IVF + ICSI

In vitro fertilization (IVF) is a treatment method applied to women who cannot conceive through conventional methods. It is based on the principle of transferring embryos formed by the fertilization of male (sperm) and female (egg) reproductive cells under laboratory conditions into the uterus.Fertilization, conducted in laboratory conditions, can occur either spontaneously (in vitro fertilization-IVF) or through manual intervention, by injecting a single sperm into a single egg (intracytoplasmic sperm injection-ICSI).IVF treatments worldwide now consist of three standardized fundamental steps. The IVF treatment begins with the stimulation of the ovaries to produce a large number of egg cells. The next step involves collecting these eggs and fertilizing them to create embryos. After fertilization, the embryos are stored in laboratory incubators for 5 days until they are ready to be transferred to the mother’s uterus. A pregnancy test is conducted 12 days after the embryo transfer.

IVF + ICSI Procedure

First Consultation and Examination

The medical treatment protocol will be determined based on the patient’s condition. For some patients, specific medication may be required around the 20th to 21st days of the menstrual cycle to suppress ovarian activity. In certain cases, birth control pills may be used before the treatment.During the initial consultation, a careful and comprehensive medical history is taken, previous tests are reviewed, and examinations are conducted. If the semen analysis is normal and there are no issues with sexual function, a physical examination of the man may not be necessary. However, a thorough examination of the woman is crucial in determining the chances of achieving pregnancy through IVF. The examination assesses the capacity of the ovaries, the presence of any cysts within the ovaries, the structure of the uterus, the presence of fibroids or congenital abnormalities, and the existence of formations such as fibroids or polyps within the uterine lining. If not done recently, a Pap smear test and, if there is discharge, a culture should be performed during the examination.Following the evaluation of the medical history, examination, and test results, the stages of the procedure are explained in detail, providing realistic information about the pregnancy success that the couple can expect from the treatment. Information should be provided about the outcomes of previous procedures performed in the unit, the number of embryos to be transferred, and the center’s implantation rates (the chance of each transferred embryo attaching to the uterus). Potential side effects of the procedure and long-term risks (for both the mother and the baby) should also be discussed with the couple. In a country where the desire for multiple pregnancies is common, complications related to multiple pregnancies should be clearly explained.

Preparation for IVF Treatment

Preparations for IVF treatment may include:

• Quitting smoking
• Starting a multivitamin containing folic acid
• Maintaining regular sleep patterns, including night sleeps, and minimizing stress as much as possible during the IVF treatment
• No specific diet has been proven to be beneficial, although animal studies have shown the advantages of a protein-rich diet
• Depending on the treatment protocol, certain medications may need to be taken around the 20-21st days of the menstrual cycle to suppress the ovaries (such as Lucrin, Suprecur, Synarel, Suprefact, Decapeptyl)
• In some cases, birth control pills or estrogen (such as Estrofem) may be used before treatment.
• Laboratory tests, including hormone levels, hepatitis B and C screening, HIV screening, rubella IgG, complete blood count, and blood typing
• TORCH

Stages of In Vitro Fertilization (IVF)

• Ovarian Stimulation:

In all protocols used in IVF treatment, on the second or third day of the menstrual bleeding, a basic ultrasound examination and estrogen measurement in the blood are performed to determine the dosage of medications. After the stimulation treatment starts, the patient is called for regular check-ups at specific intervals.During these check-ups, vaginal ultrasound is used to monitor the number and size of developing follicles. Occasionally, blood estrogen measurements may be required depending on the condition of the ovaries.The goal of IVF treatment is to obtain as many follicles with a diameter of 16-20 mm as possible. During follow-up appointments, medication dosage adjustments can be made by checking blood estrogen levels. Egg retrieval is performed 35-36 hours after the hCG injection.Another factor evaluated during ultrasound follow-ups is the lining of the uterus, called the endometrium. The adherence and thickness of the endometrium are crucial as it will host the pregnancy. If the endometrium is 6 mm or thinner on the day of hCG, the chances of pregnancy decrease. An endometrial thickness exceeding 14 mm can also have negative effects, increasing the likelihood of miscarriage even if pregnancy is achieved.

