In Vitro Fertilization

In vitro fertilization is an umbrella term for a series of procedures carried out for couples who have difficulty in conception to help them conceive. In vitro fertilization (IVF) has certain stages.

1. Use of medications to induce growth of more than one egg.
2. Monitoring growth of egg through ultrasound scans at an interval of several days.
3. Oocyte pick-up under guidance of vaginal ultrasound, when follicles reach a pre-defined size. This procedure is usually performed under anesthesia.
4. Picked up oocytes are fertilized by sperms at laboratory settings to obtain embryos.
5. Development of embryo is followed up and it is transferred into uterine cavity, when sufficient maturity is achieved. Embryo transfer is a pain-free procedure and it does not require anesthesia induction.

What Is Drug-free in Vitro Fertilization?

No use of any medication to stimulate release of eggs is the factor that distinguishes natural IVF from conventional in vitro fertilization.

A woman releases only one egg in each period under normal circumstances. A medication is administered for 8 to 12 days to stimulate release of more than one egg in in vitro fertilization patients. In natural in vitro fertilization, no medication is administered or in other words, natural menstrual cycle is followed. This method allows release of one egg, but it is most probably a high-quality one, as it is selected and developed by the body. Oocyte pick-up lasts for a short time and no anesthesia is administered depending on preference of the patient. Rest of the procedure is identical to the conventional in vitro fertilization; picked up oocytes are fertilized by sperms at laboratory settings and embryos are transferred into uterine cavity at the appropriate developmental phase. However, one should remember that the chance of pregnancy is lower than conventional in vitro fertilization, as only one oocyte is picked up.

Certain conditions favor natural IVF. The first one involves patients who fail pregnancy despite conventional in vitro fertilization attempts, as no or too little oocyte could be harvested. In such cases, natural maturation of follicles is tracked with ultrasound scan and oocytes are picked up, after they reach a certain size. Moreover, it is preferred by patients who do not want to use medications and hormones. This approach - the in vitro fertilization method that is closest to natural reproduction – is successfully performed in our center.

Phases of In Vitro Fertilization

• Baseline Assessment and Evaluation of Couple

In the first encounter with couples at our in vitro fertilization center, our physicians focus on and decide which treatment modality is more appropriate for the couple and whether they need extra treatment or procedure before initiation of in vitro fertilization therapy. In this initial assessment, the couple is evaluated regarding past history of treatments, obstetric history (previous pregnancies, miscarriages and deliveries), documented diseases and past history of operations and reports of all previous tests and examinations (all blood and hormone analyses, hysterosalpingography, chromosome analysis, spermiogram) are reviewed. In this baseline visit, all patients presenting to our clinic have a comprehensive gynecological examination and ultrasound scan. Appropriate treatment and correct time to start therapy are determined in the light of data gained from patients.

• Ovulation Induction and Release of Eggs

Medicines that induce ovulation are administered (injection therapy) in order to obtain numerous oocytes from ovaries. Dose of medicine and duration of use are determined in the baseline assessment according to age and ovarian reserve of the patient. Therefore, not all patients are managed with same treatment for identical duration. The period of ovarian stimulation lasts for 8 to 12 days in average until administration of another medicine to assist hatching.

• Oocyte Pick-up

Oocytes are picked up 34 to 36 hours in average after the medicine that assists hatching is administered; mature oocytes are aspirated using a needle that is inserted through vaginal route under anesthesia and guided by transvaginal ultrasound; these oocytes are stored at laboratory settings for fertilization. Semen specimen is collected from the spouse of patient with masturbation method, as is the case with spermiogram specimen, while or immediately before the oocyte pick-up.

• In Vitro Fertilization or Microinjection (Intracytoplasmic Sperm Injection – ICSI)

Conventional In Vitro Fertilization (IVF): This technique had been more widely used at the preliminary era of in vitro fertilization, before microinjection (intracytoplasmic sperm injection – ICSI) was discovered. Recently, IVF technique is not as commonly preferred as in the past, as the fertilization rate is lower relative to ICSI. *Microinjection (Intracytoplasmic Sperm Injection - ICSI): This technique is far more commonly used also in our clinic; ICSI involves injecting a sperm that is held in a very thin needle directly into the egg under microscope. Resultant embryos of this procedure are developed until Day 7 in an incubator – a device that creates a culture medium, which mimics the temperature of a human body.

