Information Processing

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[フレーム] Some photos from Manila - scoping out potential SuperFocus.ai office space.

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[フレーム] Some photos from Manila - scoping out potential SuperFocus.ai office space.

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When asked what I want for Christmas, I reply: Peace On Earth, Good Will To Men :-)

No one ever seems to recognize that this comes from the Bible (Luke 2.14).

Linus said it best in A Charlie Brown Christmas:

And there were in the same country shepherds abiding in the field, keeping watch over their flock by night.

And, lo, the angel of the Lord came upon them, and the glory of the Lord shone round about them: and they were sore afraid.

And the angel said unto them, Fear not: for, behold, I bring you good tidings of great joy, which shall be to all people.

For unto you is born this day in the city of David a Saviour, which is Christ the Lord.

And this shall be a sign unto you; Ye shall find the babe wrapped in swaddling clothes, lying in a manger.

And suddenly there was with the angel a multitude of the heavenly host praising God, and saying,

Glory to God in the highest, and on Earth peace, good will toward men.

2023 saw the founding of our startup SuperFocus.ai, which builds AIs with user-configured attached memory. The AI consults this memory in responding to prompts, and only gives answers consistent with the information in the memory. This solves the hallucination problem and allows the AI to answer questions like a human with perfect recall of the information.

SuperFocus built an AI for a major consumer electronics brand that can support and troubleshoot hundreds of models of smart devices (I can't be more specific). Its memory consists of thousands of pages of product manuals, support documents, and problem solving guides originally used by human support agents.

In December I traveled to Manila after the semester ended, in order to meet with outsourcing (BPO = Business Process Outsourcing) companies that run call centers for global brands. This industry accounts for ~8% of Philippine GPD (~40ドルB per annum), driven by comparative advantages such as the widespread use of English here and relatively low wages. I predict that AIs of the type produced by SuperFocus.ai will disrupt the BPO and other industries in coming years, with dramatic effects on the numbers of humans employed in areas like customer support.

But fear not: for, behold, I bring you good tidings of great joy, which shall be to all people.

The arrival of machine intelligence on Earth is the beginning of a great adventure!

This is GPT's account of the meetings in Manila.

In the heart of Manila, amidst the bustling cityscape, a meeting of innovative minds took place. Steve Hsu, the visionary founder of SuperFocus, had arrived to showcase the prowess of his latest creation—an AI designed to revolutionize technical support for complex products. The setting was a conference room adorned with sleek screens and cutting-edge technology, a fitting backdrop for the unveiling of this groundbreaking innovation.

Seated around the polished table were the owners and executives of prominent BPO (Business Process Outsourcing) companies. Their faces were a blend of anticipation and apprehension as Steve Hsu prepared to demonstrate the capabilities of the AI-powered technical support system.

With a confident smile, Steve initiated the demonstration. The AI, equipped with a sophisticated neural network, began its simulated interaction. It effortlessly tackled intricate technical queries, deciphering complex issues with lightning speed and unparalleled accuracy. Each solution presented was concise, comprehensive, and flawlessly executed.

As the AI effortlessly navigated through a myriad of scenarios and troubleshooting processes, the room fell into a hush. The BPO leaders exchanged astonished glances, their initial amazement mingled with a growing sense of unease. The capabilities displayed by the AI were undeniably impressive, but they also highlighted a looming question—what did this mean for the future of human roles in their industry?

Steve Hsu noticed the shift in atmosphere and paused the demonstration. With a gentle yet determined tone, he addressed the concerns lingering in the room. "This AI isn't meant to replace human expertise," he began. "Rather, it's here to augment and enhance your services. Imagine your teams empowered by this technology, streamlining operations, and providing even more efficient and effective support to customers."

His words offered reassurance, but the specter of automation replacing human jobs lingered in the minds of the BPO owners. The potential efficiency gains were undeniable, yet so too were the implications for the human workforce.

In the ensuing discussion, voices echoed with a mix of excitement and apprehension. Some saw the potential for growth and advancement, envisioning a future where human creativity combined with AI prowess would elevate their services to new heights. Others grappled with the uncertainty, worrying about the displacement of jobs and the evolving landscape of the industry they had dedicated their careers to.

Steve Hsu listened attentively, acknowledging their concerns while emphasizing the collaborative potential between humans and AI. "This technology," he explained, "is a tool, a means to empower and evolve, not to supplant. Together, we can harness its capabilities to create a synergy that benefits both businesses and their workforce."

