Araştırma Makalesi
BibTex RIS Kaynak Göster

Nedeni Açıklanamayan İnfertilite Olgularında Sperm DNA Bütünlüğünün Fertilizasyon Başarısı ve Erken Embriyoner Gelişime Etkisi

Yıl 2020, Cilt: 46 Sayı: 1, 77 - 84, 01.04.2020
https://doi.org/10.32708/uutfd.690101

Öz

İnfertilite olgularının yaklaşık %15’inde infertilite sebebi olabilecek bir patoloji saptanmayıp, açıklanamayan sebeplerle konvansiyonel gebelik gerçekleşmemektedir. Araştırmalar, sperm DNA hasarının üremeye yardımcı tekniklerin (ÜYT) sonucunu olumsuz etkilediğini ortaya koymuştur. Çekirdek bütünlüğü korunmuş olan spermleri seçmeye yönelik non-invaziv yöntemler geliştirilmekle birlikte, bu yöntemlerin açıklanamayan infertilite olgularında ÜYT başarısı üzerindeki etkisi henüz tartışmalıdır. Bu çalışmada DNA hasarlı spermlerin dansite gradient santrifüjü (DG) yöntemi ile tek başına ve non-invaziv manyetik aktivasyonla hücre ayırma (MACS) yöntemiyle birlikte eliminasyonu sonrası kullanılan spermlerin fertilizasyon ve erken embriyoner gelişime etkisi karşılaştırılarak uygun semen hazırlama yönteminin saptanması hedeflenmiştir. Açıklanamayan infertilite tanısıyla ÜYT programına alınan çiftlerde, DG yönteminin tek başına ve MACS yöntemiyle birlikte kullanımının, kaliteli sperm elde etmedeki başarısı, her iki yıkama metoduyla elde edilmiş spermlerde TUNEL yöntemi ile DNA bütünlüğü açısından ve Hematoksilen Eosin boyamasıyla morfolojik açıdan değerlendirildi. Klinik parametrelere etkisini değerlendirmek amacıyla, her iki yıkama yöntemiyle elde edilen spermlerin ICSI sonrası fertilizasyon ve embriyo gelişimsel potansiyeline bakıldı. MACS+DG yöntemiyle yıkanan sperm örneklerinde sperm DNA fragmantasyon oranının ve vakuol (+) sperm oranının DG yöntemiyle elde edilen spermlere kıyasla istatistiksel olarak anlamlı düzeyde azaldığı görüldü. DG veya MACS+DG ile yıkanan spermlerle mikroenjeksiyonu gerçekleştirilen oositler arasında fertilizasyon ve embriyo gelişimsel potansiyelinde bir farklılık oluşmaması intrasitoplazmik sperm enjeksiyonu uygulamalarında spermin doğal seçiliminin söz konusu olmamasının bir sonucu olduğu düşünülerek, MACS tekniğinin ICSI protokollerinde gerekli olmadığı, spermin doğal seçiliminin gerçekleştiği intrauterin inseminasyon (IUI) ve IVF uygulamalarında daha etkin olacağı sonucuna varıldı.

