InfertilityEarly Phase 1NCT02358759
Management of Abnormally Fertilized Zygotes? InVitro Correction of 3PN
A Early Phase 1 study testing Correction of abnormally fertilized oocytes in people with Infertility, run by Ahmad Mustafa Mohamed Metwalley at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 45 years
- Conditions the study is for
- Infertility
- What is being tested?
- Correction of abnormally fertilized oocytes
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jun 2014to Sep 2015
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Giant oocytes
- 3 PNs developed embryos at day 1 post ICSI.
Who cannot join
- Patient refused to involving their abnormal oocytes at our study.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Egypt1 site
Ibn Sina IVF Center- Ibn Sina Hospital
Sohag, Sohag Governorate, 15006
About this study
Official title: Treatment of Abnormally Multinucleated Zygotes Before Before Division Starting.
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.
Read the 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.
- 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
- Infertility
- Being tested
- Correction of abnormally fertilized oocytes
- Keywords
- Abnormal zygote fertilization, 3PNs correction, Giant oocyte management, triploidy fertilization, Maternal nucleus removal
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Correction of abnormally fertilized oocytesProcedure or surgery
Removing of extra developed nucleus from fertilized oocyte.
| Study group | Role | What they receive |
|---|---|---|
| Giant Oocytes after ICSI | Active comparator | abnormally produced oocyte after ART or Controlled ovarian stimulation. Correction of abnormally fertilized oocytes using nucleus removal. Receives: Procedure: Correction of abnormally fertilized oocytes |
| 3PNs zygotes developed after ICSI | Active comparator | Abnormally developed embryos these produced 3PNs. Correction of abnormally fertilized oocytes using nucleus removal. Receives: Procedure: Correction of abnormally fertilized oocytes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Normal Embryos Developed
At 18 hours after ICSi nucleus to be removed in-order to make genetic correction for abnormally developed embryos. Final result is normal embryos produced with 2PNs evaluated by FSIH study for 5 chromosomes.
This indicated the genetic correction process was successful process, and applicable to produce normal growing embryos.
Measured: Day 1 or 18 hours post ICSI nucleus removal
Secondary outcomes (2)
Day 3 embryo available for blastomer biopsy
Availability of successful nucleus removal from zygote to be developed to active dividing embryo available for cytogenetic study.
That indicated normal embryogenesis processing
Measured: 1 Year
5 chromosomes FISH study
chromosomes 13, 18, 21, X and Y to be screened using fluorescence insitu hybridization (FISH). In order to check primary euploid developed with male (XY) or female (XX) embryos.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2015 (estimated)
- Study startJun 2014
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ahmad Mustafa Mohamed Metwalley
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ahmad Mustafa Mohamed Metwalley, Al Baraka Fertility Hospital
- Investigators
- Ahmad M Metwalley, Principal investigator, Al Baraka Fertility Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02358759
- Sponsor's protocol ID
- AlBarakaSD3
- Status last verified
- Jan 2016
- First submitted
- 15 Jan 2015
- Last updated
- 12 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 686684Rosenbusch 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.
PubMed 23271027Wolf 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.
PubMed 25573721Vogel 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.
PubMed 24558137Amato 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.
PubMed 24382342
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Abnormally Multinucleated Zygotes Before Before Division Starting.
- ClinicalTrials.gov ID
- NCT02358759
- Acronym / sponsor ID
- AlBarakaSD3
- Conditions
- Infertility
- Keywords
- Abnormal zygote fertilization, 3PNs correction, Giant oocyte management, triploidy fertilization, Maternal nucleus removal
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Ahmad Mustafa Mohamed MetwalleyUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 9 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Giant Oocytes after ICSI | Active comparator | Procedure: Correction of abnormally fertilized oocytesabnormally produced oocyte after ART or Controlled ovarian stimulation. Correction of abnormally fertilized oocytes using nucleus removal. |
| 3PNs zygotes developed after ICSI | Active comparator | Procedure: Correction of abnormally fertilized oocytesAbnormally developed embryos these produced 3PNs. Correction of abnormally fertilized oocytes using nucleus removal. |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Giant oocytes
- 3 PNs developed embryos at day 1 post ICSI.
Key exclusion criteria (1 listed)
- Patient refused to involving their abnormal oocytes at our study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Correction of abnormally fertilized oocytesRemoving of extra developed nucleus from fertilized oocyte. | Procedure or surgery | 3PNs zygotes developed after ICSI, Giant Oocytes after ICSI |
Primary outcome
Normal Embryos Developed
Time frame: Day 1 or 18 hours post ICSI nucleus removal
At 18 hours after ICSi nucleus to be removed in-order to make genetic correction for abnormally developed embryos. Final result is normal embryos produced with 2PNs evaluated by FSIH study for 5 chromosomes. This indicated the genetic correction process was successful process, and applicable to produce normal growing embryos.
2 secondary outcomes
Day 3 embryo available for blastomer biopsy
Time frame: 1 Year
5 chromosomes FISH study
Time frame: 1 Year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2016.
- Results publication: PubMed 686684Jacobs 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.
- Results publication: PubMed 23271027Rosenbusch 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.
- Results publication: PubMed 25573721Wolf 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.
- Results publication: PubMed 24558137Vogel 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.
- Results publication: PubMed 24382342Amato 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahmad M Metwalley principal investigator
Al Baraka Fertility Hospital
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Correction of abnormally fertilized oocytes in people with Infertility, run by Ahmad Mustafa Mohamed Metwalley at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Bahrain, Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Normal Embryos Developed (time frame: Day 1 or 18 hours post ICSI nucleus removal). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02358759, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2016.