About
The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
ArchiveEthical StandardsSubscription
For authors
InstructionsInformed consent policyContract offerEASE GuidelinesICJME CriteriaWAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications
Reviewing
Procedure for reviewingReviewers 2023-2024
About
The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
ArchiveEthical StandardsSubscription
For authors
InstructionsInformed consent policyContract offerEASE GuidelinesICJME CriteriaWAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications
Reviewing
Procedure for reviewingReviewers 2023-2024
Logout
Obstetrics and Gynegology2022№6
Evaluation of extracellular DNA as...

Evaluation of extracellular DNA as a method for non-invasive preimplantation genetic testing of embryos in infertility treatment programs using assisted reproductive technologies

DOI
https://dx.doi.org/10.18565/aig.2022.6.13-19

Lisitsyna O.I., Makarova N.P., Dolgushina N.V.

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia
A number of factors, the key one of which is the quality of the embryo transferred into the uterine cavity, influence the effectiveness of assisted reproductive technology programs. The embryo quality is most commonly assessed on the basis of morphological criteria and the results of preimplantation genetic testing for aneuploidy (PGT-A). However, these methods have a number of limitations. The detection of extracellular genomic and mitochondrial DNA in the used culture medium has opened up new prospects for the development of non-invasive diagnostic methods in reproductive medicine. To date, a number of scientific papers have already traced the possible implementation of non-invasive PGT-A (niPGT-A). The frequency of correspondence between the results obtained from the analysis of extracellular DNA (ecDNA) of the used culture medium and the results of the assessment of embryonic DNA has been assessed in the study of polar bodies, trophectoderm cells, and the entire embryo. This review discusses in detail the diagnostic possibilities of using niPGT-A methods in the spent culture medium, as well as the effectiveness and future prospects for their use in clinical practice. Particular attention is paid to the technical aspects of the embryological and laboratory stages. The main areas for further full study of the problem are outlined.
Conclusion: The new non-invasive approach to assessing the quality of embryos will be able to more efficiently select embryos with a high potential for further development, ongoing pregnancy and the birth of a healthy baby. The above procedure will allow more patients to receive the necessary medical care, the time to pregnancy to be reduced, and the diagnostic process to be also made more cost-effective.

Keywords

extracellular DNA
genomic DNA
non-invasive preimplantation genetic testing for aneuploidy (n-PGT-A)
used culture medium
Full text (in Russian)

