Azoospermia is found as a result of semen analysis in one out of every 10 men who do not have children. Azoospermia means no sperm cells in the semen. If there are no cells in the semen, it can have two meanings. Either the semen transport channels are blocked or the testicles are not working enough.
The treatment of the obstruction is surgery, and as a result, the chance of pregnancy can be gained naturally. Obstructions in the semen ducts may be in the part where the ducts come out of the testicles, or they may be found at more advanced levels. If there is an obstruction close to the testicles, the definitive diagnosis of these can only be made by surgery. If such a duct obstruction is detected, the obstruction is removed under the microscope in treatment. According to the location of the obstruction, 2 types of surgery are performed: vasovasostomy and vasoepididmostomy.Microscopy is always used in surgeries (microsurgical technique).
vasovasostomy it is done with the request of reopening the canals in men who have previously been connected to the canals due to birth control. Apart from this, it is also applied in the treatment of cases where the canals are accidentally connected during surgeries such as hernia surgery. Rarely, reasons such as falling or hitting may also cause obstruction in these channels and vasovasostomy is required for treatment. Here, the occluded part is removed and the two exposed ends are joined together using very thin suture materials.
vasoepididymostomy If there is an obstruction at the level of the epididymis, it is necessary. The epididymis is a gland formed by the ducts carrying sperm cells just after they exit the testis. It is attached to the outer-posterior surface of the testis. Obstruction in the epididymis may be due to the ligation of the ducts, as well as the congenital absence or underdevelopment of the semen ducts, previous inflammations, trauma or unknown reasons. Approximately 3-6% of men examined for infertility have an obstruction at the level of the epididymis. The diagnosis is often made from a history of infection in the anamnesis or by palpation of nodular hardness on the epididymis during physical examination. However, surgery is often required to make a definitive diagnosis.
The reason why epididymovasostomy and vasovasostomy is the first choice is based on its high success. However, it should not be forgotten that an important factor affecting the success rate depends on the center where the microsurgery is performed or the experience of the surgeon. It has been demonstrated in many studies that as the number of treated cases increases, the success to be achieved also increases.
If adequate opening in the semen ducts is not achieved or microsurgery cannot be performed due to anatomical condition, sperm obtained by sperm aspiration (MESA) from the epididymis under the operating microscope or sperm extraction from the testis (TESE) can be used in ICSI.
Regardless of the method, pregnancy can be achieved between 24-81% by using the sperm obtained in obstructive azoospermia cases in in vitro fertilization (ICSI).
If the testicles are not functioning in azoospermic men, treatment varies. In this case, it is first investigated whether there is a hormonal disorder. Because if there is a hormonal imbalance, the chances of re-growth of cells in the semen and even spontaneously having children increase as a result of their treatment with medication. Congestion and hormonal disorders, transrectal ultrasonographyand FSH, LH, Testosteronecan be detected by blood tests.
If, despite all researches, it is not possible to get sperm cells in the semen with medication or surgery, then the tissue can be removed from the testicles by surgery and when sperm is searched in this tissue, enough sperm cells are found in about half of the patients and they can be used in in vitro fertilization to have a child. This processing TESEcalled ( obtaining sperm from the testicles by surgery).
The TESE procedure is performed in the operating room and under the microscope ( microTESE ). TESE performed by microsurgical method increased the rate of obtaining spermatozoa from the testicles from 16-45% to 42-63% compared to standard TESE. Performing the surgery using a microscope during TESE not only minimizes vascular trauma and eliminates the risk of bleeding in the testis, but also significantly reduces the amount of tissue removed. General anesthesia is preferred since the procedure will take a long time. But it can also be done with good local anesthesia following sedation. The testicles are opened and the most mature tubes containing semen are found and removed. These removed tubes are then subjected to some processes in the laboratory, and the sperm cells inside are separated. The obtained cells are injected into the woman’s eggs by ICSI.
