Op. Dr. Niyazi Emre Turgut

What is in vitro fertilization (IVF)?

IVF is the treatment method that allows fertilizing female eggs with male sperms in the environment of an embryology laboratory, ensuring the natural fertilization process. After an egg is fertilized with a sperm it develops into an embryo, which is later transferred back into the womb to form an expected pregnancy. Today, IVF is used as the common name for all IVF practices. Essentially IVF holds special meaning, it is the method used on the day IVF first began. The first healthy live birth following IVF treatment was in 1978. IVF is still practiced by physicians today. It is usually applied in couples with a high number of eggs and low count of sperms, weak movement of sperm (poor mobility), or irregular sperm size and shape.

What do IVF, ICSI, and IMSI mean?

IVF (In Vitro Fertilization): female egg and male sperm are placed in the same environment under laboratory conditions. Fertilization occurs spontaneously, as in natural pregnancy.

ICSI (Intra-Cytoplasmic Sperm Injection): sperms are selected under a microscope with a magnification of around 200 and are then injected into eggs with special straws. It's the most common fertilization technique.

IMSI (Intra-Cytoplasmic Morphologically Selected Sperm Injection): Sperms are selected under a special microscope that allows sperm cells to be magnified to about 6,000 times, and the selected sperms are then injected into eggs. The main purpose of this technique is to choose sperms with the best shape. In particular, the shape of the sperm’s head is examined in detail as it holds the DNA or genetic material.

What are the benefits of choosing sperms with the microchip method?

Heads, necks, and tails of sperms are examined under a microscope when we are choosing sperms following the classical method, and selected sperms with the best shape are injected into eggs. The head of the sperm is the most important. It holds the genetic structure of sperm cells, the DNA. There may be fragmentation of sperm DNA for reasons such as malnutrition, smoking, alcohol, varicoceles, obesity, and an inactive lifestyle. This adversely affects embryo development and thus overall IVF success. With microchip methods developed in recent years, we can achieve more successful results by selecting better sperms, i.e. sperms with lower DNA fragmentation specifically for patients with recurrent IVF failure and sperm quality disorder.

Is IVF the only way to get pregnant?

During our first conversation with our couples, we try to learn more about them. We perform certain tests to understand a couple's fertility potential. The following list is just some of the information that we review at the very beginning: female age, menstruation cycle, how many years they have wanted to have children, previous treatments, HSG (x-ray of uterus and tubes) analysis, details of any operations performed such as laparoscopies or hysteroscopies, and of course sperm analysis. Based on that, we offer optimal treatment options, taking into account the preferences of the couple. If the woman's egg reserve is normal, fallopian tubes are known to be open, if the couple has been trying to conceive a baby for less than 2 years, and if sperm analysis is normal, we primarily prefer simple non-invasive treatment methods. These treatment methods are ovulation follow-up and intercourse planning or Intrauterine Insemination (IUI).

What tests should we have done for an initial assessment?
  • Total Blood Count to understand if there is anemia;
  • TSH, free T4, Anti-TPO (thyroid peroxidase), and Anti-TG (Thyroglobulin) tests to understand if there are problems with the thyroid gland;
  • Fasting blood sugar and fasting insulin to determine if there is insulin resistance;
  • Vitamin D3 and Vitamin B12;
  • AMH (Anti- Mullerian Hormone) to measure ovarian reserve.

Other required tests:

  • HBsAg, anti-HCV, and anti-HIV is a groups of tests referred to as serology tests. These are infectious diseases that potentially can affect the baby. Both men and women are required to have these tests done.
  • Sperm analysis is one of the key tests to check the sperm count, movement, and shape anomalies.
  • Hysterosalpingogram (HSG) - x-ray procedure used to see whether the fallopian tubes are patent (open) and if the inside of the uterus (uterine cavity) is normal.
What is Anti-Mullerian Hormone (AMH) test? What is it made for? Does it indicate egg quality?

AMH test is a blood test. Its main purpose is to measure ovarian reserve. It can be done on a hungry or full stomach any day of the menstruation cycle. If a woman is using contraceptive pills, this test can show a lower level. The normal range of this test is between 1 and 3 ng/ml. A level below 1 ng/ml indicates reduced ovarian reserve, or in other words lower number of eggs. Values above 3 ng/ml indicate that the ovarian reserve is high. The AMH test does not give any indication of egg quality.

How do you manage the treatment of your international patients who want to come from abroad?

