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Over the past few years, reproductive medicine has undergone a revolution and has two of the world's most promising new methods. Pronuclear and spindle transfer are techniques developed to prevent mother-to-child transmission of mtDNA diseases. It offers enormous hope for parents with the risk of transmitting such pathologies in the nuclear genome to their offspring. At five to six days after fertilization, once human embryos reach the blastocyst stage, it emerges from the zona pellucida and begins the process of implantation in the uterus. Although both procedures entail the mtDNA carryover among human oocytes, they have significant distinctions. Moreover, both methods have advantages and disadvantages, and ethical considerations apply.

The final decision as to which method to use should be made on a case-by-case basis, according to the particular medical circumstances and the parents' preferences. This article will address the differences between pronuclear transfer and spindle transfer.

What is Pronuclear Transfer?

Pronuclear transfer program is a reproductive method of transferring the nuclear DNA of a fertilized egg into a donor egg from which it has been removed. This technique is used to prevent maternally inherited mitochondrial DNA abnormalities. Mitochondrial replacement therapy is responsible for energy production in stem cells, so when this process is disrupted, it can lead to several health problems, including neurological and embryonic development disorders.

Pronuclear transfer (PNT) is accomplished by fertilizing the mother's egg with the father's sperm in a blastocyst culture. The pronuclei, representing the nuclei of the sperm and egg, are subsequently removed and transferred to a donor oocyte that also had its pronuclei extracted. Afterward, the embryo is transferred to the mother's uterus for implantation.

What is Maternal Spindle Transfer?

Spindle transfer is another reproductive approach to prevent mitochondrial diseases. However, unlike pronuclear transfer, it involves the transfer of a spindle, a tiny structure containing chromosomes, from a maternal egg to a donor egg in which the nucleus has been removed. This procedure is also known as "maternal spindle transfer."

Spindle transfer entails removing the nucleus from the donor egg and inserting the spindle, containing the maternal chromosomes, into the oocyte. The egg is inseminated with the father's sperm for in vitro fertilization and transferred to the mother's uterus for implantation and embryo development.

Differences Between Spindle Transfer and Pronuclear Transfer?

The primary distinction between pronuclear transfer and spindle transfer is that part of the oocyte is transferred into the donor egg. In pronuclear transfer, the pronuclei are transferred, while in spindle transfer, the spindle is transferred. The difference in technique further affects which step these procedures are performed. The pronucleus transfer is done shortly after fertilization, whereas the spindle transfer is done before fertilization.

Another main difference between these two techniques is the likelihood of preimplantation genetic diagnosis. A pronuclear transfer implies the transfer of maternal and paternal genetic material into the egg, which can lead to abnormalities in the received embryo. Conversely, a spindle transfer involves transferring only maternal genetic material, reducing the risk of hereditary defects.

Furthermore, the regulatory approval of the two techniques varies. The pronuclear transfer has been approved for clinical use in the UK, while spindle transfer has not yet received regulatory approval in any country.

Ethical Considerations

Both pronuclear transfer and spindle transfer raise ethical concerns. Some analysts claim that utilizing donor eggs and creating human embryos with genetic material from three or more people is morally problematic.

However, proponents of these technologies argue that they enable couples to have healthy children without the risk of mitochondrial disease. They also point out that creating embryos with genetic material from several people is not unique to these procedures since egg and sperm donation has been used in traditional IVF for decades.

Which Technique is Right for You?

The decision concerning which method of mitochondrial donation is suitable for you can be complex and involves a thorough consideration of your medical history & individual circumstances. The availability and regulatory approval of techniques within your country may also influence the decision.

Overall, both methods have shown tremendous potential for preventing mitochondrial DNA disease. The nuclear transfer is used for a higher success rate of reconstructed embryos, allowing you to have a genetically related child despite the mtDNA mutations. Nonetheless, this procedure is more complicated than spindle transfer and requires enormous quantities of donor oocytes. Spindle transfer, on the other hand, is a more straightforward procedure necessitating fewer donor eggs. It allows transferring of genetic material before human fertilization, which may be preferable for some individuals. The success rate for spindle transfer is lower than for pronuclear transfer, though, and it can be more challenging to maintain the integrity of the transferred genetic material.

Promising Advances in Reproductive Medicine

Pronuclear and spindle transfer are two up-and-coming practices in assisted reproductive technology, facilitating people carrying the risk of passing on mtDNA disease to future generations. Both techniques need further studies to determine their long-term safety and efficacy; thus, they have advantages and disadvantages, the capability to prevent mitochondrial disorders via these methods is a significant breakthrough in reproductive medicine. It is necessary to determine which one to choose by consulting a qualified reproductive medicine specialist.

It's also worth noting that mitochondrial replacement techniques are no substitute for traditional genetic counseling and testing from a reliable company like IFG. Couples with the risk of handing down mutant mtDNA in the nuclear genome should consult with a skilled genetic counselor to identify their options and risks.

by Dr. Uliana Dorofeyeva

M.D., IVF specialist, gynecologist, reproductive endocrinologist, expert of ultrasound diagnostics.