“In Vitro Fertilization”
In vitro fertilization, which is one of the methods that enables individuals with various problems related to fertility to have children, is one of the most preferred assisted reproductive techniques today. In case women cannot conceive naturally, in vitro fertilization treatment includes many methods, especially vaccination.
Inability to conceive due to sperm or ovaries also affects the couples psychologically. The method to be used in in vitro fertilization treatment, which is applied to make the couples’ dreams of having children come true, is decided according to the health conditions of the patients and the evaluations of the experts. The aim of the treatment is always to achieve fertilization and to have a healthy pregnancy period.
What is IVF Treatment?
IVF treatment; It is an assisted reproduction method that involves the fertilization of the egg cells (oocyte) taken from the woman and the semen cells (sperm) taken from the male in the laboratory environment and the implantation of the fertilized embryo into the woman’s uterus. Pregnancy obtained from a certain number of selected and placed embryos in the uterus proceeds in the same course as the pregnancy provided by normal means. In this sense, the only difference between natural pregnancy and IVF treatment is that fertilization is carried out in laboratories with appropriate conditions.
The first case of successful IVF treatment, founded by Robert G. Edwards in 1971, was seen in England in 1978. In Turkey, the first successful pregnancy through IVF has resulted in the Aegean University in 1989. Today, thanks to the developing medical techniques and technologies, different in vitro fertilization techniques are applied and successful results are obtained.
Which Methods Are Used?
According to fertilization of the ovaries, IVF treatment is applied by classical IVF or microinjection (ICSI) methods. The frequently preferred IVF method is generally preferred when there is no problem in sperm count and quality, and sperm fertilization is performed by itself. In the ICIS method, the egg is made ready for injection and the sperm are placed in a single egg.
When Is It Applied?
In order to apply IVF treatment, it is necessary to have sexual intercourse for at least 1 year without using birth control methods and pregnancy should not be seen during this period. This condition is also called infertility. In the absence of pregnancy during this period, IVF treatment is applied.
What Is the Age Limit in IVF?
In vitro fertilization treatment up to the age of 45 is applied to women whose ovarian functions are found suitable with the tests performed on the 3rd day of the menstrual period. At the same time, it is checked whether embryos are suitable by genetic diagnosis method. However, women over the age of 40 are less likely to be successful with this method than younger women. Decrease in the number and quality of eggs in women, especially after the age of 35, also affects the chances of success.
Although there is no age limit for men, it is considered that sperm quality decreases due to changes in sperm DNA as age progresses.
Who Are the Right Candidates for IVF?
IVF treatment is applied depending on some factors:
The ovarian canals (fallopian tubes) in women are closed, damaged or removed,
- The presence of adhesiveness that prevents the fallopian tubes from catching the eggs,
- Women are at an advanced age when fertility is low,
- Inability to achieve pregnancy with medication,
- Low sperm count and low quality or no sperm cells in men.
Especially women over the age of 30 with irregular menstrual bleeding and men with low sperm count as well as testicular health problems should apply to IVF centres in order to obtain pregnancy.
In some cases, various health problems are primarily treated with medications or surgical methods, and normal pregnancy is expected to occur. If normal pregnancy is not seen after these problems are solved, IVF treatment is applied. For example, laparoscopic surgical procedures are used first in intra-abdominal adhesion that prevents the retention of eggs. In vitro fertilization treatment is also applied if pregnancy cannot be achieved by normal means despite the treatment of adhesions that develop due to ovarian cysts or inflammations and the function of fallopian tubes to hold eggs.
In women, in vitro fertilization is also used in the case of endometriosis, which is a disease of the endometrium tissue that is discharged during the menstrual period and is located in the fallopian tubes or intestines.
This treatment is also used in immunological infertility, where antibodies develop in the ovaries that prevent sperm attachment. If pregnancy cannot be achieved due to infertility seen especially in men, the microinjection method provides successful results.
What are the Stages of IVF Treatment?
After evaluating the general health status of the couples and the reasons for pregnancy failure, specialist physicians inform the couples and the treatment process begins.
Stage#1: Stimulation of Eggs
Stimulation of the ovaries and obtaining a large number of eggs are the basis of IVF treatment. On the 3rd day of the menstrual period of women, medicated treatment including hormone injections is started. After informing women, they can do the injection themselves. The stimulation process, which lasts for about 10-12 days, varies from woman to woman according to the reaction of the ovaries to the medication. In this process, in which the ovaries should be closely monitored, ultrasonography control is performed every 2-3 days on average. During these controls, the dose of the drugs is adjusted according to the hormone level of the women. At the same time, in some cases, a hormone antagonist is given from the navel to prevent premature rupture of the ovaries.