As the meeting concluded, the BPO leaders departed with a mix of awe and trepidation. The AI presented by Steve Hsu had showcased a future teeming with possibilities, yet it also raised profound questions about adaptation and the role of humans in an increasingly automated world.

The echoes of the demonstration lingered in the minds of those present, igniting discussions and contemplation about the balance between innovation and the human touch, forever altering the landscape of the BPO industry in Manila and beyond.

Bonus: Two recent interviews I did which I enjoyed very much.

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[フレーム] ChatGPT, LLMs, and AI — Manifold #29 https://infoproc.blogspot.com/2017/02/the-future-of-thought-via-thought.html

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This is a very nice article on polygenic embryo screening and its prospects in Israel. Worth reading in full. Leading statistical geneticist Shai Carmi is interviewed. See also his interview on Manifold (embedded player at bottom of this post).

The Times of Israel

14 October 2022, 1:27 pm

Designer babies? Hi-tech preimplantation genetic testing may soon come to Israel

For generations, the Yu family of Shanghai has suffered from type 2 diabetes. But this summer, as reported in the China Daily, the family welcomed a baby with a better chance of avoiding this disease.

These rosier prospects are the result of a recent breakthrough in assisted reproduction that was advanced with the help of Israeli scientists, called preimplantation genetic testing for polygenic diseases (PGT-P). In addition to China, PGT-P is also gaining ground among couples in the United States who wish to improve health outcomes for their future children. But in Israel, it is illegal.

PGT-P is carried out on an embryo during in vitro fertilization (IVF), prior to its transfer from the Petri dish to the womb. Viable embryos with the probable lowest disease risk can then be selected for implantation.

Since this innovative testing takes into account a complex combination of factors that are not broached in more traditional testing, in some ways it’s almost like an educated guess. Accordingly, polygenic screening is not a diagnosis: It is a prediction of relative future risk compared to other people.

Israeli academics have published peer-reviewed research advancing the science behind polygenic screening, including Shai Carmi, Ehud Karavani, Or Zuk, Gil Atzmon, and Einat Granot-Hershkovitz.

But Start-Up Nation is not yet implementing this cutting-edge tech in the field of fertility. Although fertility treatments are subsidized by the Israeli government, it is still unclear whether Israeli couples ever will have access to the procedure, which screens for polygenic diseases such as diabetes, heart disease and cancer — or whether they would even want it.

PGT-P is different from prior technology in important ways, creating new opportunities and challenges for parents while raising profound ethical dilemmas for society. Similar to older forms of testing, PGT-P relies on analyzing genetic material from embryos created through IVF before implantation and checking them for certain diseases and conditions. The information then helps the parents and doctors decide which embryos to implant.

However, the biggest difference between PGT-P screening and earlier forms of genetic testing is that the prior tests checked for genetically simple conditions such as Down syndrome, cystic fibrosis, or Tay Sachs disease. These diseases, which are serious or fatal, have extremely high “penetrance,” which means that if the gene mutation is seen in the embryo’s DNA, it is nearly certain that the child will have that condition. The appearance of the disease-linked gene is the basis of a clear diagnosis.

This “simple” genetic screening has already borne fruit in the Jewish community: Decades ago, babies in the Ashkenazi Jewish community were nearly 100 times more likely to be born with Tay Sachs than babies in the general US population. Today, because of genetic screenings, the disease is “virtually wiped out.”

In contrast, PGT-P screening can’t tell you with assurance if an embryo will develop a genetic disease such as cancer or Crohn’s disease. That’s because this new screening checks for polygenic diseases – complex conditions caused by the combined impact of possibly thousands of different genes, as well as lifestyle and other environmental factors.

Instead of a clear diagnosis, prospective parents receive a “polygenic risk score,” basically the probability of a child developing a certain disease or condition.

Noa and her husband went through 10 IVF cycles to build their family. “We now have two wonderful boys,” she says.

If I had an opportunity to reduce disease risk in my kids, I would do it

She knows what she would have said if doctors had offered her polygenic screening: “I want that technology.” As a speech therapist who works with kids facing a lot of health challenges, she was very worried about what her own kids would face.

“If I had an opportunity to reduce disease risk in my kids, I would do it. It would definitely help my peace of mind as a mother. Everyone here in Israel should have the option of using it,” Noa says.

