From infertility suffer in our population around 12% of couples and it presents important problem from the psychological, medical, social and financial point of view.
A couple is considered to be infertile after one year of unsatisfied trial for pregnancy. A revolution in the infertility treatment brought IVF method – in vitro fertilization. The infertility treatment through IVF method was originally evolved to treat patients with missing or remediless damaged fallopian tubes. Later it started to be used even for other indications of infertility treatment.
An individual method presents artificial insemination (IUI - intra-uterine insemination), which increases significantly the hope for reaching pregnancy in combination with suitable stimulation of ovaries in indicated cases. The causes of infertility that are the reasons for IVF treatment are following:
Tubal infertility
Tubal infertility is a main indication for in-vitro fertilization. It is a disease of fallopian tubes that causes their obstruction and therefore disables transport of the fertilized egg into the uterus. There are various severe damages of fallopian tubes. The most dangerous is so-called sactosalpinx – liquid in the obstructed fallopian tube created mostly on the basis of inflammation. The liquid has also toxic influence on the fetus in the uterus and can even unfriendly influence in-vitro fertilization treatment. Therefore it is recommended to remove the fallopian tubes before the treatment.
Infertility caused by andrology (male subfertility)
It is a male disease, by which there is a problem in sperm creation, i.e. the amount of sperm that is able to fertilize the egg and also in the mobility of sperm. Thanks to in-vitro fertilization there are tests that examine their fertility ability (for example CASA – computer assisted sperm analysis, HOS – hypoosmotic test, HZS – hemizona assay, ARIC – examination of acrosomal reaction) and more precise morphological sperm evaluation.
An important invention in the treatment of infertility caused by andrology is Intracytoplasmic sperm injection (ICSI). This method enables also treatment of men with azoospermia, either obstructive or non-obstructive (problem in the area of testicle). The sperm for ICSI is taken either from epididymis (MESA - microsurgical epididymal sperm aspiration) or directly from the testicle tissue (TESE – testicular sperm extraction). The choice of suitable procedure depends on the setting of the cause and type of disease.
Infertility by endometriosis
Severe endometriosis is frequent cause of sterility. It is present in 60% of infertile women during diagnostic laparoscopy. The tissue that lines inside the uterus grows into the abdominal cavity.
Immunologically caused infertility
In couples with immunologically caused sterility there are antibodies that negatively influence natural transport of sperm. It also causes disruption of fusion of egg and sperm during the fertilization and therefore also the evolution of fetus can be negatively influenced. Those antibodies are mainly antispermatozoid (ASA), antiphospholipide (APA) and antizonal (AZA). The antispermatozoid antibodies can negatively influence the transport of sperm, the actual fertilization or already created embryo.
Antiphospholipide antibodies are known mainly in relation with pregnancy complications (antiphospholipide syndrome). They are more often found in infertile women treated for IVF. They can negatively influence the follicular maturation, ovulation and also fertilization by its attachments to superficial structures to oocyte or sperm. Antizonal antibodies forming against zona pellucida disable normal process of egg fertilization.
Idiopathic (unexplained) infertility
It is necessary to eliminate hidden androgenic factor and immunological cause of infertility. Only then can be the infertility considered as unexplained. If the infertility lasts more than three years, the probability of impregnation without the treatment is very low and the IVF method is recommended.
Infertility requesting donated eggs
This treatment is indicated especially in patients without functional ovaries (Turner syndrome, premature failure of ovaries, surgical castration caused by medical reasons and so on). In special cases like genetic indication, ovaries inaccessible to puncture, syndrome of defected ovaries, repeated failure of IVF with own eggs or ovaries that do not react on stimulation, it can be used even in women with kept function of ovaries.
During treatment of infertility through donated eggs a complete hormonal substitution of a cycle is necessary. The aim is to reach hormonal support by absence of corpus luteum. Treatment through donated eggs is very successful.
 |
Stimulation of ovaries by methods of assisted reproduction
Stimulation and evocation of ovulation is made with hormones. In patients without menstruation or with prolonged cycle they have been used already for several decades. With the development of in-vitro fertilization they have started to be used even in women with regular ovulation and normal menstruation cycle. The reason is creation of more eggs and embryos of optimal quality by the stimulation. Good material is gained for IVF and extra embryos can be frozen and used in case of failure in another cycle of assisted reproduction.
Reactions on stimulation of ovaries differs individually and depends especially on the age (reactivity of ovaries reduces with age). Moreover it depends also on the ability of maturing eggs (follicles) to react on stimulation by hormone gonadotropin. In some patients so-called hyperstimulation syndrome can appear. It means excessive reaction on hormonal stimulation, when huge amount of eggs are formed. In case this syndrome is in full process, the health of the woman can be severely threatened. The liquid in the cavities is accumulated and the tendency for blood coagulation is increased. A greater risk for syndrome creation is in women with primary diagnosis of polycystic ovaries.
The stimulation is made by clomiphene citrate, which is a drug that reacts like antiestrogen and it causes increased production of gonadotropins by attacking natural regulations. The combination of clomiphene citrate (CC) and gonadotropins (hMG) has been the most used form of ovarian stimulation until the 80’s. New stimulating methods have gradually pushed away the clomiphene citrate from the usage n assisted reproduction.
The gonadotropins are follicle-stimulating hormone (FSH) and luteinizing hormone (LH), both necessary for normal process of steroidogenesis (production of sex hormones) and follicular genesis (the process of egg development). It is completed with chorionic gonadotropin (hCG), which replaces the ovulation increase of LH in the stimulating methods and enables optimal timing of the treatment cycle. Human menopausal gonadotropins (hMG) extracted from the urine of menopausal women is also used to evoke ovulation. Gonadotropins have been also extracted from the urine of menopausal women and they have contained the same amount of FSH and LH. Gradually the amount of LH has been reduced and now preparations with only clear FSH are produced.
