The purpose of the hormone treatment is to stimulate the ovaries to produce more than the one follicle that a woman produces in a normal cycle. The hormone stimulation aims at making 8-12 eggs for oocyte pick-up, but in some instances less will do. The number of cells can vary a lot depending on the woman’s age and response to the stimulation.
We monitor the follicle growth by transvaginal ultrasound scans. In this way, the size and number of follicles can be determined. The size of the follicle indicates the maturity of the egg contained in the follicle. When the follicles have reached a size of 17-20 mm the eggs are mature and ready for oocyte pick-up. The oocyte itself has a diameter of 0.12 mm and is not visible at the ultrasound scan.
In our clinic, we use different hormone stimulation schemes. We mostly use treatment with ‘long down- regulation’ (we call it scheme 3) and the so-called ‘short antagonist protocol’ (we call it scheme 4). In some cases we use stimulation based on chlomiphene citrate, ‘agonist flare-up’ or ‘CRASH’. Very rarely, we may do IVF without hormone stimulation.
The treatment is always tailored to the individual woman based on her cause of infertility and on experience from previous successful or less successful treatments.
When a treatment cycle starts, we will provide you with detailed information about the treatment plan, use of medicine, possible side effects and we plan the next consultation and ultrasound scan.
Hormone treatment with ‘long down-regulation’ (scheme 3)
This treatment starts with ‘down-regulation’ close to day 21 of the menstrual cycle. Ideally the down-regulation is begun approximately one week before the next expected menstrual bleeding, so if your cycle is not between 26-30 days down-regulation may be initiated earlier or later than day 21. We perform an ultrasound scan to ensure that the down-regulation starts at the correct time in the cycle.
The down-regulation inhibits the secretion of FSH and LH from the pituitary gland. These hormones stimu- late the ovaries to produce eggs. The down-regulation also prevents the pituitary from secreting the peak of LH that will induce ovulation when there are mature follicles. This prevents ovulation before the oocyte pick-up.
Down-regulation can be done with a nasal spray (Synarela® 3 puffs daily or Suprecur® 4 puffs daily) evenly distributed over the hours that you are awake. Alternatives are one daily injection with Suprefact® or Gonapeptyl® or one depot injection with Zoladex® or Decapeptyl®.
While you take the down-regulation medicine, you will have your menstrual bleeding. It may be slightly delayed. You should just proceed with the down-regulation. The bleeding may be slightly different than usual.
If the menstrual bleeding is more than one week delayed, you should take a pregnancy test. It may occasionally happen that the test shows that you are pregnant. If so, you should stop taking the down-regulation. It does not harm the pregnancy that you took the down-regulation medicine.
Because the down-regulation induces a hormonal stage that resembles the menopause, you may experience side effects resembling menopausal symptoms: Hot flushes, headache and mood disturbances. However, most women will have very few symptoms from the medicine. If you experience side effects, they normally disappear when the hormone stimulation starts.
The hormone stimulation normally starts approximately 14 days after the down-regulation began. At least three days should have elapsed since the onset of the menstruation. The down-regulation continues during the hormone stimulation.
Before starting the hormone stimulation, we perform an ultrasound scan to make sure that the endometrium has been properly shedded and that no cysts are present in the ovaries.
When everything is ok, the daily injections with stimulating hormone are begun (Gonal-f®, Puregon®, Pergoveris® or Menopur®). The injections are taken once daily at approximately the same time (within +/- a few hours. The injections are taken subcutaneously. We will inform you about how to do it so you can take the injections yourself. Everybody can learn how to do it. If you – after having had detailed instruction from us – are unable to take the injections they can be given by our nurses in the clinic (during our opening hours), or you may know a doctor, a nurse or another competent person who can assist you.
After 8-10 days with the daily injections and the continued down-regulation, we will perform an ultrasound scan. We will determine the size and number of follicles and measure the thickness of the endometrium. Often we will need to do one or two more scans before the follicles have reached a size (17-20 mm) where we can plan the time of the final oocyte maturation injection (hCG) and the oocyte pickup.
