Clinical Application of Non-invasive PGT-A

Genetic Testing Clinical Trial

Official title:

Clinical Application of Non-invasive Preimplantation Genetic Testing for Aneuploidies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04856696
• Other study ID #: KSVGH20-CT12-16
• Status: Recruiting
• Phase: N/A
• Start date: March 24, 2021
• Est. completion date: June 30, 2023

Study information

• Verified date: March 2022
• Source: Kaohsiung Veterans General Hospital.
• Contact: Li-Te Lin
• Phone: +88673464027
• Email: litelin1982[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aims to investigate the difference of in vitro fertilization (IVF) outcomes among non-invasive PGT-A, PGT-A and combined non-invasive PGT-A and PGT-A.

Description:

Background Chromosome abnormality is a leading cause of implantation failure and miscarriage. Chromosome abnormality increases with age, resulting in reduced pregnancy rate. Nowadays, preimplantation genetic testing for aneuploidies (PGT-A) could be used for detection of aneuploidy. However, PGT-A needs embryo biopsy which is invasive and may cause embryo damage. It was found that cell free DNA could be isolated from culture media. The cell free DNA from culture media also could be used to detect embryo ploidy, called non-invasive PGT-A.

Objective The study aims to investigate the difference of in vitro fertilization (IVF) outcomes among non-invasive PGT-A, PGT-A and combined non-invasive PGT-A and PGT-A. Another aim of this study is to check the concordance rate between non-invasive PGT-A and PGT-A.

Methods The prospective cohort study will be performed at the reproductive medical center of Kaohsiung Veterans General Hospital, in Kaohsiung, Taiwan. Participants who plan to receive an IVF cycle and preimplantation genetic testing for aneuploidies will be enrolled in this study. The investigators will divide the participants into 3 groups: (1) combined non-invasive PGT-A and PGT-A; (2) PGT-A; (3) non-invasive PGT-A. Basal characteristics, infertility history, ovarian reserve and embryo development of the three groups will be recorded. The samples will be detected ploidy by using next generation sequencing (NGS). Then, the investigators will choose embryo to transfer according to the embryo ploidy and follow the pregnancy outcomes after embryo transfer.

Outcome

1. Concordance rate between non-invasive PGT-A and PGT-A

2. The relationship between morphological grade and ploidy of non-invasive PGT-A

3. IVF outcomes among non-invasive PGT-A, PGT-A and combined non-invasive PGT-A and PGT-A

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 30 Years to 44 Years

Eligibility

Inclusion Criteria:

• Infertile women who undergo IVF with PGT

• BMI:18~30 kg/m2

Exclusion Criteria:

• Primary ovarian insufficiency

• Congenital uterine anomaly

• Severe male infertility (azoospermia)

• One of the couples with chromosome abnormality

• Malignancy

Related Conditions & MeSH terms

• Genetic Testing

Intervention

Diagnostic Test:
• PGT-A
trophectoderm biopsy in blastocyst stage for euploidy testing using next generation sequencing platform
• non-invasive PGT-A
cell-free DNA collected from spent culture media for euploidy testing using next generation sequencing platform

Locations

Country	Name	City	State
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung

Sponsors (2)

Lead Sponsor	Collaborator
Kaohsiung Veterans General Hospital.	Sofiva Genomics Co., Ltd.

Country where clinical trial is conducted

Taiwan, 

References & Publications (19)

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Fang R, Yang W, Zhao X, Xiong F, Guo C, Xiao J, Chen L, Song X, Wang H, Chen J, Xiao X, Yao B, Cai LY. Chromosome screening using culture medium of embryos fertilised in vitro: a pilot clinical study. J Transl Med. 2019 Mar 8;17(1):73. doi: 10.1186/s12967-019-1827-1. — View Citation

Farra C, Choucair F, Awwad J. Non-invasive pre-implantation genetic testing of human embryos: an emerging concept. Hum Reprod. 2018 Dec 1;33(12):2162-2167. doi: 10.1093/humrep/dey314. Review. Erratum in: Hum Reprod. 2019 Mar 1;34(3):590. — View Citation

Fesahat F, Montazeri F, Hoseini SM. Preimplantation genetic testing in assisted reproduction technology. J Gynecol Obstet Hum Reprod. 2020 May;49(5):101723. doi: 10.1016/j.jogoh.2020.101723. Epub 2020 Feb 26. Review. — View Citation

Fragouli E, Munne S, Wells D. The cytogenetic constitution of human blastocysts: insights from comprehensive chromosome screening strategies. Hum Reprod Update. 2019 Jan 1;25(1):15-33. doi: 10.1093/humupd/dmy036. Review. — View Citation

Homer HA. Preimplantation genetic testing for aneuploidy (PGT-A): The biology, the technology and the clinical outcomes. Aust N Z J Obstet Gynaecol. 2019 Apr;59(2):317-324. doi: 10.1111/ajo.12960. Epub 2019 Feb 27. — View Citation

Huang L, Bogale B, Tang Y, Lu S, Xie XS, Racowsky C. Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy. Proc Natl Acad Sci U S A. 2019 Jul 9;116(28):14105-14112. doi: 10.1073/pnas.1907472116. Epub 2019 Jun 24. — View Citation

