As an sssisted reproductive technique, In Vitro Fertilization or IVF treatment consist of certain stages. As I mentioned in my previous contents, the main goal of treatment is to perform the steps that normally occur naturally in the pregnancy process, but in a controlled manner and in a laboratory environment.
Before going into details about the question "What are the stages of IVF treatment?", I will provide some details in order explain the process more clearly.
The first stage of IVF treatment is the harvesting of egg cells from the woman. Before the realization of this stage, the expectant mother is started hormone therapy in order to harvest more egg cells. Since our main goal is to create as many healthy embryos as possible, we need to trigger the ovulation process for the women.
With hormone therapy, we can ensure that more eggs are formed in the monthly cycle and harvest them when they mature. At this step, the male factor comes into play. We take semen samples from men and separate the quality sperm from it. According to the results of semen analysis, we have different options to choose from.
If there is no problem in the sperm quality of the men, we do not make an additional intervention for the merging of egg cells and sperms and we expect fertilization to occur outside the body in a controlled laboratory environment. But men's sperm don't always make this possible. In other words, we also need to intervene in the fertilization process. In this case, we need to select the highest quality sperm and inject it in the egg using a special technique.
We follow up when fertilization occurs and our embryos are formed. We identify high-quality embryos and transfer them to the uterus of women with a simple procedure and expect them to hold. Of course, all these listed steps can be customized. We may need to support the basic stages with Auxiliary Methods in IVF Treatment. The couble-specific approach is extremely important. Although the stages of IVF treatment are generally standard, it should not be forgotten that intermediate treatments may be necessary.
After all the necessary examinations have been performed as part of IVF treatment, if it is concluded that the couples is suitable for treatment, the ovaries of the woman are first over-stimulated.
Under normal conditions, one or two egg cells mature in the ovaries every month. During the stimulation of the ovaries, which is carried out at the initial stage of IVF treatment, women are given daily hormone supplements. These hormones mimic the body's natural hormones. During the cycle, it is possible to evaluate different protocols within the treatment carried out with the aim of developing a minimum of 3 eggs. After the examinations performed, the most ideal ovarian stimulation protocol for women can be selected.1 The ovarian stimulation phase covers a period of 10 – 12 days on average. Drug treatment begins on the second day of menstruation.
Since it is aimed to obtain both the ideal number and ideal quality oocytes with the stimulation of the ovaries, it is important to consider variables such as the age of women, her ovarian reserves, basal FSH and E2 levels, AMH levels, body mass index values, when determining the doses of the drugs to be administered.
At the stage of ovulation induction, both the use of hormonal drugs and the follow-up of the process are required. When the stimulation of the ovaries begin, ultrasound examination is needed at regular intervals to measure the size of the egg sacs and determine the response of the eggs to drugs.
If, during the check-ups, data are obtained indicating that at least three eggs have matured and the follicles have reached over 17 mm, cracking injections are administered. The purpose of cracking injections in IVF treatment is to fully mature the eggs. Cracking injections are HCG hormone injections that mimic the hormone Luteinizing that is normally secreted by the pituitary gland and allows the eggs to crack in the natural cycle.2 These injections can be made intramuscularly or under the skin.
The timing of the cracking injections is extremely important. The most important thing to consider is that the egg harvesting process, which is the second stage of IVF treatment, should be done before the eggs are cracked. If the cracking injectiong is performed early or the egg harvesting stage is performed late, the matured eggs cannot be used for IVF treatment. For this reason, it is recommended that the egg harvesting process be performed 34 – 36 hours after the cracking injection.3
The ovaries were stimulated, followed up with ultrasound, and when their size reached 16 – 20 mm, a cracking injection was applied. With the cracking injection, the eggs reached optimum maturity. It is at this stage that the maturing eggs need to be harvested before they crack and move into the abdominal cavity.
In the past years, techniques such as laparotomy and laparoscopy were used to harvest eggs. It was possible that these techniques were extremely complex and led to complications such as severe tubal disease and multiple adhesions. Today, egg harvesting is done by a highly developed and minimally invasive method.4
The egg harvesting process, also called OPU, is an extremely comfortable procedure performed under sedation. It is performed via vaginal ultrasound. During the procedure, the follicles are viewed via ultrasound and with the help of a special syringe, the maturing follicles are reached from the vaginal canal and the fluid containing the oocyte is collected. Although it varies from patient to patient, usually, between 3 and 10 eggs are harvested. The duration of the procedure varies between 15 – 30 minutes depending on the number of eggs to be harvested. During egg harvesting, in order not to spoil the fluid aspirated from the maturing follicles, it is necessary to quickly send it to the embryology laboratory.
