Microinjection (ICSI) Treatment

Microinjection

IVF treatment consists of assisted reproductive methods along with many techniques that offer solutions to very complicated problems such as infertility, which prevent having children in normal ways. Approximately 3 million babies in our country have been born with IVF treatment method. The majority of these babies were born after a successful pregnancy process with the microinjection technique. Microinjection technique is the injection of a single healthy sperm cell obtained from the father-to-be directly into the egg cell obtained from the mother-to-be with a thin injection under the microscope and subjected to fertilization.

Microinjection method provides the opportunity to have a child with a single quality sperm obtained from fathers with insufficient sperm count and motility. For this reason, it is the most preferred method today because a healthy fertilization process is performed with only one motile sperm and sufficient morphological characteristics among the sperms that are not capable of fertilizing the egg. The stages after it is brought together with the egg proceed as in IVF treatment.

What is the difference between IVF and microinjection?

Classical in vitro fertilization (IVF) is the selection of the best quality embryos resulting from bringing together a large number of reproductive cells obtained from the mother-to-be and father in a laboratory environment and transferring them to the uterus of the mother-to-be. In the microinjection technique, only one of the sperms obtained from the father-to-be is injected into the egg cell with a special medical injection under the microscope.

In short, as a result of bringing together more than one reproductive cell in the laboratory environment with IVF, the sperm is expected to fertilize the egg cell on its own. However, in the ICSI technique, a single sperm is injected directly into the egg and subjected to fertilization. Apart from this, there is no difference between IVF and microinjection technique. Other procedures are performed as in classical IVF stages.

What are the advantages of the microinjection (ICSI) technique?

In the microinjection technique, the possibility of fertilization is higher by directly injecting the sperm cell into the egg. In addition, it is much more difficult to obtain embryos in classical IVF treatment for fathers who do not have sufficient sperm count and quality. Even in cases of azoospermia, where no sperm is found in the semen, in vitro fertilization treatment is not possible. However, in the microinjection technique, sperm cells can be obtained from the testicles of the father-to-be with micro-TESE and fertilization can be performed even with sperm, which has the ability to fertilize only one egg cell.

How is the microinjection technique performed?

The highest quality sperm cell is determined by examining the semen sample of the father-to-be. It is taken by means of a sensitive microscopic catheter without damaging the tail structure that provides the mobility of the sperm cell. Then, it is injected into the egg cell obtained from the mother-to-be and subjected to fertilization. However, before the microinjection procedure, the mother-to-be should be in the metaphase 2 stage where the egg cell is mature.

Who can benefit from microinjection (ICSI) technique?

• Cases with very low sperm count and azoospermia
• More than 95% defects in sperm morphology
• Those who have not been successful in classical IVF treatment before
• Couples undergoing preimplantation genetic diagnosis (PGD)
• Cases of unexplained infertility
• Anti-sperm-antibodies that cause infertility

What is the chance of pregnancy with microinjection technique?

Pregnancy rates obtained by microinjection method are higher than classical IVF treatment. However, if the egg reserves and egg quality of the mother-to-be are good, which affects the success, fertilization occurs between approximately 50-80%. However, according to the existing problems, not all embryos obtained may result in pregnancy.

Sperm Selection in Microinjection Method

It is necessary to select quality sperms to increase the chances of pregnancy. A quality selected sperm cell may be good in terms of its appearance, but it may not give an idea of the excess, deficiency or maturity of the number of chromosomes in the sperm cell. If there is damage to the DNA of the sperm cell, pregnancy can result in miscarriage. For the microinjection method, the selection of the sperm cell is therefore very important.

Sperm cells are grown with special systems. In this way, it is examined more easily and sperm cells that do not have problems in shape are detected. When selecting sperm cells, they are not only examined in terms of shape. The smooth shape of the sperm cell does not give a clue to the smoothness or maturity of its DNA. In the microinjection method, sperm cells are distinguished from special fluids called sperm slow.

