Trophectoderm可用於胚胎植入前基因檢驗

 trophectoderm (TE) 與 inner cell mass (ICM)均可用於胚胎植入前基因檢驗(PGD)

使用基因晶片microarray molecular karyotyping

其基因或染色體吻合度相當高 (96%)
TE因較不會傷及胚胎更具優勢


http://molehr.oxfordjournals.org/content/16/12/944.full

Comprehensive analysis of karyotypic mosaicism between trophectoderm and inner cell mass

1. D.S. Johnson1,4,*, 
2. C. Cinnioglu1, 
3. R. Ross2, 
4. A. Filby3, 
5. G. Gemelos1, 
6. M. Hill1,
7. A. Ryan1, 
8. D. Smotrich2, 
9. M. Rabinowitz1 and 
10. M.J. Murray3

+Author Affiliations

1. ¹Gene Security Network, Inc., 2686 Middlefield Road, Suite C, Redwood City, CA 94063, USA
2. ²La Jolla IVF, 9850 Genesee Avenue #610, La Jolla, CA 92037, USA
3. ³Northern California Fertility Medical Center, 1130 Conroy Lane, Suite 100, Roseville, CA 95661, USA
4. ⁴Present address: GigaGen Inc., 409 Illinois St, San Francisco, CA 94158, USA

1. *Correspondence address. E-mail: seasquirtdoctor@gmail.com

• Received March 23, 2010.
• Revision received July 6, 2010.
• Accepted July 12, 2010.

Next Section

Abstract

Aneuploidy has been well-documented in blastocyst embryos, but prior studies have been limited in scale and/or lack mechanistic data. We previously reported preclinical validation of microarray 24-chromosome preimplantation genetic screening in a 24-h protocol. The method diagnoses chromosome copy number, structural chromosome aberrations, parental source of aneuploidy and distinguishes certain meiotic from mitotic errors. In this study, our objective was to examine aneuploidy in human blastocysts and determine correspondence of karyotypes between trophectoderm (TE) and inner cell mass (ICM). We disaggregated 51 blastocysts from 17 couples into ICM and one or two TE fractions. The average maternal age was 31. Next, we ran 24-chromosome microarray molecular karyotyping on all of the samples, and then performed a retrospective analysis of the data. The average per-chromosome confidence was 99.95%. Approximately 80% of blastocysts were euploid. The majority of aneuploid embryos were simple aneuploid, i.e. one or two whole-chromosome imbalances. Structural chromosome aberrations, which are common in cleavage stage embryos, occurred in only three blastocysts (5.8%). All TE biopsies derived from the same embryos were concordant. Forty-nine of 51 (96.1%) ICM samples were concordant with TE biopsies derived from the same embryos. Discordance between TE and ICM occurred only in the two embryos with structural chromosome aberration. We conclude that TE karyotype is an excellent predictor of ICM karyotype. Discordance between TE and ICM occurred only in embryos with structural chromosome aberrations.

Table I

Per fraction microarray results.

	TE	ICM
Number of biopsies	80	51
Number of embryos	51	51
Euploid	66 (82.5%)	41 (80.4%)
Simple aneuploid	12 (15.0%)	7 (15.7%)
Complex aneuploid	4 (3.8%)	3 (5.9%)
Maternal monosomy	6 (7.5%)	4 (7.8%)
Paternal monosomy	3 (3.8%)	3 (5.9%)
Maternal trisomy	4 (5.0%)	2 (3.9%)
Paternal trisomy	2 (2.5%)	2 (3.9%)
Maternal meiotic trisomy	4 (5.0%)	2 (3.9%)
Paternal meiotic trisomy	2 (2.5%)	1 (1.9%)
Maternal haploid	1 (1.3%)	1 (1.9%)
Structural chromosome aberrations	2 (2.5%)	3 (5.8%)
No result	0 (0.0%)	0 (0.0%)

• Aneuploidy rates classified by mechanism and parental source of aneuploidy, computed per biopsy and segregated into TE and ICM biopsies.

Table II

Mosaicism in aneuploid embryos.

Embryo	Maternal age	Family	ICM	TE-1	TE-2	Mosaic
2–252	37	252	45XY, −16(mat)(struct)(mei)	45XY, −16(mat)	45XY, −16(mat)	Yes
4–253	29	253	45XX, −14(mat)	45XX, −14(mat)	45XX, −14(mat)	No
6–149	28	149	45XY, −16(mat)	45XY, −16(mat)		No
9–249	31	249	45XY, −12(mat)(struct)	45XY, −12(mat)(struct)		No
2–148	22	148	45X, −X(pat)	45X, −X(pat)		No
2–255	34	255	23X, −1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, sex(pat)	23X, −1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, sex(pat)	23X, −1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, sex(pat)	No
7–249	31	249	46XY, −12(pat)(struct), +13(pat)mit	45XY, −12(pat)(struct)		Yes
3–252	37	252	47XXY, +sex(pat)mei	47XXY, +sex(pat)mei	47XXY, +sex(pat)mei	No
4–149	28	149	49XX, +3(mat)mei, +6(mat)mei, +19(mat)mei	49XX, +3(mat)mei, +6(mat)mei, +19(mat)mei	49XX, +3(mat)mei, +6(mat)mei, +19(mat)mei	No
4–249	31	249	47XY, +15(mat)mei	47XY, +15(mat)mei	47XY, +15(mat)mei	No

• Concordance between ICM and TE fractions for the 10 aneuploid embryos. Karyotypes are indicated with standard nomenclature, except ‘mat’ indicates maternal source, ‘pat’ indicates paternal source, ‘mei’ indicates meiotic mechanism, ‘mit’ indicates mitotic mechanism and ‘struct’ indicates a structural chromosome aberration. The ‘Mosaic’ column indicates whether any one chromosome differed between any pair of biopsies from the same embryo.

Table III

Structural chromosome aberrations.

Embryo	Maternal age	Family	ICM	TE-1	TE-2	Mosaic?
2–252	37	252	−16:p11.2-qter (mat), +16:p11.2-pter (mat)(mei)	ND	ND	Yes
7–249	31	253	−12:q14.2-qter (mat)	−12:q14.2-qter (mat)	NA	No
9–249	31	149	−12:q14.2-qter (pat)	−12:q14.2-qter (pat)	NA	No

• Summary of specific karyotype for the three embryos that suffered structural chromosome aberrations. In the karyotype annotation, ‘mat’ indicates maternal source, ‘pat’ indicates paternal source and ‘mei’ indicates meiotic mechanism. ‘ND’ indicates that no structural chromosome aberration was detected and ‘NA’ indicates that no measurement was made. The ‘Mosaic’ column indicates whether any one chromosome differed between any pair of biopsies from the same embryo.