Destekleyen Kurum

Bursa Uludağ Üniversitesi

Kaynakça

  • Referans1. Nallella KP, Sharma RK, Aziz N et al Significance of sperm characteristics in the evaluation of male infertility. Fertil Steril 2006;85:629-634.
  • Referans2. Zinaman MJ, Brown CC, Selevan SG et al Semen quality and human fertility: a prospective study with healthy couples. J Androl 2000;21:145-153.
  • Referans3. Cinthia M Feijio, Sandro C Diagnostic accuracy of sperm chromatin dispersion test to evaluate sperm deoxyribonucleic acid damage in men with unexplained infertility. ANDROFERT, Andrology and Human Reproduction Clinic, Referral Center for Male Reproduction, Campinas, S~ao Paulo, Brazil DOI: 10.1016/j.fertnstert. 2013.09.002.
  • Referans4. Nuñez-Calonge R, Caballero P, López-Fernández C et al An improved experimental model for understanding the impact of sperm DNA fragmentation on human pregnancy following ICSI. Reprod Sci 2012;19:1163-1168.
  • Referans5. Aitken RJ & Koppers AJ.Apoptosis and DNA damage in human spermatozoa. Asian J Androl 2011;13:36-42.
  • Referans6. Chohan KR, Griffin JT, Lafromboise M et al Comparison of chromatin assays for DNA fragmentation evaluation in human sperm. J Androl 2006;27:53-59.
  • Referans7. Delbes G, Hales BF, Robaire B.Toxicants and human sperm chromatin integrity. Mol Hum Reprod 2010;16:14–22.
  • Referans8. Henkel R.Sperm preparation: state-of-the-art--physiological aspects and application of advanced sperm preparation methods. Asian J Androl 2012;14(2):260-269.
  • Referans9. Almeida C, Sousa M, Barros A. (2009) Phosphatidylserine translocation in human spermatozoa from impaired spermatogenesis. Reprod Biomed Online 2009;19(6): 770–777.
  • Referans10. Grunewald S, Paasch U.Sperm selection for ICSI using annexin V. Methods Mol Biol 2013;927:257-262.
  • Referans11. Kasai T, Ogawa K, Mizuno K et al.Relationship between sperm mitochondrial membrane potential, sperm motility, and fertility potential. Asian J Androl 2002;4: 97-103.
  • Referans12. Taylor SL, Weng SL, Fox P et al Somatic cell apoptosis markers and pathways in human ejaculated sperm: potential utility as indicators of sperm quality. Mol Hum Reprod 2004;10:825-834.
  • Referans13. Weng SL, Taylor SL, Morshedi M.Caspase activity and apoptotic markers in ejaculated human sperm. Mol Hum Reprod 2002;8:984-991.
  • Referans14. Glander HJ, Schiller J, Suss R et alDeterioration of spermatozoal plasma membrane is associated with an increase of sperm lyso-phosphatidylcholines. Andrologia 2002;34: 360-366.
  • Referans15. Grunewald S, Paasch U, Glander HJ.Enrichment of non-apoptotic human spermatozoa after cryopreservation by immunomagnetic cell sorting. Cell Tissue Bank 2001;2:127-133.
  • Referans16. Lukaszuk K, Wcislo M, Liss J et alFirst Pregnancy, Somatic and Psychological Status of a 4-Year-Old Child Born following Annexin V TESA Sperm Separation. AJP Rep 2015;5:105-108.
  • Referans17. Simopoulou M, Gkoles L, Bakas P et al Improving ICSI: A review from the spermatozoon perspective. Syst Biol Reprod Med 2016; 20:1-13.
  • Referans18. Rienzi L, Ubaldi F, Iacobelli M, et al. Day 3 embryo transfer with combined evaluation at the pronuclear and cleavage stages compares favourably with day 5 blastocyst transfer. Hum Reprod. 2002;17(7):1852-1855.
  • Referans19. Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999;11(3):307-311.
  • Referans20. Beshay VE & Bukulmez O.Sperm DNA damage: how relevant is it clinically? Curr Opin Obstet Gynecol 2012;24:172-179.
  • Referans21. Shamsi MB, Imam SN & Dada R.Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility. J Assist Reprod Genet2011; 28:1073-1085.
  • Referans22. Cissen M, Wely MV, Scholten I et alMeasuring Sperm DNA Fragmentation and Clinical Outcomes of Medically Assisted Reproduction: A Systematic Review and Meta-Analysis. PLoS One. 2016.11: e 0165125.
  • Referans23. Aziz N, Agarwal A.Evaluation of sperm damage: beyond the World Health Organization criteria. Fertil Steril 90:484-485;2008.
  • Referans24. Duran HE, Morshedi M, Kruger T et alIntrauterine insemination: a systematic review on determinants of success. Hum Reprod Update 2002;8:373-384
  • Referans25. Oleszczuk K, Augustinsson L, Bayat N Prevalence of high DNA fragmentation index in male partners of unexplained infertile couples. Andrology 2012;1(3):357-360
  • Referans26. Thomson LK, Zieschang JA, Clark AMOxidative deoxyribonucleic acid damage in sperm has a negative impact on clinical pregnancy rate in intrauterine insemination but not intracytoplasmic sperm injection cycles. Fertil Steril. 2011;96:843-847.
