Long ovarian stimulation Protocol
The golden protocol for IVF is the long one. This protocol is divided into three phases
- Phase of suppression with GnRH analogues. This phase is starting from the luteal phase of the previous cycle (usually on the 21st or 22nd day of a 28-day cycle) and lasts for about 10-14 days.
- Stimulation phase with gonadotropins (Menopur, Gonal, Puregon, Altermon). This phase begins after we make sure with hormonal blood testing that the suppression has worked. In fact; this is confirmed by an estradiol test on the 10th day of suppression. If estradiol levels are below 50 pg/mL, stimulation can be initiated. The exact dosage of the stimulation drugs is determined by the expected reaction of the ovaries according to the preparation exams that are done before we start an attempt. When a severe reaction is expected, gonadotropins are given in very mild doses due to the risk of an excessive ovarian reaction and overstimulation. On the other hand, when a poor reaction is expected, up to 450 units per day can be administered, which are proved to be clinically useful in achieving pregnancy. Exceeding this dose is proved with certainty in a Cochrane Review, that doesn’t improve results. The duration of this treatment is from 12 to 16 days and during this period, ultrasound scans and biochemical blood tests to check estradiol and progesterone levels, have to be performed.
Phase of triggering, egg retrieval, fertilization and embryo transfer. Once the stimulation bears fruit and egg collection date is determined, the last triggering injection known as chorionic gonadotropin (Ovitrelle, Arvekap) is injected and approximately 36 hours later the egg collection is performed under sedation. The eggs are collected and the partner is also asked to give his sperm. In cases of sperm donation the donor’s sperm is thawed at this point to be used for the fertilization. The sperm is specially processed in order to get rid of germs and to select the most suitable sperm for utilization. This is followed by either conventional fertilization or micro-fertilization and 3 to 5 days after the embryo transfer or the freezing of the embryos follow.
Short ovarian stimulation Protocol (flare-up)
The short or flare-up protocol is used in those cases where the long one yielded only a few eggs or when for technical reasons concerning the patient the protocol should be short. In these cases the suppression starts from the second day of the cycle and the stimulation one day later. Ultrasound and biochemical testing is performed on the 8th day and the protocol lasts a total of about 12-14 days.
GNRH-Antagonist protocol
The antagonist protocol begins directly with stimulation on the second day of the cycle, where an ultrasound is performed to check the ovarian state. During the stimulation period the scans and
blood tests (measurement of estradiol and LH) and based on the findings, the simultaneous administration of an antagonist (Orgalutran, Cetrotide) to prevent premature ovulation starts at a certain day. Egg collection usually takes place on the 12th to 14th day.
The advantages of this protocol are that it is more patient friendly, simple, lasts less and presents a lower risk of overstimulation. Perhaps the only disadvantage is that in certain categories of patients such as those with a history of endometriosis, it has slightly lower success rates.
Single Injection Protocol
The most recent protocol is that of ONE INJECTION, as it is called. It is essentially chorifolitropin α (ELONVA) which is given once on the second day of the cycle and essentially replaces the seven-day injections! From the 6th day it is combined with an antagonist and from the 8th day, if the stimulation is not completed, a daily extra dose of gonadotropins is added. This is an even more simplified antagonist protocol with similar efficacy and perhaps a slightly higher rate of ovarian hyperstimulation syndrome.
