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Letter| Volume 35, ISSUE 4, P432, October 2017

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Oocyte spindle transfer for prevention of mitochodrial disease: the question of membrane fusion technique

      To the Editor
      I read with interest the report on the live birth after oocyte spindle transfer recently published in RBMOnline (
      • Zhang J.
      • Liu H.
      • Luo S.
      • Lu Z.
      • Chávez-Badiola A.
      • Liu Z.
      • Yang M.
      • Merhi Z.
      • Silber S.J.
      • Munné S.
      • Konstantinidis M.
      • Wells D.
      • Huang T.
      Live birth derived from oocyte spindle transfer to prevent mitochondrial disease.
      ). I wish to congratulate the authors on this important breakthrough in the prevention of the transmission of mitochondrial disease. As presented, however, the article has a number of weaknesses and limitations in a number of areas, as also pointed out in the accompanying Editorial (
      • Alikani M.
      • Fauser B.C.J.
      • García-Valesco J.A.
      • Simpson J.L.
      • Johnson M.H.
      First birth following spindle transfer for mitochondrial replacement thrapy.
      ). This letter is focused on one of them – the method of membrane fusion used for spindle transfer.
      • Zhang J.
      • Liu H.
      • Luo S.
      • Lu Z.
      • Chávez-Badiola A.
      • Liu Z.
      • Yang M.
      • Merhi Z.
      • Silber S.J.
      • Munné S.
      • Konstantinidis M.
      • Wells D.
      • Huang T.
      Live birth derived from oocyte spindle transfer to prevent mitochondrial disease.
      used electrofusion, a technique known to produce premature activation of human oocytes (
      • Cohen J.
      • Scott R.
      • Alikani M.
      • Schimmel T.
      • Munné S.
      • Levron J.
      • Wu L.
      • Brenner C.
      • Warner C.
      • Willadsen S.
      Ooplasmic transfer in mature human oocytes.
      ), a condition suspected to be at the origin of embryo aneuploidy (
      • Paull D.
      • Emmanuele V.
      • Weiss K.A.
      • Treff N.
      • Stewart L.
      • Hua H.
      • Zimmer M.
      • Kahler D.J.
      • Goland R.S.
      • Noggle S.A.
      • Prosser R.
      • Hirano M.
      • Sauer M.V.
      • Egli D.
      Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants.
      ). In fact, three out of four blastocysts obtained from reconstituted oocytes in the report by
      • Zhang J.
      • Liu H.
      • Luo S.
      • Lu Z.
      • Chávez-Badiola A.
      • Liu Z.
      • Yang M.
      • Merhi Z.
      • Silber S.J.
      • Munné S.
      • Konstantinidis M.
      • Wells D.
      • Huang T.
      Live birth derived from oocyte spindle transfer to prevent mitochondrial disease.
      were aneuploid.
      In the first scientifically documented experimental work on spindle transfer between mature human oocytes (
      • Tesarik J.
      • Nagy Z.P.
      • Mendoza C.
      • Greco E.
      Chemically and mechanically induced membrane fusion: non-activating methods for nuclear transfer in mature human oocytes.
      ), which was not cited in the paper by
      • Zhang J.
      • Liu H.
      • Luo S.
      • Lu Z.
      • Chávez-Badiola A.
      • Liu Z.
      • Yang M.
      • Merhi Z.
      • Silber S.J.
      • Munné S.
      • Konstantinidis M.
      • Wells D.
      • Huang T.
      Live birth derived from oocyte spindle transfer to prevent mitochondrial disease.
      , two methods that avoided premature oocyte activation were used. Fusion between a karyoplast and an enucleated oocyte was achieved either chemically, with polyethylene glycol, or by mechanical manipulation. Both methods resulted in a low degree of spontaneous oocyte activation and a high capacity of the reconstructed oocytes to undergo subsequent calcium-induced activation (
      • Tesarik J.
      • Nagy Z.P.
      • Mendoza C.
      • Greco E.
      Chemically and mechanically induced membrane fusion: non-activating methods for nuclear transfer in mature human oocytes.
      ). It is evident that the optimal methodology of spindle transfer for mitochondrial replacement therapy is far from being established, and future research is urgently needed.

      References

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        • Johnson M.H.
        First birth following spindle transfer for mitochondrial replacement thrapy.
        Reprod. Biomed. Online. 2017; 34: 333-336
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        • Scott R.
        • Alikani M.
        • Schimmel T.
        • Munné S.
        • Levron J.
        • Wu L.
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        • Warner C.
        • Willadsen S.
        Ooplasmic transfer in mature human oocytes.
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        • Goland R.S.
        • Noggle S.A.
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        • Egli D.
        Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants.
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        Chemically and mechanically induced membrane fusion: non-activating methods for nuclear transfer in mature human oocytes.
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        • Zhang J.
        • Liu H.
        • Luo S.
        • Lu Z.
        • Chávez-Badiola A.
        • Liu Z.
        • Yang M.
        • Merhi Z.
        • Silber S.J.
        • Munné S.
        • Konstantinidis M.
        • Wells D.
        • Huang T.
        Live birth derived from oocyte spindle transfer to prevent mitochondrial disease.
        Reprod. Biomed. Online. 2017; 34: 361-368