In vitro fertilization: on the path to happy motherhood
Birth in 1978 of Louise Brown, conceived through in vitro fertilization ( IVF) method, became a huge breakthrough in the treatment of infertility. The technology of "in vitro" fertilization has critically changed the treatment options for infertile couples, leading to the emergence of various ancillary assisted reproductive technologies (ART). Just 20 years elapsed, in vitro fertilization technique became true reproductive medicine cornerstone and today in daily use of IVF clinic we find technologies that only generation ago seemed a kind of science fiction. Namely through in vitro fertilization, many infertile couples earlier unsuccessfully treated by other methods, have born healthy children. More than two million of IVF-conceived children were born in the world by this date.
Artificial insemination in Odessa
Stages of infertility IVF-treatment:
The IVF process is a newest advancement of modern medical science
Reasons for IVF failure
The IVF cycle involves several stages, compulsory requirement for successful transition to the next stage being effective overcoming the previous one’s problems:
Following this scheme, the implantation still remains a kind of mystery to scientists, asking why not every embryo becomes a child?
Using modern technologies, we have been successful in getting the embryos in the laboratory, but still can not control the implantation process. We do not know which embryo will succeed becoming a child, that brings sometimes a lot of frustration, both to the doctor and the patient.
IVF in Odessa
The implantation embraces a very complex process. First of all, the embryo must continue developing to the blastocyst stage, and then leave his shell (pellucide zone). The hatched blastocyst further should be implanted in the uterine endometrium within a short period of time, called the implantation window. Three main phases of implantation are known as opposition, adhesion and invasion. Opposition, or embryo orientation in the uterus, starts at the moment when the uterus is reduced due to the maximum absorption of the fluid located therein by pinopods (small lumpy formations appearing on the outer membrane of the uterus lining cells). Adhesion of the blastocyst represents a chain of biochemical reactions resulting in its attachment to the endometrium . Many molecules such as cytokines, growth factors and integrins play an important role in this complex process, when the blastocyst and maternal endometrium come into a kind of "dialogue". Invasion represents a self-controlled process that allows deep penetration of embryonic trophoblast (blastocyst cells, which later become placental cells) into the maternal caducous tissue (endometrial cells, which later form the maternal part of the placenta) and infiltrate into the endometrium bloodstream. This is due to the production of special chemical substance called proteinase. For blastocyst successful implantation also very important are the immune mechanisms to ensure dialogue between mother and embryo tissues, genetically and immunologically distinct. Activated caducous cells and trophoblast cells produce large amounts of immunologically active substances causing the necessary immune reactions.
Assisted reproductive technology in Odessa
The process of internal regulation and mechanisms of implantation remains a mystery, but it is worth noting that this process for humans has surprisingly low efficiency. It turns out that the nature is not always so competent as expected. An absolutely healthy couple has only 20-25 % chance to conceive during each menstrual cycle. Thus the responsibility for such a low efficiency is carried by the embryo by itself and the abnormalities in the embryo – endometrium dialogue. Today, we know that one of the main reasons for embryos’ unsuccessful implantation refer to its genetic pathology. The fundamental research in this domain are of great interest because, apparently, namely the implantation is a major factor limiting the effectiveness of ART. However, we need a lot more to learn before we can really control this process.
Failed IVF cycle analysis
Having not get pregnant after the first IVF attempt, of course, the patient will be very upset and disappointed. However, we must remember that here we are at the early beginning that should never be sought as the total fail. After an unsuccessful IVF cycle, the patient consults the attending doctor to analyze what conclusions can be drawn; here the doctor pays much attention to the quality of embryos and endometrium, as well as other important points :
Even if you do not become pregnant, the very fact that you have tried through IVF, will allow you living with the thought of having done all that you could , using the latest technology modern medicine has to offer.
Repeated IVF cycle
Most doctors recommend to wait at least one month before starting the next cycle of treatment. Although medically possible is to conduct repeated IVF cycle in the next month, most patients require a break to gather strength and to restore emotional balance before starting all over again. Depending on the previous cycle results, the doctor may introduce some changes into the treatment regimen . Ex.g. the ovarian response to stimulation being insufficient, the dose for inducing superovulation can be increased, or the stimulation protocol can be reviewed. If fertilization has not occurred, you may need ICSI. The ovocytes’ quality being insufficient, the doctor may recommend the use of donor ovocytes. However, if the previous cycle results were satisfactory, the doctor may recommend repeating the same regimen as the experience witness: often all that is required for the IVF cycle patients’ success, these are time and another attempt. Interesting is that the couples undergoing repeated IVF cycle, are usually much calm and better control the situation. Perhaps this is due to the fact that they are already aware of the necessary medical procedures , being better prepared, as well as to that they have already established personal contact with the doctor and the clinic staff.