A semen sample should also be taken from men on the day the eggs are harvested. In order for the ideal number and quality of sperm to be collected, couples should abstain from sexual intercourse for 3 – 5 days before the procedure. The semen sample taken from the man is examined, and if the sperm quality is not considered sufficient, intracytoplasmic sperm injection (ICSI) may be recommended. The main difference between ICSI and traditional IVF has to do with how the egg is fertilized. In classical IVF treatment, the selected sperm and egg cells are brought together under special conditions and fertilization happens spontaneously. In the ICSI process, the highest quality sperm is selected and injected into the egg cell. Thus, it is ensured that the sperm can enter into the egg cell and the probability of fertilization is increased.5
All these listed stages are valid if spermatozoa are present in the semen. However, for the men diagnosed with azoospermia, we need to resort to sperm collection techniques. The technique to be applied to get the sperm from a man varies according to the type of azoospermia. If sperm production is present in the testicles, but there is no sperm in the semen, there is azoospermia due to obstruction, and in this case, sperm can be collected from the testicles, epididymis or vas deferens.
In patients with non-obstructive azoospermia who do not have sperm production in their testicles, an advanced surgical technique called MicroTese becomes a necessity. During the MicroTESE surgery, which is performed under general anesthesia, all sections of the testicles where sperm are likely to be present are scanned and the testicular tissues that are likely to host sperm are collected. While the surgery is still going on, the embryology laboratory starts the sperm examination. The operation of patients with azoospermia, which is not due to obstruction, can be performed in a different time periods. Sperm can be frozen if the eggs have not yet been harvested, or if the eggs have been harvested before the operation, these eggs can be frozen.
It is the stage where the egg cells taken from the woman and the sperm collected from the man are brought together in the laboratory environment. As just elaborated, in the traditional method, egg cells and sperm are kept together under special conditions, waiting for fertilization to occur spontaneously. In case of poor sperm quality, a healthy single sperm cell is injected into the egg. After the performed procedures, it is followed whether fertilization has occurred, whether the embryo has formed.
If fertilization occurs, the embryos are monitored. If deemed necessary, Assisted Hatching (weakening of the embryo membrane) and preimplantation genetic testing methods can be applied.6
After fertilization has occurred, the embryos formed are monitored for 3 to 5 days and then transferred to the uterus.7 During the procedure, the selected embryo is taken into the catheter. The catheter is released into the uterus after being passed through the vaginal canal and the cervix. It is an extremely simple and comfortable procedure. The number of embryos to be released into the uterus is determined by various factors. Transferring more than one embryo can increase the risk of multiple pregnancies. For this reason, no more than 2 embryos are transferred at a time.
5th day embryos are called blastocyst embryos. At this stage, the embryos have grown in size and are further developed. They resemble a ball of cells with a liquid inside. The most important indicators that give an idea about the quality of blastocyst embryos are their width and the appearance of the internal and external cell mass. It is understood that the wider the embryos, the better quality they are. They are classified by a number scale from 1 to 6. 6 represents the highest quality embryo. The inner and outer cell masses are also classified as a, b and c. A is the highest quality.
Embryo freezing can be performed in the presence of high-quality embryos that could not be transferred. Thus, if the IVF treatment fails, the second trial can be performed with just the embryo transfer.8
Embryo transfer is the final stage of IVF treatment. After this stage, the embryo is expected to attach the uterus (implantation).
In order to understand whether pregnancy has occurred after the transfer, about two weeks of waiting time is required. During this process, women may need to take the progesterone. Thanks to progesterone, the probability of implantation can be increased. Hormone therapy needs to be carefully planned.9
A pregnancy test can be performed 12 days after embryo transfer. After IVF treatment, the formation of pregnancy and the healthy birth of the baby may vary according to the age of the mother, the quality of the embryo, past pregnancies, the cause of infertility and mother's lifestyle.10
1 https://uihc.org/health-topics/ovarian-stimulation-and-monitoring
2 https://www.nhs.uk/conditions/ivf/what-happens/
3 https://www.urmc.rochester.edu/ob-gyn/fertility-center/services/infertility/ivf/ivf-step-by-step.aspx
4 https://www.cambridge.org/core/books/abs/textbook-of-clinical-embryology/ovum-pickup-opu/1ECFC3432B54CCFE131D133B76A67ED0
5 https://www.nice.org.uk/guidance/cg156/ifp/chapter/What-happens-in-IVF#pre-treatment
6 https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
7 https://medlineplus.gov/ency/article/007279.htm
8 https://www.nice.org.uk/guidance/cg156/ifp/chapter/What-happens-in-IVF#pre-treatment
9 https://medlineplus.gov/ency/article/007279.htm
10 https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
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