When a couple cannot conceive a baby for a long time, and medicine cannot help them with medicines and other methods, then in vitro fertilization is recommended. With IVF, the egg is fertilized outside the female body, in a test tube. If the fusion of the sex cells of a man and a woman does not occur in the laboratory bowl, then it is too early to despair, because one of the methods of artificial insemination - ICSI - can come to the rescue. We will tell you about what it is and how such a procedure is carried out in this article.
Definition
The abbreviation "ICSI" comes from the English "ICSI" - IntraCytoplasmic Sperm Injection, which literally means "intracytoplasmic sperm injection". ICSI is a modern method of treating various forms of infertility, which has allowed thousands of couples with complex forms of reproductive disorders to find the joy of motherhood and fatherhood.
This method should not be confused with IVF in general or with artificial insemination. With intrauterine insemination, fertilization occurs inside the female body, where it is provided by nature - in the ampullar part of one of the fallopian tubes. Sperm is simply inserted through a thin catheter into the uterine cavity, which allows more male germ cells to survive and successfully reach the egg. In IVF, the egg is fertilized with sperm in a laboratory Petri dish. In this case, sperm "storm" the oocyte membrane in almost the same way as they do in natural conditions during natural conception.
ICSI is required when spermatozoa are incapable of fertilizing an egg even in an embryological laboratory, with all its nutrient compositions, preliminary purification of the ejaculate from impurities and seminal fluid. Then the doctors perform a real miracle, which requires a great deal of experience and a certain amount of "jewelry" from them - they inject the healthiest sperm with a thin needle directly under the shell of the egg, into its cytoplasmic fluid. By being right where it is needed, the sperm has a better chance of fertilization.
With natural conception, insemination or IVF in a Petri dish, sperm have to overcome several obstacles - the radiant crown, the shiny shell of the egg, and only the most hardy can penetrate under the shell. ICSI allows you to "shorten" the path.
Russian doctors most often call the ICSI method with the stressed last vowel, and only the doctors of St. Petersburg, when pronouncing the name of the procedure, emphasize the first "I".
The method was first used by Belgian doctors in 1992. Then at the Brussels Reproduction Center in this way they helped to conceive a baby to a couple who had unsuccessfully been treated for infertility and even had several IVFs for 20 years.
In Russia, the method took root a little later, the main contribution to its development was made by scientists from NIIAP - the Scientific Research Institute of Obstetrics and Pediatrics. The first attempts to "manually" deliver spermatozoa into an egg were made earlier, back in the days of the USSR, when the first two successful IVFs were carried out in Moscow and Leningrad in 1986. However, at that time, medicine did not have high-precision equipment that would allow achieving accuracy at the cellular level.
Today there are such opportunities, the ICSI procedure is considered high-tech. It is carried out for medical reasons, which are stipulated by the Order of the Ministry of Health, which stipulates the procedure for providing assisted reproductive assistance to Russians.
You can make ICSI either at your own expense or free of charge - according to a regional or federal quota.
The procedure is carried out with the sperm of the husband, as well as with the sperm of the donor, if there are strict medical indications for that or at the woman's own will, if she lives alone, does not have a permanent sexual partner. Most often, ICSI is recommended for IVF with the husband's sperm, since donor sperm is distinguished by excellent "health", confirmed and proven by laboratory tests. In some cases, ICSI can also be performed with the donor's biomaterial, but this is relevant if a woman is lonely, and her oocytes, due to age or for other reasons, have too dense membranes, which cannot be penetrated even by healthy spermatozoa.
Indications
According to statistics, IVF with ICSI accounts for approximately 65% of all in vitro fertilization protocols. This means that intracytoplasmic sperm injection is in high demand. The need for a high-tech procedure does not always arise. It is indicated for poor spermogram, the causes of which could not be eliminated by conservative or surgical treatment. Here are just a few pathological conditions in which the couple is shown IVF + ICSI:
- The total number of sperm in the ejaculate is reduced to a critical level (oligozoospermia), or they are absent due to retrograde ejaculation, or ejaculation does not occur at all.
- The mobility of the male sex cells is noticeably impaired (asthenozoospermia) - immobile and sedentary spermatozoa predominate in the ejaculate, as well as sperm with an incorrect trajectory of movement, impaired coordination.
- Teratozoospermia is a condition in which morphologically altered germ cells-mutants predominate in the ejaculate (two heads in one sperm, two tails or the absence of a tail, various modifications of the structures of the male reproductive cell.
- Presence of antisperm antibodies in semen.
- Idiopathic infertility, the causes of which could not be identified after a thorough medical examination.
- Low quality of oocytes caused by natural aging of oocytes (in women over 40 years old), or other causes (hormonal, congenital, the consequences of external negative influences, etc.). With some changes, the oocyte membrane becomes impermeable to sperm.