Medical risks associated with IVF depends on the stage of treatment. Superovulation stimulation entails the risk of ovarian hyperstimulation syndrome (OHSS). The OHSS is caused by the development of a large number of follicles (over 15) and respectively the ovaries’ high activity, leading to high levels of estrogen (female sex hormone) in the blood. High levels of estrogen contributes to disorder of vascular permeability, resulting in that the fluid from vessels emerges first in the pelvic cavity and then into the abdominal cavity. As a result, the accumulation of fluid in the peritoneal and pleural cavities may cause the patient feeling distension, nausea, vomiting, anorexia. About 30% of patients undergoing ovarian stimulation , reveal the mild OHSS, to overcome which it is enough to limit physical activity and take painkillers . When the OHSS average degree the patient’s body accumulates fluid in the abdominal cavity, that involves pain in the region of the gastrointestinal tract. These women are in need of constant supervision, but usually outpatient treatment care is sufficient. Gradually, such patients’ condition improves without intervention, but in the case of pregnancy the improvement process may take several weeks. 1-2 % of patients demonstrate severe OHSS, characterized by fluid accumulation in the peritoneal and pleural cavities, electrolyte disturbances , increased blood clotting , and. sometimes, clots in the blood. If there arise difficulties in breathing, the condition may require fluid pumping from the abdominal cavity. Patients with severe OHSS do require hospitalization to improve their condition, which may take several weeks As a rule, after superovulation stimulation for some time the ovaries are enlarged in size up to 1.5 - 2 folds. This is due to the fact that at the aspirated follicles place formed are the "yellow bodies", supporting pregnancy up to 10-12 weeks. Enlarged ovaries become extremely mobile, and can, in rare cases become twisted on its bonds. Ovarian torsion leads to deficient blood circulation and subsequent necrosis,id.e. death of the ovary. The torsion reveals with sharp pain, of constantly increasing intensity. In such situations necessary is the laparoscopic surgery for ovary "untwisting", or, when irreversible changes occurred, removal of ovary part or whole organ. Another rare complication that requires laparoscopic surgery relates to bleeding from enlarged ovarian cysts. The bleeding is manifested with general weakness, drowsiness, palpitations, sometimes abdominal pain. After embryo transfer, patients should carefully monitor their condition. In order to prevent the development of serious complications, advised is to limit physical activity and to exclude sexual contacts during the first two months of IVF-induced pregnancy. Although some earlier publications supposed that the stimulant drugs’ use may increase the risk of ovarian cancer, numerous recent studies have found no association between the drugs to induce superovulation and ovarian cancer, or other organs oncology. Certain risk is associated with the ovarian puncture procedure. It can involve the same complications as any surgical procedure requiring anesthesia. In addition, puncture carries a small risk of bleeding, infection, injury to the bladder, bowel or blood vessel. However, some operative intervention to eliminate complications after ovarian puncture is required for less than one patient in a thousand. In rare cases, it may happen the inflammatory process development after the embryo transfer. During pregnancy and childbirth there may appear different pathologies of fetal development, ectopic pregnancy, spontaneous abortion, stillbirth, multiple pregnancy and birth of a child with congenital abnormalities. When being IVF-treated, the patient should know that by itself such factors like infertility, age, multiple-pregnancy may increase the risk of premature birth or stillbirth. The multiple pregnancy increases the preterm birth risk and risk of neurological diseases such as ICP. When multiple pregnancies (pregnancy with twins or triplets) required is the supervision of an experienced obstetrician - gynecologist who, if necessary, will refer the patient to a medical facility having appropriate neonatal service. The risk of multiple pregnancy is actual whichever option of assisted reproductive technologies being, due to the transfer of more than one embryo. While many patients believe twins very good outcome of treatment, multiple pregnancy is associated with many problems during pregnancy and childbirth, and these problems are much more common and become more serious in the case of triplet pregnancy and each subsequent fruit. Women with multiple pregnancies may need to spend weeks or even months in bed or in the hospital trying to avoid premature birth. Risk of preterm birth when multiple pregnancies is very high, and children may be born too early to survive. Premature babies require prolonged, intensive care and often have multiple health problems throughout life.