Company’s names of used drugs – gonadotropins are with LH activity for example Pergonal, Metrodin, without LH activity e.g. Gonal – F, Puregon.
Other drugs used for stimulating methods – agonists GnRH stimulating creation of FSH and LH. There is long, short and ultra short protocol. In all protocols analogues of GnRH and gonadotropins are used. The dosage varies not only in the length but also in the success rate. The most effective is considered long protocol.
Last group of medications used by assisted reproduction are antagonists GnRH acting against stimulation of FSH and LH. These drugs can reduce the risk of creation of hyperstimulation syndrome.
Methods of assisted reproduction
Methods of assisted reproduction involve all medical processes and techniques that request manipulation with embryonic cells (eggs and sperm).
IVF/ET - in vitro fertilization and embryo transfer (transfer of fetus)
It is practically useful in almost all infertility disorders. IVF includes hormonal stimulation, monitoring of a cycle with ultrasound examination and setting the level of hormones in the blood. The eggs are taken from the vagina under the ultrasound control and afterwards they are fused with sperm in a “tube”. The sperm is prepared by centrifugation and washing device. The egg collection is done out-patiently only with analgesics intravenously.
The fertilized eggs are then cultivated in the laboratory. Also embryos can be cultivated. In such case it is a prolonged cultivation. Till 1994 there have been transferred maximum four embryos in the Czech Republic. Since 1999 three embryos. At present there is a tendency to transfer only one embryo because of frequent early childbirth of twins by IVF. The excessive embryos can be frozen and used in case of failure in another cycle. The embryo transfer is done with special sets. In case of so-called assisted hatching the embryo transfer is performed 20 minutes to 2 hours after micromanipulation. By developing ovarian hyperstimulation syndrome the transfer is not performed. Transport of the defrosted embryo into the uterus is called KET – cryoembryotransfer. Part of the whole process is also hormonal support and diagnosis of early pregnancy.
GIFT - transfer of gametes (eggs and sperm) into the fallopian tube
GIFT is an alternative method to IVF in women with functional and free fallopian tubes, most often in idiopathic infertility. Eggs and sperm are both transferred laparoscopically or transvaginally with the help of catheter into the fallopian tube. The laboratory part of the fertilization is simpler nevertheless this method is not almost used anymore.
ZIFT - transfer of zygote into the fallopian tube
It is a transfer of fertilized eggs, it is performed 24 hours after the collection. Today it presents already only rarely performed method.
 |
Some techniques of assisted reproduction
ICSI – intracytoplasmic sperm injection
The method consists in the direct injection of one sperm into the cytoplasm of mature egg. ICSI is dominating technique of assisted fertilization and next to IVF also most frequent method of assisted reproduction. The procedure is performed on the micromanipulation device that consists of microscope and micromanipulators.
AH – assisted hatching
It is a technique of gentle invasion of zona pellucida of embryo before its transfer to the uterus. It can be performed mechanically through cut with the use of micromanipulation device, chemically or also through laser micro beam. The aim of AH is to ease the release of embryo from the zona pellucida and to increase its ability to settle in the womb. Usual indication for assisted hatching is the age of patient over 35 years, repeated failure by fertilization of embryotransfer of good quality or also increased level of FSH. This method is also recommended in case of optically thicker zona pellucida.
Microsurgical sperm collection from the testicle or epididymis
In men with azoospermia (immobility of male sex cells) it is possible to obtain sperm surgically. ICSI must be used to fertilize eggs in sperm obtained in such way.
MESA - Microsurgical Epididymal Sperm Aspiration
In case of irredeemable obstructive azoospermia a collection of fluid containing sperm from epididymis is performed. The microscopically cut tubules are adequately treated after the procedure and the extra amount of sperm is used for ICSI. The rest of obtained sperm is frozen. An alternative to this technique is Percutaneous Epididymal Sperm Aspiration – PESA. It means suction of the liquid from epididymis with the help of pipette through skin. This technique is faster and is performed under local anesthesia.
TESE - Testicular Sperm Extraction
It is performed in men with non-obstructive azoosperm or in case of unsuccessful MESA or PESA. A tissue from testicle is taken and sperm is received from it in the laboratory.
Preimplantation genetic diagnosis (PGD)
PGD is frequent prenatal diagnosis related to techniques of assisted reproduction. It enables by genetic examinations of one to two cells (blastomeres) taken from the developing embryo to uncover specific genetic abnormalities of future fetus. The embryo is not damaged by this procedure because each cell in this stage is capable to develop itself. Examination of three to seven embryos is optimal. Usually trisomy of chromosome 13, 18, 21 and setting gonosome X, Y is examined. It is necessary to consult a geneticist for setting other diseases.
Freezing and storing eggs, sperm and embryos
Cryoconservation is a process of gentle freezing of sperm, embryos or eggs. They are stored in special containers with liquid nitrogen in -196°C. Freezing of sperm leads up to half reduction of the ability to reproduction. In spite that sufficient amount of moving sperm stays after defrosting for all types of insemination. Sperm is stored for donating insemination, possible sterility, radiotherapy or chemotherapy, preventive guarantee for cycles of assisted reproduction or excessive sperm after microsurgical collection.
Ruled controlled embryos freezing is done by two or three the most. The reason is excess of embryos in the IVF program, donation, hyperstimulation syndrome, storage before chemotherapy and radiotherapy etc.
Freezing of oocytes is possible in same cases as with embryos. Although research in this field is intense, the success rate of egg fertilisation after defrosting is low and so this process is not very common in routine clinical practice.
