臨床婦人科産科76巻4号

2022年04月発行

増刊号 最新の不妊診療がわかる！―生殖補助医療を中心とした新たな治療体系 第2章　生殖補助医療とその手技 胚培養―着床率の高い受精卵を選別して妊娠率を向上させる

PGT-Aによる染色体正常胚の選別―その適応と臨床的意義

著者： 原田枝美¹ 河野康志¹

所属機関： ¹大分大学医学部産科婦人科

ページ範囲：P.71 - P.76

▶PGT-Aの施行は，特に高齢女性（AMA）の患者に高い有効性が示される．ただし，胚移植あたりの臨床成績は有意に改善するが，患者あたりの臨床成績改善には至っていない．
▶モザイク胚を移植する際は，慎重に移植胚の選択を行い，十分な遺伝カウンセリングのもとに施行する．
▶現時点ではPGT-Aが出生児にもたらす負の影響は報告されていないが，長期的な予後については不明であり，今後のデータ集積が待たれる．

参考文献

1）Mastenbroek S, et al : In vitro fertilization with preimplantation genetic screening. N Engl J Med 357 : 9-17, 2007

2）Twisk M, et al : No beneficial effect of preimplantation genetic screening in women of advanced maternal age with a high risk for embryonic aneuploidy. Hum Reprod 23 : 2813-2817, 2008

3）Checa MA, et al : IVF/ICSI with or without preimplantation genetic screening for aneuploidy in couples without genetic disorders : a systematic review and meta-analysis. J Assist Reprod Genet 26 : 273-283, 2009

4）Kushnir VA, et al : Effectiveness of in vitro fertilization with preimplantation genetic screening : a reanalysis of United States assisted reproductive technology data 2011-2012. Fertil Steril 106 : 75-79, 2016

5）Chen M, et al : Can comprehensive chromosome screening technology improve IVF/ICSI outcomes? A meta-analysis. PLoS One 10 : e0140779, 2015

6）Dahdouh EM, et al : Comprehensive chromosome screening improves embryo selection : a meta-analysis. Fertil Steril 104 : 1503-1512, 2015

7）van Montfoort A, et al : ESHRE PGT Consortium data collection XIX-XX : PGT analyses from 2016 to 2017. Hum Reprod Open 2021 : hoab024, 2021

8）Harton GL, et al ; PGD Practitioners Group : Diminished effect of maternal age on implantation after preimplantation genetic diagnosis with array comparative genomic hybridization. Fertil Steril 100 : 1695-1703, 2013

9）Franasiak JM, et al : The nature of aneuploidy with increasing age of the female partner : a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril 101 : 656-663, 2014

10）Munné S, et al : Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients : a multicenter randomized clinical trial. Fertil Steril 112 : 1071-1079.e7, 2019

11）Simopoulou M, et al : PGT-A : who and when? Α systematic review and network meta-analysis of RCTs. J Assist Reprod Genet 38 : 1939-1957, 2021

12）Irani M, et al : Does maternal age at retrieval influence the implantation potential of euploid blastocysts? Am J Obstet Gynecol 220 : 379.e1-379.e7, 2019

13）Stephenson MD : Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril 66 : 24-29, 1996

14）Hodes-Wertz B, et al : Idiopathic recurrent miscarriage is caused mostly by aneuploid embryos. Fertil Steril 98 : 675-680, 2012

15）Sugiura-Ogasawara M, et al : Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage. Hum Reprod 27 : 2297-2303, 2012

16）Sui YL, et al : In vitro fertilization with single-nucleotide polymorphism microarray-based preimplantation genetic testing for aneuploidy significantly improves clinical outcomes in infertile women with recurrent pregnancy loss : a randomized controlled trial. Reprod Dev Med 4 : 32-41, 2020

17）Bhatt SJ, et al : 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 36 : 2339-2344, 2021

18）Greco E, et al : Comparative genomic hybridization selection of blastocysts for repeated implantation failure treatment : a pilot study. Biomed Res Int 2014 : 457913, 2014

