How common is genetic screening in IVF?

In 2020, about 1-2% of live births in the US involved assisted reproduction, with IVF being the most common. Approximately 40% of those IVF conceptions underwent some form of genetic screening, totaling around 30,000 babies annually, and this number is increasing.

What are the different types of PGT tests?

There are four main types: PGT-A (aneuploidy screening for chromosome number abnormalities), PGT-M (for monogenic/single-gene disorders), PGT-SR (for structural chromosomal rearrangements), and PGT-P (for polygenic traits, influenced by multiple genes). Sex determination is also a basic screening.

What are the ethical concerns surrounding PGT?

Ethical concerns include parental selection of desirable traits, potential for 'designer babies,' health implications of selection for traits like height or intelligence, the use of 'savior siblings,' and the decision-making process in pregnancies involving genetic abnormalities.

Is PGT-A effective in increasing pregnancy success rates?

Studies show mixed results. Some indicate no significant increase in live birth rates, while others suggest benefits for specific age groups (e.g., women over 37 or 38), though these findings are debated and may depend heavily on the lab's quality.

What are the limitations of polygenic screening (PGT-P)?

Current PGT-P limitations include non-representative DNA databases (over-representing European ancestry), the complexity of gene-environment interactions, and the fact that correlation doesn't equal causation. Clinical research on its diagnostic effectiveness is still lacking.

What is the legal status of genetic screening in different countries?

Regulations vary significantly. The EU generally prohibits sex-selection and restricts PGT for incurable diseases. Russia allows it for hereditary disorders only. China has guidelines but sex-selection is common. The US has no specific legal regulation, making it a 'wild west' in some aspects, though sex selection is legal.

Are there any proposed ethical frameworks for PGT?

A 'Welfarist Model' has been proposed, allowing selection for traits associated with well-being or against traits that reduce it. However, the definition of 'well-being' itself is a subject requiring further ethical and philosophical research.

Key Moments

Genetic Screening of Embryos: Risks and Benefits

Sabine Hossenfelder

Science & Technology3 min read24 min video

Jan 28, 2023|206,619 views|8,193|1,949

genetics genetic testing genetic screening how does genetic screening work is genetic testing legal how does genetic testing relate to race is testing genes for sex legal is sex selection of babies legal preimplantation genetic diagnosis preimplantation genetic testing hossenfelder science without the gobbledygook

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Key Moments

TL;DR

Genetic screening of embryos offers trait selection but raises ethical concerns and lacks conclusive evidence for benefits beyond specific cases.

Key Insights

Preimplantation Genetic Testing (PGT) allows selection of embryos based on genetic makeup, moving beyond chance in inheritance.

PGT encompasses various tests: PGT-A (aneuploidy), PGT-M (monogenic diseases), PGT-SR (structural rearrangements), and PGT-P (polygenic traits).

PGT-A's benefit is most evident for women nearing the end of their fertile years, but outcomes are highly dependent on lab quality.

PGT-M is effective for single-gene disorders but relies on understanding gene-disease correlation, which isn't always deterministic.

PGT-P, for polygenic traits like height or intelligence, is the most controversial due to unreliability in current data and ethical implications.

Legal regulations for embryo genetic screening vary significantly worldwide, with some countries prohibiting sex selection and others having no specific laws.

INTRODUCTION TO PREIMPLANTATION GENETIC TESTING (PGT)

The advent of Preimplantation Genetic Testing (PGT) marks a significant shift, allowing prospective parents to influence their child's genetic inheritance beyond chance. Typically performed on three-to-five-day-old embryos, PGT involves analyzing cells for genetic makeup to decide which embryos to implant or discard. This technology, often integrated with In-Vitro Fertilization (IVF), is becoming increasingly common globally, with a notable percentage of IVF procedures incorporating these screenings.

TYPES OF GENETIC SCREENING TESTS AVAILABLE

PGT encompasses several distinct types of tests. PGT-A screens for aneuploidy, or abnormal chromosome numbers, identifying conditions such as Down syndrome. PGT-M targets single-gene disorders like cystic fibrosis or Huntington's disease. PGT-SR investigates structural chromosomal rearrangements that can lead to developmental issues. Finally, PGT-P, the most debated, assesses polygenic traits influenced by multiple genes, including predispositions to common diseases or complex traits like intelligence and height.

EFFICACY AND BENEFITS OF PGT-A AND PGT-M

PGT-A, the most common type, shows a potential benefit for women nearing the end of their reproductive years by increasing the chances of a successful pregnancy and reducing miscarriage rates. However, the effectiveness is highly dependent on the laboratory's proficiency. PGT-M is valuable for families with known hereditary genetic diseases, offering a way to avoid passing these conditions to offspring, though the interpretation of risk and genetic predisposition remains complex.

THE CONTROVERSIAL REALM OF PGT-P AND POLYGENIC TRAITS

PGT-P is highly controversial because it examines traits influenced by numerous genes, where genetic factors often indicate only an increased likelihood rather than a certainty of developing a condition. The technology uses sophisticated AI to analyze correlations between specific DNA markers (SNPs) and health outcomes. While simulations suggest potential risk reduction for diseases and even enhancements in traits like height or IQ, the reliability of these predictions is hampered by data biases and a lack of clinical validation in embryos.

ETHICAL DILEMMAS SURROUNDING TRAIT SELECTION

The ability to select genetic traits for offspring raises profound ethical questions. Concerns include potential parental bias in selecting for traits like intelligence or height over health, the possibility of creating 'savior siblings' for medical donation, and the long-term societal impact of altering human genetic diversity. The definition of what constitutes a 'disease' versus a 'trait' is subjective, leading to complex moral considerations about parental autonomy and the child's future well-being.