Assisted reproductive technology in Odessa
Some couples may consider the possibility of multiple pregnancy reduction to reduce the risks associated, but it is likely to be a very difficult decision. At selective reduction the development of one or more embryo is stopped (normally by administration of toxic chemical substances such as potassium chloride, in the heart of the fetus under ultrasound control) . In most cases, this fetus is then reabsorbed, the others continuing to develop. Of course, there exists the risk of all fetuses’ loss as a result of abortion (when accidental injury at reduction procedure), and it amounts to about 10% even when this procedure is performed by a very experienced physician. Bloody spotting in the pregnancy first trimester may indicate a miscarriage started or ectopic pregnancy. Spotting started, the patient urgently needs to be screened for cause identification. According to some reports, early spotting is more common for women after IVF , but that is not necessarily linked to the risk of pregnancy cease, just as in the case of women who conceive naturally. Therefore forbidden is to stop independently taking drugs for pregnancy support, administered after the embryo transfer as early spotting does not always mean the beginning of menstruation. Risk of ectopic pregnancy after IVF amounts to 2-3% . The ectopic pregnancy does not happen because of the IVF procedure itself, but due to the fact that many women undergoing IVF treatment have damaged fallopian duct which increases their susceptibility to ectopic pregnancy. Risk of inborn pathology in the case of IVF does never exceed the risk of birth defects with natural conception. Certain risk of genetic abnormalities exists regardless of whether the child is conceived through IVF or naturally. During ICSI applied because of severe male infertility the genetic defects causing the male infertility, can be transmitted from father to son. The assisted reproductive technologies require significant physical, financial and emotional expenses from the couple. There exist chance of psychological stress, and many couples say that experiencing real psychological shock and the necessary treatment is very expensive. Typically, patients hope only for a favorable outcome, but the treatment cycle may end also in failure. The patient may feel frustration, anger, resentment and loneliness. Sometimes frustration leads to depression and low self-esteem, especially immediately after a failed IVF attempts. At this point very important is the support of friends and relatives. As an additional means of support and stress management advised is to visit a psychologist who can help overcome stress, fear and moral pain associated with infertility and its treatment.
ICSI (intracytoplasmic sperm injection) is a relatively new, but already well-established laboratory procedure, which was for the first time performed in 1992. ICSI has been developed to overcome the male infertility factor. With ICSI a single sperm introduction into the ovocytes cytoplasm ia produced using a fine glass needle. In 1992T has been born first child in the result of ICSI. The ICSI replaced the two laboratory techniques previously used - PZD (partial dissection of the pellucide zone) and SUZI (insemination under pellucide zone), since it allows much higher percentage of fertilization.
In this section you will find complete information about ICSI procedure:
Description of ICSI
ICSI under the microscope
The first stages of ICSI are the same as under the standard IVF cycle. The woman obtains injections of hormonal drugs that stimulate the maturation of multiple follicles in the ovaries. The ova are removed during an outpatient procedure under ultrasound control and placed in a special culture medium. After obtaining ova they are examined under a microscope to assess their quality, afterwards they are placed in the incubator for 2-6 hours, then the cells surrounding the oocyte are removed to evaluate the degree of maturity of oocytes as ICSI can be performed only with mature ovum. Immature oocytes can be left in the culture medium for ICSI assigned to the next day, when they will be ready. Spermatozoa obtained from the ejaculate by testicular biopsy or epididymal biopsy ( TEZA / TEZE / PESA ), are treated with special environments. Sperm cells may also be obtained from a frozen sperm sample. After assessing the maturity of oocytes the sperm is placed in a special environment, where a sample is selected of sperm with normal morphology; the immobilized sample is suck on the tip of a very fine glass needle and then injected directly into an oocyte. The oocyte thus is held in place by gentle suction on the opposite side of the holding pipette. This is a very delicate procedure and its implementation requires a micromanipulator . This sequence is repeated for each of the obtained mature oocytes. Ovum membrane is very elastic, and the microscopic hole of microneedles is very quickly recovered, but about 1% of oocytes may be damaged during the ICSI. The next morning the oocytes are examined to verify fertilization. Developing embryos are cultured for the next 2-5 days, during which fragmentation and their further development takes place. Not all fertilized eggs begin splitting, and some embryos can stop in development at the earliest stages. Usually 2 embryos (in exceptional cases, 3 embryos) are transferred in the uterus. The remaining embryos of good quality are cryopreserve for future transfer into the uterus. The drug therapy for luteal phase support is administered in the same manner as after standard IVF cycle.