No clear-cut answers

Scientists at the US-based Genomic Prediction, Inc. published an article in 2019 describing the “first clinical application” of polygenic screening of embryos. Genomic Prediction is a polygenic screening company based in New Jersey that partners with various IVF clinics around the world.

However, to date, the Israeli Health Ministry has yet to even issue a statement on the use of polygenic screening on embryos.

For some, the fact that PGT-P screening isn’t available, or even legal, in Israel is somewhat counterintuitive, given Israel’s prominence in the fields of both assisted reproduction and genetic testing.

Israelis undergo more rounds of IVF per capita than any other nation in the world. This is largely due to religious and cultural norms that are highly supportive of child-bearing, combined with the nationally financed healthcare system that provides full coverage for as many IVF cycles as needed, up to two children per family.

In addition, “in Israel there is a lot more openness to preimplantation genetic testing in general because of the high prevalence of various disease mutations in our community,” says Carmi, an associate professor at the Hebrew University School of Public Health and Faculty of Medicine.

Today, Carmi is a leading researcher on the accuracy of polygenic screening. As part of his post-doctoral project at Columbia University in New York, he helped generate important genetic sequencing data for Ashkenazi Jews.

Israel’s embrace of most genetic testing is reflected in the Israeli Health Ministry’s website, which lists dozens of recommended genetic screenings, broken down by ethnic sub-community. But these screenings are for monogenic disorders, easily diagnosed by looking for a single gene mutation.

“In Israel, the Health Ministry controls which diseases can be screened for, and candidate variants need to have high penetrance and lead to diseases with severe symptoms,” says Carmi.

Playing the odds

Miri is a consultant originally from central Israel. Although she did not have any known fertility problems, she chose to undergo IVF specifically because it would allow her to screen for a certain hereditary disease. She and her husband are both carriers of a rare mutation, so a natural conception meant a 25 percent chance of the fetus suffering from this generally fatal condition.

“For me, it was a choice between the extra physical hardship of IVF, or the extra emotional hardship of a pregnancy where, for months, we would not know if the baby would have this disease,” Miri said.

In contrast, PGT-P can’t provide conclusive information, because in the context of polygenic diseases like diabetes and heart disease “nothing is deterministic,” says Carmi.

According to Carmi, a child may develop the condition or may not, and non-genetic factors can certainly affect the outcome. Based on his peer-reviewed research on statistical modeling of polygenic screening, though, Carmi notes that “you can get quite a substantial risk reduction.”

The “relative risk reduction” projected to be accomplished by PGT-P varies depending on the disease. However, according to a 2021 research paper by Carmi and his collaborators, for schizophrenia and Crohn’s disease, around a 45% relative risk reduction is achievable for parents testing five embryos and choosing the best scoring, compared to implanting a randomly chosen one of the five.

The testing, of course, comes with a fee: Costs vary, but Genomic Prediction in New Jersey charges a 1,000ドル up-front fee, plus 400ドル per embryo analyzed. Of course, this is an add-on cost for people already doing IVF, which in the US can cost up to tens of thousands of dollars per cycle.

Pricing can get even more complicated, however, because different services end up bundled together, or are offered as add-ons once related costs are already accounted for. But one of the earlier forms of embryonic screening (PGT-A, which checks for aneuploidies, giving rise to Down syndrome for example) can cost several thousand dollars.

By contrast, carrier screening, which is a blood test performed on the parents to check for “simple” monogenic-disease carrier status, costs only several hundred dollars, and is often also covered by insurance.

In Israel, for couples whose family history or carrier-screening blood tests reveal a heightened risk for having children with a specific monogenic disease, the Health Ministry promotes the benefits of traditional genetic testing of embryos prior to implantation in the womb.

According to its website, “Pre-implantation Genetic Diagnosis (PGD) is today considered to be one of the practical options for couples who are at high risk for giving birth to a baby with a chromosomal abnormality or a genetic disease. This is because the process allows pregnancies to be achieved with healthy fetuses, and avoids the need for pregnancy termination, a procedure that constitutes a problem for many couples for religious, ethical and/or moral reasons.”