• Embryo Transfer

Embryos stay in incubator for 2 to 6 days and their growth is closely monitored; next, they are transferred into uterine cavity using special catheters in a pain-free procedure that does not require anesthesia administration. Embryo transfer lasts for 10 to 15 minutes in average.

• Pregnancy Test

Pregnancy is verified by quantifying a hormone, called β-HCG, in a blood test that is done 10 to 12 days after embryo transfer. The patient should be checked with ultrasound to verify presence of gestational sac approximately 10 days after β-HCG test points to constant elevation or the concentration of hormone is sufficiently high.

Factors That Affect Success Rate of In Vitro Fertilization Treatment

• Advanced Maternal Age

Ovarian reserve decreases in women older than 35, especially above 40 years. As number and quality of oocytes (eggs) are usually poor at this age range and genetic disorders are more prevalent, chance of spontaneous pregnancy decreases along with decline in “ongoing pregnancy” achieved with assisted reproductive techniques.

• Co-existing Diseases and Habits

Co-existing diseases or endocrine disorders in couple, especially in woman, may result in incompliance to in vitro fertilization treatment and lower efficiency of treatment. Particularly, negative effects of smoking on oocyte and sperm quality are clearly known. This result has been proven by numerous studies. To list a few, co-existing diseases that decrease the success are endometrioma, adenomyosis and hydrosalpinx.

• Genetic Problems

Sperm count and quality: Low sperm count and morphological disorders of sperm also affect pregnancy rates.

Treatment protocols and their type: Experience of physicians and embryologists and laboratory conditions at in vitro fertilization centers are also important factors that play a role in success rate.

What Should Be Taken Into Consideration While Choosing A Center for In Vitro Fertilization Treatment?

In vitro fertilization center should have a license that is issued by Ministry of Health to verify that in vitro fertilization therapies can be performed. Also, physicians of the center should be qualified to perform in vitro fertilization therapies. This qualification is acquired by the doctors from education and training centers that are determined and authorized by Ministry of Health. Experienced embryologists of the laboratory also increase the success rate.

A list of doctors and embryologists, treatment protocols, quality certificates of the center, licenses and certifications should be available on official websites of in vitro fertilization centers. These issues should be given attention in a preliminary search on centers.

One should remember to prefer a center, where all phase of in vitro fertilization can be reviewed and advanced examinations, investigations and operations are performed, if required, as these criteria will strengthen the patient-doctor interaction and facilitate access of patients to their doctors.

Repeated failures In In Vitro Fertilization: Should You Stop or Keep Going?

Failed in vitro fertilization attempts can be wearing both emotionally and financially for patients. This fact is also verified by patients with obstetric history of failed in vitro fertilization attempts who present to our center and form a substantial part of admissions. Therefore, investigating the potential underlying causes rather than further attempts of in vitro fertilization in patients with a certain number of failed attempts offers an opportunity of targeted therapy. A healthy pregnancy and its continuum depend on the relation between embryo and endometrium (innermost lining of the uterus). The aim should be to create a healthy relation from the outset.

Conditions that may cause recurrent failure are listed as follows:

• Uterus-related factors (anatomic disorder, adhesion, polyp, myoma etc.)
• Endometrial dysfunction
• Thrombophilia (blood coagulation problem)
• Immunologic factors (immune system)
• Genetic factors
• Cessation of embryonic development in the uterus

At In Vitro Fertilization Center of Yeditepe University Hospitals, detailed examination is planned especially to investigate above mentioned factors for the patients with history of failed in vitro fertilization attempts in the past. Since treatment options vary for each problem that may lead to recurrent failure of in vitro fertilization, “personalized treatment approach” is adopted for all patients.

For some patients, exact cause of infertility may not be identified and pregnancy cannot be achieved, although a high quality embryo is transferred. Studies demonstrate that new treatment modalities, such as intrauterine PRP injection and growth hormone (G-CSF), improve endometrial function and increase pregnancy rates in this group of patients. Maximum attention is paid to patient selection for these novel treatments at our center and positive outcomes are obtained in certain groups of patients.

