It is, therefore, crucial to design a systematic stimulation protocol in order to:
→ achieve the best ovarian response to gonadotropins,
→ retrieve a sufficient number of oocytes,
→ obtain better quality embryos and
→ avoid ovarian hyperstimulation syndrome.
The more commonly used stimulation protocols are:
Long agonist protocol
Agonist administration initiates on day 21 of the previous menstrual cycle, with daily injections that cause rapid desensitization of the pituitary gland. When spontaneous menstruation starts, the doctor performs a vaginal ultrasound scan and measures ovarian/pituitary hormones in order to verify successful downregulation. Then the woman is ready to proceed with her treatment, with gonadotropin injections that will stimulate the ovaries. Gonadotropin injections usually are administered for 10 to 12 days. When follicular maturation is confirmed, ovulation is induced by administrating hCG and after 36 hours egg retrieval is performed.
The long protocol has a total duration of 1,5 – 2 months, starting from the day of the first injection to the day of the pregnancy test. The protocol lasts longer, in cases where pretreatment with oral contraceptives is necessary.
Short agonist protocol
This protocol starts when menstrual bleeding begins. On cycle day 2, a vaginal ultrasound and hormonal blood levels measurement is performed. According to the monitoring results, the woman initiates GnRH injections with a much smaller dosage of agonist compared to the long protocol. On cycle day 3, gonadotropin treatment starts, while GnRH agonist is still administered. When follicular maturation is confirmed, ovulation is induced by administrating hCG and after 36 hours egg retrieval is performed. The duration of this protocol is around one month.
Short antagonist protocol
Women, who are low-responders to ovarian stimulation protocols that involve the use of GnRH agonists or are at risk of developing Ovarian Hyperstimulation Syndrome (OHSS), such as women with Polycystic Ovarian Syndrome (PCOS), may receive better stimulation if an antagonist is used instead. In some cases, pre-treatment with oral contraceptives may be necessary.
The GnRH antagonist is usually initiated on approximately the 6th day of gonadotropin administration, started on cycle day 2 that stimulates the development of follicles in the ovary. Ultrasound is performed and sometimes hormone measurements are required to determine the correct timing of egg retrieval. For some women, a minor alteration of this protocol including pre-treatment with estrogen, two weeks before menstrual bleeding starts, may be beneficial.
Elonva (Corifollitropin alfa)
Elonva is indicated in combination with a GnRH antagonist. Due to its ability to initiate and sustain multiple follicular growth for 7 days, a single subcutaneous injection may replace the first seven injections of any daily administered gonadotropin.
Mini-IVF or Micro-IVF
This protocol shares the same principals as conventional stimulation protocols but with lower doses of medication used during stimulation. Contrarily to conventional stimulation which aims to create the maximum possible number of mature follicles, the aim of mini-IVF is the creation of 2-3 good quality embryos.
The cycle begins with the administration of contraceptive pills until the start of menstruation. On the 3rd day of the new menstrual cycle, stimulation begins using small doses of injectable gonadotrophins, combined with clomiphene citrate, until ovulation is induced using hCG. This type of protocol is recommended for patients without a complex cause of infertility but can also be applied to women of advanced age or poor responders.