A) PRELIMINARY EVALUATION
İRENBE is also a ‘Women’s Health Center’. Every woman who applies to our clinic is also evaluated in terms of her general and gynecological condition.
According to personal information, complete blood count, blood group, fasting blood glucose, lipid profile, blood levels of certain vitamins, thyroid function tests, cervical smear evaluation (pap smear), breast examination - ultrasonography and mammography are performed. Necessary consultations are also requested regarding your known diseases.
With the examination usually performed on the 2nd or 3rd day of the menstrual period, your ovarian reserve and possible gynecological problems are investigated. If necessary, some hormone tests may be requested. Immediately after the menstrual period ends, a uterine film (HSG) may be requested to determine the condition of the uterine cavity and tubes.
For male patients, a sperm sample is given after 3-5 days of sexual abstinence. In patients whose sperm analysis results are problematic, a new sample may be requested after 2-3 weeks, and if necessary, urological examination, hormone analysis, and genetic analysis may also be required.
Depending on the problems detected through examination and tests, hysteroscopy under anesthesia (observation of the uterine cavity with a camera), laparoscopy (evaluation of the abdominal cavity with a camera and performing the necessary intervention = closed surgery) may be required.
In applying couples, if present, correction of existing health problems (diabetes, thyroid disease, anemia, heart disease), weight loss for patients with high body mass index, and quitting smoking may be necessary approaches before starting treatment. If deemed necessary, supplementation of missing vitamins and antioxidant medications may also be provided.
What is ovarian reserve?
Every woman is born with a certain number of egg cells. While in the mother’s womb, a female baby has approximately 7 million eggs at the 20th week of pregnancy; from this week onward, this number gradually decreases to 2 million at birth and to 400 thousand during puberty. These cells, which are naturally programmed to disappear, are selected during the first 5 days of each menstrual bleeding, and usually one or two of them are matured. A woman can ovulate approximately 400 of her eggs throughout her entire reproductive life. Ovarian age does not always progress parallel to body age. Although the decrease in ovarian reserve becomes more evident after the age of 35, in some women this decrease may progress extremely rapidly and/or early. Genetic factors, smoking, poor living conditions, surgeries performed on the ovary, the presence of chocolate cysts (endometrioma), chemotherapeutic agents, and radiation can also negatively affect the number of eggs. Patients with such histories should be evaluated earlier.
Many methods used to evaluate egg reserve such as AFC (the number of existing egg sacs seen by ultrasonography during menstruation), FSH-Estradiol, and AMH can determine your response to treatment, but may not always clearly show your pregnancy rate.
B) STARTING TREATMENT
Even if the reason for IVF treatment is a male factor, the woman undergoes treatment. For the treatment to be effective, obtaining a sufficient number of high-quality eggs and sperm is essential. In this sense, there are many ovarian stimulation protocols applied. Which of these treatments is appropriate is decided in light of personal data (age, number of eggs, body mass index, smoking, procedure characteristics-PGD, etc.). The treatments and medications applied in this regard are as follows;
1) Long protocol
It usually starts on the 21st day of the menstrual cycle preceding the month when treatment will begin in patients with sufficient ovarian reserve. Birth control pills may also be given beforehand. GnRH analogs are administered in certain doses to suppress your body’s own control system. The aim is to prevent your ovaries from functioning outside our control. These medications are continued until egg collection. Once menstruation begins, egg-stimulating medications adjusted for you are administered for 10-12 days.
2) Short protocol (antagonist)
After examination on the 2nd or 3rd day of menstrual bleeding, egg-stimulating medications are started. According to your response to treatment, GnRH antagonist medications are added on certain treatment days to prevent your eggs from ovulating on their own. This treatment can be applied to all patient groups, but it is mostly used in patients with low ovarian reserve.
3) Co-flare and microdose protocol
This treatment is mostly applied to patients with decreased ovarian reserve. In the co-flare protocol, treatment is applied by starting GnRH agonist on the 1st or 2nd day of menstruation and adding egg-stimulating medications in the following days.
4) Modified protocol in which Co-flare and antagonist protocol are applied together (ultrashort agonist + antagonist protocol)
5) Clomiphene citrate or letrozole in antagonist protocol
6) Sequential stimulation
Stimulation twice within the same cycle (this application is beneficial in cases with low ovarian reserve.)
