Андрология и генитальная хирургия. 2023; 24: 67-72
Значение фрагментации ДНК сперматозоидов при выборе метода лечения мужского бесплодия с применением внутриматочной инсеминации и вспомогательных репродуктивных технологий
Олефир Ю. В., Ефремов Е. А., Родионов М. А., Живулько А. Р., Попов Д. М., Монаков Д. М.
https://doi.org/10.17650/2070-9781-2023-24-4-67-72Аннотация
Введение. Фрагментация ДНК сперматозоидов является важным маркером мужской фертильности и может оказывать влияние на результаты лечения бесплодия с применением вспомогательных репродуктивных технологий. Многочисленные исследования посвящены оценке влияния этого показателя на репродуктивные исходы, однако степень этого влияния при различных методиках вспомогательных репродуктивных технологий остается предметом дискуссии.
Материалы и методы. Проведены поиск, анализ и систематизация публикаций, представленных в базах данных PubMed и eLIBRARY, с использованием ключевых слов: мужское бесплодие (male infertility), фрагментация ДНК сперматозоидов (sperm DNA fragmentation), внутриматочная инсеминация (intrauterine insemination), экстракорпоральное оплодотворение (in vitro fertilization), интрацитоплазматическая инъекция сперматозоида (intracytoplasmic sperm injection). Нами было отобрано 49 источников, которые включены в данный обзор литературы.
Результаты и обсуждение. Наличие высокого уровня фрагментации ДНК сперматозоидов сопряжено с низкой частотой наступления беременности естественным путем, а также успешного выполнения внутриматочной инсеминации и, по всей видимости, оказывает негативное влияние на репродуктивные исходы экстракорпорального оплодотворения и интрацитоплазматической инъекции сперматозоида (ИКСИ), но степень этого влияния на результаты ИКСИ менее выражена. Для преодоления бесплодия, вызванного высоким уровнем фрагментации ДНК сперматозоидов, при выполнении ИКСИ могут быть использованы тестикулярные сперматозоиды, однако данные о преимуществе такого подхода перед стандартным методом ИКСИ противоречивы.
Выводы. Высокий уровень фрагментации ДНК сперматозоидов ассоциирован с низкой частотой наступления беременности естественным путем и успеха при выполнении внутриматочной инсеминации и экстракорпорального оплодотворения. Необходимо проведение крупных хорошо организованных исследований для определения места ИКСИ с использованием тестикулярных сперматозоидов в лечении пациентов с высоким уровнем фрагментации ДНК сперматозоидов.
Список литературы
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7. Agarwal A., Majzoub A., Esteves S.C. et al. Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios. Transl Androl Urol 2016;5(6):935–50. DOI: 10.21037/tau.2016.10.03
8. Aitken R.J. Oxidative stress and the etiology of male infertility. J Assist Reprod Genet 2016;33(12):1691–2. DOI: 10.1007/s10815-016-0791-4
9. Aitken R.J. DNA damage in human spermatozoa; important contributor to mutagenesis in the offspring. Transl Androl Urol 2017;6(Suppl 4):S761–4. DOI: 10.21037/tau.2017.09.13
10. Bui A.D., Sharma R., Henkel R., Agarwal A. Reactive oxygen species impact on sperm DNA and its role in male infertility. Andrologia 2018;50(8):e13012. DOI: 10.1111/and.13012
11. Esteves S.C., Gosálvez J., López-Fernández C. et al. Diagnostic accuracy of sperm DNA degradation index (DDSi) as a potential noninvasive biomarker to identify men with varicocele-associated infertility. Int Urol Nephrol 2015;47(9):1471–7. DOI: 10.1007/s11255-015-1053-6
12. Rima D., Shiv B.K., Bhavna C. et al. Oxidative stress induced damage to paternal genome and impact of meditation and yoga – can it reduce incidence of childhood cancer? Asian Pac J Cancer Prev 2016;17(9):4517–25.
13. Коршунов М.Н., Коршунова Е.С., Даренков С.П. Клиническая эффективность использования тестикулярных сперматозоидов в программах репродуктивных технологий при высоком показателе ДНК-фрагментации. Урологические ведомости 2017;7(5):57–8.
