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Initial Evaluation

Infertility is diagnosed when couples who have a desire for pregnancy do not achieve pregnancy for one year despite regular unprotected intercourse.  This period is limited to 6 months if the age of the expectant mother is over 35. Firstly, 3 tests are recommended. These are; sperm analysis, hysterosalpingography (uterine x-ray test) and hormonal tests of the expectant mother.  Male factor infertility, i.e. a problem in the sperm test, changes the treatment plan. If there is no sperm (azoospermia) and no functional sperm is found in the testicular biopsy, sperm donation can be performed.  The hormone levels of the expectant mother are evaluated and the ovarian reserve is assessed with the AMH result. Thyroid hormones and prolactin hormone disorders are treated.  HSG (hysterosalpingography), i.e. uterine x-ray, is a highly reliable test. With this simple imaging method, intrauterine adhesions, structural anomalies of the uterus, adhesions in the tubes or hydrosalpinx (fluid accumulation in the tubes) can be easily detected.

 

Unexplained infertility is diagnosed if the expectant mother has regular periods and all tests are normal. Mild disorders in sperm motility can be treated within a few months with smoking cessation and antioxidant supplements. Severe sperm disorders require direct in vitro fertilisation. If there is a severe bilateral obstruction in the tubes, IVF treatment is necessary.  Adhesions in the uterus can be removed by hysteroscopy.  Pathological conditions such as fibroids or polyps in the uterus can also be operated by hysteroscopy.  

 

If there is a severe decrease in ovarian reserve, it is also recommended to start in vitro fertilisation treatment as soon as possible. It is important to note that the number of eggs decreases with each passing month.  In case of completely depleted ovarian reserve or menopause, egg donation would be the right option. In addition to these infertility tests and treatments, pre-pregnancy tests should also be performed. Systemic diseases that may cause problems in pregnancy should also be taken under control. If there are any vitamins deficiencies, they should be supplemented before treatment, and folic acid and vitamin B12 should be taken. In IVF treatment, each couple is evaluated and treated individually.

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IVF Medicines

There have been significant advances in drug technologies since the first IVF treatment.  One purpose of the drugs used in IVF treatment is to ensure the collection of eggs in the highest quantity and quality. They also reduce miscarriage rates after embryo transfer and protect the mother from the side effects of high dose estrogen. Since there may be confusion during the application, it is important to carefully listen to the person explaining the medication. The drug treatment scheme is given in writing to the expectant mother and father. If possible, all drug applications take place in the IVF centre. 

 

1. Folic acid and Vitamin B12 

Supplementation of these two vitamins before pregnancy reduces the risk of nervous system abnormalities in the baby. Both are vital for cell division and proliferation.

 

2. Clomiphene and Letrazole

This is the simplest treatment option used in assisted reproductive technologies.  These two medicines increase the natural secretion of FSH (follicle stimulating hormone) from the human brain. They are taken orally.

 

3. HMG (Human Menopausal Gonadotropins) 

HMGs contain the same amount of purified FSH and LH hormones obtained from menopausal urine. Their aim is to stimulate the ovaries to develop more eggs. This group of medicines is administered under the skin (around the navel).

 

4. Urinary FSH 

Urinary FSH is the only FSH hormone obtained by purification from menopausal urine. It does not contain LH. Its purpose and method of use are the same as HMG.  

 

5. Recombinant FSH 

It is pure FSH produced by genetic engineering in laboratory environment. Its intended use is the same as HMG and urinary FSH. Its advantage is that it is pure and dose calibration is much more sensitive than human preparations. It is injected subcutaneously. 

 

6. GnRH Agonists 

Gonadotropin-releasing hormone is secreted from the higher centres of the brain and regulates ovulation and pregnancy mechanisms. GnRH agonists suppress the secretion of FSH and LH and ensure synchronous growth of follicles during IVF treatment. They are also used for egg maturation (hatching). They are ideal for patients with a high risk of OHSS. They are available as nasal spray or subcutaneous injection. 

 

7. GnRH Antagonists

Antagonists are used in IVF treatment to prevent the eggs from hatching spontaneously. They can be started after the follicles (fluid sacs containing eggs) reach a diameter of 14 mm or on the 6th day of treatment. The method of administration is subcutaneous injection. 

 

8. Progesterone 

It helps the endometrium (uterine wall) to form and the embryo to attach to the uterine wall. Progesterone is necessary for the continuation of pregnancy. Using it at the wrong time may cause the IVF treatment to fail. Progesterone can be administered orally, intramuscularly, vaginally or subcutaneously. 

 

9. hCG (Human Chorionic Gonadotropin)

Although HCG is a pregnancy hormone, it is used in in vitro fertilisation to mature the eggs. Although this task belongs to the LH hormone in the natural ovulation cycle of human beings, the use of LH during treatment is not practical.  The method of administration is subcutaneous injection. 

 

10. Blood thinners

Since high levels of oestrogen during IVF treatment can increase the mother's intravascular clotting, blood thinners are used. These may be in form of an aspirin or subcutaneous injection. 

 

11. Intralipid© and immunosuppressants

These drugs are believed to increase success in recurrent IVF transfer failures. Intralipid is a nutritional product given intravenously. Tacrolimus or methylprednisolone are oral immunosuppressants. 

