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

• 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
• DOI: 10.1093/humrep/der080
• EISSN: 1460-2350
• ISSN: 0268-1161

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.