In the solution called sperm slow, there is a substance around the ovary that the ovary uses in sperm cell selection. Since the sperm cells selected by this process have completed their maturity and have a high percentage of normal chromosomes compared to previous selection methods, it can be definitively decided. At the same time, quality embryos can be obtained with the microinjection method and more successful results can be obtained.

Microinjection Method

IVF treatment method has helped many families in the world to have children. The IVF method has led to the birth of almost 3 million babies in Turkey. Approximately half of these babies were born with the microinjection method.

When was the first microinjection method performed?

Microinjection method was performed for the first time in Turkey in 1992. The microinjection method is a revolution for male infertility problems. Microinjection method can be performed not only in male-induced infertility, but also in cases where the egg shell is too thick to pass through the sperm, in the candidates who have fertilization problems in the previously tried IVF treatments and especially in the elderly and low egg women.

Assisted reproductive techniques in modern types; classical IVF or in-vitro fertilization (IVF) and microinjection or intracytoplasmic sperm injection (ICSI). The difference between IVF and micro injection; is the form of fertilization. Microinjection, or ICSI for short, is one of the latest innovations in reproductive techniques. With the microinjection technique, the sperm has the opportunity to enter the egg directly.

What are the differences between microinjection and IVF method?

In the classical IVF method, a large number of sperm cells are placed around one egg cell under laboratory conditions. One of these sperms fertilizes the egg cell on its own. The fertilization that occurs here is similar to the way sperm fertilizes the egg cell in normal pregnancies. Only this fertilization is formed not in the womb of the mother-to-be, but in laboratory conditions.

In the ICSI (microinjection method), only one of the sperms of the father-to-be is taken. It is injected into the woman’s egg cell by microscopic methods. That’s why this technique is called microinjection. Here, the sperm does not fertilize the egg cell spontaneously, but is placed directly inside the egg cell.

What are the advantages of the microinjection method?

With the microinjection method, the chance of fertilization is much higher.
In men with very low sperm count and quality, it is more difficult to achieve pregnancy with the normal IVF method. This difficulty, problems such as azoospermia, manifest themselves as the inability to achieve pregnancy in any way. In these male patients, it is possible to achieve fertilization by microinjection method. Because, even a single sperm in microinjection is enough to ensure fertilization. If no sperm can be found in the semen in people with azoospermia, sperm cells can be found in the testicle by methods such as Micro-TESE. Fertilization can be created with these sperms, which are also found by microinjection method.

How is microinjection performed?

For the microinjection method, the highest quality sperm in the semen is used. The tail of the sperm cell is removed with immobilized and highly sensitive microscopic injectors. The sperm taken is put into the egg cell with the syringe. Without this process, the cells around the egg are cleaned.

Which patients are treated with microinjection (ICSI)?

• In patients with very low sperm count, azoospermia problem and sperm can be obtained by micro TESE method,
• In people who produce antisperm-antibodies as one of the causes that lead to infertility,
• In people who have not achieved success with the classical IVF technique before,
• In people who will undergo preimplantation genetic diagnosis (PGD),
• In candidates with unexplained infertility problems, microinjection method can be applied.
• Does fertilization by microinjection definitely occur?
• In the microinjection technique, sperm is placed inside the egg cell by microscopic methods, but fertilization is still not guaranteed. The quality of the sperm and egg are factors that play a major role in the realization of fertilization. For this reason, new techniques are developed to select better quality sperm. One of the most important factors determining sperm quality is the extent of experience of the embryologist.

What are the pregnancy rates in candidates who underwent microinjection method?

In addition to microinjection, fertilization and pregnancy rates in ICSI technique are slightly higher than in classical IVF method. However, the most important factor to ensure success is the quality of the egg and sperm. Although this rate may vary according to the age of the mother-to-be, the chance of fertilization is usually between 50-80%. But not all of these fertilizations may result in having a baby.