14. González-Marín C., Gosálvez J., Roy R. Types, causes, detection and repair of DNA fragmentation in animal and human sperm cells. Int J Mol Sci 2012;13(11):14026–52. DOI: 10.3390/ijms131114026
15. Simon L., Brunborg G., Stevenson M. et al. Clinical significance of sperm DNA damage in assisted reproduction outcome. Hum Reprod 2010;25(7):1594–608. DOI: 10.1093/humrep/deq103
16. Simon L., Emery B.R., Carrell D.T. Review: diagnosis and impact of sperm DNA alterations in assisted reproduction. Best Pract Res Clin Obstet Gynaecol 2017;44:38–56. DOI: 10.1016/j.bpobgyn.2017.07.003
17. Simon L., Lutton D., McManus J., Lewis S.E. Sperm DNA damage measured by the alkaline Comet assay as an independent predictor of male infertility and in vitro fertilization success. Fertil Steril 2011;95(2):652–7. DOI: 10.1016/j.fertnstert.2010.08.019
18. Simon L., Murphy K., Shamsi M.B. et al. Paternal influence of sperm DNA integrity on early embryonic development. Hum Reprod 2014;29(11):2402–12. DOI: 10.1093/humrep/deu228
19. Simon L., Proutski I., Stevenson M. et al. Sperm DNA damage has a negative association with live-birth rates after IVF. Reprod BioMed Online 2013;26(1):68–78. DOI: 10.1016/j.rbmo.2012.09.019
20. Santi D., Spaggiari G., Simoni M. Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management – meta-analyses. Reprod Biomed Online 2018;37(3):315–26. DOI: 10.1016/j.rbmo.2018.06.023
21. Spanò M., Kolstad A.H., Larsen S.B. et al. The applicability of the flow cytometric sperm chromatin structure assay in epidemiological studies. Asclepios. Hum Reprod 1998;13(9):2495–505. DOI: 10.1093/humrep/13.9.2495
22. Evenson D.P., Jost L.K., Marshall D. et al. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod 1999;14(4):1039–49. DOI: 10.1093/humrep/14.4.1039
23. Evenson D.P., Wixon R.L. Environmental toxicants cause sperm DNA fragmentation as detected by the Sperm Chromatin Structure Assay (SCSA®). Toxicol Appl Pharmacol 2005;207(2 Suppl):532–7. DOI: 10.1016/j.taap.2005.03.021
24. Malić Vončina S., Golob B., Ihan A. et al. Sperm DNA fragmentation and mitochondrial membrane potential combined are better for predicting natural conception than standard sperm parameters. Fertil Steril 2016;105(3):637–44.e.1. DOI: 10.1016/j.fertnstert.2015.11.037
25. Vandekerckhove F.W., De Croo I., Gerris J. et al. 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;3:63. DOI: 10.3389/fmed.2016.00063
26. Bungum M., Humaidan P., Axmon A. et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod 2007;22(1):174–9. DOI: 10.1093/humrep/del326
27. Bungum M., Humaidan P., Spano M. et al. The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI. Hum Reprod 2004;19(6):1401–8. DOI: 10.1093/humrep/deh280
28. Duran E.H., Morshedi M., Taylor S., Oehninger S. Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study. Hum Reprod 2002;17(12):3122–8. DOI: 10.1093/humrep/17.12.3122
29. Rilcheva V.S., Ayvazova N.P., Ilieva L.O. et al. Sperm DNA integrity test and assisted reproductive technology (Art) outcome. J Biomed Clin Res 2016;9:21–9. DOI: 10.1515/jbcr-2016-0003
30. Chen Q., Zhao J.Y., Xue X., Zhu G.X. The association between sperm DNA fragmentation and reproductive outcomes following intrauterine insemination, a meta-analysis. Reprod Toxicol 2019;86:50–5. DOI: 10.1016/j.reprotox.2019.03.004
31. Sugihara A., Van Avermaete F., Roelant E. et al. The role of sperm DNA fragmentation testing in predicting intra-uterine insemination outcome: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2020;244:8–15. DOI: 10.1016/j.ejogrb.2019.10.005
32. Li Z., Wang L., Cai J., Huang H. Correlation of sperm DNA damage with IVF and ICSI outcomes: a systematic review and meta-analysis. J Assist Reprod Genet 2006;23(9–10):367–76. DOI: 10.1007/s10815-006-9066-9
