Our Test: PGT-WGS

Preimplantation Genetic Testing (PGT) is a process in which embryos are screened for genetic conditions. The types of conditions that are screened for depend on the type of PGT testing being performed. PGT is not diagnostic testing, and it is imperative that you work with your provider to follow up with any relevant diagnostic testing.

There are four different types of PGT testing: o PGT-A - Preimplantation Genetic Testing for Aneuploidy (PGT-A) screens embryos for chromosomal disorders, genetic conditions in which an embryo has a missing or an extra chromosome, such as Down syndrome. o PGT-M - Preimplantation Genetic Testing for Monogenic/Single Gene Disorders (PGT-M) screens embryos for inherited genetic conditions such as cystic fibrosis, fragile X syndrome, spinal muscular atrophy, and Huntington’s disease. o PGT-SR - Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) screens embryos for inherited chromosomal rearrangements called translocations and inversions. o PGT-WGS - Preimplantation Genetic Testing for Whole Genomic Sequencing (PGT-WGS) screens embryos for inherited genetic conditions, chromosomal disorders/aneuploidies, chromosomal rearrangements, and de novo mutations (new mutations introduced at fertilization).

PGT-WGS can benefit any patient undergoing IVF. Some specific situations where PGT-WGS may be especially useful include: o Recurrent unexplained pregnancy loss o Multiple failed IVF cycles or embryo transfers o Previous pregnancy affected by a genetic disorder o Abnormal genetic carrier screening results for you or your partner o Family history of a known genetic condition or chromosome abnormality o Advanced maternal age over 35 years old o Advanced paternal age over 40 years old o Use of donor eggs or sperm from an older donor o Desire for comprehensive genetic screening to maximize chances of a successful pregnancy

The comprehensive testing provided by PGT-WGS allows thorough inspection of the embryo's genome, beyond what traditional PGT can detect. If you, your provider, and your genetic counselor believe that PGT-WGS is the best option for your fertility journey, we would love to work with you and your IVF clinic. Please get in touch with us at team@genembryomics.com for more information.

Yes, if there is a known genetic condition that runs in your family, PGT-WGS can very likely detect mutations or variants associated with that disorder in embryos.

The main advantage of PGT-WGS over traditional testing is its ability to screen for nearly any genetic abnormality by analyzing the whole genome sequence. So if you are aware of a particular syndrome, disease, or mutation present in your family history, our comprehensive genome-wide approach should be able to pick that up in embryos during IVF screening.

We have experience detecting a wide variety of single- gene disorders, copy number variations, chromosomal rearrangements and complex conditions with inheritable components. Our advanced next- generation sequencing and bioinformatics pipelines are designed to leverage the full power of the embryo's genetic code.

If you have any questions on whether PGT-WGS would be able to test for a specific familial genetic condition, please don't hesitate to reach out and provide us with those details at team@genembryomics.com.

Absolutely. Even without a known family history of genetic conditions, PGT-WGS can still provide very useful information. Here are some key reasons it may be beneficial: o Sporadic mutations — Many genetic mutations happen spontaneously during embryo development and are not inherited. PGT-WGS can detect these de novo mutations. o Unknown family history — There may be unknown conditions in the family lineage not apparent from just a pedigree. The comprehensive testing from PGT-WGS helps uncover these. o Recessive conditions — You may be a carrier for a recessive gene mutation that only causes disease if your partner is also a carrier. PGT-WGS will detect if embryos inherited both recessive copies. o Low risk is not zero risk — Even for low risk patients, PGT-WGS reduces the chances of rare genetic conditions occurring from very unlikely to virtually zero. o Peace of mind — The deep genetic insight from PGT-WGS may provide you with valuable peace of mind about your future child's health.

At 5 or 6 days into development, cells are removed from IVF embryos via biopsy and sent to a genetics lab. The DNA is extracted, amplified, and sequenced to read the complete genome. We use our proprietary technology to comprehensively analyze each embryo's genetics, checking for abnormalities or mutations. In about three weeks, the lab sends your doctor a report summarizing the results for each embryo. Essentially, PGT-WGS allows thorough testing of embryo genetics to identify and transfer only healthy embryos, giving your potential future child the best chances of being born without genetic disease.

