IVF treatment techniques
Types of stimulation
Native - natural IVF cycle
During the native IVF cycle no hormonal stimulation of the ovaries takes place. The aim of the puncture is to retrieve a single egg that ripens in the woman’s ovary. The success rate of this method is relatively low, which is caused by the use of only one egg. On the other hand the method is suitable for older women with lower oocyte reserve or for women who do not wish any hormonal stimulation.
The aim of minimum stimulation is to retrieve 2-6 ripe eggs. This type of stimulation is very gentle for the woman (antiestrogen pills are given or injection preparations in very low doses are applied). The retrieved eggs are mostly fertilised through the ICSI method. The produced embryos are usually transferred into the uterus after 3 days of cultivation. The success rate of this method is 25-35 % pregnancies per embryotransfer (ET) and usually there is no risk of ovarian hyperstimulation syndrome.
Long protocol stimulation with GnRH analogy
The long protocol was the golden standard of stimulation in extracorporeal fertilisation programme using a combination of two medicaments. At the beginning of the stimulation the patient uses a preparation suppressing the activity of ovaries and later another medicament is added that stimulates the ovaries. This method yields very good results with gain of sufficient number of eggs. However, it is more often complicated by the ovarian hyperstimulation syndrome. The success rate of this treatment ranges around 40 % pregnancies per embryotransfer. The protocol is suitable for young women with a good ovarian reserve. It is not suitable for women with poloycystic ovarian syndrome (PCOS) or women of higher age.
Stimulation protocol s with GnRH antagonists
This stimulation protocol is currently the most frequently used stimulation protocol, it involves the lowest consumption of stimulating hormones and the treatment is shorter than the long protocol. It also uses a combination of two types of preparations . The oocyte yield is usually sufficient. Success rate of the treatment is 40 % of pregnancies per embryotransfer. It is specifically suitable for women with PCOS, older women and for those who did not achieve success through long protocol stimulation.
Course of stimulation
How does ovarian stimulation take place?
For success of artificial fertilisation treatment method it is necessary to gain quality eggs. The more quality eggs we have, the higher the probability of producing quality embryos for embryotransfer. However, with the number of retrieved eggs increases also the risk of complications - the ovarian hyperstimulation syndrome (OHSS).
The number of released eggs is influenced also by the age of the patient, the condition of her ovaries (ovarian reserve) and type of stimulation protocol. Correct and controlled stimulation leads to growing and ripening of an appropriate number of follicles and gain of sufficient number of eggs. It is therefore absolutely crucial to use all the medicaments as prescribed by the treatment plan.
How to use stimulation medicaments?
The method is individual for every woman. The patient uses hormonal prescriptions according to a carefully prepared plan designed by the physician. On the 6th or 7th day of stimulation we perform ultrasound examination, during which we check the number and size of the individual follicles. Upon this examination, and if necessary, we increase or decrease the dose of the stimulating hormones. For the following 2 days(or 34-36 hours) prior to the planned egg retrieval the woman applies a hCG injection (Pregnyl), which triggers egg ripening.
OHSS - Hyperstimulation syndrome
It is a reaction of the ovaries to hormonal stimulation . OHSS is accompanied by pains in the lower abdomen, nausea, presence of loose liquid in the abdominal cavity and enlarged ovaries. More severe forms of OHSS with disorder of the internal environment, blood clotting disorder are nowadays very rare.
Prevention of OHSS includes careful monitoring of the hormonal levels during stimulation, regular ultrasound checkup of the ovaries and individual adjustment of dosing of the hormonal preparations used for stimulation.
How does egg retrieval take place?
Egg retrieval takes place after 34 – 36 hours after the application of hCG (Pregnyl ) under ultrasound supervision and in general anaesthesia. Every retrieved egg is checked under microscope, placed into a special cultivation dish and put into incubator.
On the day of the retrieval the woman comes in the morning on the given time (without make-up and also without any valuables). From the midnight of the previous day she shall not eat or drink anything and refrain from smoking.
What comes after egg retrieval?
After egg retrieval the patient stays in bed for about 2 hours, in the meantime she receives information about the number of retrieved eggs and quality of sperm (her partner hands over his semen sample on the day of the egg retrieval). After the procedure we can provide a sick leave certificate upon request.
After release from our clinic the patient needs to be accompanied on her way home, she must not drive a motor vehicle. After the procedure she starts using the medicaments prescribed by the physician. These medicaments are used until pregnancy test. If pregnancy is achieved, continue using them approximately until the 12th week of pregnancy, unless otherwise specified by the physician. Patients, who are taking other medications (e.g. Estrofem) are continuing taking them according to the physician’s recommendation.
Sick leave certificate after puncture
Ask the nurse at the reception and she will issue it for you.
Fertilisation (classical, ICSI, PICSI)
Classical artificial fertilisation - IVF
Classical artificial fertilisation is used for couples with good sperm count results and sufficient number of eggs . After retrieval eggs are placed in ideal conditions mimicking the environment in the human body. Treated partner’s or donor sperm is then added. After 24 hours following the sperm addition the embryologist checks, under a microscope, if eggs were fertilised. Success rate of fertilisation ranges between 50-70 % depending on the quality of sperm and eggs.