Stage#2: Collection of Eggs
After the eggs reach a certain size, hormone injections are applied to ensure that they crack and the collection process is performed. Timing is of great importance in the collection process; Eggs are collected 34-36 hours after hormone injection, mostly under general anesthesia. In the process, the needle guided by ultrasound is passed through the vagina and the eggs are reached. While generally 1 to 40 eggs are obtained, there may be cases where eggs are not obtained, although very rarely. The couples are discharged a few hours after the collection process, which takes an average of 20-30 minutes.
Stage#3: Fertilization of Eggs
The collected eggs are fertilized by various methods in a suitable laboratory environment and embryo formation is provided. After fertilization, which takes an average of 12 to 15 hours, the day is planned to be placed in the uterus by selecting quality eggs.
Stage#4: Embryo Transfer
In the transfer of fertilized eggs, also known as pre-embryo or zygote, into the uterus, a maximum of 2 days is expected according to the quality of the embryos. Transfer involves leaving the embryos taken into the catheter through the cervix. Embryo transfer, which is performed without the need for anesthesia, is performed with ultrasonography. While the number of embryos transferred in women under the age of 35 is one, it is at most two in other women. After embryo transfer, couples can leave the hospital immediately.
Progesterone or estrogen hormone is supplemented by injection for two weeks following the transfer.
Stage#5: Pregnancy test
A pregnancy test is performed in order to understand whether pregnancy occurs on average 12-14 days after embryo transfer. If the test is positive, an ultrasound control is performed approximately 10 days later to see the condition of the gestational sac.
What is Assisted Hatching?
Although embryo is formed during IVF treatment in some cases, pregnancy does not occur. This is usually caused by the problems that occur during the embryo attachment stage to the uterus. Assisted nesting method; It ensures that the embryo, which reaches a certain size, gets rid of the membrane (zona pellucida) surrounding it and adheres to the endometrial tissues. It is aimed for the embryo to tear this membrane by opening a hole in the membrane with chemical methods or laser technology. During this process, the embryo is fixed, but no damage is done to the embryo.
Assisted Hatchinng method is mostly applied in cases where the zona pellucida is thick, women are over 35 years old and after unsuccessful IVF treatments.
What is Vaccination (IUI)?
Vaccination, also known as Intrauterine Insemination (IUI); It is the implantation of the sperm cell into the egg during the ovulation or near ovulation period of women. Vaccination; It is applied to patients with unexplained infertility and early stage endometriosis and vaginismus. However, vaccination is also suitable in cases where the passage of sperm through the cervix is prevented and premature ejaculation or erection problems are seen.
What Is the Difference Between Vaccination and IVF?
In some cases, the vaccination method is preferred before IVF treatment. Vaccination is one of the most suitable treatment methods for infertility, which is also known as infertility. In order for vaccination to be applied, in addition to unexplained infertility in men, one of the fallopian tubes should be open in women and advanced endometriosis (such as chocolate cyst) disease should not be seen. At the same time, sperm count and quality should not be too low in men.
What is Microinjection (ICSI) Therapy?
In IVF, the classical IVF method, sperm and eggs are brought side by side and the sperm are expected to fertilize the egg. In the microinjection method, also known as intracytoplasmic sperm injection (ICSI), the sperm cell taken into a glass needle is injected directly into the egg and fertilization is provided. Microinjection applications are performed when the sperm count is insufficient, the motility is below normal and the cells cannot fertilize the egg.
The most important advantage of the microinjection method is that men who have problems with sperm motility and count can also benefit from the IVF method.
Who Are the Right Candidates for Microinjection Therapy?
Microinjection, which differs from the IVF method only during the fertilization process, is applied in cases where sperm count and quality is low, as well as in the presence of sperm antibodies that prevent fertilization, in cases where fertilization does not occur with the classical method and there is a problem in fertilization, although there is no specific sperm problem.
What is Drug-Free IVF Treatment?
