Management of Abnormally Fertilized Zygotes? InVitro Correction of 3PN

NCT ID: NCT02358759

Last Updated: 2016-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-30

Study Completion Date

2015-09-30

Brief Summary

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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

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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.

Conditions

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Infertility

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Giant Oocytes after ICSI

abnormally produced oocyte after ART or Controlled ovarian stimulation. Correction of abnormally fertilized oocytes using nucleus removal.

Group Type ACTIVE_COMPARATOR

Correction of abnormally fertilized oocytes

Intervention Type PROCEDURE

Removing of extra developed nucleus from fertilized oocyte.

3PNs zygotes developed after ICSI

Abnormally developed embryos these produced 3PNs. Correction of abnormally fertilized oocytes using nucleus removal.

Group Type ACTIVE_COMPARATOR

Correction of abnormally fertilized oocytes

Intervention Type PROCEDURE

Removing of extra developed nucleus from fertilized oocyte.

Interventions

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Correction of abnormally fertilized oocytes

Removing of extra developed nucleus from fertilized oocyte.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Giant oocytes
* 3 PNs developed embryos at day 1 post ICSI.

Exclusion Criteria

* Patient refused to involving their abnormal oocytes at our study.
Minimum Eligible Age

20 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ahmad Mustafa Mohamed Metwalley

OTHER

Sponsor Role lead

Responsible Party

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Ahmad Mustafa Mohamed Metwalley

IVF unit director

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Ahmad M Metwalley

Role: PRINCIPAL_INVESTIGATOR

Al Baraka Fertility Hospital

Locations

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Al Baraka Fertility Hospital

Manama, Adliyah, Bahrain

Site Status

Ibn Sina IVF Center- Ibn Sina Hospital

Sohag, Sohag Governorate, Egypt

Site Status

Countries

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Bahrain Egypt

References

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Jacobs PA, Angell RR, Buchanan IM, Hassold TJ, Matsuyama AM, Manuel B. The origin of human triploids. Ann Hum Genet. 1978 Jul;42(1):49-57. doi: 10.1111/j.1469-1809.1978.tb00930.x.

Reference Type RESULT
PMID: 686684 (View on PubMed)

Rosenbusch B. The potential significance of binovular follicles and binucleate giant oocytes for the development of genetic abnormalities. J Genet. 2012;91(3):397-404. doi: 10.1007/s12041-012-0195-x.

Reference Type RESULT
PMID: 23271027 (View on PubMed)

Wolf DP, Mitalipov N, Mitalipov S. Mitochondrial replacement therapy in reproductive medicine. Trends Mol Med. 2015 Feb;21(2):68-76. doi: 10.1016/j.molmed.2014.12.001. Epub 2014 Dec 10.

Reference Type RESULT
PMID: 25573721 (View on PubMed)

Vogel G. Assisted reproduction. FDA considers trials of 'three-parent embryos'. Science. 2014 Feb 21;343(6173):827-8. doi: 10.1126/science.343.6173.827. No abstract available.

Reference Type RESULT
PMID: 24558137 (View on PubMed)

Amato P, Tachibana M, Sparman M, Mitalipov S. Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases. Fertil Steril. 2014 Jan;101(1):31-5. doi: 10.1016/j.fertnstert.2013.11.030.

Reference Type RESULT
PMID: 24382342 (View on PubMed)

Other Identifiers

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AlBarakaSD3

Identifier Type: -

Identifier Source: org_study_id

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