33. Zhao J., Zhang Q., Wang Y., Li Y. Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Fertil Steril 2014;102(4):998–1005e.8. DOI: 10.1016/j.fertnstert.2014.06.033
34. Osman A., Alsomait H., Seshadri S. et al. The effect of sperm DNA fragmentation on live birth rate after IVF or ICSI: a systematic review and meta-analysis. Reprod Biomed Online 2015;30:120–7. DOI: 10.1016/j.rbmo.2014.10.018
35. Deng C., Li T., Xie Y. et al. Sperm DNA fragmentation index influences assisted reproductive technology outcome: a systematic review and meta-analysis combined with a retrospective cohort study. Andrologia 2019;51(6):e13263. DOI: 10.1111/and.13263
36. Lewis S.E.M. The place of sperm DNA fragmentation testing in current day fertility management. Middle East Fertil Soc J 2013;18(2):78–82. DOI: 10.1016/j.mefs.2013.01.010
37. Meseguer M., Santiso R., Garrido N. et al. Effect of sperm DNA fragmentation on pregnancy outcome depends on oocyte quality. Fertil Steril 2011;95(1):124–8. DOI: 10.1016/j.fertnstert.2010.05.055
38. Zini A., Jamal W., Cowan L., Al-Hathal N. Is sperm DNA damage associated with IVF embryo quality? A systematic review. J Assist Reprod Genet 2011;28(5):391–7. DOI: 10.1007/s10815-011-9544-6
39. Moskovtsev S.I., Jarvi K., Mullen J.B. et al. Testicular spermatozoa have statistically significantly lower DNA damage compared with ejaculated spermatozoa in patients with unsuccessful oral antioxidant treatment. Fertil Steril 2010;93(4):1142–6. DOI: 10.1016/j.fertnstert.2008.11.005
40. Greco E., Scarselli F., Iacobelli M. et al. Efficient treat ment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa. Hum Reprod 2005;20(1):226–30. DOI: 10.1093/humrep/deh590
41. Arafa M., AlMalki A., AlBadr M. et al. ICSI outcome in patients with high DNA fragmentation: testicular versus ejaculated spermatozoa. Andrologia 2018;50(1). DOI: 10.1111/and.12835
42. Zhang J., Xue H., Qiu F. et al. Testicular spermatozoon is superior to ejaculated spermatozoon for intracytoplasmic sperm injection to achieve pregnancy in infertile males with high sperm DNA damage. Andrologia 2019;51(2):e13175. DOI: 10.1111/and.13175
43. Pabuccu E.G., Caglar G.S., Tangal S. et al. Testicular versus ejaculated spermatozoa in ICSI cycles of nor mozoospermic men with high sperm DNA fragmen tation and previous ART failures. Andrologia 2017;49(2). DOI: 10.1111/and.12609
44. Hayden R.P., Wright D.L., Toth T.L., Tanrikut C. Selective use of percutaneous testis biopsy to optimize IVF-ICSI outcomes: a case series. Fertil Res Pract 2016;2:7. DOI: 10.1186/s40738-016-0020-y
45. Esteves S.C., Sánchez-Martín F., Sánchez-Martín P. et al. Comparison of reproductive outcome in oligozoospermic men with high sperm DNA fragmentation undergoing intracytoplasmic sperm injection with ejaculated and testicular sperm. Fertil Steril 2015;104(6):1398–405. DOI: 10.1016/j.fertnstert.2015.08.028
46. Mehta A., Bolyakov A., Schlegel P.N., Paduch D.A. Higher pregnancy rates using testicular sperm in men withsevere oligospermia. Fertil Steril 2015;104(6):1382–7. DOI: 10.1016/j.fertnstert.2015.08.008
47. Bradley C.K., McArthur S.J., Gee A.J. et al. Intervention improves assisted conception intracytoplasmic sperm injection outcomes for patients with high levels of sperm DNA fragmentation: a retrospective analysis. Andrology 2016;4(5):903–10. DOI: 10.1111/andr.12215
48. Alharbi M., Hamouche F., Phillips S. et al. Use of testicular sperm in couples with SCSA-defined high sperm DNA fragmentation and failed intracytoplasmic sperm injection using ejaculated sperm. Asian J Androl 2020;22(4):348–53. DOI: 10.4103/aja.aja_99_19
49. Esteves S.C., Roque M., Bradley C.K., Garrido N. Reproductive outcomes of testicular versus ejaculated sperm for intracytoplasmic sperm injection among men with high levels of DNA fragmentation in semen: systematic review and meta-analysis. Fertil Steril 2017;108(3):456–67.e1. DOI: 10.1016/j.fertnstert.2017.06.018.
