NCT05739890

Brief 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. 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.

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
100

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Jun 2023

Geographic Reach
2 countries

4 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 13, 2023

Completed
9 days until next milestone

First Posted

Study publicly available on registry

February 22, 2023

Completed
3 months until next milestone

Study Start

First participant enrolled

June 1, 2023

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2024

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2024

Completed
Last Updated

September 25, 2023

Status Verified

September 1, 2023

Enrollment Period

9 months

First QC Date

February 13, 2023

Last Update Submit

September 21, 2023

Conditions

Fertility IssuesSingle-Gene Defects

Keywords

Genome Sequencing IVF

Outcome Measures

Primary Outcomes (2)

  • 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.

    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).

    Month 6

Study Arms (1)

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.

Other: Embryo genome sequencingOther: Parents genome sequencing

Interventions

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.

Age >18yrs
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.

Age >18yrs

Eligibility Criteria

Age18 Years - 48 Years
Sexall
Age GroupsAdult (18-64)
Sampling MethodNon-Probability Sample
Study Population

Couples undergoing IVF with 1≥ embryo sample unsuitable for transfer due to genetic or chromosome abnormalities.

You may not qualify if:

  • Female patients with low ovarian reserve (\< 10 follicles or FSH\>10, AMH \<1).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Neway Fertility

New York, New York, 10024, United States

NOT YET RECRUITING

ORM Fertility

Portland, Oregon, 97205, United States

NOT YET RECRUITING

Poma Fertility

Kirkland, Washington, 98034, United States

NOT YET RECRUITING

Preimplantation Genetic Testing Unit ART and Reproductive Genetics Unit, Memorial Sisli Hospital

Istanbul, Okmeydani-Sisli, 34385, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

InfertilityGenetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Genital DiseasesUrogenital DiseasesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

  • Nicholas Murphy, PhD

    GenEmbryomics Pty. Ltd

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Santiago Munné, PhD

CONTACT

+1-646-2072897santiago.munne@gmail.com

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
OTHER
Target Duration
1 Day
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 13, 2023

First Posted

February 22, 2023

Study Start

June 1, 2023

Primary Completion

March 1, 2024

Study Completion

August 1, 2024

Last Updated

September 25, 2023

Record last verified: 2023-09

Locations

US(3)TU(1)