Preembryonic diagnosis for sickle cell disease.

Embryos found to be abnormal during preimplantation genetic diagnosis are discarded or analyzed to confirm the diagnosis. The destruction of affected embryos is ethically unacceptable to some couples. We developed a preembryonic genetic diagnosis, that uses sequential first and second polar body removal, followed by oocyte freezing at the pronuclear stage. This was applied in a patient at risk of having a child with sickle cell disease, who suffered hyper-stimulation syndrome. Fourteen oocytes were obtained and tested for the maternal sickle cell allele by PCR analysis of the first and second polar body. Immediately after procedure of polar body removal, the pronuclear-stage oocytes were frozen. Six mutation-free oocytes detected by polar body analysis were then thawed, allowed to cleave, and transferred in the two consecutive clinical cycles, both resulting in clinical pregnancies, one of which resulted in birth of a healthy child. The oocytes predicted to contain abnormal beta-globin gene were not further cultured, to avoid formation and discard of the affected embryos. The results demonstrate feasibility of preembryonic diagnosis for single gene disorders, avoiding the establishment and destruction of mutant embryos.