chromosomal anomalies monogenic diseases
Conditions
Interventions
None listed
Sponsors
Medisch Universitair Ziekenhuis Maastricht
Eligibility
Inclusion criteria
Inclusion criteria: Group inclusion criteria: To be eligible to participate in this study, a couple must meet all of the following criteria: Couples that have or are carrier of a known severe genetic disorder that choose to do in vitro fertilization (IVF) following preimplantation genetic testing (PGT-IVF). Inclusion criteria of couples are similar to inclusion criteria from PGT that are the following: o The offspring have a high risk on inheriting a severe genetic disorder (as nationally determined by national indication committee); PGT-M. o There is a high risk of miscarriage due to an unbalanced translocation or a high risk of an ongoing pregnancy of a child with an unbalanced translocation (PGT-SR). • Couples meet the requirements for IVF. • The comprehensive, sequencing-based haplotyping analysis will be used for analysis of PGT-M • The VeriSeq PGS analysis method is used for PGT-SR. Sample inclusion criteria: • Oocytes are successfully fertilized and develop into d3 embryos or blastocysts (d5/6/7 embryos). • Embryos are successfully biopsied and the conventional PGT result is conclusive. • Spent culture medium samples from the PGT-IVF embryos could be collected and stored.
Exclusion criteria
Exclusion criteria: Group exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study. • Couples unable to give informed consent to any of the study aspects or unable to comply with the protocol o When participants are
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Developing non-invasive PGT based on cfDNA in SCM for monogenic disorders or structural rearrangements. • Study parameters are haplotypes present in SCM of human preimplantation embryos. • Endpoints are percentage of invalid results, concordance rates, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for genetic indication of interest and the haplotypes in niPGT compared to haplotypes in conventional PGT. 2. Developing niPGT-AO to assess the rate of aneuploidies and its origin and assess the predictive value of aneuploidy origin for a healthy baby using pregnancy outcomes. • Study parameters are aneuploidy and its origin in the SCM and in the routinely taken TE biopsy i.e. cellular (ICM/TE) and segregational (mitotic/meiotic) origin, clinical pregnancy outcomes e.g. implantation rate, live birth rate. • Endpoints are percentage of invalid results, concordance rates between SCM and TE biopsy, rate of mitotic and meiotic aberrations, the origin of the SCM, aneuploidy origin profiles for healthy babies and aneuploidy origin profiles for implantation failures. | — |
Countries
Netherlands
Outcome results
None listed