Injection of sperm into egg method - ICSI
This micromanipulation method involves implanting of a single sperm directly into the egg. ICSI is performed using a special device - micromanipulator. Success rate of fertilisation ranges up to 90 %.
This method is suitable for couples with low quality of sperm or in couples where a low number of eggs were retrieved from the woman. In some couples (severe spermatogenesis disorder) the use of this method is inevitable. The principle of ICSI, which means selection of both sperm and egg, significantly enhances the chance of producing a quality embryo compared to classical artificial fertilisation.
Injection of selected sperm into egg method - PICSI
PICSI is a modification of the ICSI method, during which only mature sperm cells are used for fertilisation. Sperm cells are specifically selected using hyaluronan gel. Hyaluronan is a substance that surrounds the egg and participates on the egg-sperm bond. Only mature sperm cells are able to make this bond - those that are less prone to chromosomal anomalies.
Cultivation of embryos
Assessing the quality of embryos
Success of fertilisation is checked by the embryologist under a microscope after 16 - 18 hours following fertilisation. The produced embryos are called pronuclei. Their quantity depends on the quality of sperm, eggs and method of fertilisation. It is very difficult to assess the quality of embryos at the pronucleus stage. Assessment of the quality of embryos is performed during so-called prolonged cultivation. Special media allow for growth of embryos to higher stages. It is possible to determine embryos, which are developing normally, from those that are slowing or ceasing their development and in this way to select quality embryos for transfer. The decision about which day of cultivation is best for embryotransfer depends on the number and development stage of the individual embryos and is fully in the competence of the embryologist.
What is assisted hatching?
Developing human embryo is covered by a thin sheet. Before nesting in the uterine mucosa the embryo must leave this sheet. In some patients, mostly of higher age, this sheet is stronger. Facilitation of the journey of the egg from the sheets is called assisted hatching and is performed with laser in a laboratory. Some scientific papers have confirmed a higher chance of achieving pregnancy with this method.
ET - embryotransfer
When does embryotransfer take place?
Transfer of embryos into the uterus takes place usually on the 2nd, 3rd or 5th day following egg retrieval. The decision about which day of cultivation is best for embryotransfer depends on the quantity and development stages of the individual embryos.
How is embryotransfer performed?
Transfer is painless, is performed without general anaesthesia. It is similar to standard gynaecological examination. The physician inserts embryos into the uterus under direct ultrasound control. The patient and her partner can see the embryos on the screen and watch their journey into the uterus.
Return to normal everyday life after the transfer
After the transfer, the woman remains in a lying position for 10 - 15 minutes at the theatre. The nurse will then prepare all the prescriptions and show her to the cash department to pay for the treatment.
On the day of the transfer and on the following two days we recommend resting. From the third day following embryotransfer it is possible to return to your normal everyday life.
Pre-implantation diagnostics (PGD)
What is PGD
The basis of pre-implantation diagnostics is a genetic examination of the embryo prior to its transfer into the uterine cavity. Genetic examination takes place on a single cell taken from the developing embryo. Sampling usually takes place on the 5th day of the embryo’s development.
This intervention does not harm the embryo, because in its early stage it is able to easily compensate for the loss of cells.
When is this examination used
The most common reason for pre-implantation genetic diagnosis of the embryo is chromosomal disorder in one of the parents. Other reasons include previous birth of child with congenital developmental disorder, higher age of the woman, repeated miscarriages and long-term unsuccessful treatment of infertility.
What is cryopreservation?
Cryopreservation - freezing of surplus quality embryos belongs to the basic methods of a good embryological laboratory. Introduction of ultra fast freezing technique – vitrification – brought significant improvement in the survival of frozen and thawed embryos and to significant increase of cryoembryotransfer success.
Success rate of cryopreservation
At our clinic we vitrify only quality embryos in the blastocyst stage (5th or 6th day of cultivation), which ensures up to 95 % success rate of survival of these embryos. The head of our laboratory performs personal checking of the embryo’s quality and decides whether or not they are suitable for freezing.
Benefits of cryopreservation
Nowadays, when worldwide trend tends to limiting the number of embryos for embryotransfer, vitrification is an integral part of treatment and gives our patients more chances for succeeding after a single stimulation. Cryoembryotransfer eliminates the risk of ovarian hyperstimulation, the need for general anaesthesia and it is very economic.
Cryopreservation is a technique of freezing gonoblasts using special media for preservation in liquid nitrogen at a temperature of -196 °C. This method can be applied to the preservation of gonoblasts for many (even tens of) years.
Conventional cryopreservation enables the preservation of embryos and sperm samples. Advanced ultrafast freezing (vitrification) also enables the preservation of eggs.
We do believe that you will be satisfied with our care and our approach.
MUDr. Marek Koudelka