Sequential FISH analysis of oocytes and polar bodies reveals aneuploidy mechanisms.
OBJECTIVE
Constitutional aneuploidy occurs in at least 5% of recognised pregnancies, with apparent preferential involvement of the X chromosome and the smaller autosomes. Molecular cytogenetic investigations of cleavage-stage embryos have revealed anomalies affecting all sizes of chromosomes. The aim was to investigate the variety of anomalies arising during maternal meiosis I by analysis of unfertilised oocytes and polar bodies to gain insight into aneuploidy mechanisms.


METHODS
Sequential FISH analysis was carried out with specific probes derived from eight chromosomes, representing all sizes. Only imbalance due to a gain of a whole chromosome or chromatid, represented by extra signals, was counted to avoid artefact.


RESULTS
Data were obtained on 236 eggs from 124 patients of average age 32.5 years (range 22-44). Ten patients (average 32.6 years) had abnormal eggs. The abnormality rate for oocytes and for polar bodies was close to 4% for each. Fourteen hyperploidies were found, seven involving additional single chromatids. The abnormalities affected chromosomes 13,16,18, 21 and X but not chromosomes 1, 9 or 12.


CONCLUSIONS
The data provide evidence for several mechanisms leading to aneuploidy, including classical non-disjunction of whole univalents; pre-division of chromatids prior to anaphase I, leading to imbalance detected at metaphase II; gonadal mosaicism for a trisomic cell line and preferential involvement of the smaller chromosomes. Monosomy for the large autosomes is not uncommon in cleavage-stage embryos and may additionally arise from anaphase lag preferentially affecting such chromosomes.
Cupisti
S
S
Department of Obstetrics & Gynaecology, University College London, 86-96 Chenies Mews, London, UK.
Conn
C M
CM
Fragouli
E
E
Whalley
K
K
Mills
J A
JA
Faed
M J W
MJ
Delhanty
J D A
JD
D000328:Adult; D000782:Aneuploidy; D002842:Chromatids; D002882:Chromosomes, Human, Pair 13; D002885:Chromosomes, Human, Pair 16; D002887:Chromosomes, Human, Pair 18; D002891:Chromosomes, Human, Pair 21; D041321:Chromosomes, Human, X; D005260:Female; D006238:Haploidy; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009865:Oocytes / Q000648:ultrastructure*