REGULATORY LANDSCAPE AND FUTURE IMPLICATIONS

Legal frameworks for PGT vary significantly across the globe. Some nations, like EU member states, restrict PGT to preventing severe hereditary diseases and often prohibit sex selection. Others, such as China and the US, have fewer legal restrictions, leading to a 'wild west' scenario in some instances, particularly regarding non-medical trait selection. The lack of robust, long-term clinical trials for all PGT types means definitive conclusions about their overall benefit and risk are still evolving.

Mentioned in This Episode

●Software & Apps

●Tools

●Companies

●Organizations

●Books

●Studies Cited

●Concepts

●People Referenced

Genetic Screening of Embryos: A Quick Guide

Practical takeaways from this episode

Do This

Consider PGT-A for women nearing the end of their fertile years, but choose a reputable lab.

Use PGT-M to screen for specific monogenic diseases if a family history exists.

Understand that PGT-SR can help identify structural chromosomal rearrangements.

Be aware that PGT-P is the most controversial and focuses on polygenic traits, with limitations in current databases.

Consult with healthcare providers and review available research due to the developing nature of the field.

Avoid This

Do not rely solely on genetic screening to guarantee a successful pregnancy, as study results are often inconclusive or contradictory.

Do not assume genetic determinism is absolute; gene expression is complex and influenced by many factors.

Be cautious with polygenic risk estimates for individuals from underrepresented ethnic backgrounds due to data limitations.

Do not expect perfect accuracy; misdiagnoses are possible, especially if tests are not performed under ideal conditions.

Avoid making decisions based on a single study's findings; consider the broader scientific consensus and individual circumstances.

Common Questions

PGT is a genetic screening process performed on embryos, typically three to five days old, by analyzing several cells to determine their genetic makeup. Based on the results, parents and doctors decide whether to implant the embryo or discard it.

Topics

Health & Longevity Science & Mathematics Embryo Selection Ethical Implications Medicine & Clinical Genetic Screening IVF Technology Hereditary Diseases Polygenic Risk Preimplantation Testing

Mentioned in this video

condition

Down syndrome

A genetic disorder caused by a third copy of chromosome 21, detectable through PGT-A tests. Individuals with Down syndrome often have distinctive physical features, lower IQ, and potential heart conditions, but can live into their 60s with good medical support.

Turner syndrome

A genetic condition caused by a missing or damaged second X chromosome, detectable through PGT-A tests.

Huntington's Disease

A monogenic disease commonly tested for using PGT-M.

Patau Syndrome

A genetic disorder caused by a third copy of chromosome 13, detectable through PGT-A tests.

Edwards syndrome

A genetic disorder caused by a third copy of chromosome 18, detectable through PGT-A tests.

Cystic fibrosis

A monogenic disease tested for using PGT-M, caused by a single gene defect.

Studies & Research

2016 study

An American study suggesting PGT-A benefits increased pregnancy chances by over threefold for women older than 37, though the sample size was small (60 women).

2019 paper

A paper indicating PGT-A doubled pregnancy chances for women over 38 but decreased them in younger age groups, highlighting confusing results.

2018 study

A study examining IVF candidates in Europe and Israel that found PGT-A screening did not increase successful pregnancy outcomes but slightly decreased miscarriage risk.

2020 study

A study using a California clinic's data that found PGT-A patients had a higher chance of having a child across all age groups, but the difference was smaller than in previous studies.

Concepts

PGT-P

The most controversial type of genetic screening test, which screens for traits influenced by multiple genes, including diseases like diabetes and heart conditions, as well as traits like height and intelligence.

Preimplantation Genetic Testing

A method performed on embryos (typically 3-5 days old) to analyze their genetic makeup, determining whether to discard or implant them.

Artificial Intelligence

Used by companies like Genomic Predictions to analyze large DNA databases and identify correlations between gene expressions and health problems for risk prediction.

In-vitro fertilization

A fertility treatment that involves fertilizing an egg outside the body. PGT is often applied to embryos created through IVF.

Sickle Cell Anemia

A monogenic disease tested for using PGT-M, caused by a single gene defect.

PGT-M

A type of genetic screening test used for conditions caused by a single gene defect, capable of avoiding over six hundred known monogenic diseases.

PGT-SR

A genetic screening test that looks for uncommon chromosome rearrangements, which can be associated with intellectual disability, speech delay, or birth defects.

Organizations

European Union

Has varying regulations on genetic screening, generally forbidding sex-selection and permitting polygenic screening only for incurable hereditary diseases.

UK Authority on Human Fertilization & Embryology

An authority that has rated PGT-A as 'red' due to insufficient evidence of benefit, indicating caution.

Cell

A journal where a 2019 paper was published simulating the effects of polygenetic screening for height and IQ over generations.

Companies

Genomic Predictions

An American company founded in 2017 that offers polygenic testing for various diseases and traits. They were behind the world's first PGT-P baby, Aurea.

MyOme

A company that offers polygenic tests.

Orchid

A company that offers polygenic tests, similar to Genomic Predictions.

Brilliant.org

A platform offering online courses in science and mathematics, including computational biology, neural networks, and quantum computing. A promotional link is provided.

Locations

China

Has no laws regarding genetic screening but has guidelines against sex-selection, which is still widely practiced.

Russia

Approves genetic screening for hereditary disorders but not sex-selection.

Events

Chernobyl

Mentioned as a hypothetical example of a common origin for gene prevalence and disease.

People

Shawn Bradley

An American NBA player whose exceptional height (7'6") is used as an introductory example to discuss genetic predispositions.

Angelina Jolie