Ovarian minimum stimulation is for women who do not wish to undergo an IVF with the usual stimulation. In this case the tablet of Clomiphen citrate (Clostilbegyt) is used for stimulation in combination with low dose injections which are used for classic IVF stimulation. The fertilization of eggs is done by using the ICSI or PICSI method. The probability of conception is lower than in classic IVF but risk of OHS is lower, and is financially less demanding.
In practice is the minimum stimulation used in those cases:
- Previous stimulation was complicated by ovarian hyperstimulating syndrome.
- A woman is afraid of higher dose hormonal stimulation.
- For women with polycystic ovary (PCO).
- Repeatedly failed infertility treatment using IVF.
- Where it is necessary to lower the cost.
The first successful attempt for artificial fertilization was performed in 1978 when thanks to Dr. R. Edwars and Dr. P. Steptoe was the first child born as a result of the IVF/ET method (Louise Brown, Great Britain). More than 3.7 million children conceived using assisted reproduction methods are born around the World every year.
It is a complex of procedures when the egg and sperm are manipulated outside of the female body.
Following the hormonal stimulation leading towards a higher number of mature eggs these are retrieved straight from ovaries and brought in to a special cultivation solution together with selected sperm. After the fertilization eggs are cultivated in to embryos in special mediums completely naturally without any other intervention. Embryos are later transferred back in to the women’s body.
Preparation for IVF:
Multiple growth of follicles increases the chances for achieving a bigger amount of quality eggs and consequently more embryos suitable for transfer. This is achieved by hormonal stimulation under constant doctor’s control.
The egg retrieval is performed under short general anesthesia guided by trans-vaginal ultrasound and it takes about 5-10 minutes. The procedure is done with a special thin needle, which goes via vaginal whole straight to an ovary. From there are the eggs suctioned. The patient is discharged about 2 hours post procedure.
The sperm collection and preparation:
A sperm sample is collected from a partner on the day of egg retrieval in special room. Sexual abstinence is recommended 2-5 days prior the collection in aim to get the best possible quality sample. Following its laboratory preparation eggs are fertilized by partner’s sperm in a special solution. Fertilization happens spontaneously, the sperm moves towards the egg and penetrates its shell. The common cultivation of eggs and sperm lasts 16-20 hours. After this time the embryologist finds out about the success of fertilization which is proved by the presence of two pronucleus and two polocyts.
If the man is in any doubt about the ability to give a sample in the day of egg retrieval, he can use the option of cryopreservation in advance.
For men who have no sperm in the ejaculate is MESA/TESE one of the options to get the sperm in IVF cycle.
Embryos are cultivated in thermostat in special mediums for 2-6 days. After this time they are transferred in to the uterus. Surplus embryos can be frozen and stored for potential use in the future.
Is a procedure when the embryos are brought back in to the womb cavity using a special thin catheter. Embryos are transferred together with a small volume of the media. This procedure is quick and in most cases painless, does not require GA. The number of embryos transferred is depending mostly on the age of the patient, number of previous failed IVF cycles and on wishes of the patient. Mostly 1-2 embryos are transferred. The patient is leaving the Clinic in about 1 hour post ET. One week after the transfer the patient is coming back to the Clinic for pregnancy test.
Extended embryo cultivation is a method which improves the results of the conception by techniques IVF and ET. Eggs, sperm and embryos are stored in a special media (cultivation solution) which is creating suitable conditions for its development. Cultivation solution is exchanged every day in the aim to provide conditions for the development of embryos as natural as possible.
Cultivation to the state of blastocyst
By using the special solutions it is possible to extend the time of cultivation of embryos for up to 5 or 6 days (state of a blastoyst). The benefit of this procedure is the option to choose the best quality embryos for transfer and increase the chances for pregnancy. Use of the long cultivation is suitable especially when the number of mature eggs is sufficient (6 and more). Determination of an optimum date for ET is very individual and can be different in repeated cycles.
A additional technique during which a small hole is made into the shell of a 2-4 day old embryo. The embryo then uses it to leave the shell. It is recommended to use this technique for embryos with thicker shell or in cases of repeated implantation fail (in previous cycles the embryo did not implant spontaneously).
Freezing of embryos is a method thanks to which we are able to preserve surplus quality embryos for as long time as needed. They are kept in liquidized nitrogen and ready for later transfer. Cryopreservation in used when there is enough of quality embryos which have not been transferred in given cycle (for example for the risk of multiple pregnancy). In case of serious Ovarian hyper-stimulation syndrome or not suitable conditions for transfer (other illness of the patient, low lining etc.) all of the embryos are frozen. Despite of standardization of the procedure not all of the embryos will survive the defrosting in a condition suitable for transfer.
