Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
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Preimplantation Genetic Diagnosis for Aneuploidy Screening in Patients with Poor Reproductive Outcome

염색체 이수성과 관련된 비정상적 임신이 예상되는 환자에서 착상전 유전진단의 결과

  • Kim, Jin Yeong (Department of Obstetrics and Gynecology, Cheil General Hospital, Sungkyunkwan University School of Medicine) ;
  • Lim, Chun Kyu (Laboratory of Reproductive Biology and Infertility, Cheil General Hospital, Sungkyunkwan University School of Medicine) ;
  • Cha, Sun Hwa (Department of Obstetrics and Gynecology, Cheil General Hospital, Sungkyunkwan University School of Medicine) ;
  • Park, Soo Hyun (Department of Obstetrics and Gynecology, Cheil General Hospital, Sungkyunkwan University School of Medicine) ;
  • Yang, Kwang Moon (Department of Obstetrics and Gynecology, Cheil General Hospital, Sungkyunkwan University School of Medicine) ;
  • Song, In Ok (Department of Obstetrics and Gynecology, Cheil General Hospital, Sungkyunkwan University School of Medicine) ;
  • Jun, Jin Hyun (Laboratory of Reproductive Biology and Infertility, Cheil General Hospital, Sungkyunkwan University School of Medicine) ;
  • Park, So Yeon (Laboratory of Genetics, Cheil General Hospital, Sungkyunkwan University School of Medicine) ;
  • Koong, Mi Kyoung (Department of Obstetrics and Gynecology, Cheil General Hospital, Sungkyunkwan University School of Medicine) ;
  • Kang, Inn Soo (Department of Obstetrics and Gynecology, Cheil General Hospital, Sungkyunkwan University School of Medicine)
  • 김진영 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 임천규 (성균관대학교 의과대학 삼성제일병원 불임연구실) ;
  • 차선화 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 박수현 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 양광문 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 송인옥 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 전진현 (성균관대학교 의과대학 삼성제일병원 불임연구실) ;
  • 박소연 (성균관대학교 의과대학 삼성제일병원 유전학 연구실) ;
  • 궁미경 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 강인수 (성균관대학교 의과대학 삼성제일병원 산부인과)
  • Published : 2006.09.30
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Abstract

Objectives: The risk of aneuploidies of embryos increases in advanced maternal age or parental karyotype abnormality and it results in poor reproductive outcomes such as recurrent spontaneous abortion (RSA) or repeated implantation failure (RIF). Preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) can be applied for better ART outcome by selecting chromosomally normal embryos. The aim of this study is to evaluate the clinical outcome of PGD-AS and which group can get much benefit from PGD-AS among the patients expected to have poor reproductive outcome. Methods: In 42 patients, 77 PGD cycles were performed for aneuploidy screening. Patients were allocated to 3 groups according to the indication of PGD-AS: group I-patients with old age (${\geq}37$) and RIF more than 3 times (n=11, mean age=42.2 yrs.), group II-patients with RSA (${\geq}3$ times) associated with aneuploid pregnancy (n=19, mean age=38.9 yrs.), group III-parental sex chromosome abnormality or mosaicism (n=18, mean age=29.6 yrs.) including Turner syndrome, Klinefelter syndrome and 47, XYY. PGD was performed by using FISH for chromosome 13, 16, 18, 21, X and Y in group I and II, and chromosome X, Y and 18 (or 17) in group III. Results: Blastomere biopsy was successful in 530 embryos and FISH efficiency was 92.3%. The proportions of transferable embryos in each group were $32.5{\pm}17.5%$, $23.0{\pm}21.7%$ and $52.6{\pm}29.2%$ (mean ${\pm}$ SD), respectively, showing higher normal rate in group III (group II vs. III, p<0.05). The numbers of transferred embryos in each group were $3.9{\pm}1.5$, $1.9{\pm}1.1$ and $3.1{\pm}1.4$ (mean ${\pm}$ SD), respectively. The clinical pregnancy rates per transfer was 0%, 30.0% and 20.0%, and it was significantly higher in group II (group I vs. group II, p<0.05). The overall pregnancy rate per transfer was 19.6% (10/51) and the spontaneous abortion rate was 20% (2/10) of which karyotypes were euploid. Nine healthy babies (one twin pregnancy) were born with normal karyotype confirmed on amniocentesis. Conclusion: Our data suggests that PGD-AS provides advantages in patients with RSA associated with aneuploidy or sex chromosome abnormality, decreasing abortion rate and increasing ongoing pregnancy rate. It is not likely to be beneficial in RIF group due to other detrimental factors involved in implantation.

