Optimized PGT-M Strategy for Patients With No Proband
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Gametes (sperm or second polar bodies, MI eggs) or arrested embryos were reserved for identification of a proband.
- Who it may be relevant to
- Registry conditions: De Novo Mutation, Preimplantation Genetic Testing, Without Proband. Basic parameters: No limits · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- China
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Optimized PGT-M Strategy Using Gametes or Arrested Embryos From Patients With No Proband
Overview
The clinical practice of PGT-M for monogenetic disease usually adopted a double-checking strategy, which detect the mutation by Sanger sequencing and meantime construct haplotypes using the DNA sample of the proband so as to avoid the risks of misdiagnosis due to recombination and allele drop out (ADO). When there is no affected parent or offspring to serve as the proband, embryo carriers identified through direct mutation detection can be preferentially taken as probands for subsequent linkage analysis. In cases where none of the embryos are detected as mutant carrier, single sperm or the second polar body (PB2) can be complementally collected in the work-up of haplotype establishment. Our study aims to develop an optimized strategy of haplotype construction using gametes or arrested embryos for PGT-M in pedigrees with single gene diseases and no proband in the setting of difficult cases, which takes into account the expected number of oocytes acquired and the gonadal mosaicism.
Interventions
- Diagnostic test Gametes (sperm or second polar bodies, MI eggs) or arrested embryos were reserved for identification of a proband
1. Targeted deep sequencing for mosaicism detection for patients with suspected gonadal mosaicism, eg. Repeated similar abortion due to the same variant while the couple were tested negative for the variant in the peripheral blood. 2. Ovarian stimulation, embryo culture, biopsy and vitrification as routinely used in the IVF clinical practice. 3. Gametes and arrested embryo preservation by the embryo laboratory during embryo culture. 4. Genetic testing, including multiple displacement amplificati
Primary outcome measures
- Consistence of the PGT-M with prenatal diagnosis with amniocentesis [Time frame: 16 weeks of gestation]
Eligibility criteria
Inclusion criteria
- The couples intended for PGT-M without proband were recruited from Shanghai JiAi Genetics and IVF Institute, Obstetrics and Gynecology Hospital of Fudan University between January 2023 and December 2024, and were included in the study if they were expected to have difficulties in the identification of an EAP, typically meeting one of the following criteria:
- the carrier of the pathogenic variant was without typical clinical symptoms or detected as gonadosomal mosaic;
- the asymptomatic parents, who had one or more children affected with the same disorder, did not possess the genomic alterations carried by the children as per Sanger sequencing or targeted deep sequencing;
- female partner with diminished ovarian reserve and therefore a low yield of embryos;
- the variants are X-linked and the karyotype of the variant carrier is 47, XXX or 47, XXY etc.
Exclusion criteria
- (1) Non-PGT-M families; (2) Pedigree of other proband samples can be obtained; (3) Patients seeking for PGT-M who strongly request no haplotype analysis in embryos and only require Sanger testing after being fully informed of the risk.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Diagnostic
Study locations
China · 1 center
- Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan Unive — Shanghai
Publications
- Summerer A, Schafer E, Mautner VF, Messiaen L, Cooper DN, Kehrer-Sawatzki H. Ultra-deep amplicon sequencing indicates absence of low-grade mosaicism with normal cells in patients with type-1 NF1 deletions. Hum Genet. 2019 Jan;138(1):73-81. doi: 10.1007/s00439-018-1961-5. Epub 2018 Nov 26. PMID 30478644
- Xiao M, Shi H, Rao J, Xi Y, Zhang S, Wu J, Zhu S, Zhou J, Xu H, Lei C, Sun X. Combined Preimplantation Genetic Testing for Genetic Kidney Disease: Genetic Risk Identification, Assisted Reproductive Cycle, and Pregnancy Outcome Analysis. Front Med (Lausanne). 2022 Jun 17;9:936578. doi: 10.3389/fmed.2022.936578. eCollection 2022. PMID 35783601
- Wilde AAM, Amin AS. Clinical Spectrum of SCN5A Mutations: Long QT Syndrome, Brugada Syndrome, and Cardiomyopathy. JACC Clin Electrophysiol. 2018 May;4(5):569-579. doi: 10.1016/j.jacep.2018.03.006. Epub 2018 May 2. PMID 29798782
- Wang Y, Zhai F, Guan S, Yan Z, Zhu X, Kuo Y, Wang N, Zhi X, Lian Y, Huang J, Jia J, Liu P, Li R, Qiao J, Yan L. A comprehensive PGT-M strategy for ADPKD patients with de novo PKD1 mutations using affected embryo or gametes as proband. J Assist Reprod Genet. 2021 Sep;38(9):2425-2434. doi: 10.1007/s10815-021-02188-z. Epub 2021 May 3. PMID 33939064
Identifiers
NCT: NCT06722313 · JIAI E2023-12