Novel IVF Stimulation Protocol
One of the most important factors in achieving successful in-vitro fertilization is the ovarian stimulation. Over the years, many stimulation protocols have been utilized in an attempt to achieve the “ideal” controlled ovarian hyperstimulation protocol. The perfect protocol would achieve the following:
1) Result in the recruitment of multiple fertilizable healthy eggs.
2) Minimize the amount of expensive pituitary hormones (gonadotropins) necessary to achieve satisfactory stimulation.
3) Shorten the number of days of stimulation and reduce the number of injections
4) Shorten the number of days of stimulation and reduce the number and reduce the total number of injections required.
5) Reduce the possibility of ovarian hyperstimulation syndrome.
The most commonly used medications for achieving ovarian stimulation include recombinant follicle stimulating hormone (FSH), human menopausal gonadotropins (HMG), GnRH agonists, GnRH antagonists, clomiphene citrate, and letrozole. GnRH agonists and antagonists serve an important function in that they prevent spontaneous release of eggs an inappropriately early time often resulting in cycle cancellation. GnRH agonists were the first drugs available for this purpose and are usually begun about 10-12 days before the beginning of the stimulation phase. The development of GnRH antagonists came years later and allowed for rapid and reliable suppression of the LH surge. They have the distinct advantage of being effective quickly and therefore only need be used for a few days when the risks of a spontaneous LH surge are greatest.
Contemporary use of GnRH agonists in a more direct manner, taking advantage of an initial stimulatory effect or “flare”, which occurs well before the LH suppressing “down regulatory” effect on the ovary.
A recently described IVF stimulation protocol from Chaim Sheba Medical Center in Israel aims to achieve most of the goals described earlier. The elements of this protocol are as follows:
1) Oral contraceptive pills are started on day 2-5 of the menstrual cycle and continued for at least 7 days.
2) Low dose GnRH agonist is begun 3 days after the last oral contraceptive pill and is continued for 3 days then stopped
3) On the 3rd day of the GnRH agonist, daily stimulation with gonadotropins is begun (FSH or HMG)
4) When the lead follicle is 13mm in diameter, daily GnRH antagonist is begun and continued until the stimulation is complete.
The authors of this paper found the following advantages with this protocol:
1) It resulted in an increase in the number of eggs retrieved and embryos transferred in patients who were poor responders, and achieved satisfactory pregnancy rates compared to previous IVF attempts
2) In patients who had previously experienced poor embryo quality, this protocol yielded a significantly higher number of top quality embryos. This resulted in an improvement in the clinical pregnancy rate
3) They were able to improve IVF success rates in patients with repeated failures by obtaining endometrial biopsies during the days of oral contraceptive administration. (Previous studies have suggested that biopsy or alternative trauma to the uterine lining results in improved embryo implantation rates.)
4) This protocol allowed the investigators to use a “Lupron trigger” for achieving final egg maturation. This approach markedly reduces the possibility of severe ovarian hyperstimulation
In summary, the stimulation protocol described here offers another valuable addition to the currently utilized ovarian stimulation protocols. Clearly there is no single stimulation protocol that works well in all patients at all times. The stimulation protocol described here was able to be initiated with minimal pre-treatment, increased the number of eggs retrieved and embryos formed. It worked well in low responders, and had satisfactory pregnancy rates in all patients treated. The protocol allowed for use of the “Lupron trigger” to minimize the chances of ovarian hyperstimulation.