The correct approach to properly managing the IVF process is to evaluate each couple’s medical history and current test results before the start of any treatment. The easiest way to do this is to meet the couple face-to-face and draw the treatment plan together. However, most of our couples who live abroad prefer not to travel to Istanbul just for initial evaluation as this requires extra expenses and days off from work. For this reason, we conduct our initial consultation with international couples online over Whatsapp, Instagram, Facebook, or simply by email. To start with, we ask couples to fill in the questionnaire that allows us to learn more about possible infertility causes and general health conditions. If there is some information missing we ask the couple to undergo the required tests. Next, we arrange a follow-up online consultation to discuss the details and determine the treatment plan. This way the couple comes to Istanbul directly to start treatment.

What are the factors that determine IVF success?

The most important factor that determines IVF success is female age. After the age of 35 egg quality begins to decline. Unfortunately, this decline continues with advancing age and picks up pace after 38. After 43 years this decline in egg quality can reach up to 80-90%. Not only egg quality declines, but egg count also tends to decrease biologically with age.

Embryos carry the genetics of both eggs and sperm. Therefore, sperm quality is one of the important factors. DNA material found in the head of the sperm activates from the third day of embryo development. It is important to closely trace embryo development to day 5 or 6 days while it reaches the blastocyst stage to better understand how both sperm and egg quality affect embryo development.

The success rate in subsequent treatments continues to decline for the couples that had 3 or more IVF failures despite the transfer of good-quality embryos.

The internal membrane of the womb is called the endometrium. This membrane is vital for the baby to implant and grow. The embryo may not implant properly if the thickness of this membrane is less than 7 mm on the day of planned embryo transfer, or if there are polyps, myomas, or adhesions present.

A woman has two fallopian tubes, one on the left and one on the right side of the uterus. It is the organ in which an egg meets sperms during the natural pregnancy process, the embryo grows and develops here in one of the tubes before moving further into the womb. In some cases fluid builds up in one or in both tubes, this is called hydrosalpinx. This pathological fluid then flows into the womb, preventing the embryo from implantation or development.

Apart from these medical factors, maintaining a healthy life, weight control, paying attention to nutrition, and abstaining from smoking and alcohol are also crucial.

Why we should choose your clinic?

Overall, IVF treatment consists of two crucial parts. During the first part, a doctor completes the clinical assessment, works out the most appropriate treatment plan specific for the couple, and manages the stimulation of the ovaries. This part requires a well-organized, experienced doctor who closely follows and implements the most recent approved developments in the field and is able to communicate well with patients. An embryology laboratory with advanced technological equipment and experienced embryologists becomes the priority during the second part.

I have been focused on providing IVF treatment for many years, while closely following all recent technological advances. I have been honored to bring happiness to thousands of families.

I work exclusively with embryology laboratories that have a minimum of 200 transactions per month. I personally manage your treatment from beginning to end, this includes overseeing the stimulation process, egg retrieval, and embryo transfer. We communicate during the whole process: before, during, and after treatment, and provide timely responses to all of your questions.

How long does IVF treatment take?

There are two main treatment strategies and the duration of each treatment depends on the chosen strategy. The first strategy is fresh embryo transfer. When we follow this strategy the treatment starts with stimulation on day 2 or 3 of the menstruation cycle. In most cases, stimulation takes 9 to 10 days. On the last day of stimulation, the patient injects trigger shots for the eggs to mature, and two days later egg collection is performed. On the same day, the collected eggs are combined with the sperms, and embryo cultivation begins in the lab. The received embryo is then transferred to the womb after being cultivated for 3 or 5 days depending on the decision of the couple and doctor. Within one month the whole treatment is completed. The second strategy is frozen embryo transfer. As during the first strategy, the doctor stimulates the ovaries starting on day 2 or 3 of the cycle. After egg collection, the embryos are cultivated and good-quality embryos are then frozen and stored in the laboratory to be transferred in the following cycles. No transfer to the womb is performed in the same cycle.

Check out the table below for an approximate timeline for both strategies:

Strategy

Stimulation Duration

Egg collection

Embryo transfer

Total duration

Fresh embryo transfer

9-10 days

Day 11-12

3-5 day

16-17 days

Frozen embryo transfer

9-10 days

Day 11-12

No

12-13 days

Which is your preferred treatment protocol?
IVF treatment protocols vary significantly. The two most commonly used protocols are short and long. In both protocols, ovarian stimulation begins on the second or third day of the menstruation cycle. The difference is that during the long protocol, suppressing GnRH analog injections start on the 21st day of the menstruation cycle that precedes the stimulation. The short protocol is a patient-friendlier treatment strategy, as we directly initiate stimulation at the beginning of the menstruation cycle. The best and most appropriate treatment protocol is selected based on the patient's condition, and this selection is very individual.
How do you select medications and dosages for your patients?

