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Standard Stimulation for IVF

Stimulation of ovulation (synonyms are superovulation or ovulation induction) for IVF comprises of using some medication that will lead to ovulation of one or several follicles, depending on the planned procedure in that cycle. In the natural cycle, one egg is usually produced during ovulation, but a certain number of women rarely ovulate (anovulatory cycles) and should take medications to ovulate.

In patients with idiopathic infertility, endometriosis, tubal factor or male factor, in ovarian stimulation protocols, GnRH agonists or antagonists are used (triptorelin, buserelin, cetrorelix) preventing premature LH elevation and ovulation prior to full follicular maturity; gonadotropins stimulate the development of numerous follicles (follitropin, menotropins); hCG supporting a final maturation of eggs in follicles, followed by one of the assisted fertilization procedures: IUI, IVF/ET, ICSI/ET, etc. Multi-follicular ovulation will result in a higher number of embryos and thus to higher chances of conception per cycle.

There are long, short, and ultra-short protocols using GnRH agonists. In long protocols, agonists are usually started on the 21st day of the previous cycle and are taken until the final HCG injection. Gonadotropins are usually started on the 2nd day of the cycle, and the first follicle monitoring ultrasound is scheduled sometime between days 7 or 8 of the cycle. In short protocol, agonists are started on day 1 of the cycle and ultra-short even later. Besides follicle monitoring, your doctor may ask for blood draws for levels of estradiol and progesterone. The number of follicle monitoring ultrasounds will depend on the reaction to medications. If there is no reaction to ovulation induction drugs, the cycle will be canceled. Therefore, injections of medications should be given each day simultaneously until the leading follicle reaches the size of 17-20 mm. Then the hCG injection is administered.

The protocol with antagonists has been introduced after the agonist protocols, and its advantage is a significantly shorter procedure and lower usage of gonadotropins. This procedure starts with gonadotropin injections between days 2 and 4 of the cycle, while the antagonist is introduced either on a fixed day of the cycle or depending on the size of follicles. The induction aims to get as many follicles as possible with a diameter of 17-20 mm, upon which hCG injection is induced, and follicle aspiration is planned in 34-36 hours, immediately before expected ovulation. The first follicle monitoring ultrasound is usually scheduled on day 6 of the cycle (earlier than the agonist protocol), especially when a flexible antagonist protocol is planned to be used. Antagonist protocol is usually used in women with normal ovarian reserve, especially in women with high ovarian reserve, because in case of hyperstimulation, an agonist trigger can be used.

Short protocols with agonists start on the first day of the cycle and are mostly used with non-responders. All protocols may be preceded by contraceptive treatment over 1-2 months in order to reduce the chances of developing ovarian cysts prior to the procedure and for timing purposes. GnRH agonists and antagonists will prevent early LH elevation and premature ovulation, resulting in cycle failure.