목 적: 배아의 염색체 이수성은 착상실패나 자연유산과 관련되며 이는 고령이나 부부의 염색체 이상이 있는 경우 그 위험이 증가되어 습관성 유산이나 반복 착상실패 등 불량한 임신결과를 초래한다. 염색체 이수성에 대한 착상전 유전진단은 정상 염색체를 갖는 배아를 선별적으로 이식할 수 있으므로 이러한 환자들에서 효과적으로 적용될 수 있다. 이에 염색체 이수성에 대한 착상전 유전진단의 임상적 결과를 알아보고 어떠한 환자군에서 가장 큰 효용성을 얻을 수 있는지 알아보고자 하였다. 연구방법: 총 42명의 환자에서 77주기의 염색체 이수성에 대한 착상전 유전진단을 시행하였다. 환자군을 적응증에 따라 세 군으로 나누어 제 1군은 37세 이상이며 3회 이상 반복 착상실패를보인 경우 (11예, 평균 나이 42.2세), 제 2군은 3회 이상의 습관성 유산 및 이 중 1회 이상 염색체 이수성을 보인 경우 (19예, 평균 나이 38.9세), 제 3군은 터너 증후군이나 클라인펠터 증후군, 47,XYY 등 성염색체 이상이나 모자이시즘을 가진 환자였다 (18예, 평균 나이 29.6세). 착상전유전진단은 제1군과 2군에서는 13, 16, 18, 21, X, Y염색체에 대한 FISH를, 제 3군에서는 X, Y 및18 또는 17번 염색체에 대한 FISH를 시행하였다. 결 과: 총 530개의 배아에서 할구 생검이 가능하였고 FISH 진단 효율은 92.3%였다. 정상 배아의 비율은 각 군에서 $32.5{\pm}17.5%$, $23.0{\pm}21.7%$, 및 $52.6{\pm}29.2%$ (mean ${\pm}$ SD)였으며 제 3군에서 유의하게 높았다 (group II vs. III, p<0.05). 배아 이식은 51주기에서 시행하였으며 이식된 배아의수는 각각 $3.9{\pm}1.5$, $1.9{\pm}1.1$ 및 $3.1{\pm}1.4$개 (mean ${\pm}$ SD)였다. 임상적 임신율은 각 군에서 0%, 30.0% 및 20.0%로 제 2군에서 유의하게 높았다 (p<0.05). 전체적인 임신율은 19.6% (10/51)였고 자연유산율은 20% (2/10)였으며 유산된 경우의 염색체는 정상이었다. 쌍태아 1예를 포함하여 총9명의 정상아가 출생되었으며, 양수검사로 정상 염색체 핵형을 확인하였다. 결 론: 염색체 이수성에 대한 착상전 유전진단은 염색체 이수성과 관련된 불량한 임신예후가 예상되는 환자에서 유용하게 이용될 수 있으며, 특히 이수성과 관련된 습관성 유산이나 성염색체 이상에서 효용성이 있으며, 반복 착상실패에서는 착상에 관련되는 다른 원인들의 복합적인 영향으로 큰 효용성이 없는 것으로 생각된다.

Keywords

References

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