IVF (Infertility)

Long-term and heavy smoking are thought to have a negative impact on the reproductive system and hormonal activity.  It must be noted that effects will be seen specifically on the ovaries, and smoking may result in significant outcomes such as menstrual irregularity, infertility and premature menopause.   When pregnancy occurs, smoking may cause insufficient development of the fetus and low birth weight. 

Tubes play one of the most important roles in the formation of a normal pregnancy.  Tubes are not only a channel that enables the egg and the sperm to unite, but also a medium where the embryo experiences its first development.  However,  in IVF treatments, the union of the egg and the sperm, i.e. fertilization, and embryo development take place in the laboratory environment.   Thus, the openness of the tubes are irrelevant in this context.  However, if due to a history of infection or operation the tubes are blocked and are filled with a fluid (Hydrosalpinx), this fluid must be removed or disconnected from the uterus prior to IVF treatment, because the inflow of this fluid into the uterine will affect the embryo trying to hold within the uterus.

In IVF treatment, there is no certain limit on the number of applications.  However, the studies performed show that there is no increased chance of success after 5-6 attempts.  In this case, before proceeding with repeat treatments, factors likely to cause infertility must be re-studied in depth, and treatment must be started after potential factors are eliminated.   There should be minimum 3 months between each application.

No. It is known that approximately 15% of natural pregnancies and pregnancies achieved via IVF end up with miscarriages.    In normal pregnancies, early miscarriages may sometimes be perceived as delayed menstruation, followed by slightly higher menstrual bleeding.    However, blood tests to be performed will show that it was a miscarriage.  Since in IVF applications, pregnancy results are monitored starting from an early phase through blood tests, miscarriages in each phase can be definitely described.  This, in return, causes a general misunderstanding that miscarriage rates are higher.

Following microinjection or IVF operation;

At 16-20 hours (1^st day), fertilization is detected. 

At 48 hours (2^nd  day) 3-4 cell- containing embryos are observed.

At 72 hours (3^rd  day) 6-8 or more cell-containing embryos are observed and cells start to unite.

On day 4 in the morning, the number of cells cannot be counted definitely, and embryos that achieve the morula phase are formed. 

On day 5 or 6, the embryo is called a blastocyst and the number of cells exceeds 60. 

Embryos that satisfy these criteria are considered as normally developing embryos.

The tests to be performed for the diagnosis and treatment of infertility in women include blood type, whole blood count, hormone tests that include FSH, LH, estradiol (on the second or third day of menstruation), TSH, free T4, prolactin, and for the detection of existing infections or immunity, HBsAg, antiHBs, antiHCV, Rubella IgM-IgG, Toxoplasma IgM-IgG tests. If deemed necessary, assays, microbiological and genetic tests may also be added for other systemic diseases.    In order to evaluate tubes and the intrauterine cavity, an x-ray of the uterine (hysterosalpingography) must be performed.  The tests to be performed on men include spermiogram, blood type, HBsAg, antiHBs, antiHCV, where necessary hormone tests (FSH, LH, total testosterone, prolactin and TSH) and genetic tests. 

The couple’s own characteristics play an important role in the chance of success of IVF treatment.  Each couple who desire to have a baby should be evaluated in detail, applying individualized treatment schemes for their individual characteristics.  Parameters such as  the woman’s age, ovary capacity, whether there is a serious male factor or not, previous unsuccessful Assisted Reproductive Techniques are the main elements that determine the success.  Through decisions to be taken in line with the center’s experience and capabilities, optimal treatment options are presented to the patient.  While the chance of success is 55% in couples whose ovary reserve is good and the woman's age is below 37, it is around 25% if the woman’s age is between 40 and 43. 

Before starting IVF treatment, some blood tests to be performed on both the woman and the man are of utmost importance so that the couple have a healthy baby. 

These tests are HbsAg, anti-Hbs, anti-HCV, anti-HIV(l+ll), Rubella lgG, Toxoplazma lgG.

The tests to be performed help to describe existing infections in the couple, thus, enable to take measures to protect the baby right after the birth.

Detection of immunity to infections such as hepatitis B and rubella enable to vaccinate the patient prior to treatment, and after immunity is confirmed, the treatment of the patient is proceeded with.

These examinations are also important for measures to be taken to protect the health professionals who carry out the treatment and to prevent infection during the freezing of semen or embryos to be obtained from the couple. 

During the first examination of the patient, it is evaluated whether there is any infection in the reproductive system.  If deemed necessary, a detailed screening may be applied via cervical culture, direct smear, mycoplasma culture and chlamydia antigen detection.  Existing infections are important for both infertility treatment and general health of the couple.