  • Referans27. Vandekerckhove FW, De Croo I, Gerris J.Sperm Chromatin Dispersion Test before Sperm Preparation Is Predictive of Clinical Pregnancy in Cases of Unexplained Infertility Treated with Intrauterine Insemination and Induction with Clomiphene Citrate. Front Med (Lausanne) 2016;23:3-63
  • Referans28. Fácio CL, Previato LF, Machado-Paula LA et alComparison of two sperm processing techniques for low complexity assisted fertilization: sperm washing followed by swim-up and discontinuous density gradient centrifugation. JBRA Assist Reprod 2016;20:206-211
  • Referans29. Ricci G, Perticarari S, Boscolo RSemen preparation methods and sperm apoptosis: swim-up versus gradient-density centrifugation technique. Fertil Steril 2009;91(2):632-638.
  • Referans30. Karamahmutoğlu H, Erdem A, Erdem M et alThe gradient technique improves success rates in intrauterine insemination cycles of unexplained subfertile couples when compared to swim up technique; a prospective randomized study. J Assist Reprod Genet 2014;31:1139-1145.
  • Referans31. Khalid S & Qureshi I Pregnancy rate improves in couples with unexplaines infertility following intrauterine insemination (IUI) with magnetically selected non-apoptotic sperms. Fertil Steril 2011;96:S25.
  • Referans32. Romany L, Meseguer M, Garcia-Herrero S et alMagentic activated sorting selection (MACS) of nonapoptotic sperm (NAS) improves pregnancy rates in homologous intrauterine insemination (IUI). Fertil Steril 2010;94:S14. https://doi.org/10.1016/j.fertnstert.2017.07.391.
  • Referans33. Alvarez Sedo C, Uriondo H, Lavolpe M et alClinical outcome using non-apoptotic sperm selection for ICSI procedures: report of 1 year experience. Fertil Steril 2010; s: 232. DOI:10.1016/j.fertnstert.2010.07.902.
  • Referans34. Dirican EK, Ozgun OD, Akarsu S et alClinical outcome of magnetic activated cell sorting of non-apoptotic spermatozoa before density gradient centrifugation for assisted reproduction. J Assist Reprod Genet 2008;25: 375-381.
  • Referans35. Gil M, Sar-Shalom V, Melendez Sivira Y et alSperm selection using magnetic activated cell sorting (MACS) in assisted reproduction: a systematic review and meta-analysis. J Assist Reprod Genet 2013;30:479-485.
  • Referans36. Troya J & Zorrilla I.Annexin V-MACS in infertile couples as method for separation of sperm without DNA fragmentation. JBRA Assist Reprod 2015;19:66-69.
  • Referans37. Van Thillo G, Guidobono M, Young E et alBiological safety and live births after selection of non-apoptotic spermatozoa during ICSI. Fertil Steril 2011;96:160-161.
  • Referans38. Nadalini M, Tarozzi N, Di Santo M & Borini AAnnexin V magnetic activated cell sorting versus swim-up for the selection of human sperm in ART: is the new approach better then the traditional one? J Assist Reprod Genet 2014;31:1045-1051.
  • Referans39. Khalid S & Qureshi IEffect of magnetic selected sperm on fertilization and embryo development: an animal model study. Fertil Steril 2011;96:S169.
  • Referans40. Rawe VY, Boudri HU, Alvarez Sedo C et alHealthy baby born after reduction of sperm DNA fragmentation using cell sorting before ICSI. Reprod Biomed Online 2010;20:320-323.
  • Referans41. Berteli TS, Da Broi MG, Martins WP et alMagnetic-activated cell sorting before density gradient centrifugation improves recovery of high-quality spermatozoa. Andrology 2017; 5:776-782.
  • Referans42. Bucar S, Gonçalves A, Rocha E et alSá R. DNA fragmentation in human sperm after magnetic-activated cell sorting. J Assist Reprod Genet 2015;1:147-154.
  • Referans43. Tavalaee M, Deemeh MR, Arbabian M & Nasr-Esfahani MHDensity gradient centrifugation before or after magnetic-activated cell sorting: which technique is more useful for clinical sperm selection? J Assist Reprod Genet 2012;29:31-38.
  • Referans44. Hammoud I, Boitrelle F, Ferfouri F, et alSelection of normal spermatozoa with a vacuole-free head (x6300) improves selection of spermatozoa with intact DNA in patients with high sperm DNA fragmentation rates. Andrologia. 2013;45(3):163-170.
  • Referans45. Pastuszek E, Kiewisz J, Skowronska P et alAn investigation of the potential effect of sperm nuclear vacuoles in human spermatozoa on DNA fragmentation using a neutral and alkaline Comet assay. Andrology 2017;5:392-8
  • Referans46. Lavolpe M, Lorenzi D, Greco E, Nodar F, Alvarez Sedó C.Relationship Between Sperm DNA Fragmentation and Nuclear Vacuoles. JBRA Assist Reprod 2015;19(2):70-74.
  • Referans47. Kruger TF, Menkveld R, Stander FS, et alSperm morphologic features as a prognostic factor in in vitro fertilization. Fertil Steril. 1986;46(6):1118-1123.
  • Referans48. Hornstein MDState of the ART: Assisted Reproductive Technologies in the United States. Reprod Sci. 2016;23:1630-1633.

