According to world statistics, every fifth married couple is infertile and is being in need of reproductive technologies assist. In the process of conception, both a man and a woman are equally involved, therefore, the problem may be on both sides, or there may also be a mixed factor, when both partners are the cause of infertility at the same time. In percentage terms, it can be said that about 30% of cases are caused by men, 30% by women, 20% when it is a combined case and 20% when the cause of infertility is inexplicable, since it cannot be diagnosed. So what causes infertility?
If we are talking about the main factors of female infertility, than those are:
- Age - by the age of 35, a woman's reproductive capacity declines, and after 40 years, the probability that she will be able to become pregnant is less than 10%.
- The so-called "Tubal factor" - for a number of different reasons, a woman may have obstruction, structural and functional disorders of the fallopian tubes.
- Endometriosis - a common condition in which the endometrium, or mucous membrane, grows outside the uterus.
- Ovarian dysfunction and lack of ovulation.
- Defects in the development and structure of the uterus, as well as fibroids.
- Immunological disorders, such as the presence of antisperm antibodies.
- Various sexually transmitted diseases.
- Hormonal problems and all kinds of chronic diseases such as cancer, thyroid disease, diabetes, asthma.
- Depression or woman taking antidepressants.
As for the factors of male infertility, they are:
- Anatomical changes in the structure of the male genital organs, as a result of which sperm during intercourse does not enter the woman's vagina.
- Various congenital anomalies or underdevelopment of the testicles, undescended testicles into the scrotum or their congenital absence.
- Dysfunction of the testicles, pathology of sperm production, namely a decrease in its quantity and quality of sperm.
- Varicocele is an enlargement of the veins of the spermatic cord and testicle.
- Diseases of the prostate, ejaculatory disorders, erectile dysfunction.
- Abnormalities in the development of the urethra, in turn leading to obstruction of the vas deferens and also to a decrease in the amount of sperm produced.
- Infertility associated with exposure to harmful factors such as infections, radiation, prolonged cooling.
- Finally, overweight.
Apart from the rare cases when difficulties with conception may be associated with problems in woman’s and/or man’s bodies (which are amenable to medical or surgical correction), if during a year of active sex life without contraception, pregnancy does not occur, we can talk about infertility with almost complete confidence. Timely awareness of the problem and a search for the way to solve it with the help of specialists will significantly reduce the time to achieve your dream of having a child. The first step is an accurate diagnosis, on the basis of which the reproductologist makes a conclusion about the need of using assisted reproductive technologies, namely - IVF.
Let's try to understand what the IVF procedure is, which has been used all over the world for almost 40 years, and what is the essence of the laws in relation to reproductive methods.
The first thing we would like to point out is the unconditional importance of a positive morale and understanding that you may need a few tries. According to statistics, about 30–45% of women become pregnant after the first IVF attempt, about 20% - after the second, and about 25% of couples become parents only after the third to seventh attempts. Of course, even if you turn to the best specialists, it is impossible to guarantee the onset of pregnancy with the help of IVF, and yet in case of unsuccessful attempts, you should not despair, because you can always be sure that you will have your baby, because you can use surrogacy.
So, what the IVF is all about?
The basic principle of IVF is that with the help of an embryologist, the sperm and the egg are met outside the female body, that is, in the test tube, which makes it possible to control the process from the very moment of the gametes meeting to the formation of a healthy embryo. Then the resulting embryo is transferred into the uterine cavity, where it will grow and develop.
The IVF method has several different modifications, thanks to which it is possible to overcome problems at any stage and thus qualitatively increase the chances
With ICSI, an IVF specialist uses an injection to place the sperm directly into the cytoplasm of the egg. For this, the doctor selects the most motile spermatozoon that have no visible pathology, relying solely on visual criteria and his own experience in their selection.
PIСSI is a modification of the ICSI procedure. The difference is that sperm selection is based on the results of a biochemical reaction with hyaluronic acid, and not on the subjective opinion of the embryologist. This procedure helps to select the most motile sperm by placing the sperm in a Petri dish with acid, where you can observe how the strongest spermatozoon attaches to the hyaluron the fastest. Indeed, it is hyaluronic acid that is included in the composition of the cells surrounding the oocyte, for the "search" of which, healthy spermatozoa have special receptors.
During the IVF procedure, in order to obtain the maximum number of eggs, the woman undergoes hormonal stimulation. But there are times when a woman's ovaries do not respond well to such stimulation, then higher doses of drug are used and the IVM protocol is applied. The point of this modification is that oocytes are taken from a woman's body in an immature form, after which they are placed in an incubator until they reach the state of full-fledged eggs.
