Male infertility can be caused by absence or qualitative defect in spermatogenesis, which usually affects patient mental and physical health. Sertoli cell-only syndrome represents the severest form of histological phenotype of male infertility. Sertoli cell-only syndrome are difficult azoospermic cases to be treated, as the only cell available in the seminiferous tubules is Sertoli supportive cells with total absence of spermatogenesis. Most cases of Sertoli cell-only syndrome cannot be explained by the already known genetic causes, including karyotype abnormalities and microdeletions of the Y chromosome. With the development of sequencing technology, studies on screening new genetic causes of Sertoli cell-only syndrome are growing in recent years. Few cases have shown success in spermatogenesis with different modalities including hormonal stimulation. Here, we describe a 40-year-old male patient with azoospermia who was diagnosed by testicular biopsy to have Sertoli-cell only syndrome and who responded to a new technology encompassing autologous bone marrow-derived mesenchymal stem cell testicular transplant. This treatment led to the formation of round cells in the seminiferous tubules, representing the first stage in the process of spermatogenesis. These results open the door for future studies, including regenerative medicine techniques to cure the difficult cases of azoospermia and infertility.

Key words : Azoospermia, Infertility, Treatment

Introduction
Infertility in general affects 15% of couples who have unprotected sex. Causes are related to women in 50% of cases, to men in 25%, and to combined causes in 25%. Azoospermia can be obstructive and nonobstructive. In the nonobstructive type, all testicular functions including spermatogenesis are preserved so that the main issue is the obstruction between rete testis and ejaculatory ducts. Nonobstructive azoospermia usually affects around 1% of people. Nonobstructive azoospermia is classified to 3 types: (1) primary hypogonadism, which is related to the testis and can be genetic or acquired; (2) secondary hypogonadism, which related to hypothalamic or pituitary causes; and (3) idiopathic. Histopathological classification includes 3 types: (1) hypospermatogenesis, (2) maturation arrest, and (3) Sertoli cell only syndrome (SCOS).^1-5 Five main germ cell clusters are in human testis, from spermatogonial to spermatozoa; supporting cells are Sertoli cells and Leydig cells. In SCOS, no germ cells are present, so only the supportive cells (Sertoli cells) are available. Fibrosis is not a part of the histopathologic pattern. Sertoli cell-only syndrome affects around one-third to one-half of cases of azoospermia. Patients with SCOS can have normal male sex features, although others can have reduced testicular volumes and high gonadotropic hormones.⁶ Sertoli cell-only syndrome represents the severest form of histological phenotype of male infertility. Sertoli cell-only syndrome is a difficult to treat azoospermic classification as the only cells available in the seminiferous tubules are Sertoli supportive cells with total absence of spermatogenesis. Few cases can be treated through sperm retrieval; however, such treatment can only be done with testicular sperm extraction and can succeed if there is a focus of spermatogenesis. Only 2 published studies have shown success in treatment of SCOS resulting in pregnancy and live birth.^7,8

Case Report
Here, we describe a 40-year-old male patient with azoospermia. The patient had defective secondary sexual characters with small testes and high gonadotrophic hormones (follicular stimulating hormone, luteinizing hormone). The patient was diagnosed by testicular biopsy to have SCOS. We treated the patient with a new technology encompassing autologous bone marrow-derived mesenchymal stem cell testicular transplant. The procedure included bone marrow aspiration under general anesthesia of 50 mL, which was centrifuged twice (4000g for 4 min) in 2 special tubes to concentrate bone marrow cells (Figure 1). This procedure was followed by aspiration of buffy coat of 2 mL that was injected in volume of 1-mL per testis under ultrasonography guidance (Figure 2). The patient was followed clinically through gonadotrophin levels and monthly testicular Doppler. In 3 months, gonadotrophic hormones had reduced after the procedure and new testicular biopsy showed the formation of round cells in the seminiferous tubules (Figure 3). This success represented the first stage in the process of spermatogenesis.

Discussion
The success in treatment of SCOS lies in the use of human recombinant gonadotrophins like follicular stimulating hormone. However, microsurgical testicular sperm extraction has shown better success than classic testicular sperm extraction with higher success in multiple biopsies in cases of SCOS.^9,10 Despite the use of recombinant human gonadotrophic hormones to stimulate spermatogenesis, success in treatment of SCOS has been rarely reported with cellular therapy and regenerative medicine techniques. Experimental co-culture of adipose-derived mesenchymal stem cells in retinoic acid and testosterone culture media with Sertoli cells has shown success in vitro.^11,12 The regenerative medicine technique includes the use of platelet-rich plasma, exosomes, mesenchymal stem cells, and other new methodologies. Here, our use of autologous bone marrow-derived mesenchymal stem cell progenitors injected locally to both testes in a patient with SCOS resulted in the reduction of gonadotrophic hormone levels and round cell formation, showing the possibility of regenerative medicine techniques in solving this major infertility issue. This success opens the door for future studies on regenerative medicine techniques to cure the difficult cases of azoospermia and infertility.