The birth of a healthy baby after transfer of a mosaic embryo in the in vitro fertilization program: clinical and ethical aspects
Background. The low effectiveness of assisted reproductive technology (ART) programs in older reproductive-aged patients is associated with a finite pool of high-quality oocytes and with a high risk for aneuploid embryos. According to the results of preimplantation genetic testing for aneuploidy (PGT-A), the pattern of embryonic chromosomal disorders differs on days 3 and 5 after fertilization, which may be due to a high degree of mosaicism in the embryo on day 3 of development and to its ability to compensate for these disorders by day 5.Kulakova E.V., Drapkina Yu.S., Alieva K.U., Zaretskaya N.V., Ekimov A.N., Makarova N.P., Sysoeva A.P., Kalinina E.A.
Case report. A 49-year-old patient came to the unit with a 5-year history of infertility with repeated failed ART attempts. The patient underwent an IVF/ICSI and PGT-A program with subsequent transfer of a mosaic embryo into the uterine cavity. She had a physiological pregnancy that ended in premature operative delivery. At the time of writing this paper, the baby is somatically healthy, developing according to age.
Conclusion. Mosaic embryos may be the only available ones to be transferred to the uterine cavity in ART programs. Despite the fact that the clinical significance of mosaicism remains to be unestablished, it is known that mosaic embryos with a high proportion of euploid cells can lead to the birth of a healthy baby. The analysis of literature sources indicates that the outcomes of ART programs during the transfer of a mosaic embryo depend on the degree of mosaicism and the type of aneuploidy. Mosaicism can be physiological in nature and it is necessary to be very balanced in the analysis of PGT-A results.
Keywords
assisted reproductive technologies
ART
preimplantation genetic testing
mosaicism
mosaic embryo
aneuploidies
embryo implantation
older reproductive age
donor oocytes
PGT
References
- Александрова Н.В., Шубина Е.С., Екимов А.Н., Кодылева Т.А., Мукосей И.С., Макарова Н.П., Кулакова Е.В., Левков Л.А., Барков И.Ю., Трофимов Д.Ю., Сухих Г.Т. Сравнение результатов преимплантационного генетического скрининга, проведенного методами CGH и NGS. Молекулярная биология. 2017; 51(2): 308-13. [Alexandrova N.V., Shubina E.S., Ekimov A.N., Kodyleva T.A., Mukosey I.S., Makarova N.P., Kulakova E.V., Levkov L.A., Barkov I.Yu., Trofimov D.Yu., Sukhikh G.T. Comparison of CGH and NGS preimplantation genetic screening results. Molecular biology. 2017; 51 (2): 308-13. (in Russian)].
- Munné S., Blazek J., Large M., Martinez-Ortiz P.A., Nisson H., Liu E. et al. Detailed investigation into the cytogenetic constitution and pregnancy outcome of replacing mosaic blastocysts detected with the use of high-resolution next-generation sequencing. Fertil. Steril. 2017; 108(1): 62-71. https://dx.doi.org/10.1016/j.fertnstert.2017.05.002.
- Zore T., Kroener L.L., Wang C., Liu L., Buyalos R., Hubert G., Shamonki M. Transfer of embryos with segmental mosaicism is associated with a significant reduction in live-birth rate. Fertil. Steril. 2019; 111(1): 69-76. https://dx.doi.org/10.1016/j.fertnstert.2018.08.057.
- McCoy R.C. Mosaicism in preimplantation human embryos: when chromosomal abnormalities are the norm. Trends Genet. 2017; 33(7): 448-63. https://dx.doi.org/10.1016/j.tig.2017.04.001.
- Fragouli E., Alfarawati S., Spath K., Babariya D., Tarozzi N., Borini A., Wells D. Analysis of implantation and ongoing pregnancy rates following the transfer of mosaic diploid-aneuploid blastocysts. Hum. Genet. 2017; 136(7): 805-19. https://dx.doi.org/10.1007/s00439-017-1797-4.