These infections impair the vaginal flora and cause flux.  Because mycoplasma and chlamidia infections frequently accompany infertility, necessary treatment will improve success in IVF treatment. 

In case of administration of drugs via injection,  there may be small purple spots and disorders in the injection site.  Nasal sprays and subcutaneous injections may give rise to tiredness, muscle and joint pains and temporary menopausal complaints.   Gonadotropins may over-stimulate the ovaries.  This condition is called  " Ovarian Hyperstimulation Syndrome (OHSS)”. This is more frequently seen in young women who are especially thin and have more eggs.  To prevent OHSS, the treatment must be applied with the lowest dose possible in these patients.  In serious OHSS cases, hospitalized treatment may be necessary.

The success of IVF treatment is greatly dependent upon the sufficient quantity and quality of the eggs obtained.  The knowledge of quantity of eggs in the ovaries and the conditions that may affect such quantity helps us understand in advance the response which the patient will develop to the treatment.  Response to the treatment may be adversely affected from female age equal to and above 35, smoking, history of ovary operations, history of infectious diseases, endometriosis, ovary cysts, FSH level above 10 mIU/ml and estradiol level above 75 pg/ml measured on day 2 or 3 of menstruation, poor response to previous treatments or use of hormonal medicines at high doses, and problems related with lining of the uterus. 

In IVF (In vitro fertilization) method, sperms and eggs are united in the laboratory environment and fertilization is expected to occur spontaneously.  Sperms with insufficient mobility and fertilizing capacity and severe abnormality of shape cannot penetrate the egg themselves and fertilization cannot be achieved. In such a  case, a sperm is injected into an egg and fertilization is achieved. This procedure is called microinjection, i.e. ICSI (intracytoplasmic sperm injection) .

The decision to apply whether IVF or ICSI to a couple is mainly determined according to sperm parameters.   However, in patients with a low quantity of eggs, because the chance of fertilization is higher, microinjection may be employed irrespective of the sperm parameters.   In this selection, the habits of the center have great importance.

In patients diagnosed with ovarian cysts prior to treatment, treatment can be initiated if the diameter of the cyst is less than 3 cm and has not elevated the estradiol level in blood.   During the use of the so-called analogue injections that are used to suppress the ovaries prior to treatment, simple cysts may be seen as a result of the inflammatory  effect of these injections.   If the cysts are smaller than 3 cm, but the hormonal level in blood is high, the analogue period may be prolonged.  However, if the cyst is bigger than 3 cm and no shrinkage is achieved despite prolonged use of the injection, this cystic fluid is withdrawn with the help of a needle, and the mechanical effect of the mass that occupies space in the ovary is eliminated.

Couples who have difficulty in having a child must be enlightened about the source of the problems through a comprehensive examination, the necessity of treatment must be determined, and the treatment method which will best help the couple to achieve pregnancy must be identified and presented to the couple.   Treatment methods are ovarian stimulation, intrauterine insemination and in-vitro fertilization.  In couples who meet certain criteria, pregnancy may be achieved via “intrauterine insemination” which means injecting the sperm, which has passed through certain procedures, into the uterus after achieving egg development with medicines.   The chance of success in this method varies between 5 to 15%.  However, the next treatment option must be IVF in patients who have a prolonged period of infertility, have undergone ovarian stimulation and intrauterine insemination, but have not achieved pregnancy.

Hydrosalpinx is a distally blocked tube filled and swollen with fluid. Whilst it may occur after an infection or an intra-abdominal operation, it may also be seen in patients with endometriosis.  Hydrosalpinx can generally be detected in uterine X-ray and sometimes in ultrasonographic examination. Initiating directly in-vitro fertilization treatment in the presence of hydrosalpinx may involve some risks.   The liquid contained in the tubes may escape back into the uterus and prevent clinging of the embryos transferred.  Also, the risk of miscarriage is increased even if pregnancy is achieved.  It is recommended that hydrosalpinxes, particularly those viewed by ultrasonography, are removed prior to treatment.   In patients with hydrosalpinx invisible to ultrasonography, but detected by uterine x-ray, first laparoscopy should be performed in order to have a definite idea about these structures.  While laparoscopy is the preferred method to extract these masses, open surgery may also be considered if there is severe intra-abdominal cohesion.  If tubes with hydrosalpinx are severely adhered to adjacent organs and it is not technically possible to extract them, it may be convenient to disconnect them from the uterus instead of extracting them.