References

  1. Ajduk A., Zernicka-Goetz M. Quality control of embryo development. Mol. Aspects Med. 2013; 34(5): 903-18. https://dx.doi.org/10.1016/j.mam.2013.03.001.
  2. Ferrick L., Lee Y.S.L., Gardner D.K., Sakkas D. Reducing time to pregnancy and facilitating the birth of healthy children through functional analysis of embryo physiology. Biol. Reprod. 2019; 101(6): 1124-39. https://dx.doi.org/10.1093/biolre/ioz005.
  3. Тимофеева А.В., Калинина Е.А., Драпкина Ю.С., Чаговец В.В., Макарова Н.П., Сухих Г.Т. Оценка качества эмбриона по профилю экспрессии малых некодирующих РНК в культуральной среде эмбриона в программах ВРТ. Акушерство и гинекология. 2019; 6: 79-86. [Timofeeva A.V., Kalinina E.A., Drapkina Yu.S., Chagovets V.V., Makarova N.P., Sukhikh G.T. Embryo quality assessment by the small noncoding RNA expression profile in an embryo culture medium in assisted reproductive technology programs. Obstetrics and Gynecology. 2019; 6: 79-86. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.6.79-86.
  4. Ярыгина С.А., Смольникова В.Ю., Калинина Е.А., Эльдаров Ч.М., Гамисония А.М., Макарова Н.П., Бобров М.Ю. Анализ метаболитов в различных средах культивирования эмбрионов человека. Акушерство и гинекология. 2020; 11: 114-23. [Yarygina S.A., Smolnikova V.Yu., Kalinina E.A., Eldarov Ch.M., Gamisonia A.M., Makarova N.P. et al. Analysis of human embryo culture medium metabolites. Obstetrics and Gynecology. 2020; 11:114-23. (in Russian)]. https://dx.doi.org/10.18565/aig.2020.11.114-123.
  5. Валиахметова Э.З., Кулакова Е.В., Скибина Ю.С., Грязнов А.Ю, Сысоева А.П., Макарова Н.П., Калинина Е.А. Неинвазивное тестирование преимплантационных эмбрионов человека in vitro как способ прогнозирования исходов программ экстракорпорального оплодотворения. Акушерство и гинекология. 2021; 5: 5-16. [Valiakhmetova E.Z., Kulakova E.V., Skibina Yu.S., Gryaznov A.Yu., Sysoeva A.P., Makarova N.P. et al. Non-invasive testing of human preimplantation embryos in vitro as a way to predict the outcomes of in vitro fertilization programs. Obstetrics and Gynecology. 2021; 5: 5-16. (in Russian)]. https://dx.doi.org/10.18565/aig.2021.5.5-16.
  6. Zmuidinaite R., Sharara F.I., Iles R.K. Current advancements in noninvasive profiling of the embryo culture media secretome. Int. J. Mol. Sci. 2021; 22(5): 2513. https://dx.doi.org/10.3390/ijms22052513.
  7. Natsuaki M.N., Dimler L.M. Pregnancy and child developmental outcomes after preimplantation genetic screening: a meta-analytic and systematic review. World J. Pediatr. 2018; 14(6): 555-69. https://dx.doi.org/10.1007/s12519-018-0172-4.
  8. Shi W.H., Jiang Z.R., Zhou Z.Y., Ye M.J., Qin N.X., Huang H.F. et al. Different strategies of preimplantation genetic testing for aneuploidies in women of advanced maternal age: A systematic review and meta-analysis. J. Clin. Med. 2021; 10(17): 3895. https://dx.doi.org/10.3390/jcm10173895.
  9. Bhatt S.J., Marchetto N.M., Roy J., Morelli S.S., McGovern P.G. Pregnancy outcomes following in vitro fertilization frozen embryo transfer (IVF-FET) with or without preimplantation genetic testing for aneuploidy (PGT-A) in women with recurrent pregnancy loss (RPL): a SART-CORS study. Hum. Reprod. 2021; 36(8): 2339-44. https://dx.doi.org/10.1093/humrep/deab117.
  10. Cimadomo D., Rienzi L., Capalbo A., Rubio C., Innocenti F., Garcia-Pascual C.M. et al. The dawn of the future: 30 years from the first biopsy of a human embryo. The detailed history of an ongoing revolution. Hum. Reprod. Update. 2020; 26(4): 453-73. https://dx.doi.org/10.1093/humupd/dmaa019.
  11. Малышева О.В., Пендина А.А., Ефимова О.А., Чиряева О.Г. Предымплантационное генетическое тестирование. В кн.: Коган И.Ю., ред. Экстракорпоральное оплодотворение. Практическое руководство для врачей. М.: ГЭОТАР-Медиа; 2021: 357-67. [Malysheva O.V., Pendina A.A., Efimova O.A. Preimplantation genetic testing. In: Kogan I.Yu., ed. In Vitro Fertilization: A Practical Guide for Physicians. Moscow: GEOTAR-Media; 2021: 357-67. (in Russian)].
  12. Rubio C., Racowsky C., Barad D.H., Scott R.T., Simon C. Noninvasive preimplantation genetic testing for aneuploidy in spent culture medium as a substitute for trophectoderm biopsy. Fertil. Steril. 2021; 115(4): 841-9. https://dx.doi.org/10.1016/j.fertnstert.2021.02.045.
  13. Brouillet S., Martinez G., Coutton C., Hamamah S. Is cell-free DNA in spent embryo culture medium an alternative to embryo biopsy for preimplantation genetic testing? A systematic review. Reprod. Biomed. Online. 2020; 40(6):779-96. https://dx.doi.org/10.1016/j.rbmo.2020.02.002.
  14. Leaver M., Wells D. Non-invasive preimplantation genetic testing (niPGT): The next revolution in reproductive genetics? Hum. Reprod. Update. 2020; 26(1): 16-42. https://dx.doi.org/10.1093/humupd/dmz033.
  15. Xu J., Fang R., Chen L., Chen D., Xiao J.P., Yang W. et al. Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization. Proc. Natl. Acad. Sci. USA. 2016; 113(42): 11907-12. https://dx.doi.org/10.1073/pnas.1907472116.
  16. Stigliani S., Anserini P., Venturini P., Scaruffi P. Mitochondrial DNA content in embryo culture medium is significantly associated with human embryo fragmentation. Hum. Reprod. 2013; 28(10): 2652-60. https://dx.doi.org/10.1093/humrep/det314.