Effect of Sperm DNA Integrity on Fertilization Success and Early Embriyonic Development in Unexplained Infertility Cases

Yıl 2020, Cilt: 46 Sayı: 1, 77 - 84, 01.04.2020
https://doi.org/10.32708/uutfd.690101

Öz

In almost 15% of infertility cases infertility related pathology cannot defined, and conventional pregnancy is prevented by unexplained factors. Investigations evidenced that sperm DNA damage adversely affects the outcome of assisted reproduction techniques (ART). Recently, non-invasive methods have been developed to select nucleus integrity protectedsperm cells. However; the effects of these methods on unexplained infertility cases remain controversial. In this study the usage of density gradient centrifugation (DG) alone and together with magnetic activating cell sorting (MACS) for sperm separation were compared and the effect of selected spermson embryonic development were investigated. In couples withunexplained infertility after DG and DG+MACS, sperm morphology and DNA quality were analyzed using TUNEL and Hematoxylin Eosin staining methods, respectively. Obtained sperms were followed up by ICSI to observe their potential for fertilization and embryo development. According to our findings, sperm DNA fragmentation and vacuole positivity were significantly lower in MACS + DG treated group as compare to DG treated group. There was no significant difference in fertilization and embryo development potential between oocytes microinjected with sperm washed with DG or MACS+DG which might be due to lack of natural sperm selection in intracytoplasmic sperm injection. Therefore, our data suggest that; MACS may be more effectively used for natural based sperm selection techniques, including; IUI and IVF, instead of ICSI.