Andrology and Genital Surgery. 2023; 24: 67-72
The importance of sperm DNA fragmentation in the choice of a method for the treatment of male infertility using assisted reproductive technologies
Olefir Yu. V., Efremov E. A., Rodionov M. A., Zhuvilko A. R., Popov D. M., Monakov D. M.
https://doi.org/10.17650/2070-9781-2023-24-4-67-72Abstract
Background. Sperm DNA fragmentation is an important marker of male fertility and may influence the outcome of the infertility treatment based on assisted reproductive technologies. Numerous studies have been done to assess the effect of sperm DNA fragmentation on reproductive outcomes, however the extent of this effect with various assisted reproductive technologies remains a matter of debate.
Materials and methods. Search, analysis and systematization of publications in the PubMed and eLIBRARY databases using the keywords: male infertility, sperm DNA fragmentation, intrauterine insemination, in vitro fertilization, intracytoplasmic sperm injection. We have selected 49 sources that are included in this literature review.
Results and discussion. The presence of a high level of sperm DNA fragmentation is associated with a low probability of natural pregnancy, as well as a low frequency of successful intrauterine insemination. The high level of sperm DNA fragmentation appears to have a negative impact on the reproductive outcomes of in vitro fertilization and intracytoplasmic sperm injection (ICSI), but the degree of this effect on the results of ICSI is less pronounced. ICSI with testicular spermatozoa can be used in treatment of male infertility associated with high sperm DNA fragmentation, however, the data on the advantage of this approach over standard ICSI are contradictory.
Conclusion. High level of sperm DNA fragmentation associated with the low likelihood of natural pregnancy and success of intrauterine insemination and in vitro fertilization. More large, well-designed studies are needed to establish the role of ICSI with testicular sperm in the treatment of patients with high levels of sperm DNA fragmentation.
References
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8. Aitken R.J. Oxidative stress and the etiology of male infertility. J Assist Reprod Genet 2016;33(12):1691–2. DOI: 10.1007/s10815-016-0791-4
9. Aitken R.J. DNA damage in human spermatozoa; important contributor to mutagenesis in the offspring. Transl Androl Urol 2017;6(Suppl 4):S761–4. DOI: 10.21037/tau.2017.09.13
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14. González-Marín C., Gosálvez J., Roy R. Types, causes, detection and repair of DNA fragmentation in animal and human sperm cells. Int J Mol Sci 2012;13(11):14026–52. DOI: 10.3390/ijms131114026
15. Simon L., Brunborg G., Stevenson M. et al. Clinical significance of sperm DNA damage in assisted reproduction outcome. Hum Reprod 2010;25(7):1594–608. DOI: 10.1093/humrep/deq103
16. Simon L., Emery B.R., Carrell D.T. Review: diagnosis and impact of sperm DNA alterations in assisted reproduction. Best Pract Res Clin Obstet Gynaecol 2017;44:38–56. DOI: 10.1016/j.bpobgyn.2017.07.003
17. Simon L., Lutton D., McManus J., Lewis S.E. Sperm DNA damage measured by the alkaline Comet assay as an independent predictor of male infertility and in vitro fertilization success. Fertil Steril 2011;95(2):652–7. DOI: 10.1016/j.fertnstert.2010.08.019
18. Simon L., Murphy K., Shamsi M.B. et al. Paternal influence of sperm DNA integrity on early embryonic development. Hum Reprod 2014;29(11):2402–12. DOI: 10.1093/humrep/deu228
