Nonobstrüktif Azospermi Olgularında Yeni Yaklaşımlar

Year 2019, Volume: 26 Issue: 1, 111 - 116, 04.03.2019

Murat Serkant Ünal Mehmet Caner Özer

https://doi.org/10.17343/sdutfd.395476

Abstract

Azospermi semende hiç sperm bulunamaması durumudur.
Obstrüktif ve nonobstrüktif olmak üzere iki kategoriye ayrılır. Azospermi
tanısı alan hastalardan elde edilen spermatozoayla, ilk gebelik ICSI işlemiyle
1993 yılında oluşmuştur. Obstrüktif azospermi olgularında sperm bulma şansı
daha yüksek olmasına karşın, erkek infertilitesinin en şiddetli formu olan
nonobstrüktif azospermide ise bu oran yaklaşık olarak %40-50 aralığındadır.
Yapılan mikro TESE işlemiyle testiste immatür germ hücreleri bulunursa ROSI
işlemi yapılır ya da in vitro kültürlerle bu hücreler farklılaştırılmaya çalışılır.
Matür germ hücresi bulunamayan bir mikroTESE sonrasında, hormon replasmanı veya
ilaç tedavileriyle spermatozoaların elde edilmesi hedeflenir.

Son yıllara kadar testislerde varlıkları bilinen
spermatogoniumlara (sperm kök hücresi) ek olarak,  yeni keşfedilen VSEL (very small
embriyonic-like stem cell) kök hücrelerinin gösterilmesi tedavi yönündeki
umutları daha da artırmıştır. Bunlardan başka deneysel olarak, hücre
kültürleri, seminifer tübül kültürleri, organ kültürleri, testiküler
organoidler, gen tedavileri ve kök hücre bazlı tedavilerin etkinliği
gösterilmiştir. İnsan üzerinde başlayan gen terapilerinde ve mezenkimal kök
hücre çalışmalarında, önemli ilerlemeler olması nedeniyle yakın bir zamanda
azospermi tedavisinde de önemli gelişmeler olacağı düşünülmektedir.

 Anahtar kelimeler:  immatür germ hücreleri, maturasyon arresti,
ROSI, fertilizasyon, in vitro kültür.

                    New Approaches in
Nonobstructive Azoopermia Cases

Abstract

Azoospermia is the complete absence of any
sperm in semen.
Azoospermia is
classified as obstructive azoospermia or non-obstructive azoospermia. The first pregnancy occured in 1993
with ICSI operation with spermatozoa obtained from azoospermic patients. While
the chance of successful retrieval of sperm in men with obstructive azoospermia
is high, the sperm retrieval rate in men with non-obstructive azoospermia is
approximately 40-50%. If immature germ cells are found in testis with
microTESE, ROSI treatment is performed or these cells are differentiated by in
vitro cultures. Mature germ cells can not be found after microTESE, obtaining
spermatozoa by hormone replacement or drug therapy is targeted.

In
addition to spermatogoniums, a population of very small embryonic-like stem
cells (VSELs) was identified in testes recently. The demonstration of VSELs  has further increased treatment prospects.
Other than these experientially, cell cultures, seminiferous tubule cultures,
organ cultures, testicular organoids, gene treatments and stem cell-based
treatments have been shown to be efficacious. In humans, gene therapy and
mesenchymal stem cell studies have made significant progress therefore it is
thought that there will be significant developments in the treatment of
azoospermia in the near future.

Keywords: immature germ cells, maturation arrest, ROSI, fertilization,
in vitro culture

