Factors Affecting Success in IVF
Despite the ongoing development of new techniques and opportunities, the success rates in IVF treatments have not yet reached the desired levels. With the birth of the first IVF baby in 1978, intensive studies to increase pregnancy rates and to investigate the factors affecting success began.
Although new information is proposed every day about the factors affecting success, only some of them have been proven to have a real effect. The effects of some of the factors mentioned could not be shown yet or are still controversial.
Success rates vary widely between countries and centers. Pregnancy rates reported from different countries and different centers differ greatly from 15% to 65%.
The most important point to remember is that IVF is a team work. It is extremely important that the doctors, nurses, biologists, embryologists and other employees in the team work in coordination and in harmony with the patient.
There are various reasons for reported pregnancy rates so differently between centers.
The main reasons are:
1. Differences between the treated patients (patient selection)
a. Differences between the age groups of the patients who applied to the centers
b. Defining a certain age limit on patients admitted to treatment
c. Cancellation of treatment or not transferring in patients whose treatment progresses is not favorable, use of different criteria for cancellation
d. Not accepting couples with a very low chance of treatment in order not to lower the success rate of the center.
e. The differences in disorders or diseases of the patients who come to treatment
2. Whether infertility specialists working in centers or embryologists and biologists working in laboratories have sufficient training and experience, or not.
3. The technical possibilities of the centers, whether they have the opportunity to apply new techniques or whether their employees have the opportunity to learn and apply new treatment methods, or not.
4. Free application of donor oocyte and donor sperm in some countries. IVF can be done using an egg (donor oocyte) taken from another young woman, or sperm from a sperm bank. In this way, the problems are overcome to a certain extent for couples with serious egg and sperm problems. As a result, high pregnancy rates are obtained in patients with very low pregnancy chances with this application.
5. Making different practices as a result of legal or ethical limitations between countries
a. Limiting the number of embryos transferred
b. Limitation on embryo transfer days (2 days)
c. Limitations on freezing embryo, sperm, or testicular tissue
d. Preimplantation genetic diagnosis (PGD)
6. When reporting pregnancy rates, it is important in fact what is actually reported.
a. Pregnancy rate per egg retrieval or embryo transfer for each patient.
b. Positive pregnancy test (including chemical pregnancies)
c. Observing a gestational sac on ultrasound (positive gestational sac)
d. Seeing the fetus and heartbeats on ultrasound (heartbeat positive)
e. Whether including miscarriages or not
f. Live birth rates (baby-take-home rate): This is the most important.
7. Report of false or exaggerated pregnancy rates by the centers
Patient factors:
Among the patient factors, the most decisive ones are as follows:
1.Female age
2.Basal FSH levels
3.Reason for in vitro fertilization (one or more disorders related to men and women)
4.Drugs used (stimulation drugs and luteal phase support)
5.Compliance of the patient with the treatment process (drug use, attending check-ups regularly)
Female age:
It is a parameter affecting negatively, especially when the age is over 35. Pregnancy rates are significantly lower in case women are over the age of 40.
1. Decreased ovarian reserve (high FSH)
2. The low numbers of developing follicles, and of eggs obtained
3. Unsuitable quality of the eggs
4. Presence of high risk of genetic or chromosomal disorders in eggs
Ovarian reserve:
Examination of FSH, E2 and LH values on the 2nd or 3rd day of menstruation can give important clues about ovarian reserves. However, there are different opinions about the levels of FSH. It is accepted that the ovarian reserve is low in women with an FSH value above 15 IU/mL on the 2nd and 3rd days of the period. Besides, if the sum of the FSH values on the 3rd and 10th days is over 25 IU/mL or more in the Clomiphene citrate test, this is also accepted as a low ovarian reserve.
High E2 values detected on days 2 and 3 of the period may also be a sign of low ovarian response.
In addition, according to recent studies, AMH (anti-mullerian hormone) level, which can be measured in the blood during every period of menstruation, provides important information about the ovarian reserve in women and how the ovaries will respond to hormonal drugs. AMH levels, like FSH, are elevated in women with advancing age, indicating decreased ovarian reserve.