Kaynakça

  • Referans1. Nallella KP, Sharma RK, Aziz N et al Significance of sperm characteristics in the evaluation of male infertility. Fertil Steril 2006;85:629-634.
  • Referans2. Zinaman MJ, Brown CC, Selevan SG et al Semen quality and human fertility: a prospective study with healthy couples. J Androl 2000;21:145-153.
  • Referans3. Cinthia M Feijio, Sandro C Diagnostic accuracy of sperm chromatin dispersion test to evaluate sperm deoxyribonucleic acid damage in men with unexplained infertility. ANDROFERT, Andrology and Human Reproduction Clinic, Referral Center for Male Reproduction, Campinas, S~ao Paulo, Brazil DOI: 10.1016/j.fertnstert. 2013.09.002.
  • Referans4. Nuñez-Calonge R, Caballero P, López-Fernández C et al An improved experimental model for understanding the impact of sperm DNA fragmentation on human pregnancy following ICSI. Reprod Sci 2012;19:1163-1168.
  • Referans5. Aitken RJ & Koppers AJ.Apoptosis and DNA damage in human spermatozoa. Asian J Androl 2011;13:36-42.
  • Referans6. Chohan KR, Griffin JT, Lafromboise M et al Comparison of chromatin assays for DNA fragmentation evaluation in human sperm. J Androl 2006;27:53-59.
  • Referans7. Delbes G, Hales BF, Robaire B.Toxicants and human sperm chromatin integrity. Mol Hum Reprod 2010;16:14–22.
  • Referans8. Henkel R.Sperm preparation: state-of-the-art--physiological aspects and application of advanced sperm preparation methods. Asian J Androl 2012;14(2):260-269.
  • Referans9. Almeida C, Sousa M, Barros A. (2009) Phosphatidylserine translocation in human spermatozoa from impaired spermatogenesis. Reprod Biomed Online 2009;19(6): 770–777.
  • Referans10. Grunewald S, Paasch U.Sperm selection for ICSI using annexin V. Methods Mol Biol 2013;927:257-262.
  • Referans11. Kasai T, Ogawa K, Mizuno K et al.Relationship between sperm mitochondrial membrane potential, sperm motility, and fertility potential. Asian J Androl 2002;4: 97-103.
  • Referans12. Taylor SL, Weng SL, Fox P et al Somatic cell apoptosis markers and pathways in human ejaculated sperm: potential utility as indicators of sperm quality. Mol Hum Reprod 2004;10:825-834.
  • Referans13. Weng SL, Taylor SL, Morshedi M.Caspase activity and apoptotic markers in ejaculated human sperm. Mol Hum Reprod 2002;8:984-991.
  • Referans14. Glander HJ, Schiller J, Suss R et alDeterioration of spermatozoal plasma membrane is associated with an increase of sperm lyso-phosphatidylcholines. Andrologia 2002;34: 360-366.
  • Referans15. Grunewald S, Paasch U, Glander HJ.Enrichment of non-apoptotic human spermatozoa after cryopreservation by immunomagnetic cell sorting. Cell Tissue Bank 2001;2:127-133.
  • Referans16. Lukaszuk K, Wcislo M, Liss J et alFirst Pregnancy, Somatic and Psychological Status of a 4-Year-Old Child Born following Annexin V TESA Sperm Separation. AJP Rep 2015;5:105-108.
  • Referans17. Simopoulou M, Gkoles L, Bakas P et al Improving ICSI: A review from the spermatozoon perspective. Syst Biol Reprod Med 2016; 20:1-13.
  • Referans18. Rienzi L, Ubaldi F, Iacobelli M, et al. Day 3 embryo transfer with combined evaluation at the pronuclear and cleavage stages compares favourably with day 5 blastocyst transfer. Hum Reprod. 2002;17(7):1852-1855.
  • Referans19. Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999;11(3):307-311.
  • Referans20. Beshay VE & Bukulmez O.Sperm DNA damage: how relevant is it clinically? Curr Opin Obstet Gynecol 2012;24:172-179.
  • Referans21. Shamsi MB, Imam SN & Dada R.Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility. J Assist Reprod Genet2011; 28:1073-1085.
  • Referans22. Cissen M, Wely MV, Scholten I et alMeasuring Sperm DNA Fragmentation and Clinical Outcomes of Medically Assisted Reproduction: A Systematic Review and Meta-Analysis. PLoS One. 2016.11: e 0165125.
  • Referans23. Aziz N, Agarwal A.Evaluation of sperm damage: beyond the World Health Organization criteria. Fertil Steril 90:484-485;2008.
  • Referans24. Duran HE, Morshedi M, Kruger T et alIntrauterine insemination: a systematic review on determinants of success. Hum Reprod Update 2002;8:373-384
  • Referans25. Oleszczuk K, Augustinsson L, Bayat N Prevalence of high DNA fragmentation index in male partners of unexplained infertile couples. Andrology 2012;1(3):357-360
  • Referans26. Thomson LK, Zieschang JA, Clark AMOxidative deoxyribonucleic acid damage in sperm has a negative impact on clinical pregnancy rate in intrauterine insemination but not intracytoplasmic sperm injection cycles. Fertil Steril. 2011;96:843-847.
  • Referans27. Vandekerckhove FW, De Croo I, Gerris J.Sperm Chromatin Dispersion Test before Sperm Preparation Is Predictive of Clinical Pregnancy in Cases of Unexplained Infertility Treated with Intrauterine Insemination and Induction with Clomiphene Citrate. Front Med (Lausanne) 2016;23:3-63