The success rate of the transfer of frozen embryos-defrosted embryos (cryo-embryo transfer) is lower than with fresh embryos. For the lady this is more convenient as she does not need to repeated hormonal therapy and egg retrieval. Based on current knowledge there is not know increased risk of abnormalities or congenital developmental defects caused by this method.
PGD, PGS are diagnostic methods, which enable us to test some of the genetic attributes of embryos prior their transfer in to the uterus. From an embryo (D3) we are able to extract 1 or 2 cells and put them through the genetic analysis. Embryos usually survive this procedure without any harm and are developing in a normal manner.
The pre-implantation screening helps to discover obtained or inherited deviations in the number or the structure of a chromosome. These abnormalities are often connected with spontaneous abortion.
Using pre-implantation tests we can also discover changes (mutations) of particular genes connected to particular inherited disease which has occurred in the family (PGD).
PGS and PGD methods are recommended to couples when:
- The age of the lady is over 35 years and therefore the risk of a birth of a child with higher number of chromosomes (i.e. Down syndrome) is increased.
- There occurred a miscarriage or birth of a fetus with chromosomal deviation.
- There are repeatedly failed IVF treatments or repeated miscarriages in early phase of gravidity.
- There is known chromosomal conversion in one of the partner’s results. Without been obviously affected this could lead to a production of affected sperm or eggs and handing it over to descendants.
- Where there is an illness connected to sex (the illness affects males only, but it is handed over by female – for example hemophilia).
- When one of the partners underwent or is undergoing chemotherapy or radiotherapy.
The Pre-implantation diagnostic can not fully guarantee the choice of an embryo which has no defect. It is given by the principle of the method. We can test only particular spectrum of deviations which could compromise the embryo of a given couple the most. As well as we are unable to guarantee the success of the IVF program meaning implantation of an embryo after the transfer and creation of a pregnancy. We can not guarantee birth of a healthy child. All this is affected by loads of other factors.
A revolution in the male infertility was the news in the 1992 about first pregnancies achieved by injecting single sperm in to the egg through its shell (zona pellucida). This method helps countless couples who’s cases were hopeless and were forced to use a donor sperm only few years before.
The method of ,,intracytoplasmatic injection of sperm (ICSI) is a elaborate micromanipulation technique when the sperm is aspirated in to a thin sharp glass capillary and inserted in to an egg through its shell.
Indication for ICSI is the inability of the sperm to fertilize the egg spontaneously (low count, low motility), immunological causes of infertility, failing of classical IVF cycles, later age, low amount of matured eggs, when cryo-preserved sperm is used or when the sperm is collected by MESA/TESE method, when donors eggs are used etc. This method has a very high success rate of fertilization. The patient has to indeed undergo the normal procedure of super-ovulation and egg retrieval and the partner has to provide the sperm. In the view of collected data we can say that by fertilization of the egg using this method is not increased risk of a child with congenital developmental defect when compared to spontaneous conception.
This is a laboratory technique (improved ICSI) which enables us to pick and transfer only single one mature sperm in to the oocyte. This increases the success rate of the infertility treatment. Naturally only matured sperm able to specifically connect to so called oocyte’s complex (hyaluronan) are able to fertilize the egg. In mature sperm was demonstrated much lower appearance of chromosomal aberrations than in immature one.
When using only the simple ICSI method the sperm is picked by its morphology and motility. This does not guarantee the sperm with optimal genetic pack will be chosen. PICSI method combines the benefits of ICSI (high probability of fertilization) with the possibility to pick the mature sperm based on its ability to connect with the hyaluronan hydrogel. PICSI is imitating the connection of the mature sperm to the oocyte’s complex which is very important for the selection of suitable sperm during the natural fertilization. This technique is possible to use only under the condition that there is enough sperm with good motility in the ejaculate.
How to increase the chance of embryo implantation?
Clinic of Reproductive Medicine and Gynaecology Zlín offers modern methods for increasing chances for succesfull treatment.
EmbryoGlue® is a special cultivation medium used for transferring embryos to the uterus. This medium contains all the necessary nutrients and energy sources which are needed for optimal embryo development. It also contains a higher concentration of hyaluronan, which is naturally present in follicular, oviductal and uterine fluids where it increases the viscosity of those fl uids.