Male Factor:
The effect of the male factor on success also depends on what the problem is. In azoospermia cases, fertilization results vary depending on whether they are obstructive (obstruction in sperm ducts) and non-obstructive (no obstruction in sperm ducts). Pregnancy rates decrease in non-obstructive azoospermia. Besides, since these men have a higher risk of having a chromosomal disorder (numerical or structural), the chance of pregnancy is greatly reduced in such a situation. If microinjection (ICSI-IMSI) is applied, low sperm count and sperm morphology do not generally affect pregnancy rates negatively.
The effect of IVF laboratory on success:
The IVF laboratory, which can be defined as the heart of IVF applications, is one of the most important factors in the success in terms of both the employees and the materials and techniques used.
The knowledge, skills and experience of laboratory staff are extremely important. Small details that may be considered insignificant in the laboratory significantly affect the outcomes of pregnancy. For example, taking longer time than required egg manipulation during the procedures, opening and closing the incubator cover too much reduces pregnancy rates (the higher the number of incubators, the higher the success. There are 8 incubators in our center.). Failure to comply with the required sterility rules, unsuitable pH and gas settings of the incubators, and not performing the procedures by experienced people play an important role in the failure. The materials used in the laboratory should be non-toxic. Appropriate culture mediums should be used according to the developmental stages of the embryos.
The effect of egg (oocyte) number and quality on the success
In IVF applications, the quality of the eggs is as important as the number of eggs retrieved on the day of egg collection. Good quality (MII) eggs are processed. The quality of the egg is extremely important for successful fertilization, division and development.
The quality and maturity of the egg are determined as follows:
Immature oocyte (prophase): No polar body is present, dark germinal vesicle, compact cumulus is present.
MI oocyte (metaphase I): No polar body and no germinal vesicles are present, cumulus is large, and oocyte is light colored.
MII oocyte (metaphase II): There is a polar body, the ooplasm is smooth, the cumulus is wide in appearance.
Post-mature oocyte: There is a clumpy or absent cumulus, polar body is present, ooplasm is dark in appearance.
Degenerated oocyte (atretic): There is no cumulus, polar body and nucleus are degenerated in appearance, vacuole is present.
MII eggs have the highest fertilization potential. MI oocytes can also become MII after culture in the laboratory for a while, and fertilized after ICSI.
The most important factors affecting egg quality are:
1. Female age
2. FSH level
3. Stimulation (drug usage), dose and timing of HCG: Accurate stimulation and follow-up, use of drugs in appropriate doses and on time are important for the success of the treatment and hyperstimulation syndrome.
HCG injection should be done on the right day and time, early or late administration may adversely affect the result.
Egg quality is lower in patients who use gonadotropins in very high doses and for a long time.
4. Timing and proper collection of egg
5. Genetic disorders
The effect of fertilization, embryo division and development on success:
High fertilization rates positively affect the number of developing embryos. Pregnancy rates are significantly lowered, if fertilization rates are low, few embryos develop and their quality is low. The number of developing embryos and their quality depend on many factors. First of all, it depends on the number and quality of eggs collected from the patient (patient factor). This is the main reason why pregnancy outcomes are better in younger patients. Also, the risk of chromosomal abnormalities in their eggs is lower in younger women. Despite this fact, approximately 20-40% of their embryos have chromosomal abnormalities (aneuploidy). With increasing age, the number and quality of eggs decreases and the risk of chromosomal disorders in embryos increases. Another factor is the quality of the sperm. It is known that embryos that develop following the procedures performed with sperms that have serious morphological problems are of lesser quality. Therefore, it is very important to choose the best sperm for injection. The IMSI system, which has been used recently and enables the best quality sperm to be detected with high magnification, is used in our center and allows us to develop quality embryos and achieve higher pregnancy rates in our infertile couples with serious sperm disorders. Undoubtedly, one of the important factors affecting embryo division and development depends on the conditions of the IVF laboratory and the knowledge and experience of the embryologists and biologists working there.
The quality of developing embryos is evaluated according to the following characteristics:
1.) In the 2nd and 3rd days embryos, symmetrical appearances of the size and shape of the blastomeres (cells) forming the embryo, and the percentage of the fragments in the embryo (cellular residue) (fragmentation)
2.) The structure of the intracellular mass that forms the baby and the trophectoderm cells that form the placenta in the 5th day blastocyst stage embryos
