Three Parent In Vitro Fertilization coming soon
The U.K. Parliament green-lit “Three Parent In Vitro Fertilization” (TPIVF) legislation last month, setting a precedent and spawning headlines around the globe. Dubbed “three parent babies” by news outlets, the law will allow the procedure to move directly into fertility clinics.
The process combines donor mitochondrial DNA with in vitro fertilization to circumvent mitochondrial-based diseases in offspring. Defects in mitochondrial function are associated with various musculoskeletal, metabolic, and neurodegenerative diseases.
In this issue we will explain the science behind TPIVF and look at its potential for approval in the U.S.
REPLACING MITOCHONDRIAL DNA IN IVF
The rationale behind TPIVF lies with mitochondria—what many of us remember as the “powerhouse” of a cell from high school biology. Recall they are the compartments that convert glucose into the energy our cells use to do work. What you may not remember is mitochondria have their own DNA that is inherited maternally. When an egg is fertilized, the mitochondria get passed on in subsequent rounds of cell division becoming a part of every cell in a developing baby’s body. A woman with defective mitochondrial DNA passes this trait onto her child. However, these mutations may be weeded out of the genetic landscape thanks to TPIVF.
During TPIVF the nuclear DNA is removed from the egg of the afflicted mother. This nuclear DNA is transferred into an enucleated donor egg (enucleated means the nuclear DNA has been removed but the mitochondrial DNA remains intact). The resulting egg is implanted back into the prospective mother and (fingers crossed) develops into a healthy baby. The resulting child has DNA from two different women and one man.
Beginning with Cytoplasmic Transfer
TPIVF has some precedent in a procedure known as cytoplasmic transfer. In the late 1990s this experimental procedure was used to help woman, whose fertility had declined, to conceive.
The prospective mother’s egg was injected with a small amount of cytoplasm from another women’s egg prior to fertilization. Cytoplasm is the liquid portion of a cell outside of the nucleus that also happens to contain mitochondria. The exact mechanism by which cytoplasmic transfer enables pregnancy is not clearly defined, but many doctors suspect some cases of infertility are caused by damaged mitochondria. The infusion of donor cytoplasm may be enough to rejuvenate these eggs.
Twenty-four women achieved pregnancy via cytoplasmic transfer two decades ago. However, the FDA had safety concerns and the practice was abandoned when fertility clinics were required to file an IND to continue the procedure. Cytoplasmic transfer is still not approved by the FDA and this policy is credited with creating a market for reproductive tourism abroad.
Cocktail Fodder: Only 37 Genes
Although it is correct to say that a baby conceived by TPIVF has genetic material from three different parents, the vast majority (~99.9%) of that baby’s genetic material will come from the nuclear DNA of the original egg and sperm. Mitochondrial DNA codes for only 37 genes, whereas nuclear DNA codes for ~21,000 genes.
The FDA Weighs In
Much like IVF involving donor eggs, TPIVF has the potential to become a routine medical procedure, but not without some close scrutiny. The FDA has asked the Institute of Medicine (Washington, DC) to consider the ethical and social ramifications raised by TPIVF and to create a consensus report to help guide future regulatory policy. As a part of this process, the Institute of Medicine will hold a series of meetings and solicit public commentary. The first meeting was held in January and the second meeting will be held March 31–April 1 in Washington D.C.
Click here to register for the public comment portion, registration ends tomorrow, March 27, at 2pm.
Emily Burke, PhD has worked in biopharma for 20 years, gaining science writing experience at The Scripps Research Institute and Ionis Pharmaceuticals. As a Ph.D. molecular biologist, she is passionate about advancing the public’s understanding of science. In addition to being a self-proclaimed “science geek,” she is regularly asked to speak at international scientific meetings. When not teaching and writing the WEEKLY for Biotech Primer, Dr. Burke swims with her swim club and performs regularly on the improv circuit in San Diego.