February 6, 2015

Three-Parent Assisted Reproductive Technology Nears Approval in U.K.

The U.K. House of Commons approved a bill this week that would allow the use of a novel assisted reproductive technology (ART) to proceed. In current media coverage, the technique has been called three-parent reproduction, and it has been developed to offer a route to reproduction for women who are likely to transmit genetically inherited mitochondrial disease. Offspring inherit their mitochondria from the egg of the mother, and can be at risk from any mitochondrial disease that has occurred to the mother or the maternal family. The proposed intervention is known as mitochondrial replacement therapy. The three parents are the father and two mother donors: the nucleus is removed from the egg of the intended but genetically impaired parent and it is inserted into the egg of a healthy female donor, whose mitochondria are not defective. The reengineered egg undergoes in vitro fertilization with the father’s sperm, and is then implanted. This week, the U.K. House of Commons approved the use of the 3-parent mitochondrial replacement technique, in amending the Human Fertilisation and Embryology Act of 2008. The House of Lords is expected to follow suit. Unlike the U.S., the U.K. has an oversight body for ART – the Human Fertilisation and Embryology Authority (HFEA) -  which regulates fertility treatments and other reproductive technologies. The U.S. has no specific regulatory agency targeting reproductive technologies, but the FDA claims a regulatory role based on its general regulation of reproductive tissues in commerce (eggs, sperm) and the agency did shut down earlier work using MRT in the late 1990's. In the U.S. the FDA and the Institute of Medicine (IOM) are considering whether the technique should be approved for use in the U.S: 
An FDA Advisory Committee (AC) met on February 25 and 26, 2014, to discuss the science regarding assisted reproductive methods involving genetic modification of eggs and zygotes for the prevention of  mitochondrial disease. FDA has requested that the Institute of Medicine produce a consensus report regarding the ethical and social policy issues related to genetic modification of eggs and zygotes to prevent transmission of mitochondrial disease.
The FDA committee agreed that any proposed clinical trials with humans could be premature:
The Committee generally agreed that there is not sufficient animal data (particularly with regard to follow-up of offspring) to support the use of the mitochondrial manipulation technologies in first-in-human clinical trials. It was also acknowledged that the use of somatic cell nuclear transfer (SCNT) following by intracytoplasmic sperm injection (ICSI) had to be weighed against alternative methods for preventing the transmission of mitochondrial diseases to offspring, including adoption, oocyte donation, and cytoplasmic/mitochondrial transfer. 
The IOM began its study last month, holding its first meeting on the subject. In general, the U.S. is lagging behind the U.K. in considering official approval of this technique; in 1978, in vitro fertilization was first used in the UK before it migrated to the U.S. soon afterward. To date, there are pro and con views on whether MRT could be a viable option for prospective parents. Critics point to safety concerns as well as fears regarding a slippery slope toward allowing other genetic interventions to produce either healthier or “better” offspring. Supporters of MRT point out that the technique offers women with mitochondrial disease to have children that are genetically related but free of the genetic defect imparting serious disease. My own view is that there might be latent genetic incompatibilities that would not be overtly evident but perhaps manifest developmentally or subtly in a way that comprises the health of an MRT-derived offspring. Looking at regulatory moves in the future, there is always the possibility of legislative action that would either allow or prohibit the use of the technique – it’s too early to have such initiatives started, but such moves would echo ongoing Congressional and state responses to the possibility of human reproductive cloning that emerged in 1997, following the creation of the cloned sheep, Dolly.

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