Innovations in IVF

Innovations in IVF

In 50% of applications due to infertility, problems related to men are detected. The most common man-related infertility reasons include structural (translocations) and/or numerical chromosomal (aneuploidies) anomalies, genetic mutations, experienced infections (mumps, etc), varicosele, azospermia (no sperm cell in semen) and numerical, motility and morphological insufficiency of sperms.

Semen analysis doesn’t give adequate information about structure of DNA packaged in sperm core. As DNA damages cannot be detected using normal sperm analysis, pregnancy may not occur in IVF trials performed using sperms with damaged DNA.

Therefore, structural anomalies and fragmentations in DNA of sperm (decomposition and separation) gain importance in male infertility. Using sperm with damaged DNA in IVF trials may lead to low pregnancy and implantation rates and early abortions.

It is observed that advanced age, smoking, air pollution, long period of sexual fasting and exposure of testis to abnormal hot environment increase damages in sperm DNA of men. It is shown that age of man is also important for sperm quality in infertile pairs. In infertile men, the anomalies based on genetic structure of sperm are seen more frequently.

The techniques used most commonly to evaluate integrity of sperm DNA are TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and SCSA (sperm chromatin structure assay) tests. These tests are used for diagnosis and guide the pairs and doctors about the next IVF trial. The men detected to have highly damaged DNA in their sperms obtained with ejaculation may be administered drugs containing vitamin E which decreases ROS (reactive oxygen species) leading to DNA damage until the next IVF trial; if they smoke, it may be suggested to give up smoking and eat organic foods.

Furthermore, in case of high DNA damage in ejaculate of man and repeatedly unsuccessful IVF trials of the pairs, it may be suggested to obtain sperm not from ejaculate but from testis during the next IVF trial. The studies performed with TUNEL and SCSA tests have shown that the sperms from testis have lower DNA damages when compared to ejaculate sperms. In such cases, it may be preferred to use testicular sperm instead of ejaculate sperm. In the studies on such cases, high rates of pregnancy and lower rates of early abortion have been detected as a result of using testis sperm.

In cases of severe sperm factor, repeating abortions, several unsuccessful IVF trial and unexplained infertilities, the IMSI (intra-cytoplasmic morphologically-selected sperm injection) system enabling selection of sperms by magnifying them 6000-8000 times with a special magnification microscope is one of the new and most important developments in this field in terms of allowing for development of quality embryos that can reach blastocyst stage.

According to the new regulation published by Turkish Republic Ministry of Health on March 2010, it is agreed to apply single embryo transfer in the first two trials to patients aged 34 and younger, maximum two transfers after the second trial, and maximum two transfers independently from number of previous IVF trials to patients aged 35 and older in our country. Consequently, selection of high quality sperms to obtain embryos in good quality and with high chance of pregnancy has gained more importance. Also, increase in number of quality embryos contributes to success of IVF. In addition to a good stimulation, selection of best quality sperms using IMSI system will also increase the rate of conception.

Acrosome reaction is an event occurring immediately after contact of sperm with oocyte. This event should occur before the sperm contacts with surrounding of oocyte (to cumulus and zoona pellucid) and fertilization starts.

When phosphodiesterase inhibitors such as caffeine, pentoxyphlline are added to semen in laboratory, they increase intracellular cAMP level, glucoses and ATP production. These substances increase rate of motile sperms and also initiate motility in living but inactive sperms. It is known that these substances stimulate frozen-thawed sperm motility.

It is thought that acrosome reaction is triggered by entry of calcium ion into the cell. It is known that progesterone increases entry of calcium into the cell by opening chlorine vessels by means of specific cell membrane receptors and has a stimulating effect on capacitation and acrosome reaction. Progesterone is added into sperm preparation mediums in order to initiate capacitation and achrosom activation of sperm. In some of infertile men, the main problem is that the sperms don’t enter into acrosome reaction. In such cases, these abilities of sperms can be tested by performing acrosome reaction test. As is mentioned, stimulation of calcium entry with agents such as calcium ionophore A23187 which will enable entry of calcium into the cell lies on the basis of these tests.

Calcium which triggers flow of calcium into cell doesn’t exist routinely in ionophore culture mediums. However, in the patient groups who have experienced low rate of conception or non-conception in previous trials, it ensures activation of oocytes (oocytes) and sperms by being added into culture mediums using a special technique in order to increase conception. In that way, high rates of conception can be obtained. It is highly possible to have success with this method in patient groups who haven’t experienced any conception with conventional IVF mediums previously.

In IVF implementations, it is essential to develop embryos in a naturally identical medium. Among these artificial mediums, Endometrial Co-Culture medium is one of the safest culture systems in which the embryos can develop before transfer. The main feature of this culture system is that the relationship between naturally developed embryo and endometrium (uterine tissue) in uterus of an expectant mother is simulated identically in the laboratory. Endometrial cells obtained from endometrium tissues taken from expectant mother in appropriate amount with a simple operation are developed in laboratory and then the oocytes fertilized with IVF/ICSI/IMSI operations are growth on these uterine cells for 3-5 days.

Endometrium tissue excretes many growth factors known to be beneficial for development of embryo into the culture medium. These growth factors increase quality of developing embryos, ensure activation of cell membrane receptors which help implantation, and therefore, increases the chance of implantation and pregnancy.

In our center, Endometrial Co-Culture has been applied successfully for years in selected patient groups. Especially, successful results are obtained in our patients who have developed bad quality embryo during the previous trials and/or experienced several unsuccessful IVF trials due to non-implantation in spite of high quality embryos.

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