Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
권호 표지

Outcome of Preimplantation Genetic Diagnosis for Chromosome Aneuploidy and Genetic Disease

유전질환 및 염색체 이상의 예방을 위한 착상전 유전진단의 결과

  • Kim, Jin-Yeong (Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Lim, Chun-Kyu (Laboratory of Reproductive Biology and Infertility, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Song, In-Ok (Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Yoo, Keun-Jai (Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Yang, Kwang-Moon (Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Han, Kuk-Sun (Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Hur, Kuol (Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Song, Ji-Hong (Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Jun, Jin-Hyun (Laboratory of Reproductive Biology and Infertility, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Min, Dong-Mi (Laboratory of Reproductive Biology and Infertility, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Park, So-Yeon (Laboratory of Genetics, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Jun, Jong-Young (Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Koong, Mi-Kyoung (Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine) ;
  • Kang, Inn-Soo (Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine)
  • 김진영 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 임천규 (성균관대학교 의과대학 삼성제일병원 불임연구실) ;
  • 송인옥 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 유근재 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 양광문 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 한국선 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 허걸 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 송지홍 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 전진현 (성균관대학교 의과대학 삼성제일병원 불임연구실) ;
  • 민동미 (성균관대학교 의과대학 삼성제일병원 불임연구실) ;
  • 박소연 (성균관대학교 의과대학 삼성제일병원 유전학 연구실) ;
  • 전종영 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 궁미경 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 강인수 (성균관대학교 의과대학 삼성제일병원 산부인과)
  • Published : 2002.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective s: Chromosome aneuploidy is associated with recurrent abortion and congenital anomaly and genetic diseases occur repeatedly in the specific families. Preimplantation genetic diagnosis (PGD) can prevent aneuploidy or genetic disease by selecting normal embryos before implantation and is an alternative to prenatal diagnosis. The aim of this study is to assess the outcome of PGD cycles by using FISH or PCR, and to determine the clinical usefulness and values in patients with risk of chromosomal aneuploidy or genetic disease. Materials and Methods: From 1995 to Apr. 2001, a total of 108 PGD cycles in 65 patients with poor reproductive outcome were analyzed. The indications of PGD were translocation (n=49), inversion (n=2), aneuploidy screening (n=7), Duchenne muscular dystrophy (n=5) and spinal muscular atrophy (n=2). PGD was applied due to the history of recurrent abortion, previous birth of affected child or risk of aneuploidy related to sex chromosome aneuploidy or old age. Blastomere biopsy was performed in 6$\sim$10 cell stage embryo after IVF with ICSI. In the single blastomere, chromosome aneuploidy was diagnosed by using FISH and PCR was performed for the diagnosis of exon deletion in DMD or SMA. Results: The FISH or PCR amplification was successful in 94.3% of biopsied blastomeres. The rate of transferable balanced emb ryos was 24.0% in the chromosome translocation and inversion, 57.1% for the DMD and SMA, and 28.8% for the aneuploidy screening. Overall hCG positive rate per transfer was 17.8% (18/101) and clinical pregnancy rate was 13.9% (14/101) (11 term pregnancy, 3 abortion, and 4 biochemical pregnancy). The clinical pregnancy rate of translocation and inversion was 12.9% (11/85) and abortion rate was 27.3% (3/11). In the DMD and SMA, the clinical pregnancy rate was 33.3% (3/9) and all delivered at term. The PGD results were confirmed by amniocentesis and were correct. When the embryos developed to compaction or morula, the pregnancy rate was higher (32%) than that of the cases without compaction (7.2%, p<0.01). Conclusions: PGD by using FISH or PCR is useful to get n ormal pregnancy by reducing spontaneous abortion associated with chromosome aneuploidy in the patients with structural chromosome aberration or risk of aneuploidy and can prevent genetic disease prior to implantation.