Advantages and disadvantages of egg freezing

One of the most important reasons for the decrease in pregnancy rates due to advancing age in women is the decrease in egg cell quality with the progression of age. In egg freezing application, the egg carries the characteristics of the age at which the woman is taken. Thus, a woman can become pregnant even at her advanced age. Eggs that have been frozen and stored and are young are not affected by the advanced age of the woman. In the following period, it is thawed and pregnancy can be achieved with the IVF method.

The disadvantage of egg freezing is how ethical it is to be a mother during or after menopause, when women’s reproductive functions end. Women with cancer fear that they will not be able to become mothers because of the treatments they will receive. In the treatment, the radiation therapy given to the body damages the ovaries, which are a sensitive area of women due to the effect of heavy drugs. Even if women recover, irreversible damage occurs to the ovaries. With the egg freezing technique, women who are treated for cancer hide their ability to become mothers after recovery. Egg freezing is very important for women who are older or have cancer. When women start cancer treatment at an early age, they lose 90% of their ovarian tissue. Each woman has a certain amount of egg storage at birth. When these are depleted, the woman enters menopause.

Egg freezing technology increases the age of a woman to become a mother

Women who have had their eggs frozen in their younger years can get pregnant at any age when they feel ready to become mothers. There is no age restriction in this regard. If desired, they can have a baby even at the age of 50-60. The frozen egg cell carries the characteristics of the age at which it was frozen. For this reason, the babies who will come into the world will be healthy. The only issue that is open to debate in this regard is how ethical it is to be a mother at a late age.

Women are highest in terms of sexual productivity in their twenties. However, not having enough knowledge about egg freezing, and even if they have it, not being able to implement this process due to financial impossibilities is a very negative situation. Egg collection is a laborious process and the medications to be used to increase egg production are expensive. Due to these factors, egg freezing may not be performed, even if necessary. In order not to lose their most natural right to fertility, women should benefit from egg freezing.

IVF and microinjection Application

We can say that most babies born with IVF treatment methods are provided by microinjection method. IVF application is created by fertilizing the egg taken from the mother and the sperm taken from the father in the laboratory environment. If the sperms are taken directly and injected into the egg to provide forced fertilization, this method is called the “Microinjection” method. We can say that the success rate is higher than other methods. It is an effective method to achieve success especially in male infertility problems. Microinjection is the name given to the method of inserting microscopic size substance through the cell wall with a micropipette obtained from glass. It is a more laborious technique than other techniques. However, despite this, it is widely used for gene transfer. This technique is used today in cases where, for any reason, the sperm cells cannot access the woman’s egg or break through the membrane of the egg. When infertility treatment is performed, the microinjection technique become involved in cases where the man’s sperm and the woman’s egg cannot meet for any reason. Microinjection is a method that provides very high success in advanced male infertility. When the microinjection method is performed, a single sperm cell taken from the man is placed into the egg obtained from the woman with a thin syringe through a microscope. Before this practice, the cells around the egg are cleaned. Mature egg metaphase is performed in 2 stages, fertilization is performed by preferring the egg cell in metaphase 2 stage.

Situations in which microinjection method should be used

In severe male infertility, especially if there is evidence that sperm function is impaired and it is thought that this situation will adversely affect the success of IVF treatment,
Couples in whom conventional IVF treatment has failed due to sperm impairment, for example, if the acrosome reaction does not occur (a reaction necessary for the sperm cell to fertilize the egg),

Using sperm surgically removed from the man’s reproductive organs

In cases where preimplantation genetic diagnosis is to be performed for the detection of genetic problems arising from one side, microinjection method is used to prevent DNA pollution of other sperms other than the sperm that provides fertilization.

What is the Success Rate of Patients Undergoing Microinjection Method?

