Dose-finding study of daily gonadotropin-releasing hormone (GnRH) antagonist for the prevention of premature luteinizing hormone surges in IVF/ICSI patients: antide and hormone levels.
BACKGROUND
The aim of this study was to define the minimal effective dose of antide (Iturelix) to prevent premature luteinizing hormone (LH) surges in in vitro fertilization (IVF) patients.


METHODS
In a prospective, single centre study, 144 IVF/ICSI patients were stimulated with r-hFSH from cycle day 2 and from cycle day 6 onwards, cotreated with daily 2 mg/2 ml (n=30), 1 mg/ml (n=30), 0.5 mg/ml (n=31), 0.5 mg/0.5 ml (n=23) and 0.25 mg/ml (n=30) GnRH antagonist (antide). Serum samples were taken three times daily during antide administration to assess antide and hormone levels. The minimal effective dose was defined as the lowest dose group with <2 LH surges (LH >12.4 IU/l and progesterone >2 ng/ml).


RESULTS
Serum antide levels, mean LH and E2 levels per day and their area under the curves were dose-related to antide. The bioavailability of antide almost doubled after dilution in larger volumes. Pre-injection LH levels gradually increased during GnRH antagonist treatment. LH surges occurred in the lowest dose groups 0.5 mg/ml (3.2%), 0.5 mg/0.5 ml (6.7%) and 0.25 mg/ml (13.3%). Hence, 0.5 mg/ml is considered to be the minimal effective dose. Antide was overall well tolerated and safe.


CONCLUSIONS
0.5 mg/ml antide is the minimal effective dose to prevent an untimely LH surge in IVF patients stimulated with r-hFSH.
Huirne
Judith A F
JA
Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Vrije Universiteit medical centre (VUmc), Amsterdam, The Netherlands.
van Loenen
Andre C D
AC
Schats
Roel
R
McDonnell
Joseph
J
Hompes
Peter G A
PG
Schoemaker
Joop
J
Homburg
Roy
R
Lambalk
Cornelis B
CB
D000328:Adult; D001682:Biological Availability; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors* / Q000097:blood; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D011374:Progesterone / Q000097:blood; D020554:Sperm Injections, Intracytoplasmic
D006727:Hormone Antagonists; D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C057022:iturelix