IVF treatment is always individual. Each treatment plan depends on the patient. Body Mass Index (BMI) is one of the most important factors. Excess weight means higher doses of medications. In some cases, where we are required to suppress ovarian function before the start of stimulation with contraceptive pills and in cases where we choose long protocols to ensure appropriate egg growth and to obtain more mature eggs we also have to use higher doses. We also have to mention polycystic ovary syndrome (PCOS) which is a special condition. This group of patients has too many eggs in their ovaries, and high doses of medications can lead to hyperstimulation. Therefore, to avoid any risks we prefer to use lower doses of medications for PCOS patients.

How do you manage the stimulation process?

Once we start stimulating the ovaries with hormone injections we control the stimulation process and egg growth by performing regular ultrasound scans and blood analyses. These follow-ups help the doctor determine the optimal dosage specific for the patient and plan egg collection at the right time. On the day we begin to stimulate the ovaries, the eggs inside are between 5 and 7 mm, and during stimulation, we follow up their growth to 19-20 mm. In most cases, 3 or 4 ultrasound scans and 2 blood tests are sufficient during the stimulation period that lasts 10-11 days.

Will I experience pain during IVF treatment?
During the treatment, you may experience two causes of pain. The first cause is the injections that you will be making daily during the ovarian stimulation, which takes around 10 days. The majority of patients do not feel significant discomfort from the injections, as pain is mild and very brief. Albeit rare, in some cases, swelling and redness around the injection area can last one to two hours. We should mention that some patients may experience bloating and pressure in the abdomen. The second possible source of pain is the egg collection procedure itself. This process is actually painful, and this is the reason we are performing egg collection under anesthetic. You may experience some spotting and cramp-like pains following the procedure.
Why are you aiming to collect many eggs during IVF treatment?
Truth be told, the natural human reproductive process is inherently counterproductive. Some eggs may be immature. Some mature eggs do not fertilize normally. Some of the embryos stop development due to some natural abnormalities of the embryo. Some of the embryos with perfect external appearance may carry genetic abnormalities. Overall we can say that the number of eggs required for a live birth depends significantly on the woman's age; but still, the fact is that most of the eggs in all women do not result in a live birth. The higher number of embryos received through IVF treatment gives us two key advantages. First, it becomes possible to select and prioritize the best among the received embryos. Second, the embryos remaining after the first embryo transfer can be frozen. This allows us to transfer embryos several times using the embryos cultivated as a result of a single egg collection. Many families succeed to have more than one child undergoing just one egg collection procedure.
Is the egg collection procedure painful? Do you use anesthesia?

Yes, the egg collection, or ovum pickup (OPU), the procedure is painful and that's why we use an anesthetic. At the same time, you have to know that it's not exactly like the strong anesthetic we use during surgeries. The one used during OPU is referred to as deep sedation. You will sleep during the procedure, and you will not feel or remember anything. The process takes about 10 minutes. You can be discharged from the hospital after 1 hour.

Does egg collection (OPU) damage my ovaries?

No. Egg collection is performed with a fine needle. You might think of it as drawing blood from your arm.

Does egg collection (OPU) reduce my ovarian reserve?
The ovaries produce a certain number of eggs each month. We only can collect the eggs produced in that specific month. Also, the medicines used to stimulate eggs and the use of contraceptives do not affect a woman's menopause age.
How much time should pass between two egg collections (OPU)?
At least two menstrual cycles should pass between two egg collections. This gives enough time for the ovaries to recover and hormones to balance back to normal.
What are the major factors that you consider when selecting a fresh or a frozen embryo transfer?

We can safely plan fresh embryo transfer when all of the following conditions are met:

  • A total of fewer than 15 eggs develop in both ovaries as a result of ovarian stimulation,
  • At the end of the stimulation process the blood estradiol level is below 2500 pg/ml and progesterone level is below 1.5 ng/ml
  • There are no polyps, myomas, adhesions, and other pathological conditions in the uterus.

We must plan frozen embryo transfer when:

  • We are using pre-implantation genetic diagnosis (PGD) to study the genetics of embryos. We are following up on embryo development in the laboratory for 5 or 6 days, and once the embryos reach the blastocyst stage we biopsy the embryos and freeze them. The result of the genetic test comes in 10-15 days.
When to transfer embryos back into the uterus on days 3, 5, or 7? What is the explanation behind this decision?