In classical IVF treatment, hormone-containing needle therapy is applied in order to obtain more eggs and embryos. However, some women’s ovarian capacity is not enough to produce too many eggs. In cases where the number of ovaries is low and the chances of success are low with hormone injections, a drug-free treatment method, in which the menstrual cycles of women are followed, is preferred. In this method, which focuses on egg quality instead of the number of eggs, women are either not given any medication or given a very low dose of hormones. Continuation of the procedures is similar to classical IVF; Following the natural spawning process, the appropriate size egg is collected with a needle. After fertilization, the embryo is placed in the uterus.
The advantages of drug-free IVF treatment preferred in women with insufficient egg reserves are as follows:
- Shorter treatment time compared to IVF, which is the classical IVF treatment,
- Low or no side effects because no medication is used,
- Less clinical and ultrasound controls,
- Very low risk of developing complications,
- Little or no injection applications,
- Its cost is lower.
What is the PRP Method?
PRP, also known as egg rejuvenation, is one of the new methods. PRP (Platelet Rich Plasma), which means thrombocyte enriched plasma, is obtained from people’s own blood and does not contain any additives. PRP method is used especially in cases where the chance of pregnancy is low due to various reasons. Platelet-rich plasma is applied to the ovaries of women and activates stem cells. Because it is a painful procedure, the procedure is usually performed under anesthesia, with the help of a needle entering the vagina and PRP injection into the ovaries. In this way, it is aimed to increase the ovarian functions. PRP applications increase the chance of pregnancy in elderly women with low ovarian reserve and individuals entering early menopause.
Sperm Collection Procedures
Sperm as well as eggs are of great importance in the realization of fertilization and obtaining quality embryos. In this sense, sperm retrieval stages are also one of the important stages of IVF treatment.
Sperm are taken from men on the day the eggs are collected. In order to obtain correct and sufficient sperm, it is recommended for men to have sexual abstinence 3-5 days before the collection day. In this way, there are more live cells in the semen obtained by various methods. Semen sample is taken in specially prepared masturbation rooms and passed through various processes in the laboratory. The highest quality and motile sperm are selected from semen extracted from waste and liquids and used for fertilization.
In some cases, no sperm cells are seen in the semen obtained by masturbation. In this condition, also called azoospermia, different surgical methods are used to take samples from men:
Epididymal Sperm Aspiration (MESA) Under the Microscope
Although normal or nearly normal sperm production is observed in the testicles as a result of the tests performed, it is the method applied in the presence of obstruction in the main channels (vas deferens) carrying sperm to the penis or if these channels are not found congenitally. In the MESA method performed under the microscope, a small incision is made and a fluid sample is taken from the epididymis, which is the channel that transmits sperms to the vas deferens. In andrology laboratories, the sperm in these liquids are separated.
Percutaneous Epididymal Sperm Aspiration (PESA)
PESA; It is the process of sperm aspiration by entering the epididymis through the skin with a small needle. One of the most important advantages of this method is that no incision is required in the operation, which is usually performed under sedation or local anesthesia.
Testicular Sperm Aspiration (TESA)
TESA method is used to obtain sperm in fertilization by microinjection method. In a surgical operation performed under local anesthesia, a needle is placed in the testicles and the sperm is aspirated from here. The quality sperm obtained is injected into the eggs after the egg collection process.
TESA; It is preferred when genital tracts of men are obstructed, testicular problems and after vasectomy operation.
Testicular Sperm Extraction (TESE)
The TESE method is usually applied in cases where testicular sperm aspiration does not work. In the biopsy operation performed by making a small incision in the testicles, tissue samples are taken from different parts of the testicle. The process of obtaining sperm cells from these tissue samples is called TESE. Surgical procedure performed under general anesthesia is performed under microscope in some cases. This process, which is called micro TESE, which is based on enlarging the tissues with a microscope, increases the possibility of finding sperm cells compared to the classical TESE method.
Under normal conditions, freezing of reproductive cells is prohibited according to the Regulation of the Ministry of Health. However, sperm cells can be frozen and stored after TESE and TESA procedures, which are under medical necessity, and can be reused after unsuccessful in vitro fertilization trials.
Men can be discharged on the same day after all these methods to obtain sperm used during fertilization in microinjection or IVF treatments. It is normal to feel pain and pain in the operation area for a few days.
What Types of Tests Are Applied Before IVF Therapy?
Before couples start IVF treatment, some tests are applied to women and men in order to understand the obstacles to pregnancy. These tests, which are performed simultaneously, generally include sperm and hormone tests for men, and hormone tests and hysteronsalpingography (HSG) tests for women. As a result of the tests, problems are determined and IVF treatment is planned.
