囊胚期胚胎之染色體仍有相當高比例之異常染色體鑲嵌(mosaic)

培養至囊胚期之胚胎之染色體仍有高達85%比例異常染色體(38% aneuploid, 38% diploid mosaic, 7% polyploid and 2% haploid)
囊胚期胚胎之染色體仍有相當高比例之異常染色體鑲嵌(mosaic)
儘管如此，異常染色體鑲嵌(mosaic)之囊胚期胚胎仍具自我修復能力‧

66%正常胚胎培養至囊胚期
<20%異常染色體胚胎培養至囊胚期

http://humrep.oxfordjournals.org/content/16/9/1954.full


Developmental ability of chromosomally abnormal human embryos to develop to the blastocyst stage

1. M. Sandalinas1, 
2. S. Sadowy, 
3. M. Alikani, 
4. G. Calderon, 
5. J. Cohen and 
6. S. Munné

+Author Affiliations

1. Gamete and Embryo Research Laboratory, The Institute for Reproductive Medicine and Science of Saint Barnabas Medical Center, West Orange, NJ 07052, USA

• Received November 6, 2000.
• Accepted May 31, 2001.

 

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Abstract

BACKGROUND: A correlation between morphology, developmental competence and chromosome abnormalities is established. However, since absolute correlations are rare, embryo selection remains one of the most arduous tasks in assisted reproduction. This study was undertaken in order to determine which chromosomal abnormalities are compatible with development to the blastocyst stage. METHODS: Embryos diagnosed by preimplantation genetic diagnosis (PGD) as chromosomally abnormal or unsuitable for transfer were cultured to day 5 or 6. Morphology and development were observed daily. After extended culture, embryos were fixed and analysed by two rounds of FISH with the same probes used for PGD. RESULTS: Some types of numerical chromosome abnormalities do not preclude full differentiation in vitro. For instance, extensive mosaicism was detected in blastocysts and trisomic embryos reached the blastocyst stage with a frequency of 37%. Interestingly, only those monosomies compatible with first trimester development (monosomy X and 21) were detected at blastocyst stage. CONCLUSION: Even though there is a strong selection against chromosomally abnormal embryos, extended culture to day 5 or 6 cannot be used as a reliable tool to select against clinically relevant chromosome abnormalities such as trisomies.

Table I.

Blastocysts and blastomeres analysed

Average maternal age (years)	38.5
Embryos in extended cultured	254
Embryos analysed	216
Total no. of nuclei analysed/fixed	5607/7719
Total no. of blastocysts	54
Blastocyst formation rate	21%
Blastocysts analysed	51
Total no. of nuclei analysed/fixed in blastocysts	3645/5774
Average of nuclei per blastocyst	113
Average of nuclei analysed per blastocyst	71

Table II.

Developmental potential of human embryos depending on their chromosome constitution

	No. of embryos:
	Arrested at day 3	Arrested at day 4	Reached blastocyst
Values in parentheses are percentages.
*Including five embryos with multiple aneuploidy (at least one monosomy).
†Including five embryos with at least trisomy.
‡One monosomy 21, one monosomy X.
§And monosomy 21.
a versus b: P = 0.001; a versus c: P = 0.014; a versus d, e: P < 0.001; a versus f: P = 0.006; a versus g: P = 0.01; h versus i: P = 0.022.
Normal: 32 (15)
9 uniformly normal 6	0	3 (33)
23 mosaic 2n/4n (<38% abnormal)	3	2	18 (78)i
Total	9 (28)	2 (6)	21 (66)a
Aneuploid: 83 (38)
23 monosomies*	14	7	2 (9)‡b
35 trisomies†	15	7	13 (37)c
24 and mosaics (>38% abnormal)	19	5	0 (0)
1 and polyploid	0	0	1 (100)§
Total	48 (58)	19 (23)	16 (19)d
Other diploid mosaics: 82 (38)
9 2n/4n (>38% abnormal)	3	3	3 (33)h
24 2n/aneuploid
6 (10–38% abnormal)	3	2	1 (17)
18 (>38% abnormal)	15	2	1 (6)
49 2n/chaotic	36	8	6 (12)
Total	57 (70)	15 (18)	11 (13)e
Polyploid: 14 (7)	11 (79)	0	3 (21)f
Haploid: 5 (2)	4 (80)

igure 1. Nuclei spread (stained with DAPI) of a mosaic blastocyst. (a) Nuclei hybridized in first round with probes for chromosome 13 (red), chromosome 16 (aqua), chromosome 18 (blue), chromosome 21 (green), and chromosome 22 (gold) and second round with probes for chromosome X (green), chromosome Y (orange) and chromosome 15 (aqua). (b) Metaphase spread hybridized with SKY technique, showing chaotic karyotype.