19）Tong J, et al : Next-generation sequencing（NGS）-based preimplantation genetic testing for aneuploidy（PGT-A）of trophectoderm biopsy for recurrent implantation failure（RIF） patients : a retrospective study. Reprod Sci 28 : 1923-1929, 2021

20）Kort JD, et al : Are blastocyst aneuploidy rates different between fertile and infertile populations? J Assist Reprod Genet 35 : 403-408, 2018

21）Munné S, et al : Detection of mosaicism at blastocyst stage with the use of high-resolution next-generation sequencing. Fertil Steril 107 : 1085-1091, 2017

22）Martín Á, et al : The morphokinetic signature of mosaic embryos : evidence in support of their own genetic identity. Fertil Steril 116 : 165-173, 2021

23）Spinella F, et al : Extent of chromosomal mosaicism influences the clinical outcome of in vitro fertilization treatments. Fertil Steril 109 : 77-83, 2018

24）Munné S, et al : Clinical outcomes after the transfer of blastocysts characterized as mosaic by high resolution Next Generation Sequencing- further insights. Eur J Med Genet 63 : 103741, 2020

25）Zhang L, et al : Rates of live birth after mosaic embryo transfer compared with euploid embryo transfer. J Assist Reprod Genet 36 : 165-172, 2019

26）Zhang YX, et al : The pregnancy outcome of mosaic embryo transfer : a prospective multicenter study and meta-analysis. Genes（Basel） 11 : 973, 2020

27）PGDIS Newsletter, PGDIS position statement on chromosome mosaicism and preimplantation aneuploidy testing at the blastocyst stage. July 19, 2016　https://www.pgdis.org/docs/newsletter_071816.html

28）Cram DS, et al : PGDIS position statement on the transfer of mosaic embryos 2019. Reprod Biomed Online 39（Suppl 1） : e1-e4, 2019

29）Mourad A, et al : Evidence-based clinical prioritization of embryos with mosaic results : a systematic review and meta-analysis. J Assist Reprod Genet 38 : 2849-2860, 2021

30）COGEN position statement on chromosomal mosaicism detected in preimplantation blastocyst biopsies. 2016　https://ivf-worldwide.com/cogen/general/cogen-statement.html

31）Bunnell M E, et al : Should embryos with autosomal monosomy by preimplantation genetic testing for aneuploidy be transferred? : Implications for embryo selection from a systematic literature review of autosomal monosomy survivors. Prenat Diagn 37 : 1273-1280, 2017

32）Victor AR, et al : One hundred mosaic embryos transferred prospectively in a single clinic : exploring when and why they result in healthy pregnancies. Fertil Steril 111 :280-293, 2019

33）Grati FR, et al : An evidence-based scoring system for prioritizing mosaic aneuploid embryos following preimplantation genetic screening. Reprod Biomed Online 36 : 442-449, 2018

34）He H, et al : Neonatal outcomes of live births after blastocyst biopsy in preimplantation genetic testing cycles : a follow-up of 1,721 children. Fertil Steril 112 : 82-88, 2019

35）Heijligers M, et al : Growth, health, and motor development of 5-year-old children born after preimplantation genetic diagnosis. Fertil Steril 111 : 1151-1158, 2019

36）Gleicher N, et al : Further evidence against use of PGS in poor prognosis patients : report of normal births after transfer of embryos reported as aneuploid. Fertil Steril 104（suppl 3） : e59, 2015

37）Greco E, et al : Healthy babies after intrauterine transfer of mosaic aneuploid blastocysts. N Engl J Med 373 : 2089-2090, 2015

38）Liu YL, et al : Healthy live births after mosaic blastocyst transfers with the use of next-generation sequencing. Taiwan J Obstet Gynecol 58 : 872-876, 2019

39）Abhari S, et al : Pregnancy and neonatal outcomes after transfer of mosaic embryos : a review. J Clin Med 10 : 1369, 2021

40）Kahraman S, et al : The birth of a baby with mosaicism resulting from a known mosaic embryo transfer : a case report. Hum Reprod 35 : 727-733, 2020

41）Rito T, et al : Self-correction of aneuploidy in human blastocysts and self-organizing gastruloids. Fertil Steril 112（suppl 3） : e127, 2019