Polyps are benign growths attached to the inner wall of the uterus and have importance in line with their sizes.  It is generally accepted that polyps smaller than 1 cm do not affect the success of the treatment.   In case of polyps above this size, these structures must be extracted by entering the uterus via a procedure called hysteroscopy.

Structures known as endometrioma or chocolate cysts  are formed as a result of a disease called endometriosis. Endometriosis is a condition in which endometrium, the lining of the uterus, flourishes outside the uterine cavity. The formation mechanism is not exactly known. The lining  of the uterus is embedded in the ovaries and causes local bleeding foci in each menstrual period.  Because menstrual blood built up in the ovaries look like a molten chocolate when viewed during an operation, they are called chocolate cysts.  Endometriomas may adversely affect quantity and development of eggs.  The size of these cysts are important for the treatment approach.  Endometriomas smaller than 3 cm do not generally require surgery.  Surgery is decided according to the condition of the couple in case of bigger cysts.  Surgery must be decided taking into account ultrasonographic examination of the ovaries, the patient’s age and previous attempts, if any. 

Myoma is generally a benign formation stemming from the muscular layer of the uterus.   If a myoma exists, the location of the myoma is important in the first place. Particularly, proximity to the lining of the uterus and whether it is growing towards the uterus where the embryo will develop are important.  If it suppresses the uterine cavity and is positioned to prevent the location of the embryo, it must be removed via hysteroscopy prior to the treatment.   In case of myomas that do not harm the endometrium, the size is relevant.  It may be considered to remove myomas which are located in the wall of the uterus (intramural) and are above 4 cm or myomas which are above 7 cm and develop on the outside of the uterus. (subserous)     Myomas of this size require surgery  because they may pose a problem if they grow higher during pregnancy.  However, if the woman is of an advanced age, i.e. above 38 years, surgery is not of priority and treatment can be started immediately in order not to lose time.   In summary, surgery must be decided taking into account the location, size of the myoma, and previous treatments, if any.   In general, treatment should be proceeded with 4-6 months after myoma surgery.

Loss of two or more pregnancies is defined as recurrent miscarriage.

In recurrent pregnancy losses, the following diagnostic tests are performed:

-To diagnose diseases of the immune system; anticardiolipin IgM-IgG, Lupus anticoagulant, homocysteine, aPTT, protein S and C must be analyzed.

- Chromosome analysis in the female and the male to reveal whether there is any genetically numerical or structural disorder (peripheral karyotype),

-Coagulation factors (Thrombophilia) panel,

-3 tests are used to examine the uterine cavity. These are saline infusion sonography (SıS), hysteroscopy, hysterosalpingography (HSG).

-To look for diseases of the endocrine system, fasting blood sugar, glucose tolerance test, HBA1c, TSH, free T4 and prolactin hormones

-If possible, a genetic analysis of the low material should be performed.

If, after these analyses and applications, a genetic cause is found, a pre-implantation genetic diagnosis (PGD) can be performed in the scope of the IVF treatment scheme.    Chromosomal disorders have been found in 50-60% of miscarriages in the first three months, in 20-25% of miscarriages in months 3-6, and in 5-10% of the miscarriages in months 6-9. These genetic disorders seen in the embryo level can be detected with pre-implantation genetic diagnosis (PGD).  PGD is used to identify chromosomal disorders and thus to transfer healthy embryos.  In PGD procedure, an embryo cell is taken and examined genetically, and normal cells are spotted and healthy ones transferred.  At our center, this method is successfully applied.

If a coagulation problem has been spotted as a result of examinations, low molecular weight heparin, and high dose folic acid, multivitamin and baby aspirin can be planned.

Called the polycystic ovary syndrome and known by people as the presence of several ovarian cysts, this case is seen in 10% of young women, and 25-45% of women who desire to have a baby.

The reason for this definition is the typical ultrasonographic finding in patients.  Several follicles sequenced side by side are viewed like a necklace surrounding the ovaries.   PCOS patients generally have irregular menstruation.  Complaints include prolonged intervals between menstruations and no menstruation in some patients.   

Hirsutism and increased weight and insulin resistance are frequently accompanying findings. 

It is a common problem seen in women who apply to infertility centers to have a child.  There is no regular egg development in the ovaries of these women.  Overweight aggravates this condition further.  For this reason, our first recommendation to our patients is to lose weight.  In patients who manage to lose weight and drop length / weight index below 28 kg/m², positive response to treatment increases, and normal pregnancies may be seen. 

In these patients, there is increased insulin resistance, and use of metformin, a drug that improves insulin sensitivity, increases the chance of success.