  17. Navarro-Sánchez L., García-Pascual C., Rubio C., Simón C. Non-invasive preimplantation genetic testing for aneuploidies: an update. Reprod. Biomed. Online. 2022; 44(5): 817-28. https://dx.doi.org/10.1016/j.rbmo.2022.01.012.
  18. Tomic M., Vrtacnik Bokal E., Stimpfel M. Non-invasive preimplantation genetic testing for aneuploidy and the mystery of genetic material: A review article. Int. J. Mol. Sci. 2022; 23(7): 3568. https://dx.doi.org/10.3390/ijms23073568.
  19. Chen Y., Gao Y., Jia J., Chang L., Liu P., Qiao J. et al. DNA methylome reveals cellular origin of cell-free DNA in spent medium of human preimplantation embryos. J. Clin. Invest. 2021; 131(12): e146051. https://dx.doi.org/10.1172/JCI146051.
  20. Rubio C., Simón C. Noninvasive preimplantation genetic testing for aneuploidy: Is the glass half-empty or half-full? Fertil. Steril. 2021; 115(6): 1426-7. https://dx.doi.org/10.1016/j.fertnstert.2021.04.002.
  21. Huang L., Bogale B., Tang Y., Lu S., Xie X.S., Racowsky C. Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy. Proc. Natl. Acad. Sci. USA. 2019; 116(28): 14105-12. https://dx.doi.org/10.1073/pnas.1907472116.
  22. Rubio C., Navarro-Sánchez L., García-Pascual C., Ocali O., Cimadomo D., Venier W. et al. Multicenter prospective study of concordance between embryonic cell-free DNA and trophectoderm biopsies from 1301 human blastocysts. Am. J. Obstet. Gynecol. 2020; 223(5): 751.e1-13. https://dx.doi.org/10.1016/j.ajog.2020.04.035.
  23. Hanson B.M., Tao X., Hong K.H., Comito C.E., Pangasnan R., Seli E. et al. Noninvasive preimplantation genetic testing for aneuploidy exhibits high rates of deoxyribonucleic acid amplification failure and poor correlation with results obtained using trophectoderm biopsy. Fertil. Steril. 2021; 115(6): 1461-70. https://dx.doi.org/10.1016/j.fertnstert.2021.01.028.
  24. Ho J.R., Arrach N., Rhodes-Long K., Ahmady A., Ingles S., Chung K. et al. Pushing the limits of detection: investigation of cell-free DNA for aneuploidy screening in embryos. Fertil. Steril. 2018; 110(3): 467-475.e2. https://dx.doi.org/10.1016/j.fertnstert.2018.03.036.
  25. Vera-Rodriguez M., Diez-Juan A., Jimenez-Almazan J., Martinez S., Navarro R., Peinado V. et al. Origin and composition of cell-free DNA in spent medium from human embryo culture during preimplantation development. Hum. Reprod. 2018; 33(4): 745-56. https://dx.doi.org/10.1093/humrep/dey028.
  26. Kuznyetsov V., Madjunkova S., Antes R., Abramov R., Motamedi G., Ibarrientos Z. et al. Evaluation of a novel non-invasive preimplantation genetic screening approach. PLoS One. 2018; 13(5): e0197262. https://dx.doi.org/10.1371/journal.pone.0197262.
  27. Capalbo A., Romanelli V., Patassini C., Poli M., Girardi L., Giancani A. et al. Diagnostic efficacy of blastocoel fluid and spent media as sources of DNA for preimplantation genetic testing in standard clinical conditions. Fertil. Steril. 2018; 110(5): 870-879.e5. https://dx.doi.org/10.1016/j.fertnstert.2018.05.031.
  28. Belandres D., Shamonki M., Arrach N. Current status of spent embryo media research for preimplantation genetic testing. J. Assist. Reprod. Genet. 2019; 36(5): 819-26. https://dx.doi.org/10.1007/s10815-019-01437-6.
  29. Capalbo A., Poli M., Rienzi L., Girardi L., Patassini C., Fabiani M. et al. Mosaic human preimplantation embryos and their developmental potential in a prospective, non-selection clinical trial. Am. J. Hum. Genet. 2021; 108(12): 2238-47. https://dx.doi.org/10.1016/j.ajhg.2021.11.002.
  30. Rubio C., Rienzi L., Navarro-Sánchez L., Cimadomo D., García-Pascual C.M., Albricci L. et al. Embryonic cell-free DNA versus trophectoderm biopsy for aneuploidy testing: concordance rate and clinical implications. Fertil. Steril. 2019; 112(3): 510-9. https://dx.doi.org/10.1016/j.fertnstert.2019.04.038.
  31. Hammond E., Shelling A., Cree L. Nuclear and mitochondrial DNA in blastocoele fluid and embryo culture medium: evidence and potential clinical use. Hum. Reprod. 2016; 31(8): 1653-61. https://dx.doi.org/10.1093/humrep/dew132.
  32. Viotti M., Victor A.R., Barnes F.L., Zouves C.G., Besser A.G., Grifo J.A. et al. Using outcome data from one thousand mosaic embryo transfers to formulate an embryo ranking system for clinical use. Fertil. Steril. 2021; 115(5): 1212-24. https://dx.doi.org/10.1016/j.fertnstert.2020.11.041.
  33. Leigh D., Cram D.S., Rechitsky S., Handyside A., Wells D., Munne S. et al. PGDIS position statement on the transfer of mosaic embryos 2021. Reprod. Biomed. Online. 2022; 20: S1472-6483(22)00150-X. https://dx.doi.org/10.1016/j.rbmo.2022.03.013.
  34. Mounts E.L., Zhu S.O., Sanderson R., Coates A., Hesla J. Mosaic embryo diagnosis correlated with abnormal 15q duplication syndrome in offspring. Fertil. Steril. 2019; 112(3): e241-2. https://dx.doi.org/10.1016/j.fertnstert.2019.07.1375.
  35. Li X., Hao Y., Chen D., Ji D., Zhu W., Zhu X. Non-invasive preimplantation genetic testing for putative mosaic blastocysts: a pilot study. Hum. Reprod. 2021; 36(7): 2020-34. https://dx.doi.org/10.1093/humrep/deab080.