Jiao J, Shi B, Sagnelli M, Yang D, Yao Y, Li W, Shao L, Lu S, Li D, Wang X. Minimally invasive preimplantation genetic testing using blastocyst culture medium. Hum Reprod. 2019 Jul 8;34(7):1369-1379. doi: 10.1093/humrep/dez075. — View Citation

Kuznyetsov V, Madjunkova S, Abramov R, Antes R, Ibarrientos Z, Motamedi G, Zaman A, Kuznyetsova I, Librach CL. Minimally Invasive Cell-Free Human Embryo Aneuploidy Testing (miPGT-A) Utilizing Combined Spent Embryo Culture Medium and Blastocoel Fluid -Towards Development of a Clinical Assay. Sci Rep. 2020 Apr 29;10(1):7244. doi: 10.1038/s41598-020-64335-3. — View Citation

Leaver M, Wells D. Non-invasive preimplantation genetic testing (niPGT): the next revolution in reproductive genetics? Hum Reprod Update. 2020 Jan 1;26(1):16-42. doi: 10.1093/humupd/dmz033. Review. — View Citation

Liang B, Gao Y, Xu J, Song Y, Xuan L, Shi T, Wang N, Hou Z, Zhao YL, Huang WE, Chen ZJ. Raman profiling of embryo culture medium to identify aneuploid and euploid embryos. Fertil Steril. 2019 Apr;111(4):753-762.e1. doi: 10.1016/j.fertnstert.2018.11.036. Epub 2019 Jan 22. — View Citation

Rubio C, Navarro-Sánchez L, García-Pascual CM, Ocali O, Cimadomo D, Venier W, Barroso G, Kopcow L, Bahçeci M, Kulmann MIR, López L, De la Fuente E, Navarro R, Valbuena D, Sakkas D, Rienzi L, Simón C. Multicenter prospective study of concordance between embryonic cell-free DNA and trophectoderm biopsies from 1301 human blastocysts. Am J Obstet Gynecol. 2020 Nov;223(5):751.e1-751.e13. doi: 10.1016/j.ajog.2020.04.035. Epub 2020 May 26. — View Citation

Rubio C, Rienzi L, Navarro-Sánchez L, Cimadomo D, García-Pascual CM, Albricci L, Soscia D, Valbuena D, Capalbo A, Ubaldi F, Simón C. Embryonic cell-free DNA versus trophectoderm biopsy for aneuploidy testing: concordance rate and clinical implications. Fertil Steril. 2019 Sep;112(3):510-519. doi: 10.1016/j.fertnstert.2019.04.038. Epub 2019 Jun 11. — View Citation

Sciorio R, Dattilo M. PGT-A preimplantation genetic testing for aneuploidies and embryo selection in routine ART cycles: Time to step back? Clin Genet. 2020 Aug;98(2):107-115. doi: 10.1111/cge.13732. Epub 2020 Apr 6. Review. — View Citation

Shamonki MI, Jin H, Haimowitz Z, Liu L. Proof of concept: preimplantation genetic screening without embryo biopsy through analysis of cell-free DNA in spent embryo culture media. Fertil Steril. 2016 Nov;106(6):1312-1318. doi: 10.1016/j.fertnstert.2016.07.1112. Epub 2016 Aug 24. — View Citation

Sullivan-Pyke C, Dokras A. Preimplantation Genetic Screening and Preimplantation Genetic Diagnosis. Obstet Gynecol Clin North Am. 2018 Mar;45(1):113-125. doi: 10.1016/j.ogc.2017.10.009. Review. — View Citation

Vera-Rodriguez M, Diez-Juan A, Jimenez-Almazan J, Martinez S, Navarro R, Peinado V, Mercader A, Meseguer M, Blesa D, Moreno I, Valbuena D, Rubio C, Simon C. Origin and composition of cell-free DNA in spent medium from human embryo culture during preimplantation development. Hum Reprod. 2018 Apr 1;33(4):745-756. doi: 10.1093/humrep/dey028. — View Citation

Xu J, Fang R, Chen L, Chen D, Xiao JP, Yang W, Wang H, Song X, Ma T, Bo S, Shi C, Ren J, Huang L, Cai LY, Yao B, Xie XS, Lu S. Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization. Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11907-11912. Epub 2016 Sep 29. — View Citation

Youssef MM, Mantikou E, van Wely M, Van der Veen F, Al-Inany HG, Repping S, Mastenbroek S. Culture media for human pre-implantation embryos in assisted reproductive technology cycles. Cochrane Database Syst Rev. 2015 Nov 20;(11):CD007876. doi: 10.1002/14651858.CD007876.pub2. Review. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ongoing pregnancy rate	continuous presence of a fetal heartbeat over 12 weeks of a pregnancy	through study completion, an average of 1.5 year
Secondary	Clinical pregnancy rate	the presence of a fetal heartbeat at 6-7 weeks of a pregnancy	through study completion, an average of 1.5 year
Secondary	Miscarriage rate	pregnancy loss before 24 weeks of gestation	through study completion, an average of 1.5 year