With the use of drugs that stimulate egg development in women who want a child (clomifen, citrate, rec-FSH) in appropriate means and doses, high rates of pregnancy are achieved.    In unsuccessful cases, IVF treatment can be tried.

In women with polycystic ovary syndrome, there is a risk to develop some important metabolic diseases like diabetes type 2 and cardiovascular diseases in time.  For this reason, it should be known that these risks will be lowered significantly and a healthy life can be led  when length / weight index is kept below 28 kg/m² with diet and exercise and insulin resistance is regulated by treatment.

The ratio of body weight to length is called the body mass index and is calculated in kg/m2. If this value is >30 kg/m2, egg development may become irregular in women.  In addition, in IVF application, women with high body mass index may have a lower response to hormonal medicines and may develop lower quantity of follicles. 

Distribution of the fatty tissue in the body is also important.   It is more dangerous if the fat is concentrated in the abdomen.   Increased waist / hip perimeter may negatively affect pregnancy when accompanied by some metabolic diseases and insulin resistance.   An example to this condition is polycystic ovary syndrome.  In patients with polycystic ovary, regular egg development may resume with loss of excessive weight and spontaneous pregnancies may develop.

It will be much effective to start treatment after losing weight through an appropriate diet and exercise in cooperation with a dietician, consulting, if necessary, the endocrine department so as to avoid, if pregnancy is achieved, some problems likely to occur in pregnancy due to fatness, such as  hypertension, gestational diabetes, a big baby, and difficult delivery.   (For further information, see our e-bulletin published in January 2010).

Metformin is a drug which is used in the treatment of diabetes to enhance insulin sensitivity.  In the polycystic ovary syndrome (see PCOS), a disease we frequently encounter in women who apply with an infertility complaint, increases insulin resistance and androgen hormones can be seen.   High blood insulin levels accompanied by increased insulin resistance and high androgen hormones that result in hairing may return to normal after about 2-months of administration of this drug, and it is possible that patients have normal menstrual cycles and get pregnant by the natural way. It is recommended that metformin is taken with meals at doses of 500 mg 3 times a day, or 850 mg 2 times a day.   Before starting the drug, liver and renal functions must be checked.  Side effects like lack of appetite, nausea, diarrhea diminish generally in a week.

Use of metformin should be continued throughout the treatment and up to 8^th - 10^th week of pregnancy.    There are no data about abnormal birth after use of this drug.

Generally, couples are recommended to consult a doctor if they fail to achieve pregnancy in 1 year although they have not used any contraceptive methods and had regular sexual intercourse.   However, due to  the increased marriage age in the present, particularly when the woman's age is above 35, couples are recommended to have a check earlier without waiting for 1 year.  If the woman’s age is above 40, it will be better to a take an earlier action.

Due to the changing social and cultural conditions of the present, more women marry at an older age and delay having a child.  In that case, it will be appropriate to have an examination of egg reserves and hormonal tests without waiting for the expiry of a year after marriage.  The woman’s age is recognized as an important factor that affects the chance of pregnancy.   With advanced age, we expect a reduction in the quantity and quality of eggs to be obtained as a result of any application.  This lowers the chance of success expected of the treatment.  If the woman’s age is above 35,  there is not much time to lose.  If the age is above 38, one should act much quickly, and very quickly if the age is above 40.   After 45 years of age, the possibility to take a healthy baby home is quite diminished.  Not only the woman’s age, but also the egg reserve is another important parameter that needs to be taken into account.  Low egg reserve means that follicles capable of developing in the ovary are reduced.   Sometimes, even if the woman’s age is young, genetic predisposition, endometriosis, history of ovarian surgery, smoking and similar factors may reduce the reserve.  Sometimes, the egg reserve may be lower than normal due to unknown reasons in the absence of any risk factor.   In that case,  it is not right to wait any longer.

Similarly, swifter action should be taken in case of congenital or acquired developmental disorders or sexual dysfunction in the man.   At the same time, in case of history of a testicle surgery or a similar surgery,  an expert must be consulted without losing much time. 

Embryo transfer, the final step of IVF treatment, is an important procedure.  Embryos that are developed after a month of treatment will now be transferred to the patient via this procedure.  The basic principle in embryo transfer is to place embryos in the uterus with minimum trauma possible.   Embryo transfer carried out under appropriate terms is a factor that improves success in IVF treatment and may not be ignored.  For this reason, the attention, care and patience of the doctor who performs the transfer is of utmost importance.  The type of catheter used and the transfer technique are other issues that affect success.

