METHOD OF USING SPERMATOGONIAL STEM CELLS IN NON-OBSTRUCTIVE AZOOSPERMIA

METHOD OF USING SPERMATOGONIAL STEM CELLS IN NON-OBSTRUCTIVE AZOOSPERMIA

Rano Zhankina

master of Medicine, Urologist, doctoral student of the Department of Urology and Andrology of NAO "Astana Medical University",

Kazakhstan, Nur-Sultan

Amin Tamadon

Bushehr University of Medical Sciences, Moallem St.,

Bushehr, Iran

Ulanbek Zhanbyrbekuly

сandidate of Medical Sciences, Associate Professor, Head of the Department of Urology and Andrology of NAO "Astana Medical University",

Kazakhstan, Nur-Sultan

Manarbek Askarov

MD, professor Head of the Center for Cell Technologies, Transplantation and Scientific Management National Scientific Medical Center, 42

Abylai Khan Av.,

Kazakhstan, Nur-Sultan

Ravil Sherkhanov

мaster of Medicine, Assistant of the Department of Urology and Andrology of NAO "Astana Medical University",

Kazakhstan, Nur-Sultan

Daniyar Akhmetov

PhD, Assistant of the Department of Urology and Andrology of NAO "Astana Medical University",

Kazakhstan, Nur-Sultan  

Dana Saipieva

senior Fellow of the Center for Cell Technologies, Transplantation and Management National Scientific Medical Center, 42 Abylai Khan Av.,

Kazakhstan, Nur-Sultan

Nurbol Keulimzhaev

assistant of the Department of Urology and Andrology of NAO "Astana Medical University",

Kazakhstan, Nur-Sultan

Introduction: Spermatogonial stem cells are differentiated spermatogonia that result in both spermatogonia differentiation and renewal to maintain the stem cell pool. These cells are potential agents for the treatment of male infertility due to the ability to revive male fertility in vivo and the ability to redistribute into male gametes in vitro [1,2]. In some clinical studies, the distinction of in vitro transport with subsequent in vivo transplantation has been made to acquire male gametes at differentiation stages [3]. Azoospermia is defined as the absence of sperm in the ejaculate. The established diagnosis must be proved by centrifugation of two samples of sperm for 15 minutes at room temperature with a centrifugation speed of at least 3000 g [4,5]. Ejaculate analysis should follow the WHO guidelines (2010) [5]. According to the world literature, azoospermia is divided into excretory, that is, obstructive and secretory [6].

The most complex and severe form of male infertility is non-obstructive azoospermia, which is characterized as the complete absence of spermatozoa in the ejaculate due to damage to spermatogenesis. The reason for the development of non-obstructive azoospermia (NOA) lies in the damage to spermatogenesis due to abnormal damage to the activity of the testicles or due to low production of gonadotropins. A complete, detailed history, hormonal assessment, physical examination data, genetic studies such as karyotherapy and Y chromosome microdeletion are necessary for an accurate final diagnosis. The presence in the patient's history of causes such as undescended testicles, antitumor chemotherapy creates damage to spermatogenesis. The use of drugs such as steroids [7], 5α-reductase inhibitors [8] can also lead to impaired spermatogenesis.

The size of the testicles reproduces the exact level of spermatogenesis, and therefore small testicles indicate a violation of spermatogenesis. Non-obstructive azoospermia is the main cause of treatment resistance in male infertility.

Mesenchymal stem cell therapy is a new medical treatment for male infertility. The results of this pilot study may become a new direction in the treatment of non-obstructive azoospermia.

Objective: The study aimed to discover a new treatment for non-obstructive azoospermia using spermatogonial stem cells.

Material and methods: 25 patients aged 25 to 35 years with a diagnosis of non-obstructive azoospermia were included in an experimental open study. Before and after treatment, all patients were assessed for LH, FSH, testosterone, inhibin B, prolactin, as well as twice conducted spermogram. All 25 men before the experiment had a low level of inhibin B, an increased level of FSH. Spermatogonial stem cells contained in the bone marrow of the iliac crest and isolated from there after 14 days of cultivation were collected from each patient. After the isolation of these cells, a testicular biopsy was performed, namely micro-TESE, and autotransplantation of own cells into the testicular network and, if possible, into the spermatic cord was performed.

These men were closely monitored during the entire period of the experiment. After three months, blood counts for sex hormones were re-examined and a spermogram was taken. The result, unfortunately, was not encouraging. That is, the hormonal levels were slightly improved, but the results of the spermogram were negative. After 6 months, we noted an improvement in the general condition of patients, an increase in libido.

Results: The initial level of FSH was [18.9; 29.8], after treatment its level decreased (p<0.001) by [6.4; 13.6], and in 9 (47.4%) patients it returned to normal. The level of total testosterone before treatment [2.8; 9.2], increased after treatment (p=0.002) by [2.9; 4.9]; in 6 (31.6%) patients it returned to normal, in 3 (15.8%) the value remained within the normal range. The level of LH before treatment increased in 9 patients, of which 6 returned to normal after treatment. In general, there is a tendency to a slight decrease (p=0.007) of its level by [0.1; 3.7]. The level of inhibin B before treatment in all patients was below the norm 7.2/5.4 [4.1; 9.3]; after treatment, there was an increase (p<0.001) by [7;14]. In 4 (21.1%) patients it returned to normal. In 4 patients (21.1%), 6 months after treatment, single spermatozoa were found in the semen, which were cryopreserved for subsequent preparation for in vitro fertilization.

Conclusions: The results obtained provide new information about the drug efficacy of spermatogonial stem cells in non-obstructive azoospermia, depending on the hormonal profile.

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