  • Referans28. Fácio CL, Previato LF, Machado-Paula LA et alComparison of two sperm processing techniques for low complexity assisted fertilization: sperm washing followed by swim-up and discontinuous density gradient centrifugation. JBRA Assist Reprod 2016;20:206-211
  • Referans29. Ricci G, Perticarari S, Boscolo RSemen preparation methods and sperm apoptosis: swim-up versus gradient-density centrifugation technique. Fertil Steril 2009;91(2):632-638.
  • Referans30. Karamahmutoğlu H, Erdem A, Erdem M et alThe gradient technique improves success rates in intrauterine insemination cycles of unexplained subfertile couples when compared to swim up technique; a prospective randomized study. J Assist Reprod Genet 2014;31:1139-1145.
  • Referans31. Khalid S & Qureshi I Pregnancy rate improves in couples with unexplaines infertility following intrauterine insemination (IUI) with magnetically selected non-apoptotic sperms. Fertil Steril 2011;96:S25.
  • Referans32. Romany L, Meseguer M, Garcia-Herrero S et alMagentic activated sorting selection (MACS) of nonapoptotic sperm (NAS) improves pregnancy rates in homologous intrauterine insemination (IUI). Fertil Steril 2010;94:S14. https://doi.org/10.1016/j.fertnstert.2017.07.391.
  • Referans33. Alvarez Sedo C, Uriondo H, Lavolpe M et alClinical outcome using non-apoptotic sperm selection for ICSI procedures: report of 1 year experience. Fertil Steril 2010; s: 232. DOI:10.1016/j.fertnstert.2010.07.902.
  • Referans34. Dirican EK, Ozgun OD, Akarsu S et alClinical outcome of magnetic activated cell sorting of non-apoptotic spermatozoa before density gradient centrifugation for assisted reproduction. J Assist Reprod Genet 2008;25: 375-381.
  • Referans35. Gil M, Sar-Shalom V, Melendez Sivira Y et alSperm selection using magnetic activated cell sorting (MACS) in assisted reproduction: a systematic review and meta-analysis. J Assist Reprod Genet 2013;30:479-485.
  • Referans36. Troya J & Zorrilla I.Annexin V-MACS in infertile couples as method for separation of sperm without DNA fragmentation. JBRA Assist Reprod 2015;19:66-69.
  • Referans37. Van Thillo G, Guidobono M, Young E et alBiological safety and live births after selection of non-apoptotic spermatozoa during ICSI. Fertil Steril 2011;96:160-161.
  • Referans38. Nadalini M, Tarozzi N, Di Santo M & Borini AAnnexin V magnetic activated cell sorting versus swim-up for the selection of human sperm in ART: is the new approach better then the traditional one? J Assist Reprod Genet 2014;31:1045-1051.
  • Referans39. Khalid S & Qureshi IEffect of magnetic selected sperm on fertilization and embryo development: an animal model study. Fertil Steril 2011;96:S169.
  • Referans40. Rawe VY, Boudri HU, Alvarez Sedo C et alHealthy baby born after reduction of sperm DNA fragmentation using cell sorting before ICSI. Reprod Biomed Online 2010;20:320-323.
  • Referans41. Berteli TS, Da Broi MG, Martins WP et alMagnetic-activated cell sorting before density gradient centrifugation improves recovery of high-quality spermatozoa. Andrology 2017; 5:776-782.
  • Referans42. Bucar S, Gonçalves A, Rocha E et alSá R. DNA fragmentation in human sperm after magnetic-activated cell sorting. J Assist Reprod Genet 2015;1:147-154.
  • Referans43. Tavalaee M, Deemeh MR, Arbabian M & Nasr-Esfahani MHDensity gradient centrifugation before or after magnetic-activated cell sorting: which technique is more useful for clinical sperm selection? J Assist Reprod Genet 2012;29:31-38.
  • Referans44. Hammoud I, Boitrelle F, Ferfouri F, et alSelection of normal spermatozoa with a vacuole-free head (x6300) improves selection of spermatozoa with intact DNA in patients with high sperm DNA fragmentation rates. Andrologia. 2013;45(3):163-170.
  • Referans45. Pastuszek E, Kiewisz J, Skowronska P et alAn investigation of the potential effect of sperm nuclear vacuoles in human spermatozoa on DNA fragmentation using a neutral and alkaline Comet assay. Andrology 2017;5:392-8
  • Referans46. Lavolpe M, Lorenzi D, Greco E, Nodar F, Alvarez Sedó C.Relationship Between Sperm DNA Fragmentation and Nuclear Vacuoles. JBRA Assist Reprod 2015;19(2):70-74.
  • Referans47. Kruger TF, Menkveld R, Stander FS, et alSperm morphologic features as a prognostic factor in in vitro fertilization. Fertil Steril. 1986;46(6):1118-1123.
  • Referans48. Hornstein MDState of the ART: Assisted Reproductive Technologies in the United States. Reprod Sci. 2016;23:1630-1633.
Toplam 48 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Üroloji
Bölüm Özgün Araştırma Makaleleri
Yazarlar