When determining the number of embryos to be transferred, the aim is both to achieve high pregnancy rates and to minimize multiple pregnancy risk to the extent it is possible.  During the first years of IVF treatment several embryos were transferred due to insufficiency of embryo selection criteria.   However, as time passed, use of appropriate protocol and drug doses chosen by experienced doctors at technologically highly advanced centers, development of embryos in culture environment which are close to the natural environment and better identification of embryo selection criteria and especially transfer of embryos in blastocyst phase increased the rates of retention in the uterus.   The number of embryos to be transferred should be selected according to the quality and period of embryos developed taking into account the woman’s age and unsuccessful past IFV attempts.  At our center, families are informed prior to the transfer procedure and the risks of multiple pregnancy, and the importance of implanting good and small number of embryos is emphasized.  The embryo transfer strategy used at our center is to place 2 embryos that have achieved morula (day 4) or blastocyst (day 5) phase in the uterus, if the quantity is sufficient.   Therefore, triplet and higher pregnancies are dramatically reduced.   Also, if the woman’s age is very young and the IVF application is performed for the first time, the transfer of a single embryo can be easily planned in the presence of good quality of blastocysts.

When determining the number of embryos to be transferred, the aim is both to achieve high pregnancy rates and to minimize multiple pregnancy risk to the extent it is possible.  During the first years of IVF treatment several embryos were transferred due to insufficiency of embryo selection criteria.   However, as time passed, use of appropriate protocol and drug doses chosen by experienced doctors at technologically highly advanced centers, development of embryos in culture environment which are close to the natural environment and better identification of embryo selection criteria and especially transfer of embryos in blastocyst phase increased  the rates of retention in the uterus.   The number of embryos to be transferred should be selected according to the quality and period of embryos developed taking into account the woman’s age and unsuccessful past IFV attempts.  At our center, families are informed prior to the transfer procedure and the risks of multiple pregnancy, and the importance of implanting good and small number of embryos is emphasized.  The embryo transfer strategy used at our center is to place 2 embryos that have achieved morula (day 4) or blastocyst (day 5) phase in the uterus, if the quantity is sufficient.   Therefore, triplet and higher pregnancies are dramatically reduced.   Also, if the woman’s age is very young and the IVF application is performed for the first time, the transfer of a single embryo can be easily planned in the presence of good quality of blastocysts.

After embryos are placed in the uterus, half-an-hour of rest is sufficient.   It has been determined that longer bed rest does not have an increasing effect on the chance of pregnancy.  We recommend our patients to avoid physical activities in the first 24 hours.  The next day, they can return to normal life and go to work, if relevant.  A pregnancy test in blood can be performed on day 14 after the egg retrieval procedure.   We recommend to avoid activities like sports, heavy work, heavy load lifting until the result of pregnancy is obtained.  Car and aircraft journeys are permissible.  There is no objection to traveling.

If after the transfer we still have embryos of good quality, these embryos can be frozen.  Aside from this,  where ovaries are over-responsive to the treatment, all embryos can be frozen to avoid hyper-stimulation or if intra-uterine thickness is not sufficient during the treatment.   After the appropriate treatment, the frozen embryos are transferred following intra-uterine preparation.

Embryos are frozen between days 1 and 5.  Frozen embryos are stored at our center for maximum 3 years according to the directive of the Ministry of Health.

In cases where sperm count is quite low, sometimes it may be necessary to take more than one sample to obtain more sperms.  For the first sample, sperms in the sperm transport channels (vas deferens) are collected.    For the second sample, it is possible to collect fresher sperms in the epididymal ducts.  The second and rarely the third sample are needed due to the possibility to obtain a sperm with higher motility.  This application is performed in men with low sperm count and very limited sperm motility.

The first part of the semen sample given is very important for it contains more sperm cells.   If the first part of the sample flows out or is lost when giving the sample, this should be communicated to the laboratory officers, and if possible, sampling should be repeated.

“Azoospermia”, having no sperm in the semen, may generally be the result of two factors: 

1. There is reduced or no sperm production in the testicle.

2. There is sperm production, but there are problems in ejaculation channels.

These two reasons can be identified in the examination  of the patient and as a result of hormonal analyses.  With the recent discovery of new genes in male infertility, genetic examination has gained more importance.

In couples without a child, male fertility accounts for half of this rate in the society.  In other words, the male factor can be a problem in half of the infertile couples.  In addition to male factors such as azoospermia (having no sperms), retrograde ejaculation, the woman’s age may require immediate initiation of treatment. 

