Whole genome preimplantation genetic testing (PGT-WGS)

GenEmbryomics' PGT-WGS utilizes whole genome sequencing to evaluate embryo genetics, while other methods like PGT-A or PGT-M focus only on certain chromosomes or a limited number of genetic markers. PGT-WGS examines the entire embryo genome sequence rather than just targeted regions, enabling the most detailed and sensitive genetic screening currently possible in IVF.

The technology behind PGT-WGS uses next-generation sequencing to read the entire DNA sequence of an embryo biopsy sample. This provides the most comprehensive information on an embryo's genetic makeup for screening purposes.

Specifically, the biopsy sample first undergoes whole genome amplification to obtain sufficient DNA quantities for sequencing. The DNA is then fragmented, barcoded, and sequenced using high-throughput, short-read NGS technologies like Illumina sequencing.

The sequencing data files are uploaded securely to GenEmbryomics for bioinformatic analysis. Our software maps the sequences to a reference genome, identifies genetic variants, and compares them to our proprietary variant database for embryo risk classification based on the latest research.

PGT-WGS with GenEmbryomics can screen for a wide range of genetic abnormalities in embryos, including: o Aneuploidies — Extra or missing chromosomes (PGT-A checks a limited number) o Translocations — Rearranged chromosome fragments o Insertions and deletions — Missing or extra pieces of DNA o Single gene mutations — Changes in DNA sequence causing genetic disorders o Copy number variants — Missing or duplicated chunks of genes o Autosomal dominant — Disease traits from one mutated gene copy o Autosomal recessive — Two mutated copies of a gene o X-linked recessive — Mutations in genes on X chromosome o Repeat expansions — Long repetitive DNA segments o SNPs — Single "letter" DNA changes associated with disease risk o De novo mutations — Spontaneous mutations that occur at the point of conception

Additionally, the GenEmbryomics variant database used for classification is continually updated as new gene-disease associations are discovered through the latest research. This allows PGT-WGS to stay current with known genetic markers that may impact embryo health.

PGT-WGS has a proven specificity of 99.998% and sensitivity of 92.2% for detecting single nucleotide variations in embryos. This indicates it is highly accurate at both detecting true genetic variants and not falsely identifying variants when none are present (specificity).

o The overall accuracy rate of PGT-WGS for single nucleotide variants is 99.997%. This is extremely high accuracy compared to other methods like PGT-A which has an accuracy rate of around 90-95% for aneuploidy screening. o PGT-WGS also has a high positive predictive value (precision) of 98.0% and a very high negative predictive value of 99.992%. This means the test rarely gives false positive results and rarely gives false negative results. o By comprehensively screening all types of genetic variants, PGT-WGS is superior at detecting a wider range of embryo abnormalities compared to PGT-A or PGT-M which are limited to aneuploidies and large-scale chromosome mutations respectively. While this is beneficial for achieving implantation, these large- scale chromosomal errors are just a small part of the genetic landscape that contributes to a healthy ongoing pregnancy and live birth.

In summary, with accuracy of over 99% across key statistical measures, PGT-WGS significantly outperforms other PGT techniques and provides the highest accuracy rate for detecting genetic abnormalities in embryos. Its comprehensive testing of all variant types makes it the most advanced methodology available.

Typically, 5-10 cells are removed during the embryo biopsy procedure for PGT-WGS. This represents a very small portion of the total embryonic cells at day 5/6 of development and is done by an embryologist/IVF clinic of the ordering provider’s choosing, not GenEmbryomics.

Multiple studies have shown that biopsies, done routinely at IVF clinics across the world, do not significantly impact the embryo's developmental potential: o In a meta-analysis of over 3,000 PGT cases, biopsy of 5-10 cells did not increase miscarriage rates or lower live birth rates compared to non-biopsied embryos. o Another large study found less than 1% difference in implantation rates between biopsied and non-biopsied embryos. o Some clinics report blastocyst survival rates of 97-99% following biopsy for PGT. o Research indicates embryo morphokinetics are not altered and blastulation timing is unaffected by biopsy of 5-10 cells for analysis.

Based on current evidence, embryonic biopsy using 5-10 cells is considered a safe, minimally invasive procedure that allows accurate screening without impairing the embryo's overall development and viability. However, an expert embryologist is recommended to perform the biopsy successfully.

Preimplantation genetic testing for whole genome sequencing (PGT-WGS) offers a very competitively priced solution compared to other commonly used PGT methodologies such as PGT-A, PGT-SR, and PGT-M. Array-based aneuploidy screening like PGT-A and comprehensive chromosome screening with PGT-M can cost two to three times as much on a per-sample basis. While quite affordable for testing one or two genetic conditions, the price per condition quickly adds up using targeted PCR techniques like PGT-SR. However, PGT-WGS allows screening of the entire embryo genome for chromosomal abnormalities, single gene disorders, and other traits of interest at a fraction of the price of these other approaches. By making comprehensive genetic screening affordable at economies of scale, PGT-WGS provides unmatched value and ensures the best chances of identifying genetically optimal embryos for a successful pregnancy. The reasonable cost per embryo also enables patients to maximize their chances by testing all embryos in a cycle rather than being limited to just one or two. In summary, PGT-WGS delivers advanced genomic screening at very competitive pricing compared to other PGT methodologies.

GenEmbryomics offers preimplantation genetic testing for whole genome sequencing (PGT-WGS) directly to fertility clinics, with set pricing that clinics pay upfront per test. At this time, GenEmbryomics does not have any direct agreements with health insurance companies and does not handle insurance claims or reimbursement for PGT-WGS testing.

For questions regarding the specific cost of PGT-WGS, please reach out to us at team@genembryomics.com to discuss partnerships.

Our partnering labs performing PGT-WGS analysis are CLIA and CAP certified to ensure the highest standards: o CLIA - All PGT labs in the US must be CLIA (Clinical Laboratory Improvement Amendments) certified. This indicates they meet federal quality standards for accuracy, reliability and timeliness of test results. o CAP - CAP (College of American Pathologists) accreditation is an additional rigorous certification representing the gold standard in laboratory quality. It includes on-site inspections and proficiency testing. Only the top ~7% of labs achieve this voluntary accreditation.

Beyond CLIA and CAP certification, we also partner with labs that adhere to the following: o Adherence to PGDIS (Preimplantation Genetic Diagnosis International Society) guidelines for PGT practices. o Participation in positive and negative quality control programs such as NEQAS to validate accuracy and precision. o Use of well-validated wet lab and bioinformatics pipelines to ensure reliability. o Ongoing proprietary and collaborative research to continuously improve testing methods. o Transparency around PGT results, methodology, and success rates.