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Tube Baby
Factors Affecting Success in IVF
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Though new techniques and opportunities are developed every day, the rates of success in test tube baby treatments are still not at the desired level.
After the birth of the first test tube baby on 1978, studies have started to increase the pregnancy rates anr examine the factors affecting the success.
Though new hypothesis are being formed each day related to the factors affecting success, only some of them are proved to be actually effective. Affects of some of the factors could not be demonstrated later on or still controversial.
Success rates among the countries or centres vary significantly. Pregnancy rates of different countries and various centres vary between 15-65%.
It should be noted that test tube baby is team work. It is important that the doctor, nurse, biologist and other members of the team work in coordination and in harmony with the patient.
There are various reasons for different pregnancy rates among centres.
The main reasons are as follows:
1. Differences among the treated patients (patient selection)
a. Different age groups of patients applying to the centres.
b. A certain age limitation for the admitted patients
c. Cancellation of the treatment in patients having a negative treatment course, the usage of different criteria for cancellation
d. Not admitting couples having a low chance in order not to show the success of the centre low
e. Different problems or diseases of the patients applying for treatment
2. Inexperienced and not sufficiently trained infertility specialists and embriyologist and biologists working at the centres or laboratories
3. Technical facilities of the centres, their oppourtunities to implement new techniques or the staff’s having the opportunity of learning and applying new treatment methods or not
4. Donor oocyte and donor sperm application’s being legal in some countries. Test tube baby application can be performed with an oocyte obtained from another healthy young woman (donor oocyte) and a sperm obtained from a sperm bank. In couples having severe oocyte and sperm problems, with this kind of application, these problems can significantly be overcomed. As a result, in patients having a low probability for pregnancy, high rates of pregnancy can be achieved.
5. Due to legal or ethical limitations among countries, performing different applications
a. Limitation of the transferred embryo number (2 or 3 at the most)
b. Limitation on the day of the embryo transfer (2 days)
c. Limitations related to the freezing of embryo, sperm or testis tissue
d. Pre-implantation genetic diagnosis
6. When pregnancy rates are reported, it is important to understand what is actually being reported.
a. Pregnancy rate per patient, per egg collection process or per embryo transfer
b. Pregnancy test positive (are chemical pregnancies included?)
c. Seeing the pregnancy vesicle with ultrasound (pregnanct vesicle positive)
d. Seeing fetus and heart beats with ultrasound (heart beat positive)
e. Including miscarriages or not
f. Live birth rates (baby-take-home rate): This is the most important one.
7. Wrong or exaggerated reportings of pregnancy rates by centres
Patient factor
The most determinative factors among patient factors are respectively as follows:
Woman’s age
This is a negatively effecting parameter especially if it is over 35. In women over the age 40, pregnancy rates decrease more significantly.
1. Decrease in ovary reserve (high FSH)
2. Low number of the developed folicule and the low number of the obtained oocytes
3. Oocytes of inappropriate quality
4. High genetic problem risk in oocytes
Ovary reserve The affect of FSH levels performed at the beginning of menstruationon pregnancy rates is well established. However, different points of views are present on the levels of FSH. For women having FSH values more than 15 IU/mL on the 2nd-3rd day of menstruation, their ovary reserve is considered to be low. In addition, having a total of 25 IU/mL or more FSH value with the Clomiphene citrate test (3rd day) and FSH (10th day) is also considered as low ovary reserve.
Hig E2 values determined on the 2nd-3rd day of pregnancy can be the indicator of low ovary response.
Male factor
Male factor’s affect on success depends on what the problem is. In azoospermia cases, ICSI results vary depending on obstructive or non-obstructive azoospermia. In non- obstructive azoospermia, pregnancy rates decrease. In addition, since the risk of having chromosome disorders (numerical or structural) increases in these men, the pregnancy chance decreases even more. If microinjection is applied, the low number of sperms and morphological disorders of the sperm usually do not affect the pregnancy rates negatively.
The affect of the test tube baby laboratory on success
Test tube baby laboratory that can be considered as the heart of the ART applications are one most important factors of the success of the system due to their staffs, materials and techniques used.
The knowledge and experience of the laboratory staff related to the subject are very important. Minor details that can be considered insignificant at the laboratory may affect the results of pregnancy significantly. For example, prolonged oocyte manipulation, opening and closing of the incubator more than usual decrease pregnancy rates. Not abiding by the required sterility rules, incubator with inappropriate pH and gas settings, conduction of the processes with inexperienced staff have an important role in failure. The material used in the laboratory should be non-toxic. Appropriate media should be used depending on the development stages of embryos.
The effect of the number and quality of the oocyte on success The quality of the eggs obtained with egg collection is as important as the number of the eggs. Mature eggs of good quality (MII) are processed. For a successful fertilization, division and development, the quality of the egg is very important.
The quality of the egg and whether they are mature or not are determined as follows:
Immature oocyte (prophase): No polar substance present, germinal vesicule is dark, compact cumulus is present.
MI oocyte (metaphase I): Polar body, germinal vesicule are not present, cumulus is wide and the oocyte is slightly colored.
MII oocyte (metaphase II): Polar body present, ooplasm regular, cumulus has a wide appereance.
Postmature oocyte: Cumulus in bulk or not present, polar body present, ooplasm has a dark appereance.
Degenerated oocyte (atretic): No cumulus present, polar body and the nucleus has a degenerated appereance, vacuole present.
The oocyes having the highest fertilization potential are MII oocytes. MI oocytes can be MII after a while in in viro culture and can be fertilized after ICSI. The most important factors aeffecting the quality of the oocyte are as follows:
1. Woman’s age
2. FSH level
3. Stimulation (drug usage), HCG dosage and timing: Performing stimulation and their follow-ups correctly, using the drugs in appropriate dosages and on time is important regarding the success of the treatment and the hyperstimulation syndrome.
HCG injection shuld be administered on the right say and time, can effect the result negatively if injected earlier or later.
In patients using gonadotropins in high dosages for a long time, the quality of the oocytes deteriorates.
4. Egg collection process should be conducted on time and appropriately
5. Genetic disorders
The affect of fertilization, embryo division and development on the success
High rates of fertilization affect the number and quality of embryos to be developed positively. If fertilization rates are low and few embryos develop and if their qualities are also low, then pregnancy rates decerease significantly. The number and quality of developed embryos depend on many factors. Above all, it depends on the number and the quality of the eggs collected from the patient (patient factor). The main reason for better pregnancy results in young patients is this. The risk of having chromosome disorders in the oocytes of young women is lower. Despite this, 20-40% of their embryos have chromosome disorders (aneuploidy). With declining age the number and the quality of the collected eggs decrease and the risk of having chromosome disoreder in embryos increase. The conditions of the test tube baby centre, the knowledge and experience of the embryologist and biologists working in that laboratory are one of the most important factors effecting the division and development of the embryo.
The quality of the developed embryos is evaluated by these properties:
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