Techniques determined and shown to be successful by Dr.Tanaka are used to obtain the round spermatid cell, prepare it, inject it into the egg and stimulate the egg (use of the electro-fusion device).

The Brussels IVF center has an experienced laboratory team in the application of the ROSI method.

What is azoospermia?

Nowadays, azoospermia is detected in approximately 1% of all men and in 10-15% of infertile men. Two conditions causing azoospermia are described; obstructive (obstructive azoospermia), in other words, obstruction or deficiency in the ejaculatory ducts and non-obstructive azoospermia.

Sperm production occurs in the testis in obstructive azoospermias, and sperm can be obtained from the testis with microTESE, TESE or TESA processes with 100% success. In the histology of non-obstructive azoospermias, cases where only Sertoli cells, which are the auxiliary cell in the sperm production are present, in other words, there are no sperm-producing mother cells (germ cell), where cells stop developmentally at one stage of sperm production or where the seminiferous tubules in the testis lose their properties are encountered.

In cellular analysis, except for the presence of Sertoli cells in the testis, i.e. no germ cells at all, production of mature sperm in certain regions or the presence of round or elongated (large-headed, short-tailed immature-immature sperm cells that have little appearance as sperm) spermatids that can be used for intracytoplasmic round spermatid injection (ROSI-ELSI) can be detected.

To whom should ROSI be applied?

Nowadays, sperm cells that have completed their maturation in nearly 50% of non-obstructive azoospermic men can be found with microTESE procedure. The only hope to become a father with the cell carrying their own genetic material for the other 50%, where no mature sperm can be found, is to use the immature germ cells called round spermatid or large-headed elongated spermatid, in ICSI, if there is production in the testis. The presence of cells that could not complete the maturation is demonstrated in approximately 30% of men without sperm cells.

The formation of a mature sperm in the testis in men generally consists of 4 stages and takes approximately 70 to 120 days. During this process, the germ cell (stem cell that turns into sperm - contains 46 chromosomes) undergoes structural and shape changes and turns into haploid sperm (containing 23 chromosomes) that carries the genetic material of the male to the egg. This process is very complex and genetics (such as 46XXY -Klinefelter syndrome, Y chromosomal microdeletions, gonadal mosaicism, genetic mutations) and hormonal changes or environmental factors (exposure to toxic effects, stress, uncontrolled anabolic steroid use) may disrupt sperm production stages and as a result, this can cause a decrease in the number of spermatozoa or even a complete halt, or a pause of the immature spermatid / elongated spermatid cell stage of the sperm that has not completely transformed into mature sperm.

As mentioned above, the only way for men who have only round spermatid/elongated spermatids in the testis or ejaculate to become fathers is to use these cells for injection into the egg, although the success rate is not high.

Are there any scientific studies in which the ROSI procedure is applied? What are the results?

The first studies where round and/or elongated spermatids are used in egg injection belong to animal studies. Although the success rates were low with ROSI and ELSI injections, live births were achieved, especially in the first studies conducted in mouse, rat and rabbit models, fertilization in eggs, embryo development. The first live birth obtained with round spermatid in humans belongs to 1996, and in many subsequent studies, applications were performed with ROSI and ELSI separated from ejaculate and/or testicular tissue. The common point of these studies is that injections with round spermatids have lower success rates compared to elongated spermatids. Besides, the rates of achieving live birth in pregnancies are really low. Most pregnancies result in early miscarriage. The reason for these lower success rates is directly related to the fact that the cells used are not fully mature. The closer the spermatid cells used are developmentally to the sperm cells, the higher is the success rates. As a result, researchers especially emphasize the use of more advanced sperm, in other words, closer in shape to mature sperm, although they are not fully mature. Therefore, the results of ELSI are more successful than those of ROSI.

Although many attempts were made with ROSI and/or ELSI injections from 1996, when the first studies started, to 2015, nearly 10 healthy babies were born. As a result, the interest in ROSI/ELSI has decreased, but until the Japanese scientist, Atsushi Tanaka published two new studies in 2015 and 2018. In these studies, it was brought to the attention of clinicians and embryologists that round spermatid injection should be considered as a last chance and recommended to cases in non-obstructive azoospermia cases.

Has a healthy birth been achieved with the ROSI procedure?

Compared with the first studies, higher fertilization, better quality embryo development, and as a result, a higher healthy delivery pregnancy was obtained using the round spermatid-ROSI injection in Dr. Tanaka's study. As a result of approximately 2600 in vitro fertilization attempts in 954 cases in the study, only 90 babies reached live births, with a success rate of around 5%. Although this rate is still very low in reality, the result is exciting considering that azoospermic men have no other choice. Technically speaking, what makes this study more successful than previous ones is the differences in the round spermatid separation method, and most importantly, the more accurate identification of the round spermatid cell. Therefore, the success of the procedure is directly proportional to the embryologist's experience in recognizing the cell. Besides, an electrofusion device was used to stimulate the egg cells in the treatment, by giving a controlled electric current to the egg at a certain voltage. With this device, it is aimed to increase the fertilization rates in injections made using immature cells.

Is ROSI procedure safe?

Congenital problems were found in 3 of 90 babies born in this study. These are cleft lip, omphalocele and ventricular septal defect. The incidence of these disorders is much lower in babies born between 1997 and 2005 in Japan, but considering that the number of babies born after ROSI is very low, it is not possible to statistically say that the risk of these disorders occurring in babies due to ROSI procedure is increased.

There was no difference between these babies and the babies born with a normal pregnancy in terms of two-year findings of the cognitive and physical development of the babies.

Currently, it is hard to say that the ROSI procedure is a completely safe procedure in the medical sense, since the number of babies born as a result of the ROSI procedure is low and the developmental follow-ups are short. It is important to carry out studies with longer-term developmental follow-ups of newborns in order to accept the ROSI procedure as a safe procedure.

Things to know before ROSI procedure.

As a result, the pregnancy rates after transfer to the uterus of embryos formed by the use of primitive cells that could not or did not complete their maturation obtained from the testis or ejaculate are low.

The rate of taking a baby home with the ROSI procedure is approximately 5%.

After ROSI, none of the eggs may be fertilized or fertilization rates may be much lower than with normal sperm injections.

None of the fertilized eggs after ROSI may remain viable until the quality embryo stage, or the developmental quality of the embryos formed may be much lower compared with normal sperm injections.

According to the study of Dr. Tanaka et al., no increased abnormality was detected in babies who reach birth after ROSI. Congenital abnormalities were detected in only 3 of the babies. In the 2-year cognitive and physical follow-ups, no remarkable negativity was detected compared to other babies.

It is important to follow up the babies born as a result of ROSI for many years to reveal that ROSI procedure is one hundred percent medically safe, and scientific studies in this area are still continuing.

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