IVF treatment has provided men with azoospermia with the opportunity to have a child.  However, in order to perform this procedure, even though low, there should be sperm production in the patient’s testicle. In other words, sperms must be obtained from the patient’s  testicles.  Obtaining sperms from the testicles is achieved using different methods according to the patient's condition.

A testicle biopsy is applied to men in whose semen analysis no sperm is detected.   In this procedure, the reason of lack of sperms is identified.  In other words, with this method, it is discovered whether the sperm does not exist in the semen for it is not produced in the testicle, or due to a blockage. 

TESE is a method employed to find small foci producing sperms in the testicle in patients with severe disorder in sperm production.   Taking pieces of a few millimeters from some foci in the testicle, existence of sperms is investigated. 

Micro Tese is the procedure to find sperms in tubes in which sperms are produced under a microscope.  In this method, it is possible to find sperms by a 36%- 68% in patients with a problem in sperm production which is not associated with obstruction.  

In Micro Tese method, the chance to find sperms in each biopsy is increased with less testicular tissue.   At our center, in patients with azoospermia, we can find sperms at a rate of 55% with Micro Tese.   This chance is higher compared with the classical TESE procedure.  In addition, another advantage is minimization of vascular damages around the testicle site during biopsy, and it helps embryologist to find sperms easily within small pieces.

Sperm retrieval in the testicles can be applied under local and general anesthesia.   Applications under local anesthesia are aspiration of sperms from the testicle with an injector (PESA-TESA) or testicular tissue extraction with a small incision (TESE).    These are methods that can be chosen when you are sure of sperm production in the testicle and sperms are not seen in the semen due to an obstruction.

At our center, we use “testicular sperm retrieval with a microscope” (Microdissection TESE) in patients who have a sperm production disorder in the testicle and who have no sperms in the semen.   This method is applied under general anesthesia.  When an operation microscope is used, it is hard for the patient to lie immobile for a long time, therefore general anesthesia is preferred.

The operation performed with a microscope has several advantages over the multiple testicular biopsy method of the past.   By examining the structures in the testicle in great detail with the operation microscope with x20 magnification capacity, samples are retrieved from sites where sperms are produced.    During testicle incision, the incision is performed on sites where there is less vascularity with the help of a microscope, which, in return, minimizes bleeding that occurs during the operation.  In addition, care is taken to protect the vascular structure that nurtures the testicle.  Since very little tissue is extracted (70 times lesser tissue than in multiple biopsy), it does not lead to reduced testosterone hormone level in blood.

Today, genetic diseases can be identified during pregnancy or after birth.  However, potential genetic diseases in the baby can be identified only in the fourth month of pregnancy via methods such as ultrasonography, amniosynthesis, and if a serious abnormality is detected, pregnancy is terminated around the 5^th month of pregnancy.  This makes a very negative impact, on the mother and father candidates, both psychologically and physically.

The recent developments in genetics allow to carry out genetic examinations on embryos developed in the laboratory environment with the IVF method before gestation and to place selected healthy embryos in the mother’s womb.   This method is called pre-implantation genetic diagnosis (PGD).

Pre-implantation genetic diagnosis is performed by taking a cell from embryos developed via fertilization of eggs and sperms retrieved from the mother and father candidates in the laboratory environment.  For genetic diagnosis, special methods called Flourescence In Situ Hybrydization (FISH), Microarray based comparative genomic hybrydization (aCGH) or Polymerase Chain Reaction (PCR) are used.  It is possible with PGD to diagnose chromosome anomalies such as monosomy or trisomy (Down syndrome and other trisomies) and single gene diseases (Hemophilia, Mediterranean anemia, cystic fibrosis, muscular dystrophies, etc.)   Therefore, healthy babies are delivered with the transfer of healthy embryos to the candidate mother.

Pre-implantation diagnosis is applied: 

- In couples carrying genetic or hereditary disorders,

- In couples with a child or children with a genetic disorder,

- For the purpose of performing HLA genotyping;

- For identifying diseases showing genetic predisposition;

- In women with an advanced age (37 years and above) accepted for assisted reproductive techniques; 

- In couples with recurrent early pregnancy losses;

- In couples who have not achieved pregnancy with assisted reproductive techniques despite several attempts, or who have lost pregnancies due to miscarriages;

- In chromosomal disorders or genetic diseases accompanied by severe male infertility.

The quantity of eggs in the ovary is directly related with the response to the treatment.   Eggs in the ovary are counted with the help of the ultrasound, and egg reserve determined.  Accordingly, patients with high, normal and poor response are identified.  This distinction is important, because the type of treatment (long or short-term) and starting dose will be adjusted accordingly.

