Advances in Preimplantation Genetic Diagnosis: Reproductive Solutions Powered by NGS

How next-generation sequencing is transforming embryo screening, non-invasive testing, and clinical outcomes in assisted reproduction

Preimplantation genetic diagnosis (PGD) and preimplantation genetic testing (PGT) are entering a new era. Driven by advances in next-generation sequencing (NGS), improved whole-genome amplification methods, and integrated bioinformatics, reproductive genetics workflows are becoming faster, more accurate, and more accessible to IVF laboratories worldwide.

During a recent Genomics Unlocked webinar, experts from MGI Tech, Yikon Genomics, and leading fertility centers in Europe and Asia shared how modern NGS-based technologies are redefining embryo screening - from traditional biopsy-based testing to emerging non-invasive approaches, and from laboratory setup to routine clinical implementation.

This article highlights the key insights from that discussion.

The Evolving Role of NGS in Reproductive Genetics

Reproductive genetic testing presents unique challenges: extremely low DNA input, high clinical risk, and the need for rapid, reliable results. Traditional methods such as arrays and early PCR-based workflows often struggle to meet these demands consistently.

NGS has become the preferred technology for PGT because it enables:

• High-resolution detection of chromosomal abnormalities

• Reduced amplification bias and technical noise

• Scalable throughput for labs of all sizes

• Seamless integration with computational analysis pipelines

As highlighted in the webinar, the move to NGS is not simply an upgrade - it represents a fundamental shift toward data-driven, standardized reproductive genetics.

Sequencing Technology Built for Clinical Confidence

MGI presented an overview of its NGS platforms designed specifically to support sensitive clinical applications such as reproductive genetics.

DNA Nanoball (DNB) Sequencing

MGI’s sequencing chemistry is based on DNA nanoball (DNB) technology, which generates amplified signals through rolling circle replication rather than traditional PCR. This approach significantly reduces:

• PCR duplicates

• Index hopping

• Error propagation

For PGT applications, this translates into greater accuracy in copy number variation (CNV) analysis and more reliable interpretation of chromosomal abnormalities - critical factors when working with single cells or limited embryonic material.

Flexible Platform Portfolio

MGI offers a broad portfolio of sequencing platforms, allowing laboratories to match throughput and turnaround time to their specific clinical needs. From compact benchtop systems to high-capacity instruments, this flexibility supports both decentralized IVF labs and centralized testing facilities.

Fully integrated platforms that automate key steps - such as library conversion, DNA nanoball generation, and flow cell loading - were highlighted as a major advantage for reducing hands-on time and ensuring reproducibility in routine clinical workflows.

MALBAC™ Amplification: Consistency at the Single-Cell Level

Yikon Genomics discussed the importance of robust whole-genome amplification in reproductive testing and introduced MALBAC™ (Multiple Annealing and Looping-Based Amplification Cycles) technology as the foundation of their assay portfolio.

MALBAC is designed to deliver uniform genome amplification, overcoming common challenges such as allele dropout and amplification bias. Key benefits include:

• High genome coverage

• Excellent reproducibility across samples

• Improved CNV detection accuracy

These characteristics make MALBAC particularly well-suited for applications such as PGT-A, PGT-SR, and combined testing strategies where precision is essential.

Comprehensive PGT Workflows in a Single Sequencing Run

A central theme of the webinar was the ability to consolidate multiple reproductive genetic tests into streamlined NGS workflows.

PGT-A and PGT-SR

Using a single wet-lab workflow and centralized analysis software, laboratories can detect:

• Whole-chromosome aneuploidies

• Segmental imbalances

• Structural rearrangements

Sequencing depth can be tailored to the clinical question, enabling rapid screening or more comprehensive analysis without unnecessary complexity.

Expanded Screening for Microdeletions and Microduplications

Beyond standard aneuploidy testing, modern PGT-A workflows increasingly include clinically relevant microdeletion and microduplication syndromes - many of which fall below the resolution of older technologies.

Importantly, speakers emphasized that this expanded diagnostic scope can be achieved without significantly increasing laboratory workload or cost, making it suitable for routine IVF practice.

Non-Invasive PGT-A: Reducing Risk While Preserving Accuracy

Non-invasive PGT-A (niPGT-A) emerged as a major area of interest during the session. Instead of embryo biopsy, niPGT-A analyzes cell-free DNA released into spent embryo culture media.

Key advantages discussed included:

• Reduced risk to the embryo

• Simplified embryology workflows

• Comparable concordance with biopsy-based results when strict protocols are followed

Clinical examples presented during the webinar demonstrated successful validation of this approach, including healthy live births following embryo selection guided by non-invasive testing.

From Technology to Practice: Clinical Implementation Insights

Fertility centers in Spain and Thailand shared real-world experiences implementing NGS-based reproductive genetics solutions.

Key success factors included:

• Purpose-designed laboratory layouts to minimize contamination

• Clear separation of amplification, library preparation, and sequencing areas

• Comprehensive vendor support during setup and training

• Extensive internal validation and participation in external quality assessment programs

One center reported detection success rates above 99%, highlighting both the robustness of the workflow and the reliability of NGS-based PGT in daily clinical use.

Intelligent Bioinformatics and AI-Assisted Decision Support

Advanced bioinformatics platforms play a vital role in translating complex sequencing data into actionable clinical insights. Centralized analysis systems discussed during the webinar enable:

• Automated data processing and reporting

• Mosaicism detection

• Customizable result visualization

• AI-supported embryo grading and prioritization

By reducing the need for in-house bioinformatics expertise, these tools allow IVF laboratories to focus on clinical decision-making while maintaining analytical rigor.

The Future of Reproductive Genetics

Looking ahead, speakers highlighted several key trends shaping the next phase of reproductive genomics:

• Expansion of PGT-M for monogenic disorders

• Integration of endometrial receptivity testing (ERT)

• Increased automation across the genetic testing workflow

• Continued use of AI to support embryo selection and reporting

These developments point toward a future where reproductive genetic testing is faster, safer, more comprehensive, and more widely accessible.

Conclusion

NGS-powered reproductive genetics is no longer experimental - it is rapidly becoming the clinical standard. As demonstrated throughout this webinar, integrated solutions combining advanced sequencing chemistry, validated amplification technologies, and intelligent software are enabling IVF centers to improve outcomes while simplifying laboratory operations.

Discover how next-generation sequencing platforms and validated PGT workflows can support embryo screening, non-invasive testing, and routine clinical implementation in IVF laboratories.

Other ressources:

→ Explore MGI sequencing products

→ Watch the full webinar on demand

→ Explore our webinar platform Genomics Unlocked