Keywords

References

  1. Handyside AH, Pattinson JK, Penketh RJ, Edlhanty JD, Winston RM, Tuddenham EG. Biopsy of human preimplantation embryos and sexing by DNA amplification. Lancet 1989;18: 347-9
  2. ESHERE PGD Consortium steering committee. ESHERE Preirnplantation genetic diagnosis (PGD) Consortium: data collection II (May 2000). Hum Reprod 2000; 15(2): 2673-83 https://doi.org/10.1093/humrep/15.12.2673
  3. Munne S, Lee A, Rosenwaks Z, Grifo J, Cohen J. Diagnosis of major chromosome aneuploidies in human preimiplantation embryos. Hum Reprod 1993; 8: 2185
  4. Munne S, Magli C, Cohen J, Morton P, Sadowy S, Gianaroli L, et al. Positive outcome after preimplantation diagnosis of aneuploidy in human embryos. Hum Reprod 1999; 14(9): 2191-9 https://doi.org/10.1093/humrep/14.9.2191
  5. Munne S, Morrison L, Fung J, Marquez C, Weier U, Bahce M, et al. J Assist Reprod Genet 1998; 15:290-6
  6. Munne S, Sandalinas M, Escudero T, Fung J, Gianaroli L, Cohen J. Outcom of preimplantation genetic diagnosis of translocations. Fertil Steril 2000;73(6): 1209-17 https://doi.org/10.1016/S0015-0282(00)00495-7
  7. Coonen E, Dumoulin JC, Dreesen JC, Bras M, Evers JL, Geraedts JP. Clinical application of FISH for sex determination of embryosin preimplantation diagnosis of X-linked diseases. J Assist Reprod Genet 1996; 13: 133-6 https://doi.org/10.1007/BF02072534
  8. Hussey ND, Dongguk H, Froiland DA, Hussey DJ, Haan EA, Metthews CD, et al. Analysis of five Duchenne muscular dystrophy exons and gender determination using conventional duplex polymerase chain reaction on single cells. Mol Hum Reprod 1999;5: 1089-94 https://doi.org/10.1093/molehr/5.11.1089
  9. Kristjansson K, Chong SS, Van den Veyver IB, Subramanian S, Snabes MC, Hughs MR. Preimplantation single cell analysis of dystrophin gene deletions using whole genome amplification. Nature Genet 1994;6: 19-23 https://doi.org/10.1038/ng0194-19
  10. Dreesen JC, Bras M, de Die-Smulders C, Dumoulin JC, Cobben JM, Evers JL. Preimplantation genetic diagnosis of spinal muscular atrophy. Mol Hum Reprod 1998;4: 881-5 https://doi.org/10.1093/molehr/4.9.881
  11. Blake D, Tan SL, Ao A. Assessment of multiplex fluorescent PCR for screening single cells for trisomy 21 and single gene defects. Mol Hum Reprod 1999;5: 1166-75 https://doi.org/10.1093/molehr/5.12.1166
  12. Moutou C, Gardes N, Rongieres C, Ohl J, Bettahar K, Wittemer C, et al. Allele-specific amplification for preimplantation genetic diagnosis of spinal muscularatrophy. Prenat Dign 2001; 21: 498-503 https://doi.org/10.1002/pd.110
  13. 임천규, 한미현, 전진현, 송견지, 김정욱, 박소연 등. 균형 전좌 또는 Robertsonian 전좌 보인자의 체외수정 및 배아이식술에서 형광직접보합법을 이용한 착상전 유전자 진단의 임상적 적용. 대한산부회지 2000; 43(7): 1147-53
  14. Munne S, Marquez C, Magli C, Morton P, Morrison L. Scoring criteria for preimplantation genetic diagnosis of numerical abnormalities for chromosomes X,Y,13,16,18 and 21. Mol Hum Reprod 1998; 4:863-70 https://doi.org/10.1093/molehr/4.9.863
  15. Choi SK, Cho EH, Kim JW, Park SY, Kim YM, Ryu HM et al. Prenatal diagnosis of the spinal muscular atrophy type I using genetic information from archival slides and paraffin embedded tissues. J Med Gen 1998;2(2): 53-7
  16. 최수경, 이은호, 이호준, 전진현, 강인수, 백은찬, 등, 근이양증 가계에서의 PEP-PCR을 이용한 착상전 유전자 진단. 대한불임학회잡지 1996; 23(1): 109-14
  17. 최수경, 김진우, 조은희, 박소연, 류현미, 강인수 등 단일 태아세포에서의 PEP-PCR을 이용한 성의 결정과 Dystrophin 유전자 분석. 대한불임학회잡지 1997;24(1): 51-6
  18. Verlinsky Y, Cieslak J, Ivakhnenko V, Evsikov S, Wolf G, White M, et al. Prevention of age-related aneuploidies by Polar body testing of oocytes. J Assist Reprod Genet 1999; 16: 165-9 https://doi.org/10.1023/A:1020304621338
  19. Fryns JP, Klczkowska A, Kubien E, Petit P, Van den Berghe H. Cytogenetic survey in couples with recurrent fetal wastage. Hum Genet 1984; 65(4):336-54 https://doi.org/10.1007/BF00291558
  20. Shaffer LG, Spikes AS, Macha M, Dunn R. Identification of a subtle chromosomal translocation in a family with recurrent miscarriage and a child with multiple congenital anomalies. A case report. J Reprod Med 1996; 41(5): 367-71
  21. Iwarsson E, Ahrlund L, Inzunza J, Rosenlund B, Fridstrom M, HiIlensjo T, et al. Preimplantation genetic diagnosis of a largepericentric inversion of chromosome 5. Mol Hum Reprod 1998; 4(7): 719-23 https://doi.org/10.1093/molehr/4.7.719
  22. Teo SH,Tan M, Knight L, Yeo SH,Ng I. Pericentric inversion 9-incidence and clinical significance. Ann Acad Med Singapore 1995; 24(2): 302-4
  23. Beggs AH, Koenig M, Boyce FM, Kunkel LM. Detection of 98%of DMD/BMD gene deletions by polymerase chain reaction. Hum Genet 1990; 86(1):45-8
  24. Pearn J. Classification of spinal muscular atrophies. Lancet 1980; 1:919-22
  25. Vandervorst M, Liebaers I, Sermon K, Staessen C, De Vos A, Van de Velde H, et al. Successful preimiplantation genetic diagnosis is related to the number of available cumulus-oocyte complexes. Hum Reprod 1998; 13:3169-76 https://doi.org/10.1093/humrep/13.11.3169
  26. Wells D, Sherlock JK. Strategies for preimplantation genetic diagnosis of single gene disorders by DNA amplification. Prenat Diagn 1998; 18: 1389-401 https://doi.org/10.1002/(SICI)1097-0223(199812)18:13<1389::AID-PD498>3.0.CO;2-6
  27. Harper JC, Coonen E, Handyside AH, Winston RM, Hopman AH, Delhanty JD. Mosaicism of autosomes and sex chromosomes in morphologically normal monospennic preimlantation human embryos. Prenat Diagn 1995; 15: 41-9 https://doi.org/10.1002/pd.1970150109
  28. Voullaire L, Wilton L, Slater H, Williamson R. Detection of aneuploidy in single cells using comparative genomic hybridization. Prenat Diagn 1999;19(9): 846-51 https://doi.org/10.1002/(SICI)1097-0223(199909)19:9<846::AID-PD657>3.0.CO;2-#