C) CONTINUING THE TREATMENT
After selecting the appropriate protocol, a follow-up period lasting 10-12 days begins. During this period, by coming to the clinic 3-4 times, ultrasonographic examination and, if necessary, hormone analysis (estradiol, LH, progesterone) are performed to check your response to treatment. According to the results obtained, medications may be added or reduced. The size of the fluid-filled sacs called FOLLICLES containing egg cells continues until approximately 18 mm. At this stage, careful continuation of the treatment is very important.
D) FINAL STAGE (EGG MATURATION OR TRIGGERING)
When your follicles reach approximately 18 mm in size, appropriate injections are administered to ensure that your eggs mature and become easy to retrieve. 34-36 hours after the medication is administered, the egg collection procedure is performed vaginally under anesthesia and ultrasound guidance.
EGG COLLECTION (OPU – Oocyte pick-up)
The procedure is performed under intravenous anesthesia. With the help of a specially designed needle and pump, the fluid-filled sacs (follicles) are aspirated and transferred into tubes. In the laboratory environment, the eggs are separated from this fluid after examination.
Sperm retrieval;
Data regarding the male patient are obtained beforehand while planning the treatment. Accordingly, on the day of egg collection, the spouse who has had 3-5 days of abstinence gives a fresh semen sample. The abstinence period is reminded during the follow-up period.
In couples receiving treatment for severe male factor infertility, the sperm sample is obtained from the TESTIS or its APPENDAGES (TESA, MICRO-TESE, PESA, MESA). Materials remaining apart from the samples used for the procedure are stored within the legal period.
In patients where no ‘motile’ sperm was found in semen during previous examinations, the TESE procedure may also be required. The aim is to obtain a higher-quality motile-live sperm sample.
LABORATORY STAGE
After the eggs are obtained, they are kept for 3-4 hours in specially prepared devices called incubators. Following this, the support cell mass around them (Cumulus oophorus-granulosa cells) is removed. After microscopic examination, their maturity is determined. In patients whose sperm count is 15 million or more, motility is sufficient (40% and above), and morphology is normal, the conventional method called the classical method may be applied, where 100 thousand sperm are placed around each egg cell. Good clinics worldwide apply this method to approximately 25% of suitable patients. In microinjection, however, 1 sperm is injected into each egg cell. This method is generally applied to patients with decreased ovarian reserve, a low number of eggs obtained, low sperm count, or where sperm is obtained by surgical methods, but it can also be applied to other patient groups. The fertilization rate in the microinjection method is around 70-80%.
Whether fertilization has occurred is usually checked 16-17 hours after the fertilization procedure (the next morning). If fertilization has occurred, cleavage controls are performed (CLEAVAGE PERIOD). In embryos under video monitoring, these processes are carried out automatically inside the incubator. Until they are returned to the mother’s uterus, fertilized eggs (embryos) are kept in special fluids and environments that mimic the uterus (incubators = devices with adjusted heat and gas properties).
EMBRYO TRANSFER
In fresh embryo transfer, embryo transfer is usually performed on the 2nd-3rd day. In suitable patients (if there are many high-quality embryos), 5th day (blastocyst) transfer may also be performed. The transfer procedure is painless and, unless there is a special condition, is performed without anesthesia and with a full bladder. It is no different from an examination. The embryos loaded into a special catheter are transferred into the uterus under ultrasound guidance. Progesterone and its derivative medications started on the day of egg collection should be continued until the pregnancy test.
In selected cases in our unit, especially in advanced age groups, 3rd and 5th day transfer can also be performed together (sequential transfer).
EMBRYO FREEZING
If you have quality embryos after the procedure, they are frozen and stored on the 3rd or 5th day according to their stage. This method reduces the cost for future attempts and ultimately increases your chance of pregnancy. In addition, embryo freezing is also used for unexpected endometrium problems, infection, allergy, intra-endometrial fluid, and for accumulating embryos for PGD. Your embryos can be stored for 5 years as stated in the law. Recently, since the success of frozen-thawed embryo transfer is higher than fresh cycles and the risk of ectopic pregnancy is lower, embryo freezing has become the preferred option in cases without time limitations.
PREGNANCY TEST
12 days after the egg collection procedure, a blood pregnancy test (b-HCG) is performed. In patients with a positive result, the test is repeated 2 days later to monitor whether the pregnancy is progressing healthily. Patients with regular increases are called for ultrasound control 10-12 days after the last test. During the first 3 months of pregnancy, medications are continued as prescribed.