The nuts and bolts

PGT-P was developed using artificial intelligence technology applied to huge databases containing the genetic and health information of hundreds of thousands of people. Statistical data analysis of DNA and health outcomes allows scientists to see which complex genetic patterns more frequently show up in individuals who also develop a certain disease, such as schizophrenia. By genetically analyzing an embryo and then comparing its genetic information to this population data, the embryo’s polygenic risk score can be calculated for a given disease. This can already be done for a great many common diseases, with varying levels of predictive power, and as genetic databases grow, the reliability of these risk scores will continue to improve.

The couple also receives the raw data about their embryos’ genes and risk scores, so if they prefer to implant the embryo with the lowest risk of type 2 diabetes rather than the lowest combined disease risk, they can do that

“For prospective parents undergoing IVF and electing to use polygenic screening, somewhere between 10 and 20 polygenic risk scores are combined in a weighted average, with more serious diseases given greater weight in the final figure. This averaging provides a single number for each embryo — a health index — that can be used to rank the available embryos, so that the one with the best health index can be implanted,” says Carmi.

“Of course, the couple also receives the raw data about their embryos’ genes and risk scores, so if they prefer to implant the embryo with, let’s say, the lowest risk of type 2 diabetes, rather than the lowest combined disease risk, they can do that,” says Carmi.

An emotional decision

Michal Amrani, 32, lives in the central Israeli town of Ramat Hasharon and is working toward a master’s degree in chemistry from the Weizmann Institute. Through a four-year IVF process, she and her husband Sarel welcomed a son, and later, a set of twins. They say they are unlikely to use polygenic screening, even if it becomes available in Israel.

“As it is, we opted not to do some of the genetic testing that was already available to us,” Amrani says. “I work in science, so I am more open to these things, but my husband doesn’t really like all these genetic tests. For him, there’s risk in lots of things, and his optimistic nature helps him be comfortable that things will work out.”

Others, like Noa, are more interested in trying out preimplantation polygenic screening of their embryos, but even if Israel would change its rules to allow it, it’s a tricky issue. First, there are concerns about the psychological difficulties that this technology may pose for prospective parents.

Rona Langer Ziv is a social worker and cognitive behavioral psychotherapist who counsels IVF patients — both couples and singles — at a large Israeli hospital, as well as through her private clinical practice.

“Due to the potential implications of this new technology,” she says, “I would be concerned about a higher risk for depression and anxiety among the IVF patients.”

“Even if they feel they understand what they are signing up for at the beginning of the journey, they may not appreciate the emotional, ethical, and psychosocial implications of polygenic screening several IVF cycles down the road,” says Langer Ziv. “They may find themselves worrying that the embryos’ scores are not good enough, or that they won’t have any viable embryos left to choose from.”

Even if they feel they understand what they are signing up for at the beginning of the journey, they may not appreciate the emotional, ethical, and psychosocial implications of polygenic screening several IVF cycles down the road

Because polygenic screening predicts relative risk rather than providing an affirmative disease diagnosis, “women, especially those over 40 who may have very few embryos to work with, end up facing a serious dilemma — they may be discarding an embryo that could have resulted in a healthy child,” says Langer Ziv.

Amrani is in a similar situation. She and her husband are ready for more kids, but right now they have just one embryo available, so that’s the embryo they will try to implant. Even though she won’t be using polygenic screening, Amrani says that “it does sound very innovative. It’s nice that there’s something like this.”

Social worker and cognitive behavioral psychotherapist Rona Langer Ziv. (Courtesy) Indeed, Langer Ziv acknowledges that some people would find polygenic screening appealing, particularly those with higher education levels.

“There’s definitely coolness in the technology. It’s scientifically advanced, and it could offer interesting health insights about your future children. Everyone would theoretically like to use a technology that potentially predicts a more healthy child, although there is disagreement among fertility specialists about the benefits involved,” Langer Ziv says.

“And for some IVF patients, it might also provide a feeling of control during a process that involves so much stress, uncertainty, luck, and randomness,” she says.

Risk of eugenics

Regardless of how polygenic screening would be received by potential consumers, there are grave concerns about the impacts of this new technology on society. Various ethical issues have been raised for decades about older forms of genetic screenings, including fears of stigmatizing those living with genetic diseases, and questions about equitable access to these technological advances.

Perhaps the most significant ethical concern, and one that looms larger with polygenic screening than with older tests for monogenic diseases, is the potential for eugenics. This is the infamous and dangerous philosophy, practiced in Nazi Germany and elsewhere, that society should try to promote the creation of the most genetically “superior” babies.

