Jennifer Ong1, Con Ngo1, Shubha Srinivasan2, Komal Vora2, Meredith Wilson3, Dale Wright1
1 Department of Cytogenetics, The Children’s Hospital at Westmead, Corner Hawkesbury Road Hainsworth Street, Westmead, NSW, 2145.
2 Department of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Corner Hawkesbury Road Hainsworth Street, Westmead, NSW, 2145.
3 Department of Clinical Genetics, The Children’s Hospital at Westmead, Corner Hawkesbury Road Hainsworth Street, Westmead, NSW, 2145.
Background: In vitro fertilisation (IVF) is an assisted reproductive technology where gametes are fertilized in-vitro with uterine transfer. Although single embryo transfer is recommended practice, occasionally two or more embryos may be transferred. IVF is also associated with increased identical and non-identical twinning. Furthermore, twins may rarely arise from embryo-fusion resulting in a tetragametic chimera. We describe monochorionic diamniotic (MCDA) ‘chimeric’ twins with discordant sex following IVF.
Methodology and Results: Phenotypic male and female twins were born after IVF with two embryo transfer. A single placenta was noted. Neonatal blood cytogenetic investigation by FISH, QF-PCR, karyotype and genome-wide SNP microarray was performed. Both twins showed 46,XX and 46,XY cell lines in approximately equal proportions. The QF-PCR profiles were identical for both twins but the STR marker D18S386 showed four alleles, suggestive of tetragametic chimerism. SNP microarray confirmed this finding. Subsequent FISH analysis of urine sediment and buccal cells showed predominantly XX cells in the female whilst the male showed predominantly XY cells. Ovaries could not be identified on ultrasound in the female but the male had bilateral descended testes. The female showed high follicle-stimulating hormone (FSH) levels (17.7 IU/L; normal range: 0.1-8.7 IU/L).
Conclusion: The distribution of XX and XY cell lines among tissues of different embryonic origin is consistent with chimeric MCDA twins that arose from fusion of two embryos [male and female], which also excludes twin-twin transfusion syndrome. We propose that embryo fusion likely occurred at the late-morula or blastocyst stages of development to account for wide-spread tissue distribution of XX and XY cells. The sex discordance likely reflects the higher proportion of XX and XY cell lines within gonadal tissues for the female and male twin, respectively. The elevated FSH levels in the female may indicate gonadal dysgenesis with a risk of gonadoblastoma, thereby necessitating ongoing assessment.
My name is Jennifer Ong. I am currently studying a Bachelor of Biomedical Science at the University of Technology Sydney and employed as a Trainee Hospital Scientist in the Cytogenetics Department at The Children’s Hospital in Westmead for over 2 and a half years. I am interested in cytogenomics.