Each failed attempt in treatment of infertility provides important clues regarding a successful in vitro fertilization attempt. Therefore, history of in vitro fertilization is comprehensively reviewed in all patients who present to our center. Complex cases are discussed in in vitro fertilization council in the light of current scientific data on weekly basis and a tailored treatment is planned for each patient.

How Much Does In Vitro Fertilization Cost?

The main approach in in vitro fertilization treatment is to reveal out the underlying causes and adopt an accurate, appropriate therapeutic approach. For example, for couples that cannot achieve pregnancy due to metabolic diseases, in vitro fertilization process should be started after the metabolic disorder is cured, if age and ovarian reserve of woman allow this approach. Thus, a treatment that requires “couple-specific approach” should always be planned for a successful in vitro fertilization treatment. The cost is influenced by many factors, including but not limited to treatment method and necessary tests.

Frequently Asked Questions About In Vitro Fertilization

• Is Oocyte Pick-up A Painful Procedure?

Oocyte (egg) pick-up is generally performed under sedation -a type of anesthesia- at our clinic, as is the case with many other centers. Sedation ensures that you do not feel pain during the procedure and you will not remember anything about the procedure. It is expected that the pain you will experience will be similar to a menstrual pain at most, as you will be administered painkillers during and after the procedure. Painkillers will be prescribed to manage pain after discharge.

• How Long Does In Vitro Fertilization Process Take?

If no additional treatment is needed after the baseline assessment, you will be started on treatment to induce ovulation in the first menstrual cycle. Ovaries are evaluated on day 2 and 3 of the period and transvaginal ultrasound is preferably scanned to select the personalized treatment protocol and adjust dose of the medication. Next, oocyte development is evaluated through intermittent ultrasound scans and hormone tests in blood. Although inter-patient variations apply to development of oocytes, the estimated average interval is 8 to 12 days. Next, a drug is administered to assist hatching and oocytes are picked up 34 to 36 hours after the injection. Sperm is injected into the egg with ICSI at laboratory settings on the same day and thus, an embryo is obtained. Embryo can be transferred 2 to 6 days after the oocyte pick-up, unless there is a condition that may affect success of the transfer adversely (polyp, myoma, OHSS risk etc.).

• What Are Signs of Successful In Vitro Fertilization Therapy?

Analysis of β-HCG hormone in blood is the first and the most accurate way to verify if pregnancy is achieved. Additional symptoms include discomfort or mild pain in groin that is similar to menstrual pain, tenderness in breasts, mild spotting-like bleeding and nausea.

• Which Treatment Methods Are Recommended for Habitual Abortion? How Is A Treatment Method Determined That Fits Needs of A Patient Best?

Today, the exact cause cannot be identified in 40 percent of recurrent miscarriages. Recurrent miscarriages can be seen secondary to uterine factors, such as polyp, myoma or congenital septum and adhesion/synechia due to prior surgeries or infections, but co-existing maternal diseases, such as thyroid dysfunction, coagulation disorders and poorly regulated diabetes mellitus may also result in recurrent miscarriages. Structural conditions that include polyp, myoma, uterine septum and adhesion / synechia can be corrected with surgery. Considering medical conditions of the mother (thyroid dysfunction, uncontrolled diabetes mellitus), treatment is planned by consultant doctors in the first encounter before the ovulation induction. For patients with history of and problems related to clotting, certain tests are ordered in the first appointment and medical treatment is started, if it is deemed necessary. Moreover, studies have demonstrated that the reason is genetic disorders of embryo in 10-15 percent of cases. Anomalies can be observed in embryos even if there is no problem in chromosomes of mother and father. Today, embryo biopsies offer a chance to find an embryo with normal genetic features without any damage to embryos. Twenty four chromosomes of embryos are screened with preimplantation genetic diagnosis (PGD) at the genetics laboratory of our hospital and embryos with normal genetic features can be identified. Thus, healthy ones are transferred into the uterus to maximize chance of a healthy pregnancy.

• Is Social Security Institution Coverage Accepted for In Vitro Fertilization Therapies?

Although Social Security Institution coverage is not valid at our in vitro fertilization center, special opportunities are provided in examinations, tests and operations performed at our hospital. For further information, please contact our center.