 

12. Antibiotics 

It can be given to expectant mothers and fathers at the beginning of IVF treatment, considering that bacteria may prevent pregnancy. 

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Stimulation of the ovaries (Ovulation Induction)

Success in IVF treatment increases in line with the number of eggs collected.  In the light of this information, the goal is to collect the maximum number of eggs without reducing their quality. IVF treatment starts with the stimulation of the ovaries. At this stage, drugs containing FSH (follicle stimulating hormone) are administered by injection around the navel. These injections are administered with very thin needles such as insulin needles. The treatment is not painful. 

 

Some medicines contain LH (luteinising hormone) as well as FSH. If necessary, LH-containing drugs are also added to the treatment. Pills that increase the body's own FSH production in support of the externally administered FSH hormone can also be used in the treatment.

 

This treatment is started on the 2nd or 3rd day of menstruation. The aim is to enlarge the fluid sacs called follicles in the ovary. Follicles are structures containing eggs. Eggs develop with the support of this hormone. Generally, 4-6 days after medication is started, the expectant mother is called for ultrasound control for the first examination. If the desired response is not obtained, the drug doses are increased. Subsequent controls are usually performed in intervals of 1-2 days. The purpose of these evaluations is to measure the response of the ovaries to the medication.

 

This allows administering the drugs that will enable the eggs to mature at the most appropriate time. The aim is to synchronise the follicle diameters with each other so that they reach an average diameter of 17-19 mm. The next stage is the administration of egg hatching injections (egg activators).

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Maturation of Eggs (Egg Cracking)

After stimulation of the ovaries (induction), the eggs need to mature. This is also done with injections (needles).  When the follicles containing the eggs reach the desired size, maturation can be performed with one or several types of injections from the navel.  Timing is very important at this stage. The eggs should be collected approximately 35.5 to 36 hours after the egg hatching injections.  

 

If the expectant mother is young, has a low body weight and a high AMH value, only GNRH agonists are used to avoid ovarian hyperstimulation syndrome. Drugs containing the pregnancy hormone hCG are avoided.  In cases where the use of hCG is not contraindicated, both GNRH agonists and hCG can be used together.

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OPU (Egg Collection)

This is one of the most important steps of IVF treatment. The procedure is performed approximately 35.5-36 hours after the egg hatching (maturation) injection.  The eggs are removed from the mother's ovaries with the help of a needle. This procedure is performed under anaesthesia in the IVF operating room. There is a guide on the vaginal ultrasound probe. This guide is passed through the OPU needle and the follicles in the ovary are reached.  Follicles are fluid-filled sacs in the ovary containing eggs.

 

When the follicle is entered, the aspirator device connected to the other end of the needle draws the fluid and the egg into a plastic tube with negative pressure. The egg is now outside the body. The tube is sent to the embryologist and the egg in the fluid is immediately found with the help of a microscope. It is removed from the fluid with the help of a special cannula.  When all the eggs are collected, they are stored in a special device called an incubator. The duration of the egg collection process varies with the number of follicles enlarged in the ovaries. It is usually completed in 10 - 30 minutes. There is usually no significant pain after the procedure. 

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Sperm Extraction

The father-to-be gives a sperm sample on the day of egg collection for IVF treatment.  If possible, there should be no ejaculation for 3 days before this procedure.  If frozen eggs will be used in the treatment or if the couple can come to our centre at different times, the sperm can be frozen on any day.  

 

Sperm retrieval is performed in the sperm room of the IVF centre under completely hygienic and appropriate conditions.  In this room, the father-to-be is not disturbed in any way. Sperm can be retrieved by TESE procedure from prospective fathers who have problems in the sperm donation phase or who have azoospermia (no sperm in the ejaculate fluid).

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Denudation (Egg Preparation)

The eggs obtained after egg retrieval (OPU) are surrounded by cells called cumulus.  These cells are responsible for the maturation of the egg. After the eggs are collected, they are kept in a closed system called incubator for 2 hours without any intervention. Then the cumulus cells around the eggs are removed from the eggs with the help of hyaluronidase enzyme and special cannulae. After this, the maturation stage of the eggs can be understood.

 

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Transfer

Perhaps the most important step of IVF treatment is the transfer of the embryos into the mother's uterus. Depending on the anatomical condition of the expectant mother and the image quality in ultrasound, the transfer time is 5 - 10 minutes. Although it seems simpler than other steps, all technical rules must be followed for the treatment to be successful.

 

The day and time of the transfer are determined in advance and the expectant mother arrives at the IVF centre with a full bladder (urine bag). This makes it easier to perform abdominal ultrasound. The transfer is performed with the guidance of ultrasound. Before the procedure, secretions and drug residues in the cervix are completely cleaned with pure water. If possible, a soft cannula is used. The transfer process is completed without the tip of the cannula touching the top of the endometrium. All of the above mentioned are important details that increase the success of treatment.

 

The transfer procedure is painless and does not require anaesthesia. While the expectant mother is in the gynaecological examination position, a very thin and soft cannula is passed through the cervix (cervix) and the area where the embryo should attach, i.e. the endometrium (uterine wall), is reached precisely. When the tip of the cannula reaches the appropriate area, the embryo(s) are deposited there with the help of the syringe at the other end. Although the post-transfer lying position and duration do not effect the pregnancy success rates or miscarriage rates, we allow the expectant mothers to stand up only after resting for 1-2 hours in our centre.