Fertility IssuesEmbryoWGSNCT05739890
Whole Genome Sequencing (WGS) on IVF Embryos and Individual Patients
An observational study of Fertility Issues and Single-Gene Defects, run by GenEmbryomics Pty. Ltd at 4 sites in 2 countries.
Trial summary
This research project aims to utilise recent advances in whole genome sequencing of preimplantation genetic diagnosis embryos to investigate the impact of paternal age on de novo mutation rates in IVF embryos. Read more about this study
- Who is it for?
- Ages 18 to 48 years
- Conditions the study is for
- Fertility Issues, Single-Gene Defects
- What is being tested?
- Embryo genome sequencing and Parents genome sequencing
- How many people
- 100 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 1 Jun 2023to Aug 2024
- How long will I take part?
- 1 Day
- Phase
- Observational
- 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 18 to 48 years
- All sexes
- Adult
Study population: Couples undergoing IVF with 1≥ embryo sample unsuitable for transfer due to genetic or chromosome abnormalities.
Who may be able to join
None listed.
Who cannot join
- Female patients with low ovarian reserve (< 10 follicles or FSH>10, AMH <1).
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites, 3 recruiting
- Not yet recruiting
Poma Fertility
Kirkland, Washington, 98034
- Not yet recruiting
Neway Fertility
New York, New York, 10024
- Not yet recruiting
ORM Fertility
Portland, Oregon, 97205
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Preimplantation Genetic Testing Unit ART and Reproductive Genetics Unit, Memorial Sisli Hospital
Istanbul, Okmeydani-Sisli, 34385
Semra Kahraman, M.D., 90 212 314 6666
Murat Cetinkaya, M.D., PhD, +90 533 266 42 24, muratcetinkaya01@gmail.com
About this study
Official title: Study of the Effect of Paternal Age on de Novo Mutation Rate by Using Whole Genome Sequencing of IVF Embryos
This research project aims to utilise recent advances in whole genome sequencing of preimplantation genetic diagnosis embryos to investigate the impact of paternal age on de novo mutation rates in IVF embryos. Embryos that are deemed unsuitable for transfer following preimplantation genetic testing for monogenic/single gene disorders (PGT-M) due to the detection of genetic abnormalities will be utilized for this study. These embryos will undergo re-biopsy, and both the biopsied samples as well as the remaining embryo tissue will be subject to whole genome sequencing. This will allow the assessment of de novo mutation rates based on the paternal age.
Read the detailed description
This project proposes a paired non-inferiority trial utilizing the retrospective testing of research embryos to establish the optimized parameters for amplified trophectoderm biopsy and whole genome sequencing compared to traditional preimplantation genetic testing for aneuploidy (PGT-A).
The primary outcome is the de novo mutation rate, which will be compared between embryos subjected to trophectoderm biopsy and whole genome sequencing versus reanalysis with Sanger sequencing. Trio testing will be performed for each embryo using DNA from the genetic parents in addition to embryo. The study will compare cases that include couples with at least one embryo deemed unsuitable for transfer. A paired study design will be used, with embryos from each couple split into two arms - one subjected to trophectoderm biopsy and whole genome sequencing, the other to reanalysis with targeted sequencing.
Biopsied trophectoderm samples and the remaining embryo tissues from the whole genome sequencing arm will undergo sequencing. Sequencing will also be performed on DNA samples from each genetic parent.
Derivation of de novo mutation rates is a key goal, as these provide insights into effects of paternal age and other factors on germline mutations in preimplantation embryos, increasing the knowledge of the risks associated with advanced paternal age. Secondary metrics will be investigated to supplement the analysis, including clean reads and clean bases indicating the amount of high-quality data for the source templates. Mapping rate, unique rate and duplicate rate, assessing data accuracy and quality. Comparison of multiple metrics will determine the optimized parameters for performing amplified trophectoderm biopsy and whole genome sequencing. This can then inform future research and clinical studies.
The de novo mutation rate will be derived by modelling the observed mutation rate as a function of parental ages, specifically the paternal age. Whole genome sequencing of embryo samples as well as both parents will identify raw numbers of de novo mutations. The paternal age coefficient for the de novo mutation rate will be calculated using a regression model with the number of de novo mutations as the dependent variable and paternal age as the key independent variable. Covariates like maternal age and sequencing quality metrics will also be included to account for potential confounding factors. The regression model will determine the increase in de novo mutations per year of paternal age, providing the paternal age coefficient. Comparing embryos from older and younger males will reveal differences in mutation rates. The overall model will establish the quantitative relationship between paternal age and de novo mutations in preimplantation embryos based on the study's whole genome sequencing data.
