0.003), and the total numbers of ampules administered were 20 (range, 7-69) and 14 (range, 7-33), respectively (P = NS). Serum FSH levels from the first day of sonographic ovarian response until the administration of hCG were constant (median increase, 2%/day) in patients receiving the low dose step-up protocol, but showed a decrease (median, 5%/day) in step-down cycles (P < 0.001). Monofollicular growth, defined as not more than one follicle 16 mm or larger on the day of hCG administration, was observed in 56% of low dose step-up and 88% of step-down cycles (P = 0.04). The percentage of patients with normal range periovulatory E2 serum levels (500-1500 pmol/L) was 33% in the low dose step-up group vs. 71% in the step-down group (P = 0.03). We conclude that a step-down protocol for gonadotropin induction of ovulation exhibits a more physiological, late follicular phase FSH serum profile than a low dose step-up protocol. This results in a shorter duration of treatment, a greater number of monofollicular cycles, and more cycles with periovulatory E2 levels within the normal range in the step-down protocol.
authors.affiliation: Department of Obstetrics and Gynecology, Dijkzigt Academic Hospital, Rotterdam, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: van Santbrink
authors.forename: B C
authors.initials: BC
authors.lastname: Fauser
mesh_terms: D000328:Adult; D000858:Anovulation / Q000188:drug therapy*; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000627:therapeutic use; D002996:Clomiphene; D004351:Drug Resistance; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage* / Q000627:therapeutic use / Q000652:urine; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000628:therapy*; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy; D011446:Prospective Studies
chemical_list: D006063:Chorionic Gonadotropin; D002996:Clomiphene; D004958:Estradiol; D005640:Follicle Stimulating Hormone