- Greco E., Minasi M.G., Fiorentino F. Healthy babies after intrauterine transfer of mosaic aneuploid blastocysts. N. Engl. J. Med. 2015; 373(21): 2089-90. https://dx.doi.org/10.1056/NEJMc1500421.
- Liu J., Wang W., Sun X., Liu L., Jin H., Li M. et al. DNA microarray revels that high proportions of human blastocysts from women of advanced maternal age are aneuploid and mosaic. Biol. Reprod. 2012; 87(6): 148. https://dx.doi.org/10.1095/biolreprod.112.103192.
- Viotti M., Victor A., Griffin D., Tyndall J., Brake A.J., Lepkowsky L., Zouves C., Barnes F. 88 mosaic embryo transfer in a single clinic: what we have learned. Fertil. Steril. 2018;110(4, Suppl.): e420.
- Bolton H., Graham S.J.L., Van der Aa N., Kumar P., Theunis K., Fernandez Gallardo E. et al. Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneploid cells and normal developmental potential. Nat. Commun. 2016; 7: 11165. https://dx.doi.org/10.1038/ncomms11165.
- Cram D.S., Leigh D., Handyside A., Rechitsky L., Xu K., Harton G. et al. PGDIS position statement on the transfer of mosaic embryos 2019. Reprod. Biomed. Online. 2019; 39(Suppl. 1): e1-4. https://dx.doi.org/10.1016/j.rbmo.2019.06.012.
Received 10.12.2020
Accepted 22.04.2021
About the Authors
Elena V. Kulakova, Ph.D., Senior Researcher at the B.V. Leonov Department of Assisted Technologies for the Treatment of Infertility, V.I. Kulakov NMRC for OG&P,Ministry of Health of Russia. E-mail: e_kulakova@oparina4.ru. 117997, Russia, Moscow, Academician Oparin str., 4.
Yulia S. Drapkina, Ph.D., Researcher at the B.V. Leonov Department of Assisted Technologies for the Treatment of Infertility, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia. E-mail: yu_drapkina@oparina4.ru. ORCID: 0000-0002-0545-1607. 117997, Russia, Moscow, Academician Oparin str., 4.
Kamila U. Alieva, Ph.D., Researcher at the B.V. Leonov Department of Assisted Technologies for the Treatment of Infertility, V.I. Kulakov NMRC for OG&P,
Ministry of Health of Russia. E-mail: kaya79@mail.ru. 117997, Russia, Moscow, Academician Oparin str., 4.
Nadezhda V. Zaretskaya, Ph.D., Head of Clinical Work, Department of Clinical Genetics, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia.
E-mail: n_zaretskaya@oparina4.ru. 117997, Russia, Moscow, Academician Oparin str., 4.
Alexey N. Ekimov, Clinical Geneticist at the Molecular Genetics Laboratory, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia. E-mail: a_ekimov@oparina4.ru.
117997, Russia, Moscow, Academician Oparin str., 4.
Natalia P. Makarova, Dr. Biol. Sci., Senior Researcher at the B.V. Leonov Department of Assisted Technologies for the Treatment of Infertility, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia. E-mail: np_makarova@oparina4.ru. 117997, Russia, Moscow, st. Academician Oparin, 4.
Anastasia P. Sysoeva, Embryologist at the B.V. Leonov Department of Assisted Technologies for the Treatment of Infertility, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia. E-mail: sysoeva.a.p@gmail.com. 117997, Russia, Moscow, Academician Oparin str., 4.
Elena A. Kalinina, Dr. Med. Sci., Professor, Head of the B.V. Leonov Department of Assisted Technologies for the Treatment of Infertility, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia. E-mail: e_kalinina@oparina4.ru. 117997, Russia, Moscow, Academician Oparin str., 4
For citation: Kulakova E.V., Drapkina Yu.S., Alieva K.U., Zaretskaya N.V., Ekimov A.N., Makarova N.P., Sysoeva A.P., Kalinina E.A. The birth of a healthy baby after transfer of a mosaic embryo in the in vitro fertilization program: clinical and ethical aspects.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2021; 7: 210-214 (in Russian)
https://dx.doi.org/10.18565/aig.2021.7.210-214
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