What Types of Tests are Applied for Women?
Basal hormone tests are applied to women primarily to understand the quality and number of eggs (ovarian reserve). E2, LH, TSH, PRL and, in some cases, DHEAS and total testosterone tests applied on the 2nd or 3rd day after menstruation provide information about whether there is low ovarian reserve. FSH values of 12 and above and E2 values above 80 pg / ml mean that ovarian reserve is low; The doses of drugs to be used in treatment are determined according to these values.
Medicated uterine film (hysterosalpingography) and office hysteroscopy tests are performed to understand whether there is any problem in the tubes of women and the structure of the uterus. The inside of the uterus that does not support the development of the baby; The presence of adhesions, fibroids and polyps and the closed fallopian tubes significantly reduce the success rate of in vitro fertilization. In this sense, thanks to the hysterosalpingography test, these situations are known in advance and precautions can be taken.
Transvaginal ultrasound applied to women in the basal period provides information about both uterus and ovaries. In addition to whether there is an anatomical problem in the uterus, the presence of fibroids and polyps can be clearly understood with this method. At the same time, the ovarian reserve is evaluated and it is determined whether there is polycystic ovary syndrome and endometrioma (chocolate cyst).
In addition to these tests for all women who will undergo IVF treatment, different tests may be requested in some cases. Aids (HIV), Hepatitis B (HbsAg) and Hepatitis C (Anti HCV) tests are performed especially in order to understand the diseases that can be passed on to the baby after pregnancy. Rubella Ig G test indicates the risk of rubella in women; The blood group test for men and women is done to determine whether there are blood incompatibilities. Protein S, Protein C, INR, aPTT and PTT tests are applied to avoid any problem in blood coagulation. In order to understand platelet and anemia problems, most women also have a complete blood count (hemogram).
What Types of Tests are Applied for Men?
Before starting IVF treatment, standard semen analysis (spermiogram) is performed for all men. Thanks to this analysis, information about sperm count, motility and quality as well as the morphological structure of the sperm is obtained.
Hormone tests requested from men when necessary are PRL, FSH, LH and total testosterone. Especially high FSH value means that testicular reserve is low. In some cases, HbsAg, HIV, Anti HCV and blood group tests, which are also applied to women, are also performed for men.
In cases where sperm reserve is low, urological examination and chromosome analysis are also performed in cases of azoospermia.
What Are the Risks of IVF Treatment?
Like any treatment method, there are some predictable and interventionable risks in IVF treatment. Risks; It occurs due to drugs used or procedures applied during treatment.
The development of an egg fertilized with sperm outside of the uterus instead of inside the uterus is called ectopic pregnancy. The possibility of an ectopic pregnancy, which is usually caused by problems in the fallopian tubes, during in vitro fertilization is less than natural pregnancy. Ectopic pregnancy, which can be diagnosed with ultrasonography and blood tests at an early stage, can be treated with medical methods or surgical operations.
The high number of embryos transferred to women increases the success rate of IVF treatment. However, the higher the number of embryos, the higher the risk of multiple pregnancy. Multiple pregnancy is seen in one out of every four successful IVF trials on average. Multiple pregnancy has negative effects on the health of both women and babies. In this case, the risks of preterm birth and miscarriage are higher than single embryo transfer. Preeclampsia, also known as diabetes, hypertension and pregnancy intoxication, may develop during pregnancy due to multiple pregnancy in women; During delivery, complications such as bleeding more than normal may occur. In babies, due to premature birth, physical and mental development disorders as well as deaths are seen. Spasticity, poor lung capacity, brain hemorrhage, multiple organ disorders and permanent disabilities are the most common problems.
The number of embryos transferred should be minimized in order to prevent multiple pregnancy, which can cause serious consequences for mothers and babies. Transferring a single embryo to women under the age of 35 in the first two attempts and transferring up to two embryos to other women significantly reduces the risk of multiple pregnancy.
What Are the Medication Related Side Effects of IVF Therapy?
Stimulating hormone drugs and other drugs used to obtain quality and large numbers of eggs cause some side effects:
- Sudden changes in emotion due to hormone supplementation,
- Redness, bruising or pain at the injection site,
- Nausea and vomiting,
- Abdominal pain,
- Allergic reaction.
