Commentary on two recently published formal guidelines on management of “mosaic” embryos after preimplantation genetic testing for aneuploidy (PGT-A)

Reproductive Biology and Endocrinology - Tập 19 - Trang 1-6 - 2021
Norbert Gleicher1,2,3,4, David H. Barad1,2, Zion Ben-Rafael5, Demian Glujovsky6, Lyka Mochizuki1, Deepak Modi7, Maximillian Murtinger8, Pasquale Patrizio9, Raoul Orvieto10, Shizuko Takahashi11, Andrea Weghofer1,4, Søren Ziebe12
1The Center for Human Reproduction, New York, USA
2The Foundation for Reproductive Medicine, New York, USA
3Stem Cell Biology and Molecular Embryology Laboratory, The Rockefeller University, New York, USA
4Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
5Department of Obstetrics and Gynecology and IVF, Laniado Medical Center, Netanya, Israel
6Fertility Argentina, Buenos Aires, Argentina
7Molecular and Cellular Biology Laboratory, ICRM-National Institute for Research in Reproductive Health, Mumbai, India
8NextXlinic IVF Centers Prof Zech, Bregenz, Austria
9Yale Fertility Center, Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Reproductive Endocrinology and Infertility, Yale University, New Haven, USA
10Infertility and IVF Unit, Department of Obstetrics and Gynecology, Sheba Medical Center, Ramat Gan and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
11Department of Biomedical Ethics and the Department of Obstetrics and Gynecology, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan
12The Fertility Clinic, Ringhospital, University Hospital of Copenhagen, Copenhagen, Denmark

Tóm tắt

Two professional societies recently published opinions on the clinical management of “mosaic” results from preimplantation genetic testing for aneuploidy (PGT-A) in human blastocyst-stage embryos in associations with in vitro fertilization (IVF). We here point out three principal shortcomings: (i) Though a most recent societal opinion states that it should not be understood as an endorsement of the use of PGT-A, any discussion of how PGT-A should be clinically interpreted for all practical purposes does offer such an endorsement. (ii) The same guideline derived much of its opinion from a preceding guidance in favor of utilization of PGT-A that did not follow even minimal professional requirements for establishment of practice guidelines. (iii) Published guidelines on so-called “mosaic” embryos from both societies contradict basic biological characteristics of human preimplantation-stage embryos. They, furthermore, are clinically unvalidated and interpret results of a test, increasingly seen as harmful to IVF outcomes for many infertile women. Qualified professional organizations, therefore, should finally offer transparent guidelines about the utilization of PGT-A in association with IVF in general.