Genetic examination of embryos is not necessary for every couple admitted to the IVF program, however, this examination is recommended to couples who have certain characteristics and risks.   These characteristics can be listed as follows:

1. In couples carrying genetic or hereditary disorders;

2. In couples with a child or children with a genetic disorder;

3. In couples with recurrent early pregnancy losses-miscarriages; 

4. In couples who have not achieved pregnancy with assisted reproductive techniques despite several attempts, or who have lost pregnancies due to miscarriages;

5. In chromosomal disorders or genetic diseases accompanied by severe male infertility;

6. For the purpose of performing HLA genotyping;

7. For identifying diseases showing genetic predisposition. 

IVF treatment is a process consisting of development of eggs, retrieval of eggs, embryo development and embryo transfer phases.  The woman does not have to stay at the hospital throughout the whole treatment process.  During the egg development process, blood tests and ultrasonography examinations are carried out generally at one day intervals and sometimes on a daily basis.  This process lasts 9-12 days on average. At the end of this period, when eggs are sufficiently mature, an injection is administered to crack the eggs and 2 days later, eggs are retrieved.  On the day the eggs are retrieved, the sperm is also taken and fertilization procedure performed.  Embryos developed are evaluated in terms of quality and quantity, and are transferred 2-6 days later.  The average period from initiation of hormonal drugs to the transfer of embryos is 15-18 days. 

1. Families have healthy children.

2. The family is protected from medical and psychological traumas associated with termination of pregnancy. 

3. In case of diseases such as thalassemia; with genotyping, the baby who is born, offers treatment possibility for the sick children of the family, if any.  

4. Pre-implantation diagnosis is a very useful and inexpensive diagnosis method compared with the health problems that patients encounter throughout their lives, the difficulties in treatment and high treatment costs.

Please consult your doctor for this issue.  You will be provided with necessary recommendation and assistance.  Even if you fail to give sperms due to stress on the day of egg retrieval, do not panic. If necessary, it is possible to retrieve sperms from the testicles with local anesthesia.

We do not ask for a n hysterosalpingography for every woman who applies for IVF.  If there is a  story of severe infection about female reproductive organs (uterus, ovaries, tubes) or intraabdominal organs such as the intestines, or a story of abdominal operation  or an suspected problem in ultrasonography, a hysterosalpignography may be required. 

In IVF treatment, the most important factor that determines success is the woman’s age and the reduced ovary capacity associated with it.  With increased age, the ovary reserves are diminished, and at the same time the genetic content of the egg is degraded.  As a result, the chance of pregnancy is reduced, and even if pregnancy is achieved, the risk of miscarriage or bearing a baby with anomalies is increased.  However, with different drug protocols to be chosen on the basis of the characteristics of the woman, acceptable pregnancy rates can be achieved.

At our center,  IVF treatment can be applied, irrespective of age, if the results of the hormone tests performed on the 3^rd  day of menstruation and the ovarian capacity results in ultrasonography show that your ovarian functions are appropriate. 

The egg is located within water-filled vesicles called the ovarian follicles.  With simulating agents, these follicles are caused to grow, and the eggs within are tried to be obtained via the egg retrieval procedure.  However, it is not always the case that big follicles contain eggs, or the eggs obtained are of desired maturity.

Average fertilization rate is 70-75%.  In some couples, higher fertilization may occur, but occasionally, no fertilization may take place without apparent reasons attributable to the egg or the sperm. 

Consanguineous marriages are marriages between people with close kinship.  According to the degrees of kinship, 1^st degree consanguineous marriages are cross-cousin marriages, which are between the children of aunts and uncles.    In our country, the rate of consanguineous marriage is 21- 40% and vary by region.  In general, 2-3 out of every 100 children born in the society  have anomalies associated with various reasons.   This risk can rise up to 4-5% in couples who have made a consanguineous marriage.  Because, in accordance with autosomal recessive inheritance model,  the likelihood of the mother and the father to have a mutation on the same gene in the inherited disease group is increased, the risk of encountering this group of diseases is increased in consanguineous marriages. 

While  stimulation of ovaries is alleged to increase breast and ovarian cancer risk, it has not been proven.   Because infertility is a risk factor for both cancer types, the increased risk observed in some studies may rather result from causes that give rise to infertility.   Furthermore, genetic factors are also relevant.  It will be better for women with a story of breast or ovarian cancer in the family  to start treatment after detailed examination and performance of necessary tests.  In this respect, studies and long-term follow-up are still in progress.  Women who receive IVF treatment and cannot get pregnant are recommended not to neglect annual gynecological checks and breast checks (if necessary breast ultrasound or mammography).

