Meiotic segregation of Robertsonian translocations ascertained in cleavage-stage embryos—implications for preimplantation genetic diagnosis

BACKGROUND The aim of this study was to ascertain the prevalence of meiotic segregation products in embryos from carriers of 13/14 and 14/21 Robertsonian translocations and to estimate the predictive value of testing single cells using the fluorescence in situ hybridization (FISH) technique, to prov...

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Published in:	Human reproduction (Oxford) Vol. 26; no. 6; pp. 1575 - 1584
Main Authors:	Bint, S.M., Mackie Ogilvie, C., Flinter, F.A., Khalaf, Y., Scriven, P.N.
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 01-06-2011
Subjects:	Abortion Age Biological and medical sciences Blastomeres Chromosome Segregation - genetics Chromosome translocations Chromosomes, Human, Pair 13 - genetics Chromosomes, Human, Pair 14 - genetics Chromosomes, Human, Pair 21 - genetics Cleavage Stage, Ovum Cohort Studies copy number Decision making Down's syndrome Embryos Female Fertility Fluorescence in situ hybridization Genetic screening Gynecology. Andrology. Obstetrics Heterozygote Heterozygotes Humans In Situ Hybridization, Fluorescence - methods Male Medical sciences Meiosis Nuclear transport Pregnancy Preimplantation Diagnosis - methods Probes Regression analysis Robertsonian translocation Translocation, Genetic Robertsonian translocation FISH meiotic segregation Preimplantation diagnosis Vertebrata Embryo Mammalia Segregation Cleavage Genetics
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Summary:	BACKGROUND The aim of this study was to ascertain the prevalence of meiotic segregation products in embryos from carriers of 13/14 and 14/21 Robertsonian translocations and to estimate the predictive value of testing single cells using the fluorescence in situ hybridization (FISH) technique, to provide more information for decision-making about PGD. METHODS In this prospective cohort study, the copy number of translocation chromosomes in nuclei from lysed blastomeres of cleavage-stage embryos was ascertained using locus-specific FISH probes. Logistic regression analysis, controlling for translocation type, female age and fertility status, was used to calculate the odds ratio (OR) of unbalanced segregation products for female and male heterozygotes. The primary diagnostic measure was the predictive value of the test result. The primary outcome measure was the live birth rate per couple. RESULTS Female carriers were four times more likely than male carriers to produce embryos with an unbalanced translocation product (OR 3.8, 95% confidence interval 2.0–7.2, P < 0.001). The prevalence of abnormality for the chromosomes tested in embryos from female or male heterozygotes was estimated to be 43 or 28%, respectively, while estimates of the predictive value were 93–100 or 96–100% for a normal test result and 79 or 57% for an abnormal test result. The live birth rate per couple was 58% for female carriers and 50% for male carriers. CONCLUSIONS For female carriers, PGD using FISH could reduce the risk of miscarriage from either translocation or the risk of Down syndrome from the 14/21 Robertsonian translocation. PGD using FISH for male carriers is unlikely to be indicated given the relatively low prevalence of chromosome imbalance and low predictive value.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0268-1161 1460-2350
DOI:	10.1093/humrep/der080