Researchers in a 2023 study performed the first maternal spindle transfer experiment in women with poor egg quality, involving the transfer of maternal DNA to donor eggs, and found improved fertilization and live birth rates, with some mitochondria carryover.
Infertility can be attributed to poor egg quality, which may be due to faulty mitochondria. Mitochondria are organelles that exist inside our cells and produce energy from sugars in the food we eat. Faulty mitochondria may have problems in producing energy, and if the egg can’t produce enough energy to perform critical functions then this can cause problems (ie. aneuploidy).
For more background on egg quality, check out my Complete guide to egg quality.
One way to get around this is to use donor eggs that have healthy mitochondria, but babies born from this will have half their DNA coming from the donor. Another option is mitochondrial donation, which can be done in different ways.
Meiotic or maternal spindle transfer is a type of mitochondrial donation that involves transferring the DNA of the patient’s egg into a healthy donor egg that has had its nucleus and DNA removed (enucleated). The “meiotic spindle” is a component of the egg involved in separating the egg’s chromosomes during meiosis (and is contained in a nucleus called a “karyoplast” — referred to a nucleus below for simplicity). The result is a donor egg that has the patient’s DNA, but the donor’s mitochondria.
Costa-Borges et al. (2023), in their prospective pilot study, performed the first maternal spindle transfer in 25 women with infertility that was attributed to poor egg quality, at a single center in Greece between 2018 and 2019. Maternal spindles were transferred from the patients’ eggs to enucleated donor eggs and IVF and neonatal outcomes were evaluated. They also investigated the extent of maternal mitochondria carryover into the donor egg.
Key information:
- 25 couples were included in this pilot study, with no previous pregnancies or mitochondrial diseases.
- The women were under the age of 40 (average age was 37.2).
- Before the study, these 25 patients had a total of 159 ovarian stimulations (average 6.4 cycles) which totaled 423 eggs retrieved and 58 embryos were transferred with no pregnancies. Nine of these patients never had a transferable embryo (average of 7.3 ovarian cycles in these patients).
This study was conducted at the Institute of Life in Greece. You can read more about the research here.
🔗 Original studies are referenced in this post or within the linked Remembryo posts.
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Maternal spindle transfer procedure
Spindles were visualized using polarized light in mature eggs and a hole was made in the zona to gently extract the karyoplast (a nucleus containing the spindle and chromosomes).
The karyoplast was placed into a mature donor egg that was enucleated (its karyoblast was removed). The maternal karyoplast was placed in the perivitelline space, which is the space between the egg and the zona, and fused to the egg using an inactivated virus (Hemagglutinating virus of Japan).
Once the maternal karyoplast was transferred, ICSI was performed and then the inseminated eggs were cultured.
IVF outcomes following maternal spindle transfer
Of the 25 patients in this study, there were a total of 28 maternal spindle transfer cycles using 122 mature eggs, 112 of which survived (survival rate 91.8%).
Before the study, the fertilization rate was 53.2% and after maternal spindle transfer the fertilization rate was 75.9%. These 85 fertilized eggs went on to form 53 good quality embryos (62.4%), 24 of which were euploid after PGT-A (45.2% euploid rate).
There was a 36.8% clinical pregnancy rate after transfer and a live birth rate of 31.6%.
Of the 25 couples in this study, 16 produced euploids. Five produced only aneuploid embryos, but they had a small number of eggs retrieved and only made an average of 1.4 blastocysts. The other four couples had fertilization failure or embryo developmental arrest, but they only retrieved an average of 2 eggs compared to 4.5 eggs.
One couple retrieved 16 mature eggs and it was decided to split the eggs up, where 9 had a maternal spindle transfer and 7 didn’t. The 9 eggs that had a spindle transfer produced 4 good quality blastocysts, while the 7 that didn’t produced no blastocysts.
Neonatal outcomes following maternal spindle transfer
The 6 babies that were born were all healthy, with an average delivery time of 37.8 weeks and body weight of 2,988.3 grams. Hammersmith Infant Neurological Examination (HINE) scores were all normal, as were development and growth over a period of 2 years.
Genetic fingerprinting was done and found that the DNA from the embryos and children was made up completely from the mother and father, and not from the donor.
Maternal mitochondria carryover a possibility
After maternal spindle transfer, the result should be an embryo with nuclear DNA from the mother and father, and mitochondria from the donor. The mitochondria also has its own DNA, called mitochondrial DNA.
The maternal spindle transfer procedure involves removing the karyoplast from the patient’s egg, a process that could introduce carryover of maternal mitochondria into the donor egg. One way to measure this carryover is to sequence the maternal mitochondrial DNA and the donor mitochondrial DNA in the embryo and baby, and compare the amounts.
Sequencing of mitochondrial DNA in the blastocysts that produced a live birth showed no carryover, however 1 of the 6 children born had a mix of maternal and donor mitochondrial DNA. This was detected at birth in the cord, cord blood, urine and peripheral blood (ranging from 36% to 51.1%). The other five children had <1% maternal mitochondrial DNA.
Six months after birth, mitochondria DNA analysis of saliva, blood and urine showed consistent levels of maternal mitochondria carryover.
Conclusions
This pilot study found that women with poor quality eggs who underwent maternal spindle transfer had improved fertilization rates and good quality blastocyst production. Previously, none of the 25 women had been pregnant after an average of 6.4 ovarian stimulation cycles, but after maternal spindle transfer 6 of them went on to have a live birth. All the babies were healthy.
Genetically, the babies were made up entirely of maternal and paternal nuclear DNA, while the mitochondrial DNA was mostly contributed by the donor. In one of the babies there was significant carryover of maternal mitochondria. The authors state that it’s not clear what impact the donor/patient mitochondrial DNA combination may have on the development of the child and longer studies are needed.
The authors point to one study where nonhuman primates were followed after maternal spindle transfer and found that maternal mitochondria levels were inconsistent between tissues, and in some organs reversal to donor mitochondria occurred (Ma et al. (2021)).
(All of this donor/patient mitochondrial DNA mixing may be relevant in all cases, however it’s more of an issue for women with known mitochondrial disorders which they certainly wouldn’t want to have transferred to their children).
The authors conclude that while the data is encouraging, this was a small pilot study and larger and well-controlled clinical trials must be done.
Reference
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About Embryoman
Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.
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