BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: IVF

A Child of Three Parents?

In 2015, the United Kingdom became the first country to legalize a procedure called Mitochondrial Replacement Therapy (MRT), which was used to prevent inheritable health conditions involving the heart, brain, and muscles caused by mitochondrial mutations. This MRT procedure, sometimes called three-person in vitro fertilization (IVF), involves transferring genetic material from the nucleus of the egg or embryo with mitochondrial mutations to a different healthy donor egg with its genetic materials previously removed, allowing the child produced to have three parents.

Early human embryos

Eight years later, the Human Fertilization and Embryology Authority (HFEA) of the United Kingdom confirmed that at least one UK child had been born using the procedure as of April 2023. Although this is the first successful case of a fully legalized MRT procedure, it has previously been done successfully unregulated as well. A US doctor used MRT successfully to prevent mitochondrial disease in a baby in Mexico in 2016. Another US doctor, John Zhang, and his team successfully performed IVF on an embryo at New Hope Fertility Center in New York City in 2016. Greece and Ukraine have also conducted MRT to treat infertility. Despite many successes and new countries such as Australia approving MRT in 2022, MRT remains restricted in most areas, including the United States. The extent of IVF’s effectiveness is still to be tested. When, inevitably, a small number of mitochondria are transferred into the donor egg or embryo, it’s unclear whether or not very low levels of mutation-bearing mitochondria cause health problems. Additionally, scientists estimate a 1 in 50 chance of a mismatch in mitochondrial DNA and nuclear DNA could result in mitochondria problems. In some cases, a phenomenon known as reversal, where the carried-over mitochondria can increase markedly over time, replacing donor mitochondria in cells and bringing back the mutation. From scientist Wells’ observation in Greece, of the 6 children born with MRT, 1 child experienced reversal, though the reversal seems to have had no effect on the child’s health. The reason for this phenomenon is not clear, but scientists hypothesize that, due to efficiency reasons, matching donor and recipient on their mitochondrial DNA or freezing the mother’s eggs before transferring the nuclear genetic material into fresh donor eggs could prevent reversal. The process of Mitochondrial Replacement Therapy (MRT) is related to our understanding of mitochondria. From what we’ve learned, mitochondria are passed down only by females and mothers, as a significant amount of mitochondrial DNA exists inside eggs from mothers, whereas no mitochondrial DNA exists in the sperm of males, and all mitochondria are lost during fertilization. This leaves the mitochondrial DNA of the embryo and child originating solely from the mother’s egg. This explains why it is not possible to be treated with simple medicine, as the mutations are passed down genetically, requiring this procedure. Although I think the other side of natural selection should be considered by scientists before widely spreading the use of this procedure, the fact that MRT is life-saving and allows families to be formed outweighs the natural philosophies, and it should be widely used one day. If you needed MRT to give birth to a healthy child, would you do it?

Embryo Gene Editing can Ensure Offspring Do Not Inherit a Deafness Gene!

Denis Rebrikov, A scientist in Russia has done research regarding ways in which he can edit the genome sequence of an embryo in order to prevent the fetus from developing certain gene mutations, specifically in this case a hearing problem or possible complete deafness. His plans are very controversial to some, who believe the possible risks of very harmful mutations to DNA that would be passed onto direct and future offspring, outweigh the possible benefits. However, some people find this scientific possibility to be worth the risk, if it means not passing a potentially very harmful gene down to offspring. If these methods are done correctly, it should alter the genome sequence in the embryo so that future offspring off that embryo will not inherit the negative mutation.

One couple shared their story in detail, in which both parties have a hearing deficiency, the man with partial deafness, and the woman completely deaf. Their biggest hope is to have children who will not inherit hearing issues, because of the apparent challenges they have had to face themselves because of them. They would be the first couple to perform this gene editing on an IVF embryo, so they obviously have some reservations. One of those being publicity, but more importantly the potential risks of using the CRISPR genome editor. They already have a daughter with hearing loss, but they never chose to test her genes for mutations, nor did they get her a cochlear implant to aid her hearing, because of the potential risks of that. When they finally tested her genes, they learned that she had the same common hearing loss mutation called 35delG in both her copies of a gene called GJB2. The parents then tested themselves, realizing they were both 35delG homozygous, meaning their daughter’s mutations were not unique to her, they had been inherited.

If either the mother or father had a normal copy of the GJB2 gene, a fertility clinic could have more easily created embryos by IVF and tested a few cells in each one to select a heterozygote–with normal hearing–to implant. At this stage, Denis Rebrikov informed them that CRISPR genome editing would be their only option. However, the process presents possibly deal breaking risks, such as mosaicism, in which a gene edit might fail to fix the deafness mutation, which could create other possible dangerous mutations like genetic disorders or cancer. The couple has not decided to go through with the editing just yet, but it is something they are open to in the future as more possible new research or test subjects become available.

Explaining the CRISPR Method: “The CRISPR-Cas9 system works similarly in the lab. Researchers create a small piece of RNA with a short “guide” sequence that attaches (binds) to a specific target sequence of DNA in a genome. The RNA also binds to the Cas9 enzyme. The modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location… Once the DNA is cut, researchers use the cell’s own DNA repair machinery to add or delete pieces of genetic material, or to make changes to the DNA by replacing an existing segment with a customized DNA sequence.” -US National Library of Medicine Genetics Home Reference

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Woman with a hearing aid 

If you had the opportunity to alter something in the gene’s of your baby’s embryo, would you? Under what circumstances would you consider this, and what risks might stop you from deciding to do it? Comment down below.

 

 

New IVF procedure makes making babies more affordable

A recent article, published in Reproductive BioMedicine Online, compared current IVF procedures with a new, simpler lab method and concluded that both methods of culturing embryos yield similar results. This was done by American and Belgian researchers. Sixteen babies have successfully been born using this new method, and it can lead to IVF being more affordable and more available to a larger field of people.

IVF babies have been limited to less than 10% of the world population in developed countries due to the high cost of having such a child.

In this method, a reduced cost IVF culture system replaced expensive incubator systems. Despite this new method, the need for surgical egg retrieval, embryo transfer, and lab staffing and egg/embryo freezing still exists.

It is still unclear as to how much less expensive this new method will be, but there is hope that the new embryo culture method will change the philosophy in IVF of using increasingly new and complex instruments.

 

Photo taken by: ESTHARNIV
http://commons.wikimedia.org/wiki/File:Baby-cute-wallpaper_2560x1600_84401.jpg

 

 

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