Management of Abnormally Fertilized Zygotes? InVitro Correction of 3PN
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional
Phase: Early Phase 1

Summary: 
      In this newly developed protocol, and idea, is to manage those abnormally developed zygotes
      from different ART procedures.

      The investigators developed the plan and requirements needed to select the target extra
      nucleus or pronuclei to be extruded from fertilized egg in order to maintain developing
      healthy normal embryo.
    

Detailed description: 
      As approved by Dyban and Baranov et al, about 15-18% of abortions caused by triploidy
      fertilization. One of sources for maternally triploidy is failure in the first meiotic
      division (Jacobs et al., 1978).

      One of Digynic triploidy is developed by fertilized giant oocyte (Dyban and Baranov, 1987)
      {nuclear but no cytoplasmic division in an oogonium or cytoplasmic fusion of two oogonia
      (Austin, 1960)}.

      Giant oocyte characterized with bigger diameter and will distinguished polar bodies at
      metaphase II.

      B. Rosenbusch et. al. 2002, cytogenetic study showed that extra haploid maternal copy
      associated with MII (46,XX/ 2N ) giant oocytes as well as triploidy with fertilized giant
      oocytes (3N with 69,XXX or 69,XXY).

      First Mitotic division plane with polar axes studies by Scott, 2001 , shows that Pn developed
      closer to 2nd polar body is the maternal origin PN.

      Giant oocytes were collected from different IVF cycles, to be injected with normal sperm
      using Intracytoplasmic sperm injection (ICSI). 18 hours post ICSI arranged for fertilization
      evaluation and PN removal for fertilized oocyte before syngamy starts.

      Video attached shows process of zygote manipulation by the way avoiding the division axis and
      focusing the extra maternal PN to be aspirated.

      Pronuclear transfer in human embryos for mitochondrial DNA correction started the methodology
      of pronuclear manipulation, for that possibility of utilizing of 3PNs developed embryos
      research tools can be started. We arranged to study available received giant oocytes during
      IVF cycles. Accordingly we arranged for pronuclear removal followed by FISH evaluation in
      order to targeting Normal males embryos that insure proper extra maternal pronucleus removal.

      Successful trials of maternal PN removal for giant oocyte collected from different cases
      summarized in table 1. All blastocyst developed arranged for FISH, so all embryos were
      utilized for cytogenetic evaluation.

      Recommendations:

      Further evaluations using STRs (Short tandem repeat ) should be used for maternal-paternal
      genome differentiation. NGS study is under evaluation for developed embryos for full CCS
      reporting and more genetic integrity. Epigenetic evaluation study recommended for triploidy
      corrected embryos for genetic expressions and early embryo developments as well as
      differentiation between paternal and maternal genomic activity.
    

Intervention name(s): Correction of abnormally fertilized oocytes
Intervention type(s): Procedure
Intervention description(s): Removing of extra developed nucleus from fertilized oocyte.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Abnormal zygote fertilization; 3PNs correction; Giant oocyte management; triploidy fertilization; Maternal nucleus removal