Yes, PGT-WGS is considered a very safe procedure for the embryos being tested: o Non-invasive - PGT-WGS requires removing just a few cells from the outer shell of the early embryo. The embryo itself remains intact. o Established procedure - Biopsy techniques to obtain cells for genetic testing are well-established with high success rates. o No evidence of harm - Extensive studies show embryo biopsy does not negatively impact future development potential. o Used widely – PGT as a whole has been performed on hundreds of thousands of embryos with excellent safety outcomes. o Performed by specialists - The embryo biopsy is conducted by highly specialized embryologists trained extensively in the procedure. o Continual improvements - Techniques continue to be refined to further limit any potential impact on the embryo.

Rest assured, PGT-WGS has been clinically validated as a safe way to gain valuable genetic information about embryos without compromising their viability.

PGT-WGS demonstrates extremely high diagnostic performance, with a specificity of 99.998% and an accuracy of 99.997% for detecting disease-causing genetic variants.

If you have undergone IVF with PGT-WGS testing on your embryos, the need for additional prenatal diagnostic testing is significantly reduced. However, professional societies recommend confirmatory prenatal testing even after genetic screening of embryos. This can typically be more targeted, based on your embryo's specific results. Your IVF doctor and genetic counselor can advise the best approach.

Inherited diseases, also called genetic disorders or hereditary conditions, are health problems caused by abnormal genes that run in families. They are caused by mutations or changes in genes that disrupt their normal function, leading to disease. The mutated gene is passed down from parent to child, so the disorder is hereditary within the family lineage. There are thousands of known inherited disorders, ranging in severity from mild to severely disabling or life-threatening. While very few cures exist, genetic testing can identify mutated genes to assess disease risk and guide family planning. IVF with preimplantation genetic testing whole genome sequencing (PGT-WGS) allows selecting of embryos without inherited genetic mutations to avoid passing diseases on to children.

De Novo mutations are genetic changes that arise spontaneously and are not inherited from a parent. They occur randomly during the formation of reproductive cells or in early embryonic development, rather than being present in the parents' genes. De Novo mutations are a common source of severe dominant conditions like neurodevelopmental disorders. The number of de novo mutations present in offspring increases with advanced paternal age at conception. Preimplantation genetic testing whole genome sequencing (PGT-WGS) screens embryos for de novo mutations that could cause disease if passed to future children. This allows the selective transfer of unaffected embryos.

While PGT-WGS can help at any age, its reproductive benefits for screening chromosomal abnormalities and mutations tend to increase with maternal and paternal age. o Advanced maternal age (over 35) leads to higher abnormality rates in eggs that can cause miscarriage or disorders like Down syndrome. PGT-WGS helps avoid transferring affected embryos. The older the intended mother is, the more PGT-WGS can improve IVF success by screening out abnormal embryos before transfer. This boosts implantation and live birth rates, especially over the age of 35. o Advanced paternal age (over 40) is linked to a higher number of de novo mutations and an increased risk of affected pregnancies. PGT-WGS screens embryos for these mutations. Sperm from older men have higher rates of new single nucleotide variants, which are missed by traditional PGT methods that focus on chromosomal abnormalities.

Actual processing time may vary slightly from patient to patient. It is important to understand that an early result or a result taking longer does not necessarily indicate any problem with the embryo quality or PGT-WGS analysis. Variations in timing can occur due to differences in sample transit, sequencing batch schedules, and other routine factors. The quality and reliability of each PGT-WGS analysis remain consistent regardless of small differences in the delivery of the results.

While PGT-WGS is a valuable technology for screening embryos, it does not guarantee a successful IVF outcome. PGT-WGS looks for specific genetic mutations in embryos, but it cannot detect all medical conditions or ensure normal development, as other non-genetic factors also influence pregnancy success. There are also limits to current sequencing technology — rare mutations may be missed and mosaicism in the embryo could create discrepancies. Even if an embryo tests negative, issues like placental abnormalities or uterine problems could still arise. Furthermore, PGT-WGS does not assess complex gene interactions that influence multifaceted traits like intelligence or appearance. While PGT-WGS can significantly improve the chances of avoiding transmission of known genetic diseases and de novo mutations to offspring, patients should have realistic expectations of the technology’s capabilities. Patients are advised to pursue follow-up prenatal testing like NIPT and imaging, as well as genetic counseling, to fully understand PGT-WGS’s capabilities in screening for genetic disorders. However, when used appropriately, PGT-WGS remains a very useful tool for screening embryos and tilting the odds favorably for a successful IVF outcome.

Patients should discuss PGT-WGS costs and insurance questions with their fertility clinic as well as their insurance company. GenEmbryomics does not have any direct agreements with health insurance companies and does not handle insurance claims or reimbursement for PGT-WGS testing.