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.