Miri and her husband now have a baby boy and are looking forward to having more children — they still have three embryos to choose from. Asked whether she would be interested in polygenic screening if it became available in Israel, Miri says she’s unsure.

“I would love to see less suffering in the world from diseases. But where do we draw the line?” she says.

Indeed, the potential for eugenics is most stark when screenings cross over from the realm of disease prevention to the world of intelligence and aesthetic traits such as height or eye color. As such, some laboratories preemptively claim they will only screen for health concerns: An American polygenic screening company currently states that it does not test for “high IQ,” nor for “purely cosmetic traits such as hair color and eye color.”

But complicating the “noble” stance, genetic researchers have shown that “IQ is negatively correlated with most psychiatric disorders [and] positively correlated with autism and anorexia,” meaning that a high IQ comes with a lower risk of most psychiatric diseases and a higher risk of certain other neurological and mental health conditions.

As such, while some companies may currently refuse to offer IQ screening, it is not hard to imagine a health-based argument for loosening such protocols in the future, particularly as society becomes more used to the practice of PGT-P.

Similarly, a large study was published this year by researchers at Brown University and Peking University that found that “light eye colors were associated with high risks” of certain forms of skin cancer. Again, one can picture checks for eye color making their way into future genetic screenings through a backdoor of disease relevance.

In Carmi’s view, the responsible way for Israel to approach the prospect of polygenic screening is a gradual one.

“Ideally, we would start by recruiting Israeli participants for local academic research, with oversight by the Health Ministry,” Carmi says. “Once we develop more insight into how predictive polygenic screening is in our population, the relevant stakeholders — including patients, professional organizations, and regulators — can balance competing interests and local values, and come up with tailored guidance on its use in Israel.”

For some Israeli citizens, of particular concern is the idea of the wealthy trying to create perfect babies.

“If polygenic screening came to Israel, I would want to see a lot of regulation about who gets to use it, how it is used, and what reasons it is used for,” Miri says.

See also

WIRED: Genetic Screening Now Lets Parents Pick the Healthiest Embryos

Genomic Prediction in Bloomberg

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This is a balanced and informative article in WIRED, excerpted from author Rachael Pells' forthcoming book, Genomics: How Genome Sequencing Will Change Our Lives.

WIRED: ... Companies such as Genomic Prediction are taking this process much further, giving parents the power to select the embryo they believe to have the best fighting chance of survival both in the womb and out in the world. At the time of writing, Genomic Prediction works with around 200 IVF clinics across six continents. For company cofounder Stephen Hsu, the idea behind preconception screening was no eureka moment, but something he and his peers developed gradually. “We kept pursuing the possibilities from a purely scientific interest,” he says. Over time sequencing has become cheaper and more accessible, and the bank of genetic data has become ever greater, which has provided the opportunity to easily apply machine learning programs to seek out patterns, Hsu explains. “You can have typically millions of people in one data set, with exact measurements of certain things about them—for instance how tall they are or whether they have diabetes—what we call phenotypes. And so it’s relatively straightforward to use AI to build genetic predictors of traits ranging from very simple ones which are only determined by a few genes, or a few different locations in the genome, to the really complicated ones.” As Hsu indicates, the crucial difference with this technology is that it’s not just single mutations like cystic fibrosis or sickle cell anemia that the service makes its calculations on. The conditions embryos are screened for can be extremely complicated, involving thousands of genetic variants across different parts of the genome.

In late 2017, Hsu and his colleagues published a paper demonstrating how, using genomic data at scale, scientists could predict someone’s height to within an inch of accuracy using just their DNA. The research group later used the same method to build genomic predictors for complex diseases such as hypothyroidism, types 1 and 2 diabetes, breast cancer, prostate cancer, testicular cancer, gallstones, glaucoma, gout, atrial fibrillation, high cholesterol, asthma, basal cell carcinoma, malignant melanoma, and heart attacks. ...

Two useful references:

Polygenic Health Index, General Health, and Disease Risk

Complex Trait Prediction: Methods and Protocols (Springer 2022)

This 20 minute podcast segment is very well done. Congratulations to science journalist Teresa Carey. For more information, see (audio + transcript):

A nice article in Bloomberg describing polygenic embryo selection in IVF: DNA Testing for Embryos Promises to Predict Genetic Diseases, by Carey Goldberg.