In case of presence of certain signs, as well as in cases of unsuccessful attempts with vitro fertilization, the hatching procedure is carried out. This procedure helps the embryo to free itself from the membrane and attach itself to the uterine cavity, which significantly increases the chances and helps to protect the embryo from death.
1. Diagnostics of the causes of infertility
To identify the causes of infertility, determine possible contraindications to IVF, select the optimal stimulation scheme and determine signs for potential additional procedures, the couple undergoes an extensive examination, visiting corresponding specialists and undergoing a number of tests, such as tests for infections, hormonal research, spermogram and evaluation of uterine pipes patency. According to the research results, if such a need arises, treatment of the identified diseases and abnormalities is carried out. If, after appropriate treatment and correction of the identified deviations, it is still not possible to achieve pregnancy, a decision is made to conduct in vitro fertilization. In general, the diagnostic stage itself can take about 2-3 months.
2. Preparation for vitro fertilization
For the IVF procedure, additional research is required, and therefore, tests for detecting infections and spermogram are repeated. There are tests and studies that are mandatory, which are assigned to all married couples, without exception, and without which it is impossible to enter the IVF protocol. And there are also additional ones that can be prescribed according to indications. Considering that vitro fertilization has a number of contraindications, such as active tuberculosis, malignant neoplasms, an acute form of infectious hepatitis, severe somatic pathology in the acute stage, a woman, in addition to a gynecological examination, should also undergo a therapist to make sure that the above contraindications to pregnancy are absent, as well as mammologist, fluorography, blood and urine tests. This stage lasts about 1 month, but it also depends on how quickly the couple manages to prepare all the necessary documents.
3. Stimulation of superovulation
Hormonal stimulation is necessary to obtain the maximum number of mature oocytes, because their number significantly increases the chances of success, and in cases of unsuccessful embryo transfer attempts, they can be used in subsequent attempts. With a good ovarian reserve, about 10 follicles mature in one cycle, from most of which it will be possible to obtain high-quality eggs in the future. The stimulation scheme is selected for each woman individually, while the main criteria for choosing this scheme and dosage are the woman's age, her ovarian reserve, the functional state of the ovaries, and, if such was the case, the previous experience of stimulation. In most cases, a woman under the age of 35 includes in the treatment cycle from 19-21 days of the menstrual cycle preceding the stimulation cycle. A woman is injected with hormonal drugs of a different mechanism of action. Immediately from this time, the introduction of decapeptyl / dipherelin / busereli begins - drugs that prepare the ovaries for stimulation. Then from the 1-3 day of the next menstrual cycle - Puregon / Gonal / Menopur, Rotnil and their analogs, which directly stimulate the growth of follicles and the maturation of eggs, as well as the growth of the endometrium, that is, the inner layer of the uterus, where the embryo is implanted. If a woman has reached 35-40 years of age, then usually she is included in the treatment cycle from the 1st day of the menstrual cycle, which is counted from the first day of menstruation. The procedure is carried out under the strict supervision of doctors, it is also due to the fact that taking hormonal drugs can cause possible complications, therefore, in order to avoid them, the constant supervision of a specialist is very important. It is important in case of any discomfort, pulling pains in the lower parts of abdomen, bloating, the appearance of allergic reactions, immediately inform the supervising doctor. The very stage of directly stimulating superovulation is from 8 to 22 days. There are cases when the stage of stimulation of superovulation is absent, since IVF in women with low ovarian reserve is often carried out in a natural cycle and at the same time hormonal preparations for the maturation of a large number of eggs are not prescribed.
4. Getting germ cells
Puncture of ovarian follicles
The process of follicular growth in a woman's ovaries is constantly monitored using ultrasound. Follicles are fluid-filled vesicles, most of which contain an egg. The follicles that have matured after stimulation of the ovaries are removed from the woman's body under the control of ultrasound scanning for their further vitro fertilization. Eggs must be removed from the body before they leave the follicles. For this, a procedure called follicular puncture is performed. This puncture is performed transvaginally, that is, through the fornixes of the vagina, with a special needle, with which the doctor takes the follicular fluid with the eggs in it. This procedure is carried out 10-22 days from the beginning of the administration of the drugs. This is done under general intravenous anesthesia and only lasts a few minutes. Due to its minimal trauma, ovarian puncture is performed on an outpatient basis, after which, after 2-3 hours of rest and examination by the attending physician, a woman can go home. The doctor immediately places the obtained precious material in a nutrient medium and transfers it to the embryologist, who in turn selects oocytes from the follicular fluid for further fertilization. As mentioned earlier, the more eggs you can get, the better, because they can be used for the next transfer attempts, and if successful on the first try, you can simply freeze them even after a few years, which is especially important for women with a low ovarian reserve. ... If it is impossible to receive the patient's eggs for one reason or another, the donor's eggs are used, which must undergo the same studies and procedures.
