Factors Affecting Success

Factors Affecting Success

Despite development of new techniques and opportunities each passing day, rates of success in IVF treatments haven’t reached the desired levels.

Following birth of the first IVF in 1978, extensive studies have been initiated to increase pregnancy rates and research the factors affecting success.

Although new information is suggested each passing day about the factors affecting success, only a part of them have been proven to have real impact. Effects of some stated factors have not been shown later or they are still being discussed.

Rates of success vary significantly between countries and centers. Rates of pregnancy notified by different countries and various centers vary between 15-65%.

It should absolutely be remembered that an IVF is a team work. It is extremely important that the doctor, nurse, biologist, embryologist and other workers in the team work coordinately and in concert with the patient.

There are various reasons for different rates of pregnancy between the centers.

The main reasons are:

1. Difference between the treated patients (selection of patient)

     a. Differences between age groups of the patients who apply to the centers

     b. A limit of age for patients accepted for treatment

     c. Cancellation of treatment or non-performance of transfer in the patients whose treatments are developing negatively, different criteria for cancellation

     d. Not accepting the patients whose chance of treatment is very low in order not to show success of the center low

     e. Difference in problems or diseases of the patients

2. Infertility specialists working in the centers or embryologists or biologists working in the laboratory don’t have sufficient training and experience

3. Whether the centers have technical opportunities, possibilities to implement new techniques or the employees have opportunity to learn and implement new treatment methods

4. Donor oocyte and donor sperm implementation is free in some countries. IVF can be implemented with oocyte (donor oocyte) taken from another young woman or sperm taken from sperm bank. In such operation applied to the pairs with severe oocyte and sperm problems, the problems can be overcome to a certain extent. As a result of this implementation, high rates of pregnancy are obtained in the patients with a very low chance of conception.

5. Various implementations between the countries as a result of legal or ethical restrictions

     a. Limitations on the number of transferred embryos

     b. Limitations on the day of embryo transfer (2 days)

     c. Limitations about freezing of embryos, sperms or testis tissues

     d. Pre-implementation genetic testing (PGT)

6. When rates of pregnancy are informed, the important point is what is actually informed.

     a. Rate of pregnancy per patient, per oocyte pick-up operation or embryo transfer

     b. Positive pregnancy test (including chemical pregnancies)

     c. Gestational sac shown through ultrasound (positive gestational sac)

     d. Fetus and heart beat shown in ultrasound (positive heart beat)

     e. Whether abortions are included or not

     f. Baby-take-home rate: This is the most important.

7. Wrong or exaggerated notifications of pregnancy rates by centers

Patient factor:

The most determining factors among patient factors are:

1. Age of woman

2. Basal FSH levels

3. Reason for IVF implementation (one or several problems related to man and woman)

4.Drugs used (stimulation drugs and luteal phase support)

5. Conformance of the patient to treatment process (use of drugs, regular controls)

Age of woman:

If a woman is over 35, this is a negative parameter. Rates of pregnancy decrease significantly in woman over 40.

1. Decrease in ovary reserve (high FSH)

2. Low number of developing follicles and oocytes

3. Low quality oocytes

4. High risk of genetic or chromosomal problems in oocytes

Ovary reserve:

Examination of FSH, E2 and LH values on 2nd or 3rd day of menstruation can give important tips about ovary reserves. However, there are different opinions about levels of FSH. It is accepted that ovary reserve is low in woman with a FSH value over 15 IU/mL on 2-3. day of menstruation. Furthermore, it is also accepted that the ovary reserve is low when total of FSH (3rd day) and FSH (10th day) values is 25 IU/mL or over in Clomiphene citrate test.

High E2 values detected on 2-3. day of menstruation can be an indicator of low ovary response.

Moreover, the recent studies show that AMH (anti-mullerian hormone) level which can be examined in blood at each period of menstruation gives significant information about ovary reserve in women and how the ovaries will respond to hormone drugs. Like FSH, AMH levels do also increase in older women and point to low ovary reserve.

