Comparing the advantages, disadvantages and diagnostic power of different non-invasive pre-implantation genetic testing: A literature review

Abstract

To improve embryo transfer success and increase the chances of live birth in assisted reproductive methods, there is a growing demand for the use of pre-implantation genetic testing (PGT). However, the invasive approaches used in PGT have led to in vitrofertilization failure and abortions, increasing anxiety levels for parents. To address this, non-invasive PGT methods have been introduced, such as the detection of DNA in blastocoel fluid of blastocysts and spent culture media (SCM). These methods have proven to be minimally invasive and effective in detecting aneuploidy in the chromosomes of human embryos. This review aims to explore the different approaches to pre-implantation diagnosis, including invasive and non-invasive methods, with a particular focus on non-invasive PGT (niPGT). The search strategy involved gathering data from scientific databases such as PubMed, Google Scholar, and Science Direct using relevant keywords. The search was conducted until January 2023. In total, 22 studies have successfully reported the detection and amplification of cell-free DNA in the embryonic SCM. It is important to note that niPGT has some limitations, which include differences in indicators such as cell-free DNA amplification rate, concordance, level of maternal DNA contamination, sensitivity, and specificity between SCM samples and biopsied cells. Therefore, more extensive and detailed research is needed to fully understand niPGT's potential for clinical applications.

Keywords: Biopsy methods; Cell-free embryonic DNA.; Non-invasive pre-implantation genetic testing; Spent culture media.

Figure 1

Flowchart of the methodology used in our study.

Figure 2

Overview of different PGT technical approaches. PGT: Pre-implantation genetic testing, PGT-A: PGT of aneuploidy, FISH: Fluorescence in situ hybridization, aCGH: Array comparative genomic hybridization, q-PCR: Quantitative-polymerase chain reaction, NGS: Next-generation sequencing, SNP: Single nucleotide polymorphism, PGD: Pre-implantation genetic, niPGT: Non-invasive pre-implantation genetic testing, miPGT: Minimally invasive pre-implantation genetic testing, PGT-M: PGT for monogenic disorders, ePGT: Expanded pre-implantation genetic testing, PGT-SR: Pre-implantation genetic testing for structural rearrangement.

Figure 3

The workflow for analysis of embryonic cfDNA in blastocyst culture medium. ICSI: Intracytoplasmic sperm injection, IVF: In vitro fertilization. (The image was designed using BioRender.com database).

Figure 4

The rate of successful amplification of niPGT studies by various WGA methods. MALBAC: Multiple annealing and looping-based amplification cycle, NICS: Noninvasive implantation capability screening.

Figure 5

Sensitivity and specificity of results in niPGT studies.

Figure 6

Comparison of different sampling methods and their results in a study by Huang et al. (51).