Abstract
The technique of pre-implantation genetic diagnosis (PGD) by fluorescence in situ
hybridization (FISH) in cases of repeated miscarriages due to parental balanced inversions
and translocations is relatively new in India. In a couple with a history of recurrent
miscarriages and implantation failures, karyotyping done in three laboratories showed
that the husband had an insertion or inversion of chromosome 12. Hence, they were
referred to us for PGD. The anomaly turned out to be more complex. A pre-PGD workup
using a series of FISH probes on metaphases accompanied by reflex FISH was required
to characterize the anomaly. For subsequent PGD, single blastomeres were biopsied
from seven embryos obtained by intracytoplasmic sperm injection. FISH analysis had
to be carried out using ten probes in four rounds. On pre-PGD workup for inversion
12 by FISH, an additional anomaly of a cryptic translocation between 9qter and 12qter
was detected in the husband. His complex karyotype according to the detailed ISCN
nomenclature was therefore 46,XY,t(9;12)(9pter→9q34.1::12q24.2→12qter),der(12)inv(12)(12pter→12p11.2::12q24.2→12p11.2::9q34.1→9qter).
After PGD, the normal and balanced embryos transferred, resulted in the birth of healthy
twins conceived in the first cycle itself. Therefore, a pre-PGD workup is important
and needs reflex FISH in the event of an unexpected cytogenetic anomaly. PGD will
need the analysis of additional chromosomes on the same cell by FISH in such cases.
An experienced in vitro fertilization and Genetics team is essential for success.
This is the first report of PGD by FISH for an inversion coupled with a cryptic translocation
from India.
Keywords
Pre-implantation genetic diagnosis - FISH - Inversion - Cryptic translocation - Pre-PGD
workup - Reflex FISH - India