Keywords

: immatür germ hücreleri, maturasyon arresti, ROSI, fertilizasyon

References

• 1)Potter SJ DeFalco, Role of the testis interstitial compartment in spermatogonial stem cell function.Reproduction 2017;153(4) 2)LeirSH,BrowneJA,EggenerSE,HarrisA.Characterization of primary cultures of adult human epididymis epithelial cells. Fertil Steril 2015;103(3):647-543)Ünal MS, Özer MC, Sönmez FH, Bayrak G, Demirbağ HO. Seminal sıvının fertilizasyondaki rolü. Androl Bul 2017; 19(3):1-64)Vloeberghs V, Verheyen G, Tournaye H. Intracytoplasmic spermatid injection and in vitro maturation: fact or fiction? Clinics (Sao Paulo) 2013;68 Suppl 1:151-6.5) Esteves SC. Clinical management of infertile men with nonobstructive azoospermia. Asian J Androl 2015;17(3):459-706)Ibtisham F, Wu J, Xiao M, An L, Banker Z, Nawab A. Progress and future prospect of in vitro spermatogenesis. Oncotarget 2017; 27;8(39):66709-66727. 7) Bakircioglu ME, Erden HF, Ciray HN, Bayazit N, Bahçeci M. Gonadotrophin therapy in combination with ICSI in men with hypogonadotrophic hypogonadism. Reprod Biomed Online 2007;15(2):156-60.8)Donker RB, Vloeberghs V, Groen H, Tournaye H, van Ravenswaaij-Arts CMA, Land JA. Chromosomal abnormalities in 1663 infertile men with azoospermia: the clinical consequences. Hum Reprod 2017;1;32(12):2574-25809)Ramasamy R, Bakırcıoğlu ME, Cengiz C, Karaca E, Scovell J, Jhangiani SN Whole-exome sequencing identifies novel homozygous mutation in NPAS2 in family with nonobstructive azoospermia. Fertil Steril 2015;104(2):286-9110)Pan Y, Zhang HG, Xi QI, Zhang H, Wang RX, Li LL. Molecular microdeletion analysis of infertile men with karyotypic Y chromosome abnormalities.J Int Med Res 2017; 0(0) 1–911)EAU Cep klavuzları, Erkek infertilitesi,Türk Üroloji Derneği,İstanbul: 2014;166-18812)Flannigan R, Bach PV, Schlegel PN. Microdissection testicular sperm extraction. Transl Androl Urol. 2017;6(4):745-75213)Hamada FN, Koshiyama A, Namekawa SH, Ishii S, Iwabata K, Sugawara H. Proliferating cell nuclear antigen (PCNA) interacts with a meiosis-specific RecA homologues, Lim15/Dmc1, but does not stimulate its strand transfer activity.Biochem Biophys Res Commun. 2007; 26;352(4):836-4214)Pansa A, Sirchia SM, Melis S, Giacchetta D, Castiglioni M, Colapietro P. ESX1 mRNA expression in seminal fluid is an indicator of residual spermatogenesis in non-obstructive azoospermic men.Hum Reprod. 2014;29(12):2620-7 15)Korbakis D, Schiza C, Brinc D, Soosaipillai A, Karakosta TD, Legare C. Preclinical evaluation of a TEX101 protein ELISA test for the differential diagnosis of male infertility. BMC Med; 2017 23;15(1):6016)Eelaminejad Z, Favaedi R, Modarresi T, Sabbaghian M, Sadighi Gilani MA, Shahhoseini M. Association between JMJD1A Expression and Sperm Retrieval in Non-Obstructive Azoospermic Patients. Cell J 2018;19(4):660-66517)Spahovic H, Göktolga Ü, Junuzovic D, Göktaş C, Rama A. Evaluation of Prognostic Factors and Determinants in Surgical Sperm Retrieval Procedures in Azoospermic Patients. Med Arch;2017;71(4):243-24518) Kim SY, Kim HJ, Lee BY, Park SY, Lee HS, Seo JT. Y Chromosome Microdeletions in Infertile Men with Non-obstructive Azoospermia and Severe Oligozoospermia,J Reprod Infertil 2017;18(3):307-315.19)Chu QJ, Hua R, Luo C, Chen QJ, Wu B, Quan S, Zhu YT. Relationship of genetic causes and inhibin B in non obstructive azoospermia spermatogenic failure. BMC Med Genet 2017; 6;18(1):9820) Althakafi SA, Mustafa OM, Seyam RM, Al-Hathal N, Kattan S. Serum testosterone levels and other determinants of sperm retrieval in microdissection testicular sperm extraction. Transl Androl Urol 2017;6(2):282-28721) Güneri Ç, Alkibay T, Tunç L. Effects of clinical, laboratuary and pathological features on successful sperm retrieval in non-obstructive azoospermia. Turk J Urol 2016;42(3):168-7722)Salehi P, Derakhshan-Horeh M, Nadeali Z, Hosseinzadeh M, Sadeghi E, Izadpanahi MH. Factors influencing sperm retrieval following testicular sperm extraction in nonobstructive azoospermia patients. Clin Exp Reprod Med 2017;44(1):22-27 23) Alfano M, Ventimiglia E, Locatelli I, Capogrosso P, Cazzaniga W, Pederzoli F. Anti-Mullerian Hormone-to-Testosterone Ratio is Predictive of Positive Sperm Retrieval in Men with Idiopathic Non-Obstructive Azoospermia. Sci Rep 2017; 15;7(1):1763824)ShiraishiK,MatsuyamaH.Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders. Endocr J 2017;27;64(2):123-131 25)Shiraishi K, Ohmi C, Shimabukuro T, Matsuyama H. Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Hum Reprod 2012;27(2):331-9. 26) Oka S, Shiraishi K, Matsuyama H. Effects of human chorionic gonadotropin on testicular interstitial tissues in men with non-obstructive azoospermia. Andrology 2017;5(2):232-23927)Garolla A, Selice R, Engl B, Bertoldo A, Menegazzo M, Finios L,Spermatid count as a predictor of response to FSH therapy.Reprod Biomed Online 2014;29(1):102-1228)Amer M, Abd Elnasser T, El Haggar S, Mostafa T, Abdel-Malak G, Zohdy W. May-Grünwald-Giemsa stain for detection of spermatogenic cells in the ejaculate: a simple predictive parameter for successful testicular sperm retrieval.Hum Reprod 2001;16(7):1427-3229)Bhartiya D, Shaikh A, Anand S, Patel H, Kapoor S, Sriraman K. Endogenous, very small embryonic-like stem cells: critical review, therapeutic potential and a look ahead. Hum Reprod Update 2016;23(1):41-76.30)WHO laboratuvar el Kitabı. Kadıoğlu A, Çev.ed, Beşinci basım , Türk üroloji derneği, Nobel tıp kitabevleri, İstanbul: 2011;1-271. 31)PatelH,BhartiyaD.Testicular Stem Cells Express FollicleStimulating Hormone Receptors and Are Directly Modulated by FSH. Reprod Sci 2016;23(11):1493-1508 32)Anand S,Bhartiya D, Sriraman K, Mallick A. Underlying Mechanisms that Restore Spermatogenesis on Transplanting Healthy Niche Cells in Busulphan Treated Mouse Testis. Stem Cell Rev 2016;12(6):682-69733)Anand S, Patel H, Bhartiya D Chemoablated mouse seminiferous tubular cells enriched for very small embryonic-like stem cells undergo spontaneous spermatogenesis in vitro. Reprod Biol Endocrinol 2015;18;13:33.34)Fazeli Z, Abedindo A, Omrani MD, Ghaderian SMH. Mesenchymal Stem Cells (MSCs) Therapy for Recovery of Fertility: a Systematic Review. Stem Cell Rev 2017 35)Kurkure P, Prasad M, Dhamankar V, Bakshi G. Very small embryonic-like stem cells (VSELs) detected in azoospermic testicular biopsies of adult survivors of childhood cancer. Reprod Biol Endocrinol 2015; 9;13:122.36)de Michele F, Vermeulen M, Wyns C. Fertility restoration with spermatogonial stem cells. Curr Opin Endocrinol Diabetes Obes 2017;24(6):424-43137)Reda A, Hou M, Landreh L, Kjartansdóttir KR, Svechnikov K, Söder O. In vitro Spermatogenesis - Optimal Culture Conditions for Testicular Cell Survival, Germ Cell Differentiation, and Steroidogenesis in Rats Front Endocrinol (Lausanne) 2014; 26;5:21.38)Chang YF, Lee-Chang JS, Panneerdoss S, MacLean JA 2nd, Rao MK. Isolation of Sertoli, Leydig, and spermatogenic cells from the mouse testis. Biotechniques 2011;51(5):341-2, 344 39) Lakpour MR, Aghajanpour S, Koruji M, Shahverdi A, Sadighi-Gilani MA, Sabbaghian M. Isolation, Culture and Characterization of Human Sertoli Cells by Flow Cytometry: Development of Procedure. Reprod Infertil 2017;18(2):213-21740)Heidargholizadeh S, Aydos SE, Yukselten Y, Ozkavukcu S, Sunguroglu A, Aydos K. A differential cytokine expression profile before and after rFSH treatment in Sertoli cell cultures of men with nonobstructive azoospermia. Andrologia 2017;49(4) 41)Alves-Lopes JP, Stukenborg JB. Testicular organoids: a new model to study the testicular microenvironment in vitro? Hum Reprod Update. 2017;1-1642)Baert Y, Rombaut C, Goossens E. Scaffold-Based and Scaffold-Free Testicular Organoids from Primary Human Testicular Cells. Methods Mol Biol. 2017;1-843) Alves-Lopes JP, Söder O, Stukenborg JB. Testicular organoid generation by a novel in vitro three-layer gradient system. Biomaterials. 2017;130:76-8944)Pendergraft SS, Sadri-Ardekani H, Atala A, Bishop CE. Three-dimensional testicular organoid: a novel tool for the study of human spermatogenesis and gonadotoxicity in vitro. Biol Reprod. 2017; 1;96(3):720-732. 45) Baert Y, De Kock J, Alves-Lopes JP, Söder O, Stukenborg JB, Goossens E. Primary Human Testicular Cells Self-Organize into Organoids with Testicular Properties. Stem Cell Reports. 2017; 10;8(1):30-3846)Tanaka A, Nagayoshi M, Takemoto Y, Tanaka I, Kusunoki H, Watanabe S, Fourteen babies born after round spermatid injection into human oocytes. Proc Natl Acad Sci U S A 2016; 17;113(20)