Elçin Tezcan 0000-0003-4340-3566

Işıl Kasapoğlu 0000-0002-1953-2475

Gürkan Uncu 0000-0001-7660-8344

Berrin Avcı 0000-0001-8135-5468

Yayımlanma Tarihi 1 Nisan 2020
Kabul Tarihi 14 Nisan 2020
Yayımlandığı Sayı Yıl 2020 Cilt: 46 Sayı: 1

Kaynak Göster

APA Tezcan, E., Kasapoğlu, I., Uncu, G., Avcı, B. (2020). Nedeni Açıklanamayan İnfertilite Olgularında Sperm DNA Bütünlüğünün Fertilizasyon Başarısı ve Erken Embriyoner Gelişime Etkisi. Uludağ Üniversitesi Tıp Fakültesi Dergisi, 46(1), 77-84. https://doi.org/10.32708/uutfd.690101
AMA Tezcan E, Kasapoğlu I, Uncu G, Avcı B. Nedeni Açıklanamayan İnfertilite Olgularında Sperm DNA Bütünlüğünün Fertilizasyon Başarısı ve Erken Embriyoner Gelişime Etkisi. Uludağ Tıp Derg. Nisan 2020;46(1):77-84. doi:10.32708/uutfd.690101
Chicago Tezcan, Elçin, Işıl Kasapoğlu, Gürkan Uncu, ve Berrin Avcı. “Nedeni Açıklanamayan İnfertilite Olgularında Sperm DNA Bütünlüğünün Fertilizasyon Başarısı Ve Erken Embriyoner Gelişime Etkisi”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 46, sy. 1 (Nisan 2020): 77-84. https://doi.org/10.32708/uutfd.690101.
EndNote Tezcan E, Kasapoğlu I, Uncu G, Avcı B (01 Nisan 2020) Nedeni Açıklanamayan İnfertilite Olgularında Sperm DNA Bütünlüğünün Fertilizasyon Başarısı ve Erken Embriyoner Gelişime Etkisi. Uludağ Üniversitesi Tıp Fakültesi Dergisi 46 1 77–84.
IEEE E. Tezcan, I. Kasapoğlu, G. Uncu, ve B. Avcı, “Nedeni Açıklanamayan İnfertilite Olgularında Sperm DNA Bütünlüğünün Fertilizasyon Başarısı ve Erken Embriyoner Gelişime Etkisi”, Uludağ Tıp Derg, c. 46, sy. 1, ss. 77–84, 2020, doi: 10.32708/uutfd.690101.
ISNAD Tezcan, Elçin vd. “Nedeni Açıklanamayan İnfertilite Olgularında Sperm DNA Bütünlüğünün Fertilizasyon Başarısı Ve Erken Embriyoner Gelişime Etkisi”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 46/1 (Nisan 2020), 77-84. https://doi.org/10.32708/uutfd.690101.
JAMA Tezcan E, Kasapoğlu I, Uncu G, Avcı B. Nedeni Açıklanamayan İnfertilite Olgularında Sperm DNA Bütünlüğünün Fertilizasyon Başarısı ve Erken Embriyoner Gelişime Etkisi. Uludağ Tıp Derg. 2020;46:77–84.
MLA Tezcan, Elçin vd. “Nedeni Açıklanamayan İnfertilite Olgularında Sperm DNA Bütünlüğünün Fertilizasyon Başarısı Ve Erken Embriyoner Gelişime Etkisi”. Uludağ Üniversitesi Tıp Fakültesi Dergisi, c. 46, sy. 1, 2020, ss. 77-84, doi:10.32708/uutfd.690101.
Vancouver Tezcan E, Kasapoğlu I, Uncu G, Avcı B. Nedeni Açıklanamayan İnfertilite Olgularında Sperm DNA Bütünlüğünün Fertilizasyon Başarısı ve Erken Embriyoner Gelişime Etkisi. Uludağ Tıp Derg. 2020;46(1):77-84.

ISSN: 1300-414X, e-ISSN: 2645-9027

Uludağ Üniversitesi Tıp Fakültesi Dergisi "Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License" ile lisanslanmaktadır.


Creative Commons License
Journal of Uludag University Medical Faculty is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

2023