Researchers from the Spanish centre Embryotools —with headquarters in the Barcelona Science Park (Parc Científic de Barcelona, PCB) — are participating in a landmark scientific event in Greece that will shape the future of assisted reproduction. In a pilot clinical trial conducted on women, which is being sponsored by the assisted reproduction centre Institute of Life in Athens, Spanish scientists have achieved the world’s first pregnancy that uses the Maternal Spindle Transfer technique to solve problems of infertility.
Maternal Spindle Transfer (MST) is one of the mitochondrial replacement therapies that has been researched in recent years with a view to preventing diseases affecting the mitochondria, cell organelles found in the cell’s cytoplasm which provide the cell with energy. The technique consists of extracting the meiotic spindle (nucleus) from an unfertilised oocyte of a patient with mutations in their mitochondrial DNA, and placing it in the ovum of a donor with healthy mitochondria, from which the original nucleus has already being removed. Finally, the resulting oocyte is fertilised with the sperm of the male partner.
The United Kingdom was the first country to approve the clinical use of MST for the treatment of mitochondrial diseases. The world’s first baby conceived using this technique was born in Mexico in 2016, thanks to the team from a clinic in the USA. In this case, however, MST was used to avoid the transmission of mitochondrial diseases, and not to solve infertility issues.
Embryotools, meanwhile, has been trialling this technique for years. Last year, with the help of scientists from Oxford University, it successfully completed a study in mice, which received an award at the prestigious American Society for Reproductive Medicine (ASRM) congress. It was during this study that Embryotools researchers discovered that the MST technique could also be successfully used to solve infertility issues caused by poor oocyte quality. In 2016, they obtained permission from the Greek authorities to start a pilot clinical trial, the preliminary results of which were presented last week in Greece.
The expectant Greek mother is 27 weeks pregnant. She is a 32-year-old woman with poor ovarian response who had already undergone two operations owing to endometriosis, and four cycles of IVF without getting pregnant. She is now on course to give birth to a baby boy after participating in the pilot study carried out in Greece. The study will also include 24 other female partners. With MST-“reconstructed” oocytes, researchers have managed to obtain eight embryos from other female partners, although these have still not been transferred to patients pending the detailed monitoring of the outcome of the first pregnancy achieved.
“Maternal spindle transfer is an experimental technique that is currently undergoing a validation process. We need to be prudent with all aspects. It cannot simply be incorporated into the routine of any assisted reproduction clinic overnight. It requires special technology and the extensive training of researchers, with a long learning curve” states Dr Gloria Calderón, co-founder and director of Embryotools. Calderón also highlights the safety demonstrated by this technique in all trials conducted to date, with no reported incidents thus far.
A method that preserves genetic inheritance
Dr Nuno Costa-Borges, scientific director and co-founder of Embryotools, stresses one of the key benefits of this technique that is not offered by other assisted reproduction techniques, like conventional egg donation, namely that more than 99% of the DNA of a conceived baby will come from its biological mother and father, even if the oocyte comes from a donor. “Even though gametes are required from a man and two different women (the patient and the donor), the nuclear or genomic DNA responsible for the vast majority of phenotypical characteristics of the future baby will come from the biological mother and father, just like in a normal fertilisation process. The donor will only provide mitochondrial DNA, which only codes 37 genes and represents less than 1% of human DNA”.
"This mitochondrial DNA provided by the donor will not be transmitted to future generations if the baby is male, because mitochondrial DNA is only transmitted maternally. Therefore, it is not believed to affect the germline”, he adds.
In this regard, Dr Costa-Borges also states that the preservation of genetic inheritance helps to eliminate reservations occasionally held by oocyte donors, worried about their genes being passed on to strangers.
Spanish law does not approve this technique
After working for several years alongside scientists of the Institute of Life in Greece, Embryotools suggested that they carry out the pilot clinical trial in Greece, receiving the required backing from the country’s health authorities.
Embryotools' researchers are open to the possibility of conducting a trial of this nature in Spain, but the project is not immediately feasible. Law 14/2006, of 26 May, on assisted human reproduction techniques, does not specifically prohibit this technique, but a list of authorised practices is provided in an annex, with a special permit being required for any techniques that do not feature in this list. Maternal spindle transfer is still not authorised by Spanish legislation. The first step will therefore be to obtain approval from the Spanish Committee of Assisted Human Reproduction (Comisión Nacional de Reproducción Humana Asistida).