Prospective International Multi-center Clinical Trial of PGT-A Upgrade

NCT07533630 | Not Yet Recruiting

• 1 other identifier: LL-SC-2026-003-01
• Study Type: observational
• Target: 1,700
• Locations: 5 countries
• Sites: 7

Brief Summary

The goals of this international multicenter cross-sectional study are:

1. 1.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;
2. 2.To perform PGT analysis on abnormally fertilized embryos, select euploid embryos with normal ploidy, and calculate embryo utilization rates;
3. 3.To reduce the false-positive rate through confirmation of mosaic embryos and subsequent analysis of its origin, thereby minimizing embryo wastage;
4. 4.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;
5. 5.To enhance international PGT testing standards through international multi-center collaboration.

Conditions

Infertility Assisted Reproductive Technology

Keywords

Preimplantation Genetic Testing for Aneuploidies; Mosaic embryos; Microdeletions/microduplications

Outcome Measures

Primary Outcomes (3)

• Incidence of microdeletions/microduplications

  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.

  Two months after oocyte retrieval

• Incidence of heteroploidy

  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.

  Two months after oocyte retrieval

• Incidence of loss of heterozygosity

  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

  Two months after oocyte retrieval

Secondary Outcomes (7)

• 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

Study Arms (1)

PGT-A upgrade group

Other: PGT-A upgrade

Interventions

PGT-A upgrade OTHER

A comprehensive PGT solution capable of simultaneously detecting embryonic chromosomal aneuploidy, mosaicism, microdeletions/ microduplications, heteroploidy, and LOH in a single assay.

PGT-A upgrade group

Eligibility Criteria

• Age: 20 Years - 46 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

This study is a cross-sectional study with a two-sided test and α = 0.05. Based on the analysis of existing data from previous PGT-A upgrade studies performed in 2PN embryos, the total incidence rate (p) of microdeletion/microduplication, heteroploidy, and UPD/LOH in euploid embryos is estimated to be 2.0%, with a margin of error (δ) of 0.005. The required number of euploid embryos is 3,012, and the calculation formula is provided below. Given that the euploidy rate is approximately 50%, a total of 6,024 embryos tested by PGT-A upgrade needs to be enrolled. Considering the potential dropout risk (10%), 6,694 embryos from two pronuclei (PN) are included. All embryos from 0PN/1PN/3PN are included.

You may qualify if:

• (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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Reproductive & Genetic Hospital of CITIC-Xiangya: lead
• The First People's Hospital of Yunnan: collaborator
• Nanjing Women and Children's Healthcare Hospital: collaborator
• Biocódices: collaborator
• Miracle: collaborator
• Institute Bernabéu: collaborator
• Thomson Hospital: collaborator

Study Sites (7)

Biocódices

Buenos Aires, Argentina

Location

CITIC-Xiangya Reproductive & Genetic Hospital

Changsha, Hunan, China

Location

Nanjing Women and Children's Healthcare Hospital

Nanjing, Jiangsu, China

Location

First People's Hospital of Yunnan Province

Kunming, Yunnan, China

Location

Thomson Hospital

Petaling Jaya, Malaysia

Location

Miracle

Daegu, South Korea

Location

Institute Bernabéu

Alicante, Spain

Location

Related Publications (8)

• Capalbo A, Poli M, Rienzi L, Girardi L, Patassini C, Fabiani M, Cimadomo D, Benini F, Farcomeni A, Cuzzi J, Rubio C, Albani E, Sacchi L, Vaiarelli A, Figliuzzi M, Findikli N, Coban O, Boynukalin FK, Vogel I, Hoffmann E, Livi C, Levi-Setti PE, Ubaldi FM, Simon C. Mosaic human preimplantation embryos and their developmental potential in a prospective, non-selection clinical trial. Am J Hum Genet. 2021 Dec 2;108(12):2238-2247. doi: 10.1016/j.ajhg.2021.11.002. Epub 2021 Nov 18.

  PMID: 34798051 BACKGROUND

• Capalbo A, Cimadomo D, Coticchio G, Ottolini CS. An expert opinion on rescuing atypically pronucleated human zygotes by molecular genetic fertilization checks in IVF. Hum Reprod. 2024 Sep 1;39(9):1869-1878. doi: 10.1093/humrep/deae157.

  PMID: 39043217 BACKGROUND

• Zhang J, Mu F, Guo Z, Cai Z, Zeng X, Du L, Wang F. Chromosome analysis of foetal tissue from 1903 spontaneous abortion patients in 5 regions of China: a retrospective multicentre study. BMC Pregnancy Childbirth. 2023 Nov 25;23(1):818. doi: 10.1186/s12884-023-06108-0.

  PMID: 38007414 BACKGROUND

• Fan Y, Li R, Huang J, Yu Y, Qiao J. Diploid, but not haploid, human embryonic stem cells can be derived from microsurgically repaired tripronuclear human zygotes. Cell Cycle. 2013 Jan 15;12(2):302-11. doi: 10.4161/cc.23103. Epub 2012 Jan 15.

  PMID: 23255130 BACKGROUND

• Huan Q, Gao X, Wang Y, Shen Y, Ma W, Chen ZJ. Comparative evaluation of human embryonic stem cell lines derived from zygotes with normal and abnormal pronuclei. Dev Dyn. 2010 Feb;239(2):425-38. doi: 10.1002/dvdy.22175.

  PMID: 19941346 BACKGROUND

• Canon C, Thurman A, Li A, Hernandez-Nieto C, Lee JA, Roth RM, Slifkin R, Briton-Jones C, Stein D, Copperman AB. Assessing the clinical viability of micro 3 pronuclei zygotes. J Assist Reprod Genet. 2023 Jul;40(7):1765-1772. doi: 10.1007/s10815-023-02830-y. Epub 2023 May 25.

  PMID: 37227570 BACKGROUND

• Destouni A, Dimitriadou E, Masset H, Debrock S, Melotte C, Van Den Bogaert K, Zamani Esteki M, Ding J, Voet T, Denayer E, de Ravel T, Legius E, Meuleman C, Peeraer K, Vermeesch JR. Genome-wide haplotyping embryos developing from 0PN and 1PN zygotes increases transferrable embryos in PGT-M. Hum Reprod. 2018 Dec 1;33(12):2302-2311. doi: 10.1093/humrep/dey325.

  PMID: 30383227 BACKGROUND

• Yao G, Xu J, Xin Z, Niu W, Shi S, Jin H, Song W, Wang E, Yang Q, Chen L, Sun Y. Developmental potential of clinically discarded human embryos and associated chromosomal analysis. Sci Rep. 2016 Apr 5;6:23995. doi: 10.1038/srep23995.

  PMID: 27045374 BACKGROUND

Study Officials

• Ge Lin

  CITIC-Xiangya Reproductive & Genetic Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pingyuan Xie

CONTACT

8613755122491; plainxie192@126.com

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 16, 2026
• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1); MY (1); ES (1); AR (1); CN (3)