On the same day, when the eggs are received from the woman's body, they are fertilized. It is performed 4-6 hours after follicle puncture. Fertilization with "fresh" sperm is preferable, therefore it is important that the spouse comes to the clinic on the day of follicle puncture to provide his germ cells. Before donating sperm, a man must maintain a healthy lifestyle for as long as possible, given that the period for a complete renewal of the sperm composition is three months. This is very important, since spermatogenesis largely depends on the impact of adverse factors. It is necessary to exclude the influence of nicotine, alcohol, stressful situations, nervous and general fatigue, as well as the impact of occupational harmful factors, because all this significantly impairs the quality of sperm.
It is also allowed to use frozen (cryo-canned) semen. This may be due to a small amount of sperm in the husband and the need for its repeated accumulation before the procedure. The advance delivery of sperm and its freezing is also carried out in the case when the spouse does not have the opportunity to be present at the clinic on the day of the egg collection. Also, frozen sperm is used by single women or in case of absolute infertility in the husband and the use of donor biomaterial for the fertilization of eggs. The sperm donor undergoes the same examinations as the married couple before starting the IVF protocol.
5. Insemination of oocytes
For extracorporeal insemination of oocytes, sperm is prepared in a special way and purified. For IVF, only spermatozoons are selected that make translational movements, but at the same time, only one sperm out of tens of thousands is needed to fertilize one egg. The embryologist then places the eggs and sperm in an incubator with a temperature of 37 ° C, a carbon dioxide concentration of 5% and high humidity, in a nutrient solution, which maintains conditions similar to those in the mother's body, where they must directly combine to form an embryo. As we mentioned earlier, the doctor can use the ICSI or PICSI method for this.
6. Cryo-freezing of embryos
The resulting remaining unused healthy embryos, if any, are cryopreserved in liquid nitrogen at a temperature of -196 ° C. This avoids re-stimulation of the ovaries, puncture and fertilization procedures. They are simply defrosted and introduced into the uterine cavity.
7. Cultivation of embryos
To obtain the most viable embryos, the technique is used for a long embryo cultivation stage (up to 120 hours). With long-term cultivation, additional criteria for assessing the quality of the embryo appear, thus, the chance of implantation is higher. In a special nutrient medium, under conditions created as close as possible to natural, fertilized eggs grow and develop for 3-5 days, meanwhile, the embryologist monitors their division and supervises their development. His task is to select the strongest embryos, in order to achieve that, he may decide to remove cells if they are not suitable for transfer into the uterine cavity.
8. Preimplantation genetic diagnosis
After cultivation in an incubator, on the 5th-7th day, pre-implantation genetic diagnosis of the embryo, or PGD, is carried out, which is a very important stage of IVF, as it allows detecting genetic abnormalities. This diagnosis is carried out on the recommendation of a reproductive specialist or at the request of future parents and is a safe method to prevent genetic and chromosomal diseases in a child. PGD is especially recommended for couples with an increased risk of detecting possible anomalies of this kind, namely in cases of genetic abnormalities in relatives, poor sperm quality, high age of one or both of the spouses. The importance of this diagnosis also lies in the fact that, as we can see from the name, it is pre-implantation which allows to do the research before embryo implantation and, accordingly, before pregnancy, which is a fundamental difference between the methods of other types of screening. Among other advantages of PGD, it can also be noted that it increases the likelihood of successful implantation and reduces the risk of pregnancy complications, helps to avoid frozen pregnancies and miscarriages.
Another important opportunity that PGD has is the choice of the sex of the child, which allows you to prevent the development of diseases in the child, because there are cases when the probability of inheriting a particular disease is most likely in the case of a particular sex and does not apply to the other. Preimplantation genetic diagnostics can also be used in this capacity and by a couple solely to achieve their preferences, which often happens, for example, when the family already has several children of the same sex, and the spouses also dream of having a child of the opposite sex.
The sampling of material for research from an embryo that has reached the blastocyst stage and already numbering about 200 cells is obtained by a biopsy method. This procedure with special devices, as well as with the help of advanced micro-manipulation laser equipment, is carried out by an embryologist, separating from 3 to 5 cells from each embryo. It is important to note that each of the cells is still pluripotent, that is, suitable for the formation of a full-fledged organism. Accordingly, we can say with complete confidence that the biopsy procedure poses absolutely no threat to the health of the unborn baby.
