First Successful Pregnancy After Pre-implantation Genetic Diagnosis by FISH for an Inversion Together with a Cryptic Translocation in India

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.