- Unsuccessful IVF protocols for 2 or more cycles, if the quality of the sex cells of a man and a woman generally corresponds to the norms.
It should be noted that ICSI makes it possible to become parents even in the most difficult situations, when no other methods and methods will help. Even if ejaculation does not occur or there is not a single living sperm in the semen, doctors always have the practical opportunity to perform a surgical sampling of germ cells, for example, to do a testicular biopsy.
It will be enough to get only a few normal cells (while there are tens of millions in the ejaculate!) For ICSI to be successful.
How is it done?
ICSI is an amazingly "delicate" work. It is absolutely impossible to inject a small spermatozoon into the cytoplasmic space of the oocyte using a conventional injection needle, the cells will be damaged and it will not be possible to obtain an embryo. For ICSI, hydraulic or electrical micromanipulators are used. They are highly accurate. The whole process takes place under powerful microscopes.
In order to "work" with such a small material as human cells, special tools are required - microneedles and micro suction cups. These tools attach to manipulators. And then the work of the doctor-embryologist resembles a fantastic film - he makes movements with his own hands and through the joysticks the manipulator repeats his movements, but only on a microscopic scale.
For fertilization, it is important that the DNA set of the sperm is not changed. Therefore, the other parts of the sperm are essentially unnecessary. At the first stage, the embryologist selects the most healthy and morphologically normal sperm, places it on the working surface under microscopes. Next, the microneedle manipulator interrupts the tail of the sperm. The cell becomes immobile - this makes it easier to work with it further.
There is no need for a tail with ICSI, because the cell does not need to swim somewhere, strive, move. The most valuable DNA is in the sperm head.
The sperm left without a tail is drawn into a micropipette needle. The oocyte is retained by the micro-suction cup. The suction cup is located on the left, the microneedle with the sperm inside is inserted opposite - on the right. After the oocyte membrane is punctured, the contents of the microneedle pipette are injected into the cytoplasmic fluid of the egg.
To the question of whether the egg can suffer from a puncture, the answer can be affirmative. But the probability of injury to the oocyte, according to available medical statistics, does not exceed 1%. In other cases, the naturally rather elastic shell of the egg quickly tightens at the puncture site and inside it, the most important processes of fusion of the genetic material of the future mother and the future father begin.
The egg is cleaned, placed in a special nutrient solution, where it will remain for the next several days. Embryologists will cultivate the embryo if fertilization took place before the decision is made to transfer it to the woman's uterus.
Procedure steps step by step
ICSI does not exist as a separate program, it is part of the IVF protocol. Therefore, the main stages of IVF + ICSI are almost the same as in conventional IVF, in the protocol of which there is no need for intracytoplasmic sperm injection. If IVF with ICSI is recommended for you, then the procedure will take place in several stages.
Training
At the preparatory stage, both partners or the woman (if fertilization is planned to be carried out with donor sperm) should undergo a detailed medical examination and pass a large list of tests. The standard list for a woman includes general urine and blood tests, blood tests for HIV, syphilis, infectious viral hepatitis B and C, for TORCH infections, for hormones, for antisperm antibodies.
It is imperative to undergo a gynecological examination, which, by order of the Ministry of Health of Russia, includes ultrasound of the pelvic organs and mammary glands (mammography for women over 39 years old), colposcopy, hysteroscopy, determination of the patency of the fallopian tubes, as well as vaginal smear tests for bacteria, microflora and infections.
The main analysis for a man is a spermogram. It must be done at least twice three months before IVF. With a poor spermogram, therapy is indicated to improve the quality of germ cells, for which vitamin and mineral preparations are used, biologically active additives that improve the process of spermatogenesis.
In addition to the spermogram, which the reproductive physician will rely on when drawing up an individual IVF protocol, a man should undergo chest fluorography, take blood tests, both general and for HIV, syphilis and sexually transmitted diseases, as well as take a smear from urethra.
The collection of all necessary tests usually takes 2-3 months. This time should be used effectively by the couple - quit smoking and refuse to take alcoholic beverages, start eating right, enriching the diet with meat, fish, cottage cheese and other dairy and sour-milk products, vegetables and fruits. The couple should go in for sports, but avoid excessive physical exertion.
It is not worth visiting the bathhouse, sauna. This prohibition especially applies to representatives of the stronger sex, who, on the eve of donating sperm for IVF, cannot expose the scrotum to any heat effect in three months. Overheating of the gonads located in it can significantly worsen the performance of the ejaculate at a crucial moment.
Protocol entry and stimulation
With the analyzes and the conclusion of the therapist that the woman is admitted to the IVF protocol, you should contact the reproductologist 14-15 days before the start of the next menstruation. On the first visit to the clinic, the couple will sign the necessary documents and will be informed about the type of protocol chosen by the doctor. If a long protocol is chosen, then even before the onset of menstruation, hormonal drugs can be prescribed to a woman, which suppress the work of the ovaries, causing a condition resembling menopause. After 2-3 weeks, the woman is prescribed other hormones that stimulate the rapid maturation of follicles in the ovaries.