• Egg Retrieval:

Once the eggs mature, the retrieval process takes place. Egg retrieval (oocyte pickup-OPU) involves using a needle to enter the ovaries through the vagina and aspirating the fluid-filled structures called follicles, which contain the eggs. The fluid collected contains tiny cells visible under a microscope, representing the eggs. The OPU procedure can be done under local or general anesthesia. For women with ovaries close to the vaginal ultrasound probe and immobile, the procedure can be performed painlessly under local anesthesia. In cases where the ovaries are farther away or behind the uterus, the procedure is done under general anesthesia. The process takes about 10-15 minutes. Not every follicle yields an egg; usually, around 70% of follicles contain an egg. Egg retrieval is typically done a few hours after collection, and the surrounding cells are cleaned to assess whether the eggs are mature. Mature eggs undergo fertilization. 

• Fertilization:

Fertilization in IVF treatment occurs through either the conventional IVF or intracytoplasmic sperm injection (ICSI) method. In conventional IVF, collected sperm is placed near the retrieved eggs, and fertilization is awaited. This method is used when the man is entirely normal, and infertility is attributed to the woman. In ICSI, a single sperm is injected into the egg using a special tool called a micromanipulator. Fertilization typically occurs about 2-4 hours after egg collection. In microinjection (ICSI), the cells surrounding the eggs (cumulus cells) are first removed. Then, the egg is held with a stabilizing pipette and injected with a very fine needle with sperm. About 70% of the collected eggs are mature and suitable for fertilization. For example, a woman with 10 eggs will likely have around 5 embryos. This is an average, and the number can be below or above this.

• Embryo Transfer:

Embryos can be transferred at any stage from the two-cell stage to the multicellular blastocyst stage, but the most commonly preferred transfer time is the blastocyst stage. Embryos usually reach this stage on the fifth or sixth day. There is a direct relationship between the number of embryos transferred and clinical pregnancy rates in IVF treatment. The best clinical results are obtained by transferring 1-2 embryos; when more than two embryos are transferred, the rates of multiple pregnancies significantly increase. However, this risk decreases with increasing maternal age. Due to the high complication rates of multiple pregnancies and increased costs, many IVF centers in various countries restrict the number of embryos transferred. Transferring more than two embryos is only done in women who have previously had unsuccessful IVF/ICSI attempts. During embryo transfer, the patient is placed in the gynecological examination position. The embryologist brings the embryos to be transferred in a catheter from the laboratory, and the physician performing the procedure places the embryos into the uterus under abdominal ultrasound guidance.Embryo transfer is a painless procedure and does not require anesthesia.After the procedure, hormone medications in the form of injection suppositories or cream are given to support the endometrium. This luteal phase support continues until the 10th week if pregnancy occurs. In cases where pregnancy does not occur and menstrual bleeding starts, the treatment is stopped.The patient is called for a pregnancy test 12 days after embryo transfer.

• Pregnancy Test:

First, a urine test and then a blood test for pregnancy (beta-hCG) are performed. Based on the result of the blood test, it is determined whether there is a pregnancy or not. Those with a positive result are called for another blood test two days later, and the relationship between the results of the two tests is evaluated to determine if the pregnancy is healthy. In a healthy pregnancy, the beta-hCG level should approximately double two days later. Occasionally, the beta-hCG level may drop to zero after some time, which is referred to as a biochemical pregnancy.Greater than expected increases in beta-hCG may suggest an ectopic pregnancy (tubal pregnancy), which is a cause for concern.Patients with positive beta-hCG results are considered clinically pregnant, and they are called in for the first pregnancy ultrasound two weeks later. In this first ultrasound, the presence of the gestational sac in the uterus is checked, and if there is a sac, the number of sacs is determined. Twins, triplets, or even more fetuses can be seen in this first ultrasound.