Is the resulting phenotype of an embryo with balanced X-autosome translocation, obtained by means of preimplantation genetic diagnosis, linked to the X inactivation pattern?

Objective: To examine if a balanced female embryo with X-autosome translocation could, during its subsequent development, express an abnormal phenotype.

Design: Preimplantation genetic diagnosis (PGD) analysis on two female carriers with maternal inherited X-autosome translocations.

Setting: Infertility center and genetic laboratory in a public hospital.

Patient(s): Two female patients carriers undergoing PGD for a balanced X-autosome translocations: patient 1 with 46,X,t(X;2)(q27;p15) and patient 2 with 46,X,t(X;22)(q28;q12.3).

Intervention(s): PGD for balanced X-autosome translocations.

Main outcome measure(s): PGD outcomes, fluorescence in situ hybridization in biopsied embryos and meiotic segregation patterns analysis of embryos providing from X-autosome translocation carriers.

Result(s): Controlled ovarian stimulation facilitated retrieval of a correct number of oocytes. One balanced embryo per patient was transferred and one developed, but the patient miscarried after 6 weeks of amenorrhea. In X-autosome translocation carriers, balanced Y-bearing embryos are most often phenotypically normal and viable. An ambiguous phenotype exists in balanced X-bearing embryos owing to the X inactivation mechanism. In 46,XX embryos issued from an alternate segregation, der(X) may be inactivated and partially spread transcriptional silencing into a translocated autosomal segment. Thus, the structural unbalanced genotype could be turned into a viable functional balanced one. It is relevant that a discontinuous silencing is observed with a partial and unpredictable inactivation of autosomal regions. Consequently, the resulting phenotype remains a mystery and is considered to be at risk of being an abnormal phenotype in the field of PGD.

Conclusion(s): It is necessary to be cautious regarding to PGD management for this type of translocation, particularly in transferred female embryos.