19. Simon L., Proutski I., Stevenson M. et al. Sperm DNA damage has a negative association with live-birth rates after IVF. Reprod BioMed Online 2013;26(1):68–78. DOI: 10.1016/j.rbmo.2012.09.019
20. Santi D., Spaggiari G., Simoni M. Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management – meta-analyses. Reprod Biomed Online 2018;37(3):315–26. DOI: 10.1016/j.rbmo.2018.06.023
21. Spanò M., Kolstad A.H., Larsen S.B. et al. The applicability of the flow cytometric sperm chromatin structure assay in epidemiological studies. Asclepios. Hum Reprod 1998;13(9):2495–505. DOI: 10.1093/humrep/13.9.2495
22. Evenson D.P., Jost L.K., Marshall D. et al. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod 1999;14(4):1039–49. DOI: 10.1093/humrep/14.4.1039
23. Evenson D.P., Wixon R.L. Environmental toxicants cause sperm DNA fragmentation as detected by the Sperm Chromatin Structure Assay (SCSA®). Toxicol Appl Pharmacol 2005;207(2 Suppl):532–7. DOI: 10.1016/j.taap.2005.03.021
24. Malić Vončina S., Golob B., Ihan A. et al. Sperm DNA fragmentation and mitochondrial membrane potential combined are better for predicting natural conception than standard sperm parameters. Fertil Steril 2016;105(3):637–44.e.1. DOI: 10.1016/j.fertnstert.2015.11.037
25. Vandekerckhove F.W., De Croo I., Gerris J. et al. 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;3:63. DOI: 10.3389/fmed.2016.00063
26. Bungum M., Humaidan P., Axmon A. et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod 2007;22(1):174–9. DOI: 10.1093/humrep/del326
27. Bungum M., Humaidan P., Spano M. et al. The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI. Hum Reprod 2004;19(6):1401–8. DOI: 10.1093/humrep/deh280
28. Duran E.H., Morshedi M., Taylor S., Oehninger S. Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study. Hum Reprod 2002;17(12):3122–8. DOI: 10.1093/humrep/17.12.3122
29. Rilcheva V.S., Ayvazova N.P., Ilieva L.O. et al. Sperm DNA integrity test and assisted reproductive technology (Art) outcome. J Biomed Clin Res 2016;9:21–9. DOI: 10.1515/jbcr-2016-0003
30. Chen Q., Zhao J.Y., Xue X., Zhu G.X. The association between sperm DNA fragmentation and reproductive outcomes following intrauterine insemination, a meta-analysis. Reprod Toxicol 2019;86:50–5. DOI: 10.1016/j.reprotox.2019.03.004
31. Sugihara A., Van Avermaete F., Roelant E. et al. The role of sperm DNA fragmentation testing in predicting intra-uterine insemination outcome: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2020;244:8–15. DOI: 10.1016/j.ejogrb.2019.10.005
32. Li Z., Wang L., Cai J., Huang H. Correlation of sperm DNA damage with IVF and ICSI outcomes: a systematic review and meta-analysis. J Assist Reprod Genet 2006;23(9–10):367–76. DOI: 10.1007/s10815-006-9066-9
33. Zhao J., Zhang Q., Wang Y., Li Y. Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Fertil Steril 2014;102(4):998–1005e.8. DOI: 10.1016/j.fertnstert.2014.06.033
34. Osman A., Alsomait H., Seshadri S. et al. The effect of sperm DNA fragmentation on live birth rate after IVF or ICSI: a systematic review and meta-analysis. Reprod Biomed Online 2015;30:120–7. DOI: 10.1016/j.rbmo.2014.10.018
35. Deng C., Li T., Xie Y. et al. Sperm DNA fragmentation index influences assisted reproductive technology outcome: a systematic review and meta-analysis combined with a retrospective cohort study. Andrologia 2019;51(6):e13263. DOI: 10.1111/and.13263
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