- Conditions
- Fertility Issues, Single-Gene Defects
- Being tested
- Embryo genome sequencing, Parents genome sequencing
- Keywords
- Genome Sequencing IVF
- Medical subject headings
- Infertility, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Embryo genome sequencingOther
This project proposes the testing of a cohort of research embryos to establish the key parameters for amplified trophectoderm biopsied embryos using minimum depth required for genome sequencing (>depth of 30x per base).The remaining embryo tissue will be whole genome sequenced to validate the results of the biopsy.
Parents genome sequencingOther
Analysis will be performed using trio testing of each embryo in addition to the DNA from the genetic parent to facilitate the derivation of de novo mutation rate.
| Study group | Role | What they receive |
|---|---|---|
| Age >18yrs | The study will compare embryos from >50 couples and their embryo samples flagged not suitable for transfer from deidentified couples with date of birth required. Receives: Other: Embryo genome sequencing; Other: Parents genome sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
De novo mutation rates
Metrics for investigation include: clean reads, clean bases (Mp), mapping rate, unique rate, duplicate rate, mismatch rate, average sequencing depth, Ti/Tv (Transition/ Transversion) ratio, true-positive rate, false-positive rate, false-negative rate which enables the derivation of de novo mutation rates.
Measured: Month 6
Variant pathogenicity, Zygosity and mode of inheritance
Variant pathogenicity; the zygosity and mode of inheritance will be assessed and documented for validation of variant calls for heritable and non-inherited variants. There will be an examination of the sequencing data from the embryo cohort by using the parental genomes as a validation reference. Initially this will focus on single nucleotide polymorphisms (SNPs) and small insertions/deletions (Indels).
Measured: Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2023
- Study start1 Jun 2023
- Primary completionMar 2024 (estimated)
- Study completionAug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fertility IssuesStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 100 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- GenEmbryomics Pty. Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nicholas Murphy, PhD, Principal investigator, GenEmbryomics Pty. Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05739890
- Sponsor's protocol ID
- RP-GE_02
- Acronym
- EmbryoWGS
- Status last verified
- Sep 2023
- First submitted
- 13 Feb 2023
- Last updated
- 25 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data sharing plan will be defined once results are available.
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Effect of Paternal Age on de Novo Mutation Rate by Using Whole Genome Sequencing of IVF Embryos
- ClinicalTrials.gov ID
- NCT05739890
- Acronym / sponsor ID
- EmbryoWGS / RP-GE_02
- Conditions
- Fertility Issues, Single-Gene Defects
- Keywords
- Genome Sequencing IVF
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- GenEmbryomics Pty. LtdIndustry (pharma, biotech, devices)
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- Mar 2024 (estimated)
- Study completion
- Aug 2024 (estimated)
- First posted
- 22 Feb 2023 (actual)
- 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.
This research project aims to utilise recent advances in whole genome sequencing of preimplantation genetic diagnosis embryos to investigate the impact of paternal age on de novo mutation rates in IVF embryos. Embryos that are deemed unsuitable for transfer following preimplantation genetic testing for monogenic/single gene disorders (PGT-M) due to the detection of genetic abnormalities will be utilized for this study. These embryos will undergo re-biopsy, and both the biopsied samples as well as the remaining embryo tissue will be subject to whole genome sequencing. This will allow the assessment of de novo mutation rates based on the paternal age.
Detailed description
This project proposes a paired non-inferiority trial utilizing the retrospective testing of research embryos to establish the optimized parameters for amplified trophectoderm biopsy and whole genome sequencing compared to traditional preimplantation genetic testing for aneuploidy (PGT-A).
The primary outcome is the de novo mutation rate, which will be compared between embryos subjected to trophectoderm biopsy and whole genome sequencing versus reanalysis with Sanger sequencing. Trio testing will be performed for each embryo using DNA from the genetic parents in addition to embryo. The study will compare cases that include couples with at least one embryo deemed unsuitable for transfer. A paired study design will be used, with embryos from each couple split into two arms - one subjected to trophectoderm biopsy and whole genome sequencing, the other to reanalysis with targeted sequencing.
Biopsied trophectoderm samples and the remaining embryo tissues from the whole genome sequencing arm will undergo sequencing. Sequencing will also be performed on DNA samples from each genetic parent.