Hormone stimulation with ‘short antagonist’ protocol (scheme 4)
The hormone stimulation is started on day 2-3 of the menstrual bleeding. The first day of ‘real’ bleeding is called day 1.
You must have an ultrasound scan before starting the stimulation. We make sure that there are no cysts (or a remaining ‘corpus luteum’ from the follicle that ovulated in the preceding cycle) in the ovaries and that the endometrial lining has been shedded.
If everything is ok you can start daily injections with stimulating hormone (Gonal-f®, Puregon®, Pergoveris® or Menopur®).The injections should be taken once daily at approximately the same time (within +/- a few hours). The injections are given subcutaneously in the skin of the lower abdomen. In the clinic, we will in struct you how to do it, so you can take the injections yourself. Everybody can learn it. If it is not possible for you to take the injections yourself, our nurses can give them in the clinic during our opening hours. Or perhaps you can ask your doctor, nurse or another competent person to assist you.
In some cases, the long-acting stimulation hormone Elonva® is used. Elonva® is given as a single injection on day 2-3 and the effect lasts for 7-8 days, so it is not necessary to take additional injections of hormone stimulation for several days.
Around 5-6 days after you started the hormone stimulation the treatment is supplemented with a so-called ‘antagonist’ (Orgalutran® or Cetrotide®).
The antagonist prevents the pituitary gland from secreting FSH and LH, which are the hormones that stimulate the ovaries to produce eggs. The antagonist also prevents the pituitary gland from releasing the ‘final oocyte maturation’ signal when there are mature eggs. In this way, the antagonist prevents the follicles from ovulating before the time of the oocyte pick-up.
The antagonist is taken as one injection every morning. Once the antagonist treatment starts, it must be continued until and including the day when you take ‘final oocyte maturation’ injection. The daily injections of stimulation hormone (FSH/hMG) are continued during this phase.
Other types of hormone stimulation
In some cases, we recommend other types of stimulation than ‘long down-regulation’ of ‘short antagonist protocol’.
Clomiphene citrate plus FSH/hMG (scheme 1)
This stimulation is based on Clomiphene tablets and the stimulation is supplemented with hormone injections with Gonal-f®, Puregon®, Menopur® or Pergoveris®. This stimulation may be good for women who produce few eggs or low-quality eggs with the ‘standard’ treatments.
Un-stimulated treatment (scheme 0)
IVF without hormone stimulation may be considered when the woman does not produce more than 1-2 eggs with hormone stimulation. Without hormone stimulation, only one follicle will develop. In such a ‘natural’ cycle without down-regulation and ’antagonist’ there is always a risk that ovulation may occur before oocyte pick-up.
CRASH (scheme 5)
We almost never use so-called CRASH treatment because we do not find that it has any advantages over other stimulation types and it yields poor results.
Final oocyte maturation injection
Pregnyl® or Ovitrelle® (hCG)
An injection with the ‘final oocyte maturation’ hormone hCG (Pregnyl® eller Ovitrelle®) is given in order to induce the final maturation of the oocytes and make them ready for pick-up and fertilisation. hCG is actually a pregnancy hormone but it has the same effect as LH which is the natural ‘ovulation’ hormone.
Injection of Pregnyl® or Ovitrelle is taken 34-36 hours prior to the scheduled oocyte pick-up. It is very important that the time of the injection be exactly as planned. We will inform you about exactly when to take the injection. The timing depends on the time of the planned oocyte pick-up.
Final oocyte maturation with Suprefact® (or another ‘GnRH agonist’)
An alternative to using hCG for final oocyte maturation is to give a single dose of Suprefact® (or another GnRH agonist). This method can only be used if you are not down-regulated, and therefore it is not used in ‘scheme 3’.
Final oocyte maturation (‘GnRH agonist triggering’) with Suprefact® may be an option if there is risk of hyperstimulation or if the final maturation of the oocytes has not worked well with Pregnyl® or Ovitrelle®. GnRH agonist triggering is also useful in oocyte donors to avoid hyperstimulation.
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Scheme 0 and 2 are not shown here.
Tel: +45 39 40 70 00