GnRH analogs in in vitro fertilization: To dose or overdose?

Gonadotropin-releasing hormone (GnRH) analogs have been used in in vitro fertilization (IVF) to prevent premature luteinizing hormone (LH) surges. Routinely, a GnRH dose is used which aims at complete desensitization of the pituitary gonadotrophs. However, full pituitary desensitization may not be necessary, or may even be detrimental by direct effects on the ovary. Our group, over recent years, has been studying the effects of lower-than-usual dosages of GnRH analogs in different treatment modalities, IVF being one of them. Initially, we studied the effect of different dosages of synthetic GnRH and designed a measure by which pituitary desensitization could be quantified in terms of the response of LH to a GnRH challenge. Next, pituitary suppression under 25, 50, 100 and 200 μg per day of triptorelin (D-Trp6-GnRH; Decapeptyl CR, Ferring, Malmo) was studied. It was concluded that both pituitary desensitization and recovery after agonist treatment were dose-dependent. Finally, the effect of 5, 15, 50, 100 μg per day of triptorelin, from the midluteal phase onwards, on the pituitary responsiveness to a 500-μg GnRH challenge at the time of human chorionic gonadotropin (hCG) application in regular IVF cycles was investigated. Results showed that dosages of 5 and 15 μg of triptorelin gave partial and 50 and 100 μg gave total suppression. A large on-going comparative study will further quantify the number of LH surges occurring under the different dosages.