With a short protocol, they do without prior suppression of the work of the female reproductive glands. But the stage of taking hormones after menstruation (on the 5-6th day of the cycle) is necessarily present.
During the entire stage, a woman often goes to an ultrasound scan and donates blood for hormones. This allows the doctor to assess the rate of follicular growth and prevent an inadequate response of the ovaries to hormonal stimulation - it may be insufficient or excessive. If insufficient, it is possible not to get the required number of mature eggs for ICSI, and if excessive, hyperstimulation syndrome may develop, which in itself is very dangerous for women's health.
As soon as the follicles (at least three) reach a size of 16 to 20 mm, the woman is injected with hCG. This hormone allows the eggs inside the follicles to mature in an accelerated mode for 36-37 hours, after which the ovarian puncture can be performed.
Egg and sperm retrieval
Sperm for the ICSI procedure is obtained in the traditional way - by masturbation. If for the delivery of the analysis it is permissible for a man to collect material at home and deliver it to the laboratory no later than 40 minutes later, then sperm must be donated for IVF in a clinic directly on the day when fertilization is planned.
On this day, the couple arrives at the clinic together - the man goes to a separate room to collect ejaculate, which is immediately delivered to the laboratory. If masturbation does not help (the man has no erection, the lower body is paralyzed, there is no ejaculate, or retrograde ejaculation occurs), the procedure for collecting germ cells is carried out under anesthesia using testicular biopsy or sperm extraction from the epididymis.
If the procedure is performed using donor sperm, it is delivered from the cryobank, slowly thawed beforehand and the sperm counts are examined after cryopreservation.
In the laboratory, the biological material of a man undergoes primary cleaning, release from semen. Among the remaining concentrated sperm, only the best cells are isolated by means of microscopic examination, and they are placed in a nutrient medium.
A woman is punctured to obtain eggs. The procedure is performed under general anesthesia, which is administered intravenously. With a long thin needle, aspiration under the control of ultrasound, a puncture is made through the vagina, the needle is brought out to the mature follicles and the fluid is drawn out of them along with the oocytes.
The patient remains in the clinic for a few more hours to recover from anesthesia. Doctors are monitoring her condition. From the day of the puncture, she is prescribed progesterone preparations, which will help prepare the endometrium for embryo implantation.
The resulting eggs are sent to the same embryological laboratory. They are freed from follicular fluid, washed, counted and the quality of the material is assessed. The best and most viable eggs are allowed to fertilize.
Fertilization and transfer
After the doctor uses a micromanipulator to transfer the selected sperm to the eggs, the observation period begins. If everything went well, then after about 16 hours the first changes are recorded at the microscopic level, and in a day the embryologist can say exactly how many embryos were obtained.
Cultivation of embryos lasts from 2 to 6 days - it depends on the protocol and individual recommendations. Then a decision is made to transfer the embryos to the woman's uterus. This procedure is fast, it will not give the patient any unpleasant sensations at all. A small amount of nutrient medium with a pre-agreed number of embryos will be injected into the uterine cavity with a thin catheter.
On the one hand, a larger number of embryos increases the likelihood of pregnancy, but on the other hand, it creates the risk of multiple pregnancies, and not every couple agrees on triplets or twins. Bioethics recommends that doctors choose the optimal number of embryos and convince their patients not to exceed it - in Russia it is 2-3 embryos.
Resection (removal of "extra" embryos after implantation) creates moral problems for many couples, and most world religions regard it as an abortion.
It is recommended to limit physical activity after the transfer. A woman is given a sick leave, and she can spend several days in bed with a clear conscience.
The wait lasts 14 days after the transfer, then the woman can have a blood test for hCG to find out if a pregnancy has occurred. After another week, you can do the first ultrasound to confirm and assess the condition of the uterus, ovaries and embryos.
Efficiency
The effectiveness of in vitro fertilization with the use of ICSI in the protocol increases the likelihood of pregnancy. If conventional IVF ends in pregnancy only in 35-45% of cases, then the success rate after intracytoplasmic sperm injection is slightly higher - at the level of 50-55%.
Embryos after ICSI develop more successfully, because the sperm for fertilization is used, without exaggeration, selective. In 85% of successful pregnancies, a woman bears a perfectly healthy child. Unfortunately, the percentage of unsuccessful completion of pregnancy and complications in bearing a fetus after ICSI does not differ from the same indicator after conventional IVF - 20% of pregnant women lose their babies in the early stages for various reasons - miscarriage, undeveloped pregnancy, ectopic pregnancy.