Although the fertilization and pregnancy rates in the microinjection method are slightly higher than the normal IVF method, there may be some situations that affect the success. The age of the mother and the status of the ovarian capacity, the chance of fertilization with differentiation according to age is mostly observed between 50-80%. However, not all of these fertilizations may result in pregnancy. The success of IVF is evaluated around 40%. However, a difference of 15-60% can be observed. There are multiple reasons for these rate differences. For these reasons, success rates vary depending on the couple.

Despite the developing technology, sometimes it is not possible to achieve success. The most important reason for failure in IVF treatment is the age of the mother-to-be. As the woman ages, decreases in the number and quality of eggs appear. Success in mothers aged 35 and under is around 40%. However, as the age advances, these rates decrease. If the age of the mother-to-be is 40 and older, the success rate decreases by half.

• Factors affecting the treatment.
• The cause and time of infertility.
• Whether you have conceived before.
• The age limit of the mother-to-be.
• The number and quality of sperm in the father-to-be.
• Previous illnesses.
• The number and quality of eggs of the mother-to-be.
• The quality of the embryo applied to the mother-to-be.
• The presence of disorders that will prevent the retention of the cyst, polyp and embryo formed in the uterus of the mother-to-be.

How long does Microinjection Treatment last?

Microinjection treatments take 15-16 days on average to stimulate the eggs, collect and transfer them. A pregnancy test is performed 12 days after the transfer. And it is determined whether the patient is pregnant or not. If there is a pregnancy, subsequent follow-up is made accordingly. She continues some of his medications. If pregnancy has not occurred, all medications are discontinued and the patient is expected to menstruate. Depending on the patient’s condition, a minimum of 1-2 menstrual periods must pass before re-treatment can be performed. During this treatment period performed with a syringe, a recovery period is required within the eggs. For the healing of the eggs, 2-3 pieces, that is, 2-3 months are sufficient. If there is no pregnancy as a result of 6 attempts, the chance of pregnancy with this method decreases very much. But it is never impossible. It is rarely seen in couples who try microinjection treatments and become pregnant for the 12th to 15th time.

Can the Unsuccessful Microinjection Method Be Performed Again?

Microinjection IVF treatment method can be performed as much as desired. There are no specific limitations in this regard. The pregnancy rate of it, which has been tried 6 times, is around 80 percent on average with our current knowledge. In other words, the fact that it can be repeated and the success rate is still high at the end of 6 trials clearly shows the degree of treatment possibility. In the remaining 20 percent, this possibility is even less. In this case, the opportunities offered by technology are unfortunately limited. Immediately after the first microinjection method that ended in failure, we cannot say that there was a negativity in its re-performing. However, since the eggs stimulated by the medications given during the treatment are forced to work at a high level, the rise of the estrogen hormone naturally creates a mess in the body. It is recommended to apply the treatment again after about 2-3 menstrual periods until the body recovers.

Sperm Microinjection Technique with High Microscopic Magnification:

This technique provides the opportunity to perform morphological analysis of sperm at the maximum level compared to classical IVF and microinjection methods. With this analysis, no harm is done to the living sperm cell in any way. In this way, it allows microinjection to be performed.

In classical microinjection techniques, live sperm cells can be enlarged a maximum of 400×2 times. In this process, the head structure, neck structure, tail structure, ie general morphological features of the sperm can be investigated. However, the structures that are in the head structure of the sperm cell or not cannot be examined. In the same way, the cell nucleus cannot be investigated.

Special microscopes are used for this technique. In the process performed by applying the Selected Sperm Microinjection technique with High Microscopic Magnification, 6000-8000 times magnification can be performed and the intracellular structures and cell nucleus morphology in live sperms are evaluated in great detail. In this way, there is a higher fertilization opportunity between 25% and 40% with the microinjection process performed after the detailed selection of normal or closest to normal sperms.

