Male-related problems are detected in 50% of the applications made due to infertility. The most common causes of male infertility can be listed as structural (translocations) and/or numerical chromosomal (aneuploidies) disorders, genetic mutations, past infections (mumps etc.), varicocele, azoospermia (absence of sperm cell in semen) and numerical, motility and morphological deficiencies of sperm.
Recent innovations in IVF treatment
Semen analyzes do not provide sufficient information about the structure of the DNA packaged in the nucleus of the sperm. Since DNA damage cannot be detected with normal sperm analysis, pregnancy may not be achieved in vitro fertilization attempts using sperm having damaged DNA.
For this reason, structural defects and fragmentation (fragmentation and separation) in the DNA of sperm gain importance in male infertility. Use of DNA-damaged sperm in IVF attempts may cause low pregnancy and implantation rates and early miscarriage.
It has been observed that advanced age, smoking, air pollution, long sexual abstinence, and exposure of the testicles to an abnormally hot environment increase the damage to sperm DNA in men. It has been shown that the age of the man is also important for sperm quality in infertile couples. Disorders related to the genetic structure of sperm are more common in infertile men compared to fertile men.
The most frequently used techniques to evaluate sperm DNA integrity are TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and SCSA (sperm chromatin structure assay) tests. These tests are used to diagnose and guide couples and physicians in the next IVF attempts. Drugs containing vitamin E, which reduces ROS (reactive oxygen species) that cause DNA damage can be prescribed to men with high DNA damage in their sperm obtained by ejaculation until the next IVF trial and if they smoke, they can be advised to quit smoking and eat more naturally.
In addition, if the man has high DNA damage in his ejaculate and the couple has repeated unsuccessful IVF attempts, it may be recommended that the sperm be obtained from the testicles instead of the ejaculate in the next IVF attempt. Studies based on TUNEL and SCSA tests have shown that sperm obtained from testicles have lower DNA damage compared to ejaculate sperm. In these cases, the use of testicular sperm may be preferred instead of ejaculate sperm. Studies conducted on such cases have found higher pregnancy and lower early miscarriage rates as a result of using testicular sperm.
In cases with severe sperm factor, recurrent miscarriages, multiple in vitro fertilization attempt failures and unexplained infertility, IMSI (intra-cytoplasmic morphologically-selected sperm injection) system, which allows the selection of sperms by magnifying 6000-8000 times with a special magnification microscope, is one of the recent and most important innovation in this field in terms of allowing the development of good embryos that can reach the blastocyst stage.
According to the new guide published by T.R. Ministry of Health in March 2010, in our country, it is considered appropriate to transfer only one embryo in the first two attempts in cases aged 34 and under, a maximum of two embryos after the second attempt, and a maximum of two embryos in cases aged 35 and above, regardless of the number of previous IVF attempts. Therefore, the selection of good quality sperm becomes more and more important in order to obtain embryos of good quality and with a high chance of pregnancy. At the same time, the increase in the number of quality embryos obtained also contributes to the increase in IVF success. In addition to a good stimulation, choosing the best quality sperm with the IMSI system will increase the fertilization rate.
The acrosome reaction is an event that occurs immediately after the sperm comes into contact with the egg. This event must occur before the sperm comes into contact with the oocyte environment (cumulus and zona pellucida) and before fertilization begins.
When phosphodiesterase inhibitors such as caffeine and pentoxifylline are added to semen in the laboratory, they increase the intracellular cAMP level, glycosylation and ATP production. These substances increase the motile-motile sperm ratio and can also initiate motility in live but immobile sperm. It is known that these substances also stimulate frozen-thawed sperm motility.
It is thought that the entry of the calcium ion into the cell triggers the acrosome reaction. Progesterone is known to have stimulating effect on capacitation and acrosome reaction by increasing the entry of calcium into the cell by means of opening chloride channels through specific cell membrane (membrane) receptors. Progesterone should be added into sperm preparation mediums to initiate capacitation and acrosome activation of sperm. The main problem in some infertile men is that their sperm cannot enter the acrosome reaction. In such situations, these abilities of sperm can be tested by performing the acrosome reaction test. As mentioned before, these tests rely on the stimulation of calcium influx with agents such as calcium ionophore A23187 or progesterone, which will ensure the flow of calcium into the cell.
Calcium ionophore, which triggers calcium influx into the cell, is not routinely present in culture media. Nonetheless it provides activation of oocytes (eggs) and sperm by means of being added to culture media with a special technique to increase fertilization, especially in patient groups who have encountered low fertilization rate or even no fertilization in previous attempts. Thus, a high rate of fertilization can be achieved. There is a high probability of success with this method in patients who have never been able to achieve fertilization with classical IVF media.
It is essential to ensure that embryos develop in an environment closest to nature in IVF applications. Among these artificial environments, the Endometrial Co-Culture medium is one of the safest culture systems in which embryos can develop before transfer. The most important feature of this culture system is that the exact imitation of the relationship between the embryo and the endometrium (uterine tissue), which occurs naturally in the mother's womb is created in the laboratory environment. Endometrial cells obtained from the appropriate amount of endometrial tissue (uterine tissue) taken from the expectant mother with a simple process are developed in the laboratory medium, and then the eggs fertilized by IVF/ICSI/IMSI processes are grown on these uterine cells for 3-5 days.
The endometrial tissue secretes many growth factors into the culture medium, which are known to be beneficial in the development of the embryo. These growth factors increase the quality of developing embryos, provide the activation of the cell membrane receptors that help the embryo to attach to the uterus, and thus increase the chance of implantation (embryo attaching to the uterus) and pregnancy.
Endometrial co-culture has been successfully practiced in selected patients in our center for years. Very successful results are obtained especially in our patients who have developed poor quality embryos in their previous attempts and/or who have had more than one unsuccessful IVF attempt where their embryos did not adhere despite the good quality embryo development.