Parents-to-be should know that ICSI does not guarantee the complete absence of congenital abnormalities in the fetus, because, unlike natural fertilization, which occurs several hours after ovulation, with ICSI there is no natural selection.
With natural conception, sperm cells are “weeded out” at each stage of the passage of the genital tract, when trying to break through the membrane with eggs. During ICSI, there is no such selection, and therefore the probability of having a baby with pathologies still exists.
Many doctors and scientists are sure that a child conceived by ICSI is likely to inherit diseases of the parents, who did not allow them to conceive a baby. If nature has not provided for the opportunity for a couple to reproduce, then this is how it protects humanity from the birth of sick individuals. The method itself has nothing to do with it. This is just an attempt by people to "deceive" nature, to force her to change her mind.
That is why it is advisable for a couple to visit a geneticist before ICSI, to do tests for compatibility and karyotyping.
If the doctor has data on hereditary diseases, he will also recommend to carry out pre-implantation diagnostics after embryo cultivation - to “screen out” the embryos that have inherited the disease, and to plant only healthy embryos in the uterus.
Pros and cons
Preparation for IVF with ICSI is identical to the usual preparation for in vitro fertilization, the couple will not have to do anything special, and this is the first plus. The undoubted advantage of the method is the increased likelihood of a successful pregnancy. But the minus is still that the probability of slightly higher than 50-55%, again, does not guarantee a couple that they can become future parents in the current protocol.
The advantages include the advanced capabilities that the technique gives to couples. This is the woman's age (over 40 and even 45 years, if necessary), the ability to carry out in vitro fertilization with HIV in a man without the risk of infection for the unborn child and a number of other situations, from which it is rather difficult to find a reasonable way out using other methods.
A clear disadvantage is the cost of the procedure, it is very high. If it is not possible to get pregnant the first time, the funds will not be returned to the couple, and the next protocol will again have to be paid at full cost.
In addition, sometimes this method cannot be applied at all - a number of somatic and mental illnesses, tumors, inflammatory ailments and malformations or post-traumatic changes in the uterus and ovaries are contraindicated. There are no contraindications on the part of a man.
Price
ICSI in the protocol leads to an inevitable and rather tangible rise in the cost of IVF. The cost is influenced by the selected region, a specific medical institution. On average, the cost due to the need for sperm injection into the cytoplasmic fluid of the oocyte increases by 50-125 thousand rubles.
Considering that the average price of IVF in Russia in 2018 is 140-250 thousand rubles, it is not difficult to calculate the minimum and maximum cost of the same procedure, but with ICSI, - 190-370 thousand rubles.
Do not believe the tempting advertising offers of clinics, which indicate on the Internet the prices for ICSI and IMSI (selection of the best sperm) within 15 thousand rubles. This is clearly an advertising move, because in this case, an incomplete cost is indicated. After adding the cost of drugs, reagents and culture media, the cost of puncture, the amount will grow to the average Russian values.
The price is high, there are no guarantees of success - this is what stops many couples from trying to conceive a baby using this method. There is good news for them - now ICSI is included in the program of state support for IVF. For the procedure, you can get a federal or regional quota and do it free of charge under the compulsory medical insurance policy. True, the amount of the quota is 141 thousand rubles in 2018. It may not cover the full cost of the protocol. In this case, you will have to pay the difference yourself.
Reviews
Positive feedback about ICSI from most women who decided to share their own experience with others on thematic forums prevails. Many, even after several unsuccessful IVF attempts, managed to conceive babies the first time after the protocol with ICSI fertilization.
However, one cannot ignore other reviews, in which women describe their two, three or more unsuccessful ICSI attempts. There are even isolated reviews of fetal pathologies revealed as a result of screening during pregnancy, which women tend to "write off" to the ICSI method, since the quality of spermatozoa, even the best of the choice that the embryologist had, leaves much to be desired.
Women who do not want to experience a heavy hormonal load, especially after several failed IVF stimulated protocols, often agree to ICSI in the natural cycle. The probability of success without the use of hormones is several times lower, because only 1 egg can be obtained (in the rarest case, two). And this does not guarantee that both will be suitable for the procedure, will be fertilized and transferred to the uterus.
Most often, women who are lucky enough to have a pregnancy after ICSI claim that they were implanted with two embryos - one was fertilized in a Petri dish using the conventional IVF method, and the other was fertilized using ICSI in order to increase the chances of a successful long-awaited pregnancy.
If doctors recommend doing ICSI, experienced women are advised to carefully choose a clinic and a specific doctor. Be sure to read all the available information about the specialist, with the reviews of his patients.
If you can contact them personally, be sure to do so and have a chat. This will help you better mentally prepare for the upcoming procedure and, with the right attitude, go to the doctor for your future happiness.
For information on how the ICSI procedure goes, see the next video.