Received 15.03.2022

Accepted 01.06.2022

About the Authors

Olga I. Lisitsyna, postgraduate student, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health
of the Russian Federation, o_yazykova@inbox.ru, https://orcid.org/0000-0002-7775-3508, 4, Oparina str., Moscow, 117997, Russia.
Nataliya P. Makarova, Dr. Bio. Sci., Leading Researcher of IVF Department, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation, np_makarova@oparina4.ru, https://orcid.org/0000-0003-1396-7272, 4, Oparina str., Moscow, 117997, Russia.
Nataliya V. Dolgushina, Dr. Med. Sci., Professor, Deputy Director – Head of the Department of Research Administration, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation, n_dolgushina@oparina4.ru,
https://orcid.org/0000-0003-1116-138X, 4, Oparina str., Moscow, 117997, Russia.

Authors' contributions: Lisitsyna O.I., Makarova N.P., Dolgushina N.V.: concept and design of the investigation, writing and editing the text.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The investigation has not been conducted without attracting additional funding from third parties.
For citation: Lisitsyna O.I., Makarova N.P., Dolgushina N.V. Evaluation of extracellular
DNA as a method for non-invasive preimplantation genetic testing of
embryos in infertility treatment programs using assisted reproductive technologies.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2022; 6: 13-19 (in Russian)
https://dx.doi.org/10.18565/aig.2022.6.13-19

Similar Articles

№8 / 2016
Sukhikh G.T., Trofimov D.Yu., Barkov I.Yu., Donnikov A.E., Shubina E.S., Korostin D.O., Ekimov A.N., Goltsov A.Yu., Bakharev V.A., Karetnikova N.A., Borovikov P.I., Tetruashvili N.K., Kim L.V., Gata A.S., Pavlovich S.V., Skryabin K.G., Prokhorchuk E.B., Mazur A.M., Pantyukh K.S.
New approaches to prenatal screening for chromosomal abnormalities: Maternal blood DNA screening
№7 / 2023
Lisitsyna O.I., Dolgushina N.V., Makarova N.P., Burmenskaya O.V.
Mitochondrial DNA as a quality marker of gametes and embryos in assisted reproductive technologies programs
By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.