The short-term GnRH-a protocol or the flare-up protocol
This type of IVF protocol stimulation exploits the initial rise (flare-up) of serum gonadotropins on follicular recruitment. Therefore, GnRH-a is administered on cycle day 2 followed by gonadotropin treatment started on day 3. Pituitary desensitisation will occur several days later while the patients are still on gonadotropin treatment.
A shorter period of GnRH-a administration for 3 – 7 days, was suggested and termed “Ultra-Short GnRH-a Protocol”.
This type of IVF protocol is based on the assumption that suppression of the endogenous LH surge, it may obtain through a very short course of GnRH-a administration.
Aforementioned protocols suggested various modifications such as:
A “micro-dose GnRH-a flare” protocol
This type of IVF protocol was developed (with several modifications) for poor ovarian responders. Those who receives OC’s during the month before stimulation, micro-doses of GnRH-a during the first days of the follicular phase, and introduce gonadotropins after several days
Other strategies used with poor-responders include:
- Increasing the dose of gonadotropins administered
- Reducing the amount of GnRH-a given
- Cotreatment with growth hormone
The low or no-dose GnRH-a appears to most effective for older women and those with an unexplained poor response to gonadotropins.
Ovarian Stimulation Using GnRH-antagonists
GnRH antagonists, as well as GnRH-a, prevent the woman from experiencing an LH surge. The GnRH antagonist acts by competing with native GnRH molecules at their binding sites in the pituitary. The action of GnRH-a is to “down-regulate” the pituitary’s ability to produce the LH surge.
This GnRH antagonist is usually initiated on (approximately) the 6th day of FSH administration. It stimulates the development of follicles in the ovary. This is usually given subcutaneously once daily and continued until hCG is given.
Give the long-acting GnRH antagonist “Cetrotide” as a single injection (in a higher 3 mg dose), rather than as daily injections of the lower 0.25 mg dose. When the single 3 mg dose is administered, Cetrotide should provide 4 days of suppression (no LH surge for 96 hours).
If the patient needs more days of stimulation beyond the 96 hours, then give daily 0.25mg Cetrotide injections until stimulation completes and the introduction of HCG. Compared to agonists, the GnRH antagonist decreases the FSH dosages required for ovarian stimulation.
However, published literature has provided evidence about the retrieval of slightly fewer eggs, fewer embryos are available on the day of transfer, and also the achievement of slightly lower pregnancy rates with antagonists than with the use of agonists.
Clinics report on Ovarian Stimulation Protocols:
Some clinics have reported that women who are low-responders to ovarian stimulation protocols that involve the use of GnRH-a. They may receive better stimulation if they use an antagonist instead.
Nevertheless, these protocols clearly identify several advantages. The compliance of patients with the GnRH antagonist protocols was excellent due to the
- Shortened exposure to GnRH analogue administration and
- Good clinical tolerance of this third generation of antagonists.
Furthermore, the need of exogenous gonadotropins(a number of) to reduce ovarian stimulation, as well as the occurrence of OHSS (ovarian hyperstimulation syndrome).
Finally, the overall cost of this regimen was significantly lower than that of the GnRH-a protocol. The new GnRH antagonists also permit the design of milder stimulation schemes, with the return to the use of clomiphene citrate, minimal stimulation, or even natural cycles.