During the natural conception process, once a fertilized egg develops into a zygote it begins to split. Following consecutive splits, the zygote becomes an embryo. Normally, the embryo reaches the blastocyst stage after 5, 6, or 7 days, it then breaks out of the shell surrounding it. At that stage, the embryo reaches the womb and tries to attach. Once the embryo is attached to the womb a successful pregnancy begins. Previously, we did not have sufficient abilities and technology to follow up embryo development to the blastocyst stage in laboratory conditions. We were following up and transferring several embryos developed to day 2 or 3. Today, owing to the advances in techniques and cleanroom technology, most high-end medical centers are able to follow up embryos to the blastocyst stage. This allows us to select better embryos for transfer as they are in a more advanced stage of development. One additional benefit of allowing embryos to develop to the blastocyst stage is that embryologists can safely perform biopsy and analysis of placental cells (trophectoderm), which in its turn allows us to confirm that the healthiest embryos are selected for transfer.

What are the risks of having multiple embryos transferred?

While increasing the number of embryos transferred increases the chances of pregnancy, it also increases the risk of multiple pregnancies (twins, triplets, etc.). It is known that complications such as miscarriages (early pregnancy loss), premature deliveries, increased sugar levels, pregnancy-specific hypertension, and cesarean sections are more common in multiple pregnancies.

When can I travel after the embryo transfer?
We recommend bed rest on the day of transfer day. You can safely travel the next day.
When do I do the pregnancy test after the embryo transfer?
You should take a pregnancy test 11 days after the transfer of a blastocyst-stage embryo. If a day three embryo was transferred, you should take a pregnancy test 13 days after transfer.
Where and for how long are eggs, sperm and embryos stored?
Gametes (sperms and eggs) and embryos are stored in andrology and embryology laboratories. They are stored in liquid nitrogen. The storage time of gametes and embryos does not affect the success rate. In Turkey, we are permitted to store for five years. When this period is over, we can get permission from the Ministry of Health and extend it for up to 8 years.
What does preimplantation genetic testing (PGT) mean?
Humans have 22 different types of chromosomes numbered from 1 to 22, and X and Y sex chromosomes. Human cells contain a total of 46 chromosomes: 22 pairs of autosomes (body chromosomes) and 1 pair of allosomes (sex chromosomes: XX for females and XY for males). We use preimplantation genetic testing (PGT) to analyze the chromosome structure of embryos before they are transferred back to the womb. Any female egg or any male sperm can carry abnormal chromosome numbers or sequences regardless of normal chromosome analyses of the couple. The most common chromosome abnormality in the world is 21, or Down Syndrome, also known as trisomy 21, which is caused by the presence of three copies of the chromosome instead of two. Currently, we can only choose the best sperm based on appearance. But exterior appearance does not mean the sperm is genetically healthy. Similarly, embryos that are genetically abnormal can receive excellent grades during microscopic evaluation and are indistinguishable from embryos that are genetically normal based on their appearance.
What are the benefits of preimplantation genetic diagnosis (PGT)?
PGT is the technology that allows us to detect excess or missing copies of 24 chromosomes or complex chromosome imbalances in the embryo. Without PGT we are not able to access this information, and such abnormalities in the embryo often lead to implantation failure, early miscarriages, baby's heartbeat failure, or disorders detected in the baby during advancing weeks of pregnancy. The embryos carrying chromosome anomalies are not transferred thanks to PGT. PGT allows us to reduce the risk of miscarriage and increase the chance of having successful implantation and a healthy baby.
For which patient groups do you prefer to use the preimplantation genetic testing (PGT)?
We often recommend this test to patients of advanced maternal age, as egg quality begins to decline rapidly in women over 37. Apart from this, we recommend PGT to couples with recurrent IVF failures, recurrent early pregnancy losses, and issues with chromosome tests of the couple.
Is preimplantation genetic testing (PGT) 100% reliable?

No. There are some risks and limitations. These are as follows: Risk of embryo biopsy:

there is a possibility that an embryo may be damaged during the biopsy, and then its development stops and it becomes unsuitable for transfer. But, when performed by highly experienced embryologists, the risk of damaging an embryo is very low. Furthermore, thousands of children born as a result of transfers following embryo biopsy since 1989 are major evidence that the biopsy process has no significant side effects on embryos.

Failure to detect anomalies: Today's PGT technique does not allow us to detect gains or losses in chromosome segments smaller than 10Mb (megabases).

Error in diagnosis: PGT technique has a 1% to 2% probability of error. It could be a false positive or a false negative. A false-positive result means normal embryos are diagnosed as abnormal. A false-negative result means abnormal embryos are diagnosed as normal.

What technique do you use for preimplantation genetic diagnosis (PGT)?

We use the latest technology, Next Generation Sequencing (NGS), to assess the genetic structure of embryos.

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