The pronuclear transplant or “three-parent technique”: a new real hope in surrogacy

Many parents come to us after a long journey through different assisted reproduction clinics. After multiple failed in vitro fertilizations and embryo transfers, they receive a clear diagnosis: for different reasons (mother’s age, risk of transmitting a disease, or poor egg quality), their own eggs cannot be used. In these cases, the only option has been to turn to a donor.

For many women, this is an emotional blow, as they feel they are giving up their genetic heritage. Until recently, it was inevitable: if the mitochondria of the oocytes did not work properly, there was no alternative.

Today, thanks to pronuclear transplant (or its variant, spindle transfer), it is possible to use one’s own eggs, even when the mitochondria are not viable.

Even in healthy women, mitochondrial DNA may pose a risk to the baby’s health. Here, science offers a solution that once seemed impossible: pronuclear transplant, also known as the “three-parent technique.” Combined with surrogacy (although also applicable in conventional assisted reproduction), it opens the door to having healthy children where it was previously impossible.

Spoiler: the baby does not have three parents. His or her genetic traits come from mom and dad. The donor only provides a healthy “engine” (mitochondria), which ensures correct cellular functioning.

Why do we talk about surrogacy?

Those who turn to surrogacy usually do so because they cannot carry a pregnancy or should not do so for health reasons. If, in addition, there is a risk of transmitting a mitochondrial disease, pronuclear transplant becomes a key tool: an embryo is created with the parents’ nuclear DNA and healthy mitochondria from the donor. That embryo is then transferred to the surrogate’s uterus, resulting in a baby genetically from the parents and free of disease.

If you want practical information and experienced guidance, you can consult Gestlife’s official sites:

Europe: www.gestlifesurrogacy.com

USA: www.gestlifesurrogacy.us

The basics, without technicalities: what is pronuclear transplant?

Think of a cell as a house. Inside, there is a nucleus (the library with almost all the information: eye color, height, etc.) and small “batteries” called mitochondria, which provide energy. In some women, those batteries carry an error that can cause very serious diseases in children.

Pronuclear transplant keeps the parents’ nucleus but replaces the “batteries” with healthy ones from a donor.

Does that make the baby “from three parents”? No. Traits, family inheritance, come from mom and dad’s nuclear DNA. The donor contributes mitochondrial DNA (very small), which does not define traits such as height, eye color, or personality.

How it’s done (in simple terms)

1. Two eggs are fertilized with the father’s sperm:
   • one is the mother’s egg,
   • the other is the donor’s egg.
2. In the donor embryo (at an early stage), the nucleus is removed.
3. The nucleus of the mother’s embryo is then placed into that donor embryo.
4. The resulting embryo has the parents’ nuclear DNA and healthy donor mitochondria.
5. That embryo can then be transferred into the mother’s uterus or into a surrogate if indicated.

It is a delicate micromanipulation in the laboratory. That is why it requires an expert team and refined protocols.

Who does it really help?

• Women carrying mutations in mitochondrial DNA (they may be healthy, but the baby would not).
• Women of advanced maternal age: over the years, egg mitochondria lose strength and chromosomal problems increase. Here, adding “young batteries” improves embryonic development.
• Patients with repeated IVF failures, embryos that do not reach the blastocyst stage, or poor egg quality.
• Those who need surrogacy for health reasons or due to the absence of a uterus and who also want to minimize the risk of mitochondrial disease in the baby.

Mitochondria: why they are the “engine” of development

Mitochondria produce ATP, the energy that drives everything in the cell. They are present in almost all our cells and have their own mitochondrial DNA, different from nuclear DNA. It is inherited only through the maternal line. If this DNA carries an error, it can cause severe diseases affecting muscles, brain, heart… and there is no definitive cure. The solution is to prevent this error from being passed on to the baby.

In addition, with age, egg mitochondria lose strength and may increase division errors in embryos. Using young donor mitochondria helps more embryos reach the blastocyst stage and be euploid (with the correct chromosomal set).

And what about “spindle transfer”? What changes?

There are two main techniques to prevent mutated mitochondria from being passed to the baby:

• Spindle transfer (MST): done before fertilization. The “spindle” (the mother’s egg chromosome set) is extracted and placed in a donor egg without a nucleus. Then it is fertilized.
• Pronuclear transfer (PNT): done after fertilization in the zygote. The nuclei of the zygotes (mother and donor) are swapped so that the embryo ends up with healthy mitochondria.

Both pursue the same goal. The choice depends on the case, egg quality, fertilization history, and what the clinical team considers safest.

Does it really work? What the data say

In studies conducted with 29 patients undergoing pronuclear transfer, the following was observed:

• 92.4% fertilization after micromanipulation (including patients with previous total failures).
• ~60% high-quality blastocysts on days 5–6.
• Average euploidy rate close to 60–70%.
• 46.97% clinical pregnancy and 48.28% live birth rate in single blastocyst transfers.
• No genetic or morphological abnormalities detected in the reported newborns.

Additionally, something important is highlighted: even in women over 42 years old, elevated euploidy rates were observed (above what is expected for that age), likely because the donated mitochondria provide sufficient energy for proper cell division.

Simple translation: more embryos develop successfully, and more of those embryos are genetically correct.

What it cannot promise (and you should know)

• Zero risk does not exist: residual altered mitochondria (residual heteroplasmy) may remain.
• Complex technique: micromanipulation requires highly trained hands and specialized equipment.
• Ethical aspects: not all countries allow it; there is public debate.
• Cost: the procedure is more expensive than standard IVF. The dossier details additional fees (for example, “pronuclear transplant” with a specific cost and additional charges for extra oocytes or PGT), making the process more expensive compared to closed egg donation programs.