Tài liệu tham khảo

Gleicher N, Albertini FD, Barad DH, Homer H, Modi D, Murtinger M, Patrizio P, Orvieto R, Takhashi S, Weghofer A, Ziebe S, Noyes N, on behalf of the International Do No Harm Group in IVF (IDNHG-IVF). The 2019 PGDIS position statement on transfer of mosaic embryos within a context of new information on PGT-A. Reprod Biol Endocrinol. 2020a;18:57. Practice Committee and Genetic Counseling Professional Group (GCPG) of the American Society for Reproductive Medicine. Clinical management of mosaic results from preimplantation enetic testing for aneuploidy (PGT-A) of blastocysts: a committee opinion. Fertil Steril. 2020;114(2):246–54. Gleicher N, Patrizio P, Brivanlou A. Preimplantation Genetic Testing for Aneuploidy - a Castle Built on Sand. Trends Mol Med. 2021;S1471-4914(20):30313-0. https://doi.org/10.1016/j.molmed.2020.11.009. Epub ahead of print. PMID: 33446425. Paulson RJ. Outcome of in vitro fertilization cycles with preimplantation genetic testing for aneuploidies: let’s be honest with one another. Fertil Steril. 2019;112(6):1013–4. Schattman GL. Preimplantation genetic testing for aneuploidy: It’s déjàvu all over again. Fertil Steril. 2019;112(6):1046–7. Practice Committee of the American Society for Reproductive Medicine. Preimplantation genetic testing: a practice Committee opinion. Fertil Steril. 2008;90:S136–43. Practice Committees of the ASRM and SART. The use of preimplantation genetic testing for aneuploidy (PGT-A): a committee opinion. Fertil Steril. 2018;109(3):429–36. Gleicher N, Caplan AL. An alternative proposal to the destruction of abandoned human embryos. Nature Biotech. 2018;36(2):139–41. Patrizio P, Shoham G, Shoham Z, Leong M, Barad DH, Gleicher N. Worldwide live births following transfer of chromosomally “abnormal” embryos after PGT/a. results of worldwide web-based survey. J Assist Reprod Genet. 2019;36(8):1599–607. PGDIS. Preimplantation Genetic Diagnosis International Society (PGDIS) Position Statement on chromosome mosaicism and preimplantation aneuploidy testing at the blastocyst stage, 2016, http://pgdis.org/docs/newsletter_071816.html. Gajecka M. Unrevealed mosaicism in the next-generation sequencing era. Mol Gen Genomics. 2016;291:513–30. Gleicher N, Metzger J, Croft G, Kushnir VA, Albertini DF, Barad DH. A single trophectoderm biopsy at blastocyst stage is mathematically unable to determine embryo ploidy accurately enough for clinical use. Reprod Biol Endocrinol. 2017;15(1):23. Orvieto R. The reproducibility of trophectoderm biopsies - The chaos behind preimplantation genetic testing for aneuploidy. Eur J Obstet Gynecol Reprod Biol.. 2020;254:57-58. https://doi.org/10.1016/j.ejogrb.2020.07.052. Capalbo A, Rienzi L. Mosaicism between trophectoderm and inner cell mass. Fertil Steril. 2017;107(5):1098–106. Bolton H, Graham SJ, Van der Aa N, Kumar P, Theunis K, Fernandez Gallardo E, Voet T, Zernicka-Goetz M. Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential. Nat Commun. 2016;7:11165. Yang M, Rito T, Metzger J, Naftaly J, Soman R, Hu J, Albertini DF, Barad DH, Brivanlou A, Gleicher N. Self-correction of mosaicism in human embryos and gastruloids. Nat Biol. 2020; In press. Orvieto R, Shimon C, Rienstein S, Janish-Grossman A, Shani H, Aizer A. Do human embryos have the ability to self-correction? Reprod Biol Endocrinol. 2020;18:98. Chen Y, Yang K, Marusic A, Qaseem A, Meerpohl JJ, et al. A reporting tool for practice guidelines in health care: the RIGHT statement. Ann Intern Med. 2017;166(2):128–32. Cram DS, Leigh D, Handyside A, Rechitsky L, Xu K, Harton G, Grifo J, Rubio C, Fragouli E, Kahramen S, Forman E, Katz-Jaffe M, Tempest H, Thornhill A, Strom C, Escudero T, Qiao J, Munné S, Simpson JL, Kuliev A. EDITORIAL. PGDIS Position Statement on the Transfer of Mosaic Embryos 2019. Reprod Biomed. 2019;39(Supple 1):e1–4. Iannone P, Costantino G, Montano N, Podda GM, Mindardi M, Dole J, Cartabellotta A. Wrong guidelines: how to detect them and what to do in the case of flawed recommendations. Evid Based Med. 2017;22(1):4–8. Scott RT Jr, Galliano D. The challenge of embryonic mosaicism in preimplantation genetic screening. Fertil Steril. 2016;105(5):1150–2. Munné S, Blazek J, Large M, Martinez-Ortiz PA, Nisson H, Liu E, Tarozzi N, Borini A, Becker A, Zhang J, Maxwell S, Grifo J, Barbariya D, Wells D, Fragouli E. Detailed investigation into the cytogenic 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. Kushnir VA, Darmon SK, Barad DH, et al. Degree of mosaicism in trophectoderm does not predict pregnancy potential: a corrected analysis of pregnancy outcomes following transfer of mosaic embryos. Reprod Biol Endocrinol. 2018;16(1):6. https://doi.org/10.1186/s12958-018-0322-5. Victor AR, Tyndall JC, Brake AJ, et al. One hundred mosaic embryos transferred prospectively in a single clinic: exploring when and why they result in healthy pregnancies. Fertil Steril. 2019;111(2):280–93. https://doi.org/10.1016/j.fertnstert.2018.10.019 [published Online First: 2019/01/30]. Munné S. Status of preimplantation genetic testing and embryo selection. Reprod BioMed Online. 2018;37(4):393–6. Paulson RJ, Treff NR. Isn’t it time to stop calling embryos “mosaic”? F&S Reports. 2020. https://doi.org/10.1016/j.xfre.2020.10.009.
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Reproductive Biology and Endocrinology

Tập 19

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