After gestation, at week 11 – 14  a biopsy of the placenta is performed (CVS) or at week 16-20, a sample is taken from the fluid in which the baby is present (amniocentesis), at week 18-22 (sometimes, later), the baby's blood is collected from the baby's umbilical cord by inserting a special needle through the abdominal wall under ultrasonography (cordocentesis).      While these operations are not recommended for risky patients, it will be much a reasonable approach to carry out some screening tests in patients who do not have a significant chromosomal anomaly risk.  At week 11 – 14, double test may be requested, looking at nuchal translucency.  In necessary cases, triple or quadruple tests are applied.  In addition, with detailed ultrasonography, it may be determined to a great extent whether there is a major anomaly in the fetus or not.  If any risk is detected as a result of these screening tests, further procedures, i.e. CVS, amniocentesis or cordocentesis, can be performed.

The hormonal therapy to be conducted to make eggs larger in IVF treatment depends on the person.  The most important parameters that influence type of treatment to be chosen and the drug dose are woman’s age, ovarian reserve, patient’s weight and response to previous treatments.  In women with low ovarian reserve, short-term treatments are preferred over long-term treatment protocols in which we suppress ovaries in advance.  Again, the hormonal dose to be administered to patients with a high body mass index should be increased.  In over-weighted women, administration of a low drug dose delays selection of eggs or causes selection of less eggs.  In case of advanced woman’s age, the type of treatment and dose change.  In the recent years, there is a consensus of opinion that use of high doses of drugs affect egg quality negatively.   For this reason, we prefer, at our center, treatment protocols called "patient-friendly therapies" which involve low drug doses.

Premature ovarian failure is a condition characterized by lack of sufficient eggs in ovaries at a young age.  Several theories are put forward about the reasons of this condition:  When the body produces some substances called antibodies to destroy its own cells which it perceives as foreign cells, a group of diseases which we call autoimmune diseases occur.  In autoimmune diseases, antibodies to ovarian cells are formed and destroy eggs, resulting in premature insufficiency.  Use of chemotherapy – radiotherapy may also result in premature egg loss.  Genetic predisposition is also important.  In about 4-5% of these women, familial history is present.  Such women, who suffer from premature loss of eggs in the ovaries, cannot get pregnant with their own eggs.  In patients with a familial history, the other young women in the family should be informed about this issue, and if they want a child, they should make a plan without waiting to get older.

Problems that occur after menopause and affect the quality of life of women are now well-established.  These women have the risk of fractures subject to osteoporosis in their future lives.   In addition, cardiovascular diseases are an important health problem in post-menopausal women.  Women with premature ovarian failure are under such risk throughout their lives.  To avoid all adverse conditions that are likely to develop, it is of great importance that they arrange their life styles, have necessary checks performed, and be supported  in applying appropriate tests. 

The hormonal therapy to be conducted to make eggs larger in IVF treatment depends on the person.  The most important parameters that influence type of treatment to be chosen and the drug dose are woman’s age, ovarian reserve, patient’s weight and response to previous treatments.  In women with low ovarian reserve, short-term treatments are preferred over long-term treatment protocols in which we suppress ovaries in advance.  Again, the hormonal dose to be administered to patients with a high body mass index should be increased.  In over-weighted women, administration of a low drug dose delays selection of eggs or causes selection of less eggs.  In case of advanced woman’s age, the type of treatment and dose change.  In the recent years, there is a consensus of opinion that use of high doses of drugs affect egg quality negatively.   For this reason, we prefer, at our center, treatment protocols called "patient-friendly therapies" which involve low drug doses.

Particularly when short treatment protocols are used, rarely eggs may crack before they are retrieved.  For this reason it is important to have frequent ultrasonography and hormone assessment during the treatment.  Elevation of LH, an important hormone in the maturing of the egg, up to critical levels in the early phase plays the most important role in premature cracking of the eggs.   When hormone LH attains peak levels, egg retrieval procedure should be performed at an earlier time, otherwise eggs may crack prematurely. 

Hyper-stimulation of eggs is characterized by excessive elevation of the estrogen hormone during the treatment, excessive growth of eggs and selection of a multiplicity of follicles.  Whilst mild and moderate hyper-stimulation does not generally call for hospitalized treatment, severe hyper-stimulation requires hospitalized treatment.   Severe hyper-stimulation rarely reaches life-threatening dimensions.  However, well-regulation of hormone doses and close follow-up prevents such situation to a great extent.  At our center, the rate of hyper-stimulation is below 1%.