According to our own experience, when microTESE is performed on men with azoospermia, between 20% and 100% sufficient cells can be obtained. The reason for such a difference is related to the severity of the disorder in the testicles. For example, in the case of what we call hypospermatogenesis, almost all such men can be successful. But SCO ( Sertoli cell only syndrome ) cells can be found in only one-fifth of the cases. The most difficult part of the job is to predict before surgery which patient will have cells and which will not. The most instructive examination in this regard is Y-chromosome genetic research. If there is a deficiency in the genes on this chromosome, the rates of finding sperm with microTESE change depending on the localization of the missing genes.
Another important issue affecting the finding of cells is the technique and experience of the andrology laboratory. Because while the cell search process takes about 1 hour in the surgery (the process can take up to 2 hours if no cells are found), the separation effort in the laboratory takes at least 2 hours. This period can be shortened even more with the enzymatic method.
Before microTESE is performed, the male must be investigated in detail and prepared by treating accordingly. hypogonadotropic hypogonadism In the case of a hormone deficiency called hormone replacement, hormone replacement significantly increases success. This condition occurs in approximately 1% of infertile men. Azoospermia is present in almost all cases. Although treatment with gonadotropins is possible, it must be maintained for at least 2 years for spermatogenesis to return to normal. The long-term requirement of the treatment to ensure sperm production in the ejaculate creates important economic and psychological problems for the patients. However, the appearance of spermatozoa in the testicles may occur earlier, before they come out in the ejaculate. In recent studies, spermatozoa were obtained in 73% of men who remained azoospermic despite gonadotropin treatment, and it was reported that 20% pregnancy was achieved after ICSI. As a result, after 3-6 months of gonadotropin replacement therapy in azoospermic men due to hormone deficiency, if no sperm is produced in the ejaculate, it is recommended to search for spermatozoa in the testicles to be used in ICSI without further waiting.
with Klinefelter syndrome(46,XXY genetic disorder)as in men, y In the treatment of azoospermia cases with testicular failure with high FSH, a treatment approach to increase the ratio between testosterone and estradiol hormones is recommended. If the testosterone/estrogen ratio remains below a certain threshold, spermatogenesis may be impaired. Among such men, those with high FSH and low testosterone are treated for 2-3 months using an aromatase inhibitor. Aromatase inhibitors can provide quantitatively significant improvement in seminal parameters in these cases. As a result, it has been shown that the success of finding spermatozoa with TESE, which is 40-48% with the classical application, increases up to 72%.
Another group of patients who are azoospermic and benefit from hormone therapy is with primary FSH deficiency are facts. In such men with low serum FSH values, seminal parameters can be improved and pregnancy can be expected with FSH treatment.
damaged DNA It has been shown that the rates of spermatozoa carrying sperm have a significant relationship with the deterioration in sperm parameters, and higher rates in infertile men. There is a negative correlation between semen parameters and DNA integrity in men. Therefore, in ICSI cases where a small number of sperm obtained from testicles are used in azoospermia due to spermatogenesis disorder, the risk of injecting DNA damaged spermatozoa into the egg will also increase. Indeed, the rates of DNA damaged spermatozoa in TESE sperm that did not achieve pregnancy were 68% higher than those with pregnancy. Similarly, most studies note the existence of a significantly negative relationship between the frequency of DNA damage and fertilization rates after ICSI. Interestingly, fertilization rates remain low or low even if sperm with normal morphology are selected during ICSI. However, our knowledge on this subject is still limited. There are also findings on the contrary, and it has been reported that fertilization and pregnancy rates are not associated with DNA damaged sperm rates in ICSI cases using semen samples containing highly DNA damaged sperm, if spermatozoa with normal morphology were injected.
Sperm DNA/chromatin The use of hormones with the effect of FSH in the treatment of injuries has been investigated in many studies. Ultrastructural studies have shown that such treatments have the effect of reducing morphological disorders in sperm genetic structure in infertile men. In a limited number of prospective, controlled, randomized studies, significant improvement in pregnancy rates was noted in couples treated with the male before ICSI. Based on the available data, hormone therapy to improve the quality of spermatozoa, which can already be obtained in small numbers with TESE, is seen as a viable option in azoospermia cases with hormones within normal limits and without duct obstruction.
