EmbryoWGS: Whole Genome Sequencing (WGS) on IVF Embryos and Individual Patients

Sponsor

GenEmbryomics Pty. Ltd (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05739890

Collaborator

(none)

100

Enrollment

Locations

Anticipated Duration (Months)

33.3

Patients Per Site

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This research project will seek to utilize developments in whole genome sequencing of preimplantation genetic diagnosis embryos to investigate the effect paternal age has on the de novo mutation rate of IVF embryos.

The study will whole genome sequence DNA obtained from biopsied embryos from infertile women to acquire the mutational burden status. This will enable ascertainment of the de novo mutation rate in addition to potential mutational hotspots.

Condition or Disease	Intervention/Treatment	Phase
Fertility Issues	Other: Embryo genome sequencing Other: Parents genome sequencing

Detailed Description

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) and whole exome sequencing (>depth of 500X per base). Analysis will be performed using multiple trio testing of each embryo in addition to the DNA from the genetic parent.

The study will compare 50 embryos from infertile women <30 years old and fathers 40 and above to 50 embryos from infertile women <30 years old and fathers <30. Biopsied trophectoderm DNA samples from the embryo will be genome and exome sequenced, with genome sequencing performed on each parents DNA sample.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Study of the Effect of Paternal Age on de Novo Mutation Rate by Using Whole Genome Sequencing of IVF Embryos

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
30-40 The study will compare 50 embryos from infertile women <30 years old and fathers 40 and above.	Other: Embryo genome sequencing 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) and whole exome sequencing (>depth of 500X per base). Other: Parents genome sequencing Analysis will be performed using multiple trio testing of each embryo in addition to the DNA from the genetic parent.
30-30 50 embryos from infertile women <30 years old and fathers <30	Other: Embryo genome sequencing 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) and whole exome sequencing (>depth of 500X per base). Other: Parents genome sequencing Analysis will be performed using multiple trio testing of each embryo in addition to the DNA from the genetic parent.

Arm

Intervention/Treatment

30-40

The study will compare 50 embryos from infertile women <30 years old and fathers 40 and above.

Other: Embryo genome sequencing

Other: Parents genome sequencing

Analysis will be performed using multiple trio testing of each embryo in addition to the DNA from the genetic parent.

30-30

50 embryos from infertile women <30 years old and fathers <30

Other: Embryo genome sequencing

Other: Parents genome sequencing

Analysis will be performed using multiple trio testing of each embryo in addition to the DNA from the genetic parent.

Outcome Measures

Primary Outcome Measures

De novo mutation rates [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 [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 30 Years

Sexes Eligible for Study:

Female

Inclusion Criteria:

Couples undergoing IVF in which the male is 40 or older
Consanguineous couples
Patients with a known genetic mutation

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neway Fertility	New York	New York	United States	10024
2	ORM Fertility	Portland	Oregon	United States	97205
3	Poma Fertility	Kirkland	Washington	United States	98034

Sponsors and Collaborators

GenEmbryomics Pty. Ltd

Investigators

Principal Investigator: Nicholas Murphy, PhD, GenEmbryomics Pty. Ltd

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

GenEmbryomics Pty. Ltd

ClinicalTrials.gov Identifier:

NCT05739890

Other Study ID Numbers:

RP-GE_02

First Posted:

Feb 22, 2023

Last Update Posted:

Feb 22, 2023

Last Verified:

Feb 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by GenEmbryomics Pty. Ltd

Genome Sequencing Mutation IVF

Additional relevant MeSH terms:

Infertility

Study Results

No Results Posted as of Feb 22, 2023