Results of preimplatation genetic screening of embryos in married couples with sperm DNA fragmentation
Objective. To determine the frequency of aneuploidies (monosomies, trisomies, disomies, nullisomies) from all chromosomes, as well as DNA deletions and amplifications in the embryos from couples with higher and normal sperm nuclear DNA fragmentation levels.Kiseleva Yu.Yu., Azova M.M., Kodyleva T.A., Ushakova I.V., Kirillova A.O., Ekimov A.N., Rakitko A.S., Volodyaeva T.O., Mishieva N.G., Abubakirov A.N.
Subjects and methods. An array-based preimplatation genetic screening program was applied to 170 couples; each couple underwent estimation of sperm concentration, motility and morphology according to the 2010 WHO standards, as well as sperm nuclear DNA fragmentation levels by the TUNEL method.
Results. A relationship was found between the level of paternal sperm DNA fragmentation and the frequency of obtaining embryos with a normal karyotype. With the increased level of DNA fragmentation, this figure is 47.96% vs 66.17% with its normal level (p < 0.02). There was also a substantially increased frequency of embryo DNA deletions and amplifications with a higher level of paternal sperm DNA fragmentation (35.89% vs 5.39% with its normal level; p < 0.001). Fragmentation does not have a statistically significant impact on abnormal chromosome number.
Conclusion. This study has demonstrated a correlation between the level of paternal sperm DNA fragmentation and the frequency of structural karyotype abnormalities in embryos.
Keywords
Supplementary Materials
References
1. Руководство ВОЗ по лабораторному исследованию эякулята человека и взаимодействия сперматозоидов с цервикальной слизью. Пер. с англ. 4-е изд. М.: МедПресс; 2001. [WHO laboratory manual for examination of human semen and sperm-cervical mucus interaction. 4th ed. WHO; 1999.]
2. Kaarouch I., Bouamoud N., Louanjli N., Madkour A., Copin H., Benkhalifa M., Sefrioui O. Impact of sperm genome decay on Day-3 embryo chromosomal abnormalities from advanced-maternal-age patients. Mol. Reprod. Dev. 2015; 82(10): 809-19.
3. Belloc S., Benkhalifa M., Cohen-Bacrie M., Dalleac A., Chahine H., Amar E., Zini A. Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation. J. Assist. Reprod. Genet. 2014; 31(5): 527-32.
4. Robinson L., Gallos I.D., Conner S.J., Rajkhowa M., Miller D., Lewis S. et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum. Reprod. 2012; 27(10): 2908-17. doi: 10.1093/humrep/des261.
5. Enciso M., Alfarawati S., Wells D. Increased numbers of DNA-damaged spermatozoa in samples presenting an elevated rate of numerical chromosome abnormalities. Hum. Reprod. 2013; 28(6): 1707-15. doi: 10.1093/humrep/det077.
6. Evgeni E., Charalabopoulos K., Asimakopoulos B. Human sperm DNA fragmentation and its correlation with conventional semen parameters. J. Reprod. Infertil. 2014; 15(1): 2-14.
7. Gandini L., Lombardo F., Paoli D., Caruso F., Eleuteri P., Leter G. et al. Full-term pregnancies achieved with ICSI despite high levels of sperm chromatin damage. Hum. Reprod. 2004; 19(6): 1409-17.
8. Руднева С.А., Брагина Е.Е., Арифулин Е.А., Сорокина Т.М., Шилейко Л.В., Ермолаева С.А., Курило Л.Ф., Черных В.Б. Фрагментация ДНК в сперматозоидах и ее взаимосвязь с нарушением сперматогенеза. Андрология и генитальная хирургия. 2014; 4: 26-33. [Rudneva S.A., Bragina E.E., Arifulin E.A., Sorokina T.M., Shileyko L.V., Ermolaeva S.A., Kurilo L.F., Chernykh V.B. Fragmentation of DNA in spermatozoa and its relationship with impaired spermatogenesis. Andrologiya i genitalnaya hirurgiya. 2014; 4: 26-33. (in Russian)]
9. Goldberg L., Kercheval A., Lee K. t‐statistics for weighted means in credit risk modeling. J. Risk Finance. 2005; 6(4): 349-65.
10. R Core Team R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2016. Available at: https://www.R-project.org/
11. Mann H., Whitney D. On a test of whether one of two random variables is stochastically larger than the other. Ann. Math. Statist. 1947;18(1): 50-60.
12. Cohen-Bacrie P., Belloc S., Menezo Y.J., Clement P., Hamidi J., Benkhalifa M. Correlation between DNA damage and sperm parameters: a prospective study of 1,633 patients. Fertil. Steril. 2009; 91(5): 1801-5.
13. Belloc S., Hazout A., Zini A., Merviel P., Cabry R., Chahine H. et al. How to overcome male infertility after 40: Influence of paternal age on fertility. Maturitas. 2014; 78: 22-9.
14. Sakkas D., Alvarez J.G. Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertil. Steril. 2010; 93(4): 1027-36.
15. Benkhalifa M., Montjean D., Belloc S., Dalleac A., Ducasse M., Boyer P. et al. Emerging molecular methods for male infertility investigation. Expert Rev. Mol. Diagn. 2014; 14(1): 37-45.
16. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010.
Received 03.10.2016
Accepted 11.11.2016
About the Authors
Kiseleva Yulia Yu., embryologist, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; graduate student of the Department of Biology and General Genetics Medical Faculty, Peoples’ Friendship University. 117997, Russia, Moscow, Ac. Oparina str. 4. Тel.: +79164171311. Е-mail: 79164171311@yandex.ruAzova Madina M., DSc, Associate Professor, Head of the Department of Biology and General Genetics Medical Faculty, Peoples’ Friendship University.
117198, Russia, Moscow, Miklukho-Maklaya str. 6. Tel.: +74954345300.E-mail: azovam@mail.ru
Kodyleva T.A., embryologist 1st gynecology department, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954382622. E-mail: t_kodyleva@oparina4.ru
Ushakova I.V., Ph.D., embryologist, department of reproductive, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79859289287. E-mail: ir_ushakova@oparina4.ru
Kirillova Anastasiya O., embryologist, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Тel.: +74954382622. Е-mail: a_kozyreva@oparina.ru
Ekimov Alexey N., researcher, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Тel.: +74954382622. Е-mail: a_ekimov@oparina4.ru
Rakitko Aleksandr S., PhD student, Department of Theory of Probability, Faculty of Mathematics and Mechanics, M.V. Lomonosov Moscow State University.
119991, Russia, Moscow, Leninskie Gory, 1. Tel.: +79104820017. E-mail: rakitko@gmail.com
Volodyaeva Tatiana O., embryologist, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Тel.: +79993255305. Е-mail: tvolo90@mail.ru
Mishieva Nona G., MD, Senior researcher of 1st gynecology department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Тel.: +79104244197. E-mail: nondoc555@mail.ru
Abubakirov Aydar N., PhD, Head of 1-st gynecology department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Тel.: +74954382622. Е-mail: nondoc555@yahoo.com
For citations: Kiseleva Yu.Yu., Azova M.M., Kodyleva T.A., Ushakova I.V., Kirillova A.O.,
Ekimov A.N., Rakitko A.S., Volodyaeva T.O., Mishieva N.G., Abubakirov A.N. Results of preimplatation genetic screening of embryos in married couples with sperm DNA fragmentation.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (8): 104-8. (in Russian)
http://dx.doi.org/10.18565/aig.2017.8.104-8