Derivation of de novo mutation rates is a key goal, as these provide insights into effects of paternal age and other factors on germline mutations in preimplantation embryos, increasing the knowledge of the risks associated with advanced paternal age. Secondary metrics will be investigated to supplement the analysis, including clean reads and clean bases indicating the amount of high-quality data for the source templates. Mapping rate, unique rate and duplicate rate, assessing data accuracy and quality. Comparison of multiple metrics will determine the optimized parameters for performing amplified trophectoderm biopsy and whole genome sequencing. This can then inform future research and clinical studies.
The de novo mutation rate will be derived by modelling the observed mutation rate as a function of parental ages, specifically the paternal age. Whole genome sequencing of embryo samples as well as both parents will identify raw numbers of de novo mutations. The paternal age coefficient for the de novo mutation rate will be calculated using a regression model with the number of de novo mutations as the dependent variable and paternal age as the key independent variable. Covariates like maternal age and sequencing quality metrics will also be included to account for potential confounding factors. The regression model will determine the increase in de novo mutations per year of paternal age, providing the paternal age coefficient. Comparing embryos from older and younger males will reveal differences in mutation rates. The overall model will establish the quantitative relationship between paternal age and de novo mutations in preimplantation embryos based on the study's whole genome sequencing data.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 1 Day
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Age >18yrs | – | Other: Embryo genome sequencing, Other: Parents genome sequencingThe study will compare embryos from >50 couples and their embryo samples flagged not suitable for transfer from deidentified couples with date of birth required. |
Who may qualify
- Ages
- 18 to 48 years
- Sex
- All
- Age groups
- Adult
- Study population
- Couples undergoing IVF with 1≥ embryo sample unsuitable for transfer due to genetic or chromosome abnormalities.
Key inclusion criteria (0 listed)
Key exclusion criteria (1 listed)
- Female patients with low ovarian reserve (< 10 follicles or FSH>10, AMH <1).
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 |
|---|---|---|
| Embryo genome sequencingThis project proposes the testing of a cohort of research embryos to establish the key parameters for amplified trophectoderm biopsied embryos using minimum depth required for genome sequencing (>depth of 30x per base).The remaining embryo tissue will be whole genome sequenced to validate the results of the biopsy. | Other | Age >18yrs |
| Parents genome sequencingAnalysis will be performed using trio testing of each embryo in addition to the DNA from the genetic parent to facilitate the derivation of de novo mutation rate. | Other | Age >18yrs |
Primary outcome
De novo mutation rates
Time frame: Month 6
Metrics for investigation include: clean reads, clean bases (Mp), mapping rate, unique rate, duplicate rate, mismatch rate, average sequencing depth, Ti/Tv (Transition/ Transversion) ratio, true-positive rate, false-positive rate, false-negative rate which enables the derivation of de novo mutation rates.
Variant pathogenicity, Zygosity and mode of inheritance
Time frame: Month 6
Variant pathogenicity; the zygosity and mode of inheritance will be assessed and documented for validation of variant calls for heritable and non-inherited variants. There will be an examination of the sequencing data from the embryo cohort by using the parental genomes as a validation reference. Initially this will focus on single nucleotide polymorphisms (SNPs) and small insertions/deletions (Indels).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2023.
- Individual participant dataSharing planned: Undecided. Data sharing plan will be defined once results are available.
Related trials for Fertility Issues
RecruitingObservational study
International Pilot Study for Dual Non-invasive Assesment of Embryo Development
Infertility
Active, not recruitingObservational study
Retrieval of Sperm From Men With Azoospermia Using Ultrasound-guided Rete Testis Aspiration
Azoospermia, Nonobstructive, Infertility, Male
Not yet recruiting
Spinery Basivertebral Nerve Ablation for Vertebrogenic Chronic Low Back Pain
Low Back Pain, Chronic Low Back Pain (CLBP)
RecruitingObservational study
Impact of Infertility on the Sexual Sphere in Couples Undergoing Assisted Reproduction
Sexual Health Quality of Life, Infertile Patients
RecruitingObservational study
Pilot Study of Discarded Blastocysts
Infertility (IVF Patients)
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.
Nicholas Murphy, PhD principal investigator
GenEmbryomics Pty. Ltd
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fertility Issues and Single-Gene Defects, run by GenEmbryomics Pty. Ltd at 4 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 0 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: status not confirmed, as of the sponsor's last update on 25 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Turkey (Türkiye). 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Santiago Munné, PhD (+1-646-2072897, santiago.munne@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
De novo mutation rates (time frame: Month 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Sep 2023.