Factor of man:

Effect of factor of man on success depends on the type of problem. In Azoospermia cases, results of conception vary according to whether it is obstructive (blocked sperm vessels) or non-obstructive (unblocked sperm vessels). Rates of pregnancy decrease in non-obstructive azoospermia. Furthermore, rate of pregnancy decreases significantly in such a case as risk of chromosomal anomaly (numerical or structural) is higher in these men. In case of micro-injection (ICSI-IMSI), low number of sperms and sperm morphology anomaly do generally not affect rates of pregnancy negatively.

Effect of IVF laboratory on success:

The IVF laboratory which can be regarded as the heart of IVF implementations is one of the most important factors affecting success of system in terms of employees, materials and techniques used.

Knowledge, skills and experiences of laboratory employees are extremely important. The details which can be considered worthless in the laboratory affect results of pregnancy significantly. For example; longer period of oocyte manipulation during operations, opening and closing incubator cap too much (the higher number of incubator, the higher success will be obtained. There are 8 incubators in our center) decrease the rates of pregnancy. Non-conformance to necessary sterility rules, improper pH and gas adjustments of incubators and performance of the operations by inexperienced people play important roles in failure. The materials used in the laboratory should be non-toxic. Culture mediums appropriate for development stages of embryos should be used.

Effect of number and quality of oocytes (oocytes) on success

In IVF implementations, quality of oocytes is important as well as the number of oocytes obtained on the day of oocyte pick-up. The high quality oocytes (MII) are subjected to operations. Quality of oocyte is very important for a successful conception, splitting and development.

Quality of oocyte and whether it is mature or not is determined as follows:

Immature oocyte (prophase): No polar body, dark germinal vesicle, compact cumulus.

MI oocyte (metaphase I): No polar body, no germinal vesicle, wide cumulus and light colored oocyte.

MII oocyte (metaphase II): Polar body, smooth ooplasm, wide cumulus.

Post-mature oocyte: Bulk or no cumulus, polar body, dark ooplasm.

Degenerated oocyte (atretic): No cumulus, degenerated polar body and core, existing vacuole.

The oocytes with highest potential for conception are MII. MI oocytes do also become MIIs after culture in the laboratory; they can be fertilized after ICSI.

The most important factors affecting quality of oocytes are:

1. Age of woman

2. FSH level

3. Stimulation (use of drugs), HCG dose and timing: Correct stimulation and follow-ups, proper doses and timing of drugs are important in terms of success of the treatment and hyperstimulation syndrome.

HCG injection should be given on the right day and time; earlier or later injection may affect the result negatively.

Quality of oocyte is lower in the patients who use gonadothropines in high doses and for long periods.

4. Performance of oocyte pick-up in due time and properly

5. Genetic anomalies

Effect of conception, split and development of embryo on success:

High rates of fertilization affect number of embryos positively. If rates of conception are low, embryos develop in low number and their qualities are low, rates of pregnancy decrease significantly. Number and quality of embryos depend on many factors. First of all, it depends on number and quality of oocytes collected from the patient (patient factor). This is the main reason why results of pregnancy are better in young patients. Furthermore, risk of chromosomal anomaly in the oocytes of young women is lower. Nonetheless, approximately 20-40% of embryos show chromosomal anomalies (aneuploidy). Number and quality of oocytes decrease due to aging and risk of chromosomal anomalies in embryos increases. Another factor is the quality of sperm. It is known that especially the embryos developed as a result of operations performed with sperms with severe morphological problems show lower quality. For this reason, it is very crucial to select the best sperms for injection. IMSI system which is begun to be used recently and allows finding of the best quality sperm with high magnification is being used in our center enables development of quality embryos in infertile pairs with severe sperm problem and higher rates of pregnancy. One of the important factors affecting split and development of embryos is undoubtedly conditions of IVF laboratories and knowledge and experiences of embryologists and biologists working in the laboratories.

Qualities of embryos are determined according to the following features:

     1. Size and symmetric shapes of blastomers (cells) making up 2nd and 3rd Day embryos and percentage of fragments within the embryos (cellular waste) (fragmentation)

     2. Structure of trophoectoderm cells making up intracellular mass and placenta for baby in the embryos of 5th Day Blastocyst period
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