Efficacy of PGT-A Upgrade in Preimplantation Genetic Testing of Embryos: An International Multicenter Prospective Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,700
- 试验地点
- 7
- 主要终点
- Incidence of microdeletions/microduplications
研究概览
简要总结
The goals of this international multicenter cross-sectional study are:
- To provide patients with a comprehensive PGT solution capable of simultaneously detecting embryonic chromosomal aneuploidy, mosaicism, microdeletions/ microduplications, heteroploidy, and heterozygosity (LOH) in a single assay, thereby reducing miscarriage and birth defects;
- To perform PGT analysis on abnormally fertilized embryos, select euploid embryos with normal ploidy, and calculate embryo utilization rates;
- To reduce the false-positive rate through confirmation of mosaic embryos and subsequent analysis of its origin, thereby minimizing embryo wastage;
- To provide molecular genetic evidence for expert consensus on clinical management of atypically fertilized embryos, of pathogenic/likely pathogenic small CNVs, optimize mosaic embryo transfer strategies, and inform preconception intervention;
- To enhance international PGT testing standards through international multi-center collaboration.
The study will enroll patients undergoing PGT-A from seven domestic and international centers, with patient enrollment expected to be completed within one year. PGT-A upgrade testing will be performed on embryos from enrolled patients, and the incidence rates of Incidence of microdeletions/microduplications, heteroploidy, LOH will be statistically analyzed. All patients who undergo embryo transfer will be followed up for clinical outcomes and birth defects.
详细描述
The study will enroll 6,694 embryos derived from typical fertilization (2PN) that meet the inclusion and exclusion criteria in patients undergoing PGT-A, as well as all embryos derived from atypical fertilization (0PN/1PN/3PN). In contrast to conventional PGT-A testing, PGT-A upgrade testing will be performed on the embryos to comprehensively analyze multiple embryonic abnormalities in a single detection, including aneuploidy, mosaicism, microdeletion/microduplication, heteroploidy, and loss of heterozygosity (LOH), and to calculate their respective incidence rates.
In addition to embryos derived from 2PN, embryos from 0PN/1PN/3PN will also be cultured to the blastocyst stage for trophectoderm (TE) cell biopsy. Euploid embryos identified by PGT-A upgrade testing will be recorded, and the utilization rate of atypically fertilized embryos will be evaluated.
For mosaic embryos, a previously established parental haplotype origin algorithm will be applied to distinguish true versus false mosaicism and identify the origin of abnormalities, thereby recognizing "false-positive" mosaic embryos and further increasing the number of transferable embryos.
Patients will receive euploid embryo transfer (from 2PN) in accordance with routine clinical practice. In cases where no 2PN-derived euploid embryos are available, transfer of 0PN/1PN/3PN-derived euploid embryos and embryos classified as "false-positive" mosaic may be considered after the patient has been fully informed of the risks and provided informed consent.
All transfer cycles will be followed up for prenatal diagnosis results and birth defects. The primary outcome measures are the incidence rates of microdeletion/microduplication, heteroploidy, and LOH. The secondary outcome measures include embryo utilization rate, clinical pregnancy rate, ongoing pregnancy rate, live birth rate, miscarriage rate, concordance rate between prenatal diagnosis results and PGT-A results, and birth defect rate.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 46 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •(1) Any one of the following conditions being met is sufficient:
- •advanced maternal age (AMA, age ≥35 years),
- •recurrent implantation failure (RIF),
- •recurrent miscarriage (RM),
- •severe male factor (SMF). (2) And at least one blastocyst is available.
排除标准
- •Couples undergoing PGT-SR due to chromosomal structural abnormalities carried by either one or both members, such as balanced translocations, Robertsonian translocations, inversions, complex chromosomal rearrangements, and pathogenic microdeletions or microduplications;
- •Couples undergoing PGT-M;
- •Conditions with established impact on uterine morphology or endometrial receptivity, including untreated uterine malformations (septate uterus, unicornuate uterus, didelphic uterus, etc.) and untreated hydrosalpinx;
- •Embryos coming from oocyte or sperm (gametes) donation;
- •Individuals with contraindications to pregnancy or assisted reproduction technology.
研究组 & 干预措施
PGT-A upgrade group
干预措施: PGT-A upgrade (Other)
结局指标
主要结局
Incidence of microdeletions/microduplications
时间窗: Two months after oocyte retrieval
Trophectoderm biopsy samples undergo whole genome amplification followed by NGS. Microdeletions and microduplications are identified according to Human Genome Assembly GRCh19 (hg19) or updated versions. The incidence will be calculated as the number of embryos with pathogenic or likely pathogenic microdeletions/microduplications (1-4M) divided by the total number of embryos.
Incidence of heteroploidy
时间窗: Two months after oocyte retrieval
Trophectoderm biopsy samples undergo whole genome amplification followed by NGS. Heteroploidy is identified according to Human Genome Assembly GRCh19 (hg19) or updated versions. The incidence will be calculated as the number of embryos with heteroploidy divided by the total number of embryos.
Incidence of loss of heterozygosity
时间窗: Two months after oocyte retrieval
Trophectoderm biopsy samples underwent whole genome amplification followed by NGS. Loss of heterozygosity were identified according to Human Genome Assembly GRCh19 (hg19) or updated versions. The incidence will be calculated as the number of embryos with loss of heterozygosity divided by the total number of embryos
次要结局
- Transferable embryo rate(Two months after oocyte retrieval)
- Clinical pregnancy rate(28-30 days after embryo transfer)
- Ongoing pregnancy rate(12 weeks after the embryo transfer)
- Live birth rate(Two weeks after the newborn's birth)
- Early miscarriage rate(12 weeks of after the embryo transfer)
- Concordance between prenatal diagnosis results and PGT-A results(16-24 weeks of gestation)
- Birth defect rate(At 1 year postpartum)