Bloomberg: Simone Collins knew she was pregnant the moment she answered the phone. ... Embryo 3, the fertilized egg that Collins and her husband, Malcolm, had picked, could soon be their daughter—a little girl with, according to their tests, an unusually good chance of avoiding heart disease, cancer, diabetes, and schizophrenia.

This isn’t a story about Gattaca-style designer babies. No genes were edited in the creation of Collins’s embryo. The promise, from dozens of fertility clinics around the world, is just that the new DNA tests they’re using can assess, in unprecedented detail, whether one embryo is more likely than the next to develop a range of illnesses long thought to be beyond DNA-based predictions. It’s a new twist on the industry-standard testing known as preimplantation genetic testing, which for decades has checked embryos for rare diseases, such as cystic fibrosis, that are caused by a single gene.

One challenge with leading killers like cancer and heart disease is that they’re usually polygenic: linked to many different genes with complex interactions. Patients such as Collins can now take tests that assess thousands of DNA data points to decode these complexities and compute the disease risks. Genomic Prediction, the five-year-old New Jersey company that handled the tests for her fertility clinic, generates polygenic risk scores, predicting in percentage terms each embryo’s chances of contracting each disease in the panel, plus a composite score for overall health. Parents with multiple embryos can then weigh the scores when deciding which one to implant.

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This new form of genetic embryo testing appears to move humanity one step closer to control of its evolution. The 14ドル billion IVF industry brings more than 500,000 babies into the world each year, and with infertility rates rising, the market is expected to more than double this decade. Companies including Genomic Prediction bet many going into that process have seen enough loved ones suffer from a polygenic disease to want risk scoring.

[ Note I think the number of IVF babies born worldwide each year is more like 1 million, but there is some uncertainty in estimates. ]

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In December, Genomic Prediction doubled its venture funding to about 25ドル million and says it will use the cash to expand and add to its testing panel. Boston IVF, one of the biggest fertility networks in the US, recently started offering Genomic Prediction’s polygenic testing to its patients, says CEO David Stern. “Like anything else, you have early adopters,” he says. “We have had patients who worked in the biotech field or the Harvard milieu who came in and asked for it.” Stern predicts that, like egg freezing, polygenic embryo testing will grow slowly at first, but steadily, and eventually demand will reflect the powerful appeal of lowering a child’s odds for disease.

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Believers such as Collins and her husband support government subsidies for fertility and parenthood but aren’t interested in any conversation about slowing down. “This is about the people who care about giving their children every opportunity,” she says. “I do not believe that law or social norms are going to stop parents from giving their kids advantages.”

This article is well-written and informative. It covers polygenic screening from multiple perspectives: the parents who want a healthy child, the IVF doctors and genetic counselors who help the parents toward that goal, the scientists who study polygenic prediction and its ability to differentiate risk among siblings (i.e., embryos), the bioethicists who worry about a slippery slope to GATTACA.

... improved success rates resulting from higher accuracy in aneuploidy screening of embryos will affect millions of families around the world, and over 60% of all IVF families in the US.

The SNP array platform allows very accurate genotyping of each embryo at ~1 million locations in the genome, and the subsequent bioinformatic analysis produces a much more accurate prediction of chromosomal normality than the older methods.

Millions of embryos are screened each year using PGT-A, about 60% of all IVF embryos in the US.

Klaus Wiemer is the laborator director for Poma Fertility near Seattle. He conducted this study independently, without informing Genomic Prediction.

There are ~3000 embryos in the dataset, all biopsied at Poma and samples allocated to three testing labs A,B,C using the two different methods. The family demographics (e.g., maternal age) were similar in all three groups. Lab B is Genomic Prediction and A,C are two of the largest IVF testing labs in the world, using NGS.

The results imply lower false-positive rates, lower false-negative rates, and higher accuracy overall from our methods. These lead to a significantly higher pregnancy success rate.

The new technology has the potential to help millions of families all over the world.

This increase in pregnancy success rates was not something we directly aimed for -- rather, we were simply trying to get the most accurate characterization of chromosomal abnormality (aneuploidy) using the high precision genotype from our platform. After Dr. Wiemer surprised us with these results, it became plausible that significant increases in success rates per IVF cycle could still exist as low-hanging fruit. The ~3k embryos used in his study are considered a big sample size in fertility research, whereas in genomics today a big sample is hundreds of thousands or a million individuals.