The most serious but rare complication due to drug use is ovarian hyperstimulation syndrome (OHSS). Ovarian hyperstimulation syndrome is the excessive reaction of the eggs against the hormone drugs applied to support egg development and obtaining a much larger number of follicles, i.e. egg sacs than desired. Generally, this syndrome, which occurs at the latest 7 days after egg collection, is seen at a rate of 2%.
Although the cause of OHSS is not known exactly, polycystic ovary syndrome, being under the age of 30, low body weight and having this syndrome before are among the risk factors. Younger women with polycystic ovary syndrome, a common reproductive disorder, are particularly at risk.
OHSS usually resolves within a few weeks, depending on the severity of the complaints and whether the pregnancy has occurred, and often does not affect the pregnancy. Symptoms of mild, moderate or high severity are abdominal bloating, nausea and vomiting, constipation or diarrhea, very rapid weight gain and shortness of breath. In the treatment of the syndrome, rest, plenty of water consumption and light exercises are recommended; In severe symptoms, pain relief can also be taken.
How to continue in vitro fertilization after ovarian hyperstimulation syndrome occurs is planned according to the pregnancy status. If the syndrome is diagnosed at an early stage, embryo transfer is delayed until recovery is achieved. The most important reason for this is that these syndromes generally exacerbate during pregnancy and recovery takes a long time.
What is the Success Rate of the Treatment?
The success rate in IVF treatment varies according to many factors. However, it is possible to talk about a success rate of one third in general. While the success rate for women under 30 is 45-50%, it is around 15-20% in advanced age. It is predicted that all in vitro fertilization trials will be successful with the techniques developed in the future.
On the success of the treatment;
- Age of women,
- Infertility of unknown cause,
- Quality and number of sperm,
- Status of ovarian reserve,
- Condition of falop tubes and uterus,
- The presence of endometriosis and fibroids that prevent the egg from holding in the uterus,
- Alcohol and smoking,
- Excess weight,
- Psychological factors such as stress are effective.
How to Increase Success Rate?
In addition to egg and sperm quality, the laboratory environment has a great effect on increasing the success rate of IVF treatment. The experience of physicians and the high equipment of embryo laboratories increase the success by an average of 80%. It is important to evaluate the medical history and problems of the couples in detail and to use the appropriate medications and to determine the correct treatment method. However, timely stimulation of eggs, collection and placement of embryos in the uterus also greatly increases the live birth rate.
Embryo Freezing: One of the most important factors that increase the possibility of pregnancy is the freezing and storage of quality embryos. Even if no transfer is made into the uterus during egg collection, quality embryos are selected. Thanks to these frozen and stored embryos, if IVF treatment fails, women do not need to undergo hormone therapy again and undergo egg collection. Although the age of the woman increases in the future, the embryos maintain their quality; this increases the chance of pregnancy.
Pre-implantation Genetic Diagnosis Test (PGD): Pre-implantation Genetic Diagnostic Test (PGT), which is performed before the embryo is transferred into the uterus, is a diagnostic method used in the early diagnosis of genetic diseases and determining the number of chromosomes. In this way, it is aimed that healthy babies are born.
The number of chromosomes is taken into consideration when determining which embryos will be used by microinjection method. By selecting embryos with normal chromosome number, the risk of miscarriage due to chromosome is reduced.
PGD diagnostic tests are generally used in older women, in recurrent IVF treatment failures and in men in advanced infertility. Thanks to genetic diagnostic tests that eliminate these factors that reduce the probability of success, embryos without anomalies are selected and the probability of success is increased.
PGD test is applied to the embryo formed by the ovary and sperm combined with microinjection method. On the 5th or 6th day of the development of the embryos, samples are taken from the cells for biopsy and chromosome scanning is performed. Today, healthy embryos, which are usually scanned for 24 chromosomes, are selected and transferred into the uterus.
In recent years, genetic diagnosis tests have been used in almost all in vitro fertilization trials. In this way, we have information about genetic anomalies that may occur both at birth and in the future, and even if couples have genetic diseases, babies are born and develop healthy.
Blastocyst Transfer: The 5th or 6th day of the development of embryos is called the blastocyst period. The main purpose of blastocyst transfer is to select embryos that are more likely to attach; Embryo transfer is not performed earlier because the embryos that come to this stage are much more likely to attach. In this sense, low quality embryos show themselves up to this stage and the treatment continues with the highest quality embryos.
Another advantage of transfers made during this period is that multiple pregnancy can be avoided. By transferring only 1 or 2 high quality embryos, both the risk of triple pregnancy is reduced and the chance of pregnancy is increased.