Mitochondrial replacement therapy, pronuclear transfer

Mitochondrial replacement

Pronuclear nuclear transfer (mitochondrial replacement therapy) — is the most advanced reproductive technology that allows couples to have a genetically related child, for whom previously reproductive medicine could only offer IVF with a donor egg.

The essence of mitochondrial replacement therapy lies in the fact that after fertilization of the egg, two nuclei are formed: one from the mother, the other — from the father. Geneticists extract these two nuclei and transfer them to a donor healthy egg, from which the original nuclei have been removed.

As a result of this procedure, a "reconstructed" egg is obtained, carrying the genetic set of nuclear DNA from the mother and father (99.9% of approximately 25,000 genes) and mitochondrial DNA from the donor (0.1% of the total genes).

The mitochondria of the donor egg only provide energy to the embryo and do not influence the genetic nuclear components. The child inherits genetic information from both the mother and father.

Mitochondrial replacement therapy is recommended in two cases:

1. In case of multiple unsuccessful attempts of conventional IVF. Embryologists have found that in women aged 40 and above, the success rate of in vitro fertilization significantly decreases. Poor quality of mitochondria in a woman's egg can lead to the cessation of embryo development at the blastocyst stage (day 5).
   Mitochondria are intracellular structures responsible for energy production and maintenance for the body's needs, thus playing a key role in providing vitality for embryo development. As women age, the quality and quantity of mitochondria in egg cells decline, leading to halted embryo development due to insufficient energy.
2. In cases where a woman is a carrier of genetic mitochondrial diseases caused by mutations in mitochondrial DNA. There's a risk of transmitting defective mitochondrial DNA with mutations from the mother to the child, potentially leading to severe mitochondrial diseases.

Comparison of Assisted Reproductive Technologies

According to statistics, 1 in 5000 children suffer from severe mitochondrial disease. Currently, there are no effective treatments for these diseases, and there is a high mortality rate before the age of 5 or during the embryonic stage. Defects in mitochondrial function can lead to central nervous system (CNS) damage, as well as muscular, respiratory, cardiac, and liver failure. Approximately 50% of mitochondrial diseases are caused by issues in one of the 37 genes present in mitochondrial DNA. Genetic disorders caused by mutations in mitochondrial DNA are inherited exclusively from the mother.

In this context, the application of pronuclear transfer (mitochondrial replacement therapy) in the IVF program is the only chance to have a genetically healthy child.

In which countries is the pronuclear transfer method applied?

Ukraine was the first country in the world to successfully apply pronuclear transfer within the in vitro fertilization (IVF) program. In 2017, the first child in the world, whose birth was made possible by pronuclear transfer, was born in Ukraine. The sensational achievements of Ukrainian embryologists gained global attention, attracting delegations from Western media, including CNN, BBC, and The Guardian, to Ukraine.

Since 2017, Ukrainian reproductive specialists have pioneered a new direction in reproductive medicine, aiming to improve egg quality by transferring the nuclei of the patient to the cytoplasm of a donor egg.

Prior to 2017, the technique of cytoplasm donation involved the following procedure: cytoplasm from a donor egg, containing healthy mitochondria, was injected into the cytoplasm of the patient's egg, where mitochondria were damaged. This basic method of mitochondrial donation improves the quality of the patient's egg and aids in correcting defects related to energy provision, leading to normal embryo development. However, cytoplasmic transfer does not remove defective maternal mitochondria, making this technology unsuitable for women at risk of passing mitochondrial diseases to their offspring.

Apart from Ukraine, pronuclear transfer has been permitted in the United Kingdom since 2015, Australia since 2022, certain states in the USA, and Mexico. Overall, as of 2025, mitochondrial replacement therapy is employed in 9 countries worldwide.

What is the cost of mitochondrial replacement therapy?

This treatment method is considered expensive. Clinics conducting research and treating patients using mitochondrial replacement therapy must have appropriate state licenses. In Ukraine, the average cost of IVF with pronuclear transfer is 15,000 euros, while in the United Kingdom, the cost of the medical procedure starts at 25,000 euros.