Clinically proven results of the use of the cultivation medium EmbryoGlue containing hyaluronan (source:Vitrolife)
Therefore, using EmbryoGlue® will increase the likelihood of pregnancy compared to using mediums without hyaluronan. It is possible to use EmbryoGlue® in all stages of embryo development. It can be used for fresh embryo transfers as well as for frozen embryo transfers. EmbryoGlue® is an extra procedure and the Embryology team need to prepare this medium in advance of its use. Please inform us should you wish to use it at any stage during your preparation for treatment.
The process of embryotransfer with the use of the cultivation medium EmbryoGlue (source: Vitrolife)
Request for application of this procedure has to be announce prior the start of the cycle. The price of the procedure is 120 EUR.
MESA- microsurgical aspiration a of the sperm from a epididymis. A procedure performed in case of distraction of a sperm transport between epididymis and urethra. The procedure is in most case performed as an open surgery in general anesthesia. That mean via cca. 3cm long cut in the scrotum access to the ipididymis is gained and the fluid is aspirated using a pipette straight from the channels. The fluid is analyzed during the procedure in the embryology laboratory. If some live sperm is present it is used for eggs fertilization using the ICSI method.
In the case there has been no sperm obtained during MESA we proceed to TESE. This is a procedure when we can get the sperm from the epithelium if the sperm is unable to travel from the testicle in to the epididymis.
Via a small cuts in the testicles cover we get a piece of the tissue. This is proceeded in the lab. If any live sperm is present it is used for fertilization. If azoospermia(no living sperm) is repeatedly confirmed, gain of a suitable sperm is not guaranteed using these methods. The patient is informed about the outcome of a procedure straight post procedure.
Diagnosis of infertility
Assessment of the fertility of a couple is a progressive process. Detail evaluation and examination of both partners helps to find the cause of infertility followed by a successful treatment. In some cases the diagnosis is simple in others it needs a deeper and more elaborate investigation.
Evaluation of all of results will give your doctor a good idea about the possible cause of the infertility and then he will be able to help and offer a optimal treatment. At the present time we are able to help up to 95% of infertile couples.
Diagnostic methods for women:
The basic examination of a woman is a trans-vaginal ultrasound of the uterus and ovaries considering the menstrual cycle, followed by gynecological examination. The ultrasound exam helps to evaluate the size and shape of the uterus, presence of any fibroids, thickness and quality of the endometrium. It also provides the information about the shape of ovaries, growth of follicles, and presence of cysts or endometriosis.
The blood test during first 3 days of menstruation gives the information on the condition of ovaries, their ability to produce mature eggs and potential answer to hormonal stimulation. Levels of The follicle-stimulating hormone (FSH) and luteinizing hormone are looked at. It is possible to determine a level of Anti-Mullerian hormone (AMH) which also informs about the ovarian reserve. A standard part of hormonal profile is a prolactin level (PRL) and thyroid hormones levels (TSH, FT4).
X ray test of the uterus allow us to see the shape of the uterus cavity and patency or obstruction of fallopian tubes. Test is done by gynecologist. A special device is inserted in to the cervix and a dye is slowly injected. Its flow is visible on the x-ray.
This is a method that enable us to visualize the uterus cavity and perform a small operation within the cavity and the cervix, removal of polyps, adhesions and septum removal. We do this at our clinic using a special optical device of a 2 millimeters gauge thanks to which we can do most of the procedures without general anesthesia.
Laparoscopy is a diagnostic method used to carefully look into the abdominal cavity and check the fallopian tubes. Laparoscopy belongs to so called minimal invasive surgery methods. Using special devices and techniques it is possible to visualize the abdominal cavity through few small cuts and perform needed surgery without opening the abdomen itself. Laparoscopy is performed for diagnostic or therapeutic reasons.
This is a examination of chromosomes that gives us an idea about the genetic profile of both partners. Abnormal findings could be one of the causes of infertility. They could also lead to a failure of the assisted reproduction methods. It could potentially lead to a repeated abortions. In men with pathological findings a failure in sperm development occurs. In those cases the tests for cystic fibrosis is advised which is often present along with those problems. And also a test for pathological micro deletion of the Y chromosome.
Immunological test is a basic part of fertility testing of women at our clinic. Antibodies against sperm, eggs and embryos are detected as well as anti-phospholipid antibodies. Where indicated (repeated miscarriages, repeated failing of assisted reproduction methods) the cell immunity is tested.
Diagnostic methods for men:
- Sperm analysis.
- Sperm cultivation.
- Andrological test.
- Sperm acrozom testing.
- DNA fragmentation of sperm.
- Immunological tests.
- Hormonal tests.