Having normal hormone levels and no maturation pause in testicular biopsy, hypospermatogenesis It has been reported in different studies that hormonal stimulation therapy significantly increased sperm count in cases of . Our own experience has also shown that in azoospermia cases with normal FSH, if the pathology is hypospermatogenesis or the presence of focal spermatogenetic foci, FSH stimulation can significantly increase the rate of retrieval of mature spermatozoa by microTESE.
On the other hand, we see that endomethacin treatment prevents the harmful effects of leukocytes by different mechanisms and increases cell output in some cases. Pentoxifylline, on the other hand, increases the blood supply of the testicles and stimulates sperm development. It has been demonstrated in many studies that antioxidant drugs significantly increase the success of IVF applications with poor quality sperm. In addition, it is extremely important to use appropriate antibiotics in men with leukocytes in the semen analysis. Our recommendation is to perform a preparatory treatment for men required by the above conditions, and then switch to microTESE.
A biopsy is also taken from the testicles during TESE. No cells were found in TESE, but the presence of cells called spermatids in the biopsy is a finding for a second TESE. Such patients can be prepared and taken to TESE for the second time after 6 months at the earliest. If the biopsy shows earlier stage cells rather than spermitids, the chance of finding cells in the second TESE is reduced. However, it should be kept in mind that sperm can be obtained with repetitive TESE surgeries despite previous failures.
Spermatogonia are stem cells in the testicles and have the potential to produce mature sperm cells. In experiments, the researchers were able to obtain mature spermatozoa by using spermatogonia, which are sperm stem cells from the testicles of mice. After the tissue samples taken from the testicles were subjected to some processing and kept in the laboratory environment for 2 months, when the tissue samples were examined, it was observed that mature sperm cells had developed in them. But it should be noted right away that for this, spermatogonium or other immature sperm cells must be found in the testicles. Studies on different techniques are continuing in cases where these are absent or in cases where no testicles are developed. On the other hand, the experiments were successful on animals, but no application has been made in humans yet. So we don’t know the consequences in humans. In a few years, maybe in a shorter time, we will be able to see how it will work in humans.
As a result, men with azoospermia have a chance to be treated with microTESE. However, it is not possible to know for certain in advance whether cells will be found with TESE. Therefore, TESE surgery seems inevitable in such men. A method called cryoTESE is applied to men who have little chance of finding cells with TESE. Here, TESE is performed and if cells are found, the cells found are frozen and stored. Then the partner is prepared and in vitro fertilization is made using frozen sperm. The benefit of this method is that since the woman will not be prepared on the TESE day, if the cell cannot be found, there is no problem for the woman. If the cell is found, there is no loss, as it will already be frozen and stored. However, an important decision is required here: if cryoTESE is performed and only a few cells are found, these cells may die or perish when frozen and subsequently thawed. In this case, it may be necessary to TESE again, and sometimes no cells may be found again!. Since the cells in the first TESE are also dead, the chances of having a child may be lost. In this respect, it is another alternative to prepare the woman for in vitro fertilization while performing TESE and to perform the procedure on both men and women on the same day. However, if no cells are found in the man, everything goes in vain and IVF is cancelled. Before TESE, these issues should be discussed and discussed with couples.
In summary, the azoospermic man who has no sperm in the semen analysis is first examined, followed by imaging methods and hormone analyzes. Appropriate treatment is given for his condition, and the semen analysis is repeated to check whether the sperm output has started. If sperm does not come out despite this, microTESE is decided. Pre-TESE genetic research is recommended. Remember, about half of azoospermic men can have children with microTESE. But again, it should be noted that the situation is not good for the other half. If it is not possible to have a child with TESE, there is no treatment option that has entered into a routine with today’s technology. Although studies such as stem cell, replication, in vitro maturation give hope for the future, they are still in the research period and their reliability has not been proven.