IMSI as advanced ICSI version
The most important ICSI point is sperm selection for incorporation into the ovum. Since in this case no natural selection factors, the embryologist must carefully select the best sperm and exclude sperm with abnormal morphology present in every man’s ejaculate. Influenced with reactive oxygen species the apoptotic bubbles are formed in spermatozoa that lead to damage: sperm DNA fragmentation, that drastically reduces the chance of pregnancy after embryo transfer resulting from in vitro fertilization of ovum with such sperm.These defects can not always be detected through a conventional microscope observation. To detect such apoptotic defects used is a special high-contrast ultrahigh resolution video microscopy system, especially designed and custom-built at optical plant following the high accuracy technical specification. This method of sperm selection takes much longer time than conventional ICSI, however, it can significantly improve the IVF efficiency when severe male infertility factor. Such method of sperm selection is also used by several the leading clinics in the world, where it is called IMSI (intracytoplasmic morphologically normal sperm injection) .
To date, the ICSI is used along more that 15 years, and hundreds thousands of children around the world are born of after such procedures. The percentage of fertilized oocytes after ICSI is about 70% and about 80 % of fertilized oocytes begin their normally development. The risk of none oocyte fertilized as a result of ICSI is less than 5% . The ICSI efficiency is comparable to the effectiveness of conventional IVF , but it can vary greatly in different clinics directly depending on the experience and professionalism of embryologists. Other factors affecting the pregnancy rate after ICSI include the woman's age, duration of infertility and the number of embryos transferred .
In addition to the well-known risks associated with standard IVF procedure, previously several experts argued the possible additional risks related to the ICSI procedure. Basically such risk concerns the fact that the defective sperm will be introduced into oocyte, because ICSI bypasses the natural selection stage sperm for fertilization, therefore that could lead to the birth of sick children. In addition, there were concerns that as a result of ICSI a defective oocyte can be fertilized (when natural conception and during standard IVF a natural selection process is applied, and the probability of defective oocyte successful fertilization is small ) However, the overall issues of studying health of children born after ICSI are very encouraging , although we still do not have enough information about the long-term aspects of the procedure There exist some data about a larger probability of genetic abnormalities occurrence for children after ICSI, in particular Shreshevsky-Turner's syndrome and Kleinfelter's syndrome (1.2% compared with 0.5% in the general population). However, there is no reason to assume that it is connected with the ICSI procedure, because ICSI is usually performed in cases of severe male infertility factor, the genetic diseases, in all probability, having led to problems with his father spermatogenesis can be transmitted by inheritance to the child.
This is supported by studies that found an association between male infertility and the following pathologies:
You can assign a visit to Reproductive health medical centre “Gameta” reproductive gynaecologist calling by phone 738-68-69
Intrauterine insemination represents the introduction of the partner’s or donor’s specially treated sperm (sperm washed from seminal plasma) into the uterine cavity through a plastic catheter inserted into the cervical canal (cervix) .
Intrauterine insemination – diagram
Artificial insemination by husband material is recommended in the cases of unexplained infertility, a slight decrease in sperm quality or difficulty during sexual intercourse. Artificial insemination can be administered in parallel with ovulation induction drugs, or natural (unstimulated) cycle, depending on the particular situation. To stimulate ovulation administered are the clomiphene citrate or gonadotropins. Ovulation stimulation increases the insemination efficiency because it leads to the maturation of two or three follicles, rather than one, as under normal menstrual cycle. A side effect of stimulation is to increase the risk of pregnancy with twins or triplets. To determine the correct time of artificial insemination applied is the ultrasound monitoring beginning from 8th -9th days of the menstrual cycle. When the dominant follicle reaches a size of 17-18 mm, an infusion of hCG to induce final oocyte maturation and ovulation is injected and by 12-40 hours after hCG injection (in periovulatory period) performed is the artificial insemination. In general, the multiplicity of inseminations during one natural or treatment cycle is determined by the estimated time of ovulation, the nature of the ovaries’ response to the ongoing ovulation stimulation and can range from 1 to 2 procedures. The specially treated sperm is placed in a syringe coupled to a thin plastic catheter. Before insemination the spermatozoides should be separated from the seminal fluid as it can irritate the uterus and cause severe cramping and pain. Sperm washing also allows to select the most motile sperm. During the procedure, the doctor gently introduces insemination catheter into the uterus through the cervical canal, and then slowly injects sperm. The insemination procedure is painless and requires no anesthesia.