Genetic and environmental factors can lead to DND damage in male sperm. In the ICSI method, which is mostly used in IVF treatment, the risk of using sperms with damaged DNA is higher. IMSI, that is, with the Sperm Microinjection Technique with High Microscopic Magnification, it is most successfully shown whether there is DNA damage in live sperm. Severe DNA damage to eggs and sperm can lead to the inability to obtain good quality embryos, pregnancy and implantation rates resulting in miscarriages.

Abnormal cell metabolism and oxidative stress weaken the maintenance of the integrity of sperm DNA chains. Apart from this, it causes various damages in DNA strands. In fathers-to-be;

• Advanced age,
• Smoking,
• Air pollution,
• Long period of sexual abstinence,
• Issues such as exposing the testicles to an extremely hot environment lead to damage to sperm DNA. If the sperm DNA damage is less than 8%, the DNA of the eggs can correct the damaged DNA of the sperm and a healthy baby can be born.

If the father-to-be is over 35 years old, DNA damage in the sperm increases, so the risk of miscarriage also increases. However, as a result of neurological examinations performed at the age of 8 with babies born with microinjection, ie ICSI, it has been reported that there is no difference between babies born with natural methods and babies born with microinjection, but major congenital anomalies are slightly more common in babies born with microinjection.

In the light of the data we have, it is not possible to predict what will happen after many years in the babies born as a result of microinjection with sperms whose DNA is damaged. In 1992, after performing the microinjection, i.e. ICSI, in the treatment of infertility, the natural selection of sperm was bypassed. With microinjection, embryos can be provided with sperms with damaged DNA that cannot be fertilized by natural methods. Embryos, which consist of sperms whose DNA is damaged and eggs that have been fertilized, can have promutations and mutations. Therefore, it may lead to infertility or children’s cancers in the future in the future babies. Although there is no conclusive evidence about the problems that DNA damage can cause, it is thought that there is less risk for babies who will come into the world when sperm with good DNA structure are extracted with IMSI.

Performing the Microinjection, or ICSI, allows the most uniform shape to be distinguished from the motile sperms under 200-400 times microscopic magnification. However, the possibility does not give a chance to detect the anomalies of the sperm, which are very important for fertilization, embryo development and pregnancy. These anomalies can be detected with special staining methods in andrology laboratories. However, these sperms cannot remain alive after staining. Therefore, it is not suitable for microinjection. With the high-magnification lenses and optical systems applied in the IMSI procedure, it is quite possible to detect and distinguish the anomalous and normal structures in the head of the sperm.

Especially in the studies that have been carried out very tightly since 2005; Fluid-filled vesicles called vacuoles, which are in the nucleus that reserves the genetic material in the sperm head, can give indications about whether there will be damage to the DNA structure. Damage to the DNA structure of the sperm can lead to problems such as failure of fertilization, cessation of embryo development, poor or slow embryo development. For this reason, the possibility of pregnancy is badly affected.

• Especially in infertility problems due to severe male factor,
• In recurrent IVF failures,
• IMSI system, which allows the differentiation of sperms with appropriate structure in cases of unexplained infertility also gives a chance to the development of good embryos that can reach the blastocyst stage. For this reason, it is a new and very important technique in this field.

Microinjection method (ICSI) is injected directly into the egg of the sperm, which does not have the ability to fertilize by natural means, and fertilization is achieved in this way. The microinjection technique has been developed especially for the treatment of severe male-induced infertility. By evaluating them in terms of shape and movement, normal sperms are distinguished and the procedures are put into practice. However, the fertilization of the egg by the sperm does not allow the detection of important anomalies related to the development of the embryo and pregnancy.

Every egg obtained in IVF laboratories, every embryo created is very valuable. The whole purpose is to attach to the uterus and create that embryo that will provide pregnancy. For this reason, the creation process and the process of selecting embryos are of particular importance. In recent years, it is possible to distinguish the sperm with the highest probability of success by performing high microscopic magnification techniques, which is known as IMSI for short, by evaluating the sperm cells to be performed in the fertilization process in a morphological detail before the procedure.