Preembryonic diagnosis for sickle cell disease

Embryos found to be abnormal during preimplantation genetic diagnosis are d iscarded or analyzed to confirm the diagnosis. The destruction or affected embryos is ethically unacceptable to some couples. We developed a preembryo nic genetic diagnosis, that uses sequential first and second polar body rem oval. 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 suffe red hyper-stimulation syndrome. Fourteen oocytes were obtained and tested f or the maternal sickle cell allele by PCR analysis of the first and second polar body. Immediately after procedure of polar body removal, the pronucle ar-stage oocytes were frozen. Six mutation-free oocytes detected by polar b ody analysis were then thawed, allowed to cleave, and transferred in the tw o consecutive clinical cycles, both resulting in clinical pregnancies. one of which resulted in birth of a healthy child. The oocytes predicted to con tain abnormal beta -globin gene were not further cultured, to avoid formati on and discard of the affected embryos. The results demonstrate feasibility of preembryonic diagnosis for single gene disorders. avoiding the establis hment and destruction of mutant embryos. (C) 2001 Published by Elsevier Sci ence Ireland Ltd.