Genetic diagnostics allows detecting possible deviations with an accuracy of more than 95%, which, of course, is a very high indicator. However, it should be noted that preimplantation analysis does not obviate the need for prenatal screenings, and in cases where a high risk of chromosomal abnormalities is detected, the patient may be prescribed invasive studies.
9. Transportation of embryos to the uterus
When the embryos have passed the necessary research, the stable and viable ones are transferred to the uterus. The procedure is simple and painless and only takes a couple of minutes. For transfer, an atraumatic catheter is used - a special device resembling a syringe with a flexible tube at the end, with which, without resorting to the expansion of the cervical canal, the embryo is placed into the uterine cavity. With successful implantation of the embryo into the mucous layer of the uterus (the endometrium) pregnancy occurs. Within the limits of what is permissible, which is 3 embryos, decisions on the number of embryos to transfer are made by the parents, who of course, should also be guided by the testimony of a doctor who assesses the chances of pregnancy. It is more common to transfer 1-2 embryos, because if you transfer only one the chance of its implantation decreases. Both of them can be implanted and then the couple may become parents of two children at once. Each case is different, and you need to take a decision seriously. On the one hand, the transfer of two embryos increases the chances of a couple, and on the other hand, it puts the health of the mother and children at risk, complications are possible in the process of pregnancy with more than one child, complications in the process of gestation and childbirth are possible, especially talking about a woman who has a predisposition to this type of problem. In such cases, when the mother's health does not allow transferring a multiple pregnancy, and also if there is preservation of embryos, a reduction procedure is applied, which is the removal of one or more oocytes. Reduction of embryos is a complex operation that is performed only with the written consent of the mother and under serious medical conditions.
Embryo transfer can be performed on the second or third day after fertilization. If there are more than 3 high-quality embryos by the third day of cultivation, it can be performed at later stages, before the formation of a morula or blastocyst is reached, which is on the fourth to fifth day after fertilization.
In this case, as a rule, no more than 2 embryos are transferred.
After embryo transfer, women do not need a bed rest, since this is not a factor that increases the frequency of pregnancy.
10. Luteal phase support
Preparing the endometrium for implantation is one of the important components of IVF, since the onset and development of pregnancy largely depends on the state of the endometrium. It begins in the proliferative, which is the follicular phase, which lasts from 6 to 14 days of the menstrual cycle and is associated with the growth of follicles in the ovaries, when under the influence of estrogens, the thickness of the endometrium increases 2-3 times. And then, the support continues during the luteal phase of the menstrual cycle, lasting from 16 to 28 days. This is necessary because sometimes a full-fledged corpus luteum does not form at the site of the follicle from which the egg was taken and accordingly, in the absence of a temporary endocrine gland, progesterone necessary for the onset and development of pregnancy is not produced. In this case, additional luteinizing hormonal drugs are prescribed, under the influence of which specific granulosa cells produce progesterone. This endogenous steroid promotes secretory transformation of the endometrium and thereby ensures its readiness for implantation of a fertilized egg. An important function in the luteal phase and in the early stages of gestation is its effect on the peristalsis of the fallopian tubes, namely, it facilitates the movement of the zygote into the uterine cavity and contributes to a decrease in the tone of the myometrium.
11. Diagnosis of pregnancy
9-12 days after the embryo was placed in the uterine cavity, they begin to monitor the level of chorionic gonadotropin, that is, the HCG hormone, which begins to be produced by the chorionic tissue after implantation of the embryo, and in case of pregnancy, its level rises sharply. Determination of the level of chorionic gonadotropin is carried out by the implementation of a blood test. The final confirmation of the onset of pregnancy is carried out using ultrasound of the uterus and ovaries 21 days after the embryo transfer. An ultrasound examines the presence of a fetal egg in the uterine cavity. After that, after one week, it is possible to record the presence of a heartbeat in the embryo, and also to see where is it attached on the placenta.
In general, the period of the IVF procedure, when all stages are carried out from ovarian stimulation to embryo incubation and monitoring the implantation progress, takes from 1 to 1.5 months. Diagnostics and preparation take most of the time in the vitro fertilization process, which is in total up to 4 months
If you have come through such long way, and you did not manage to achieve the long-awaited pregnancy on the first attempt, believe you can and you are halfway there. If you cannot get pregnant on your own, you can always turn to a surrogate mother for help.