ATHENS, Greece, 20 mars 2023 /PRNewswire/ — Results of the first clinical pilot study in maternal spindle transfer (MST) have been published online in the journal Fertility and Sterility, before the print version of the article. The project was carried out in Greece, at the Institute of Life-IASO IVF Center, and involved a multidisciplinary team of scientists from internationally renowned institutions: Embryotools (Spain); Juno Genetics (UK); University of Oxford (UK); Oregon Health & Science University (USA). The exploratory study provides the first indications of the safety and efficacy of maternal spindle transfer in humans for the treatment of infertility. The study resulted in the birth of six children in patients whose attempts at in vitro fertilization had long since failed. The article further reveals important information regarding the potential use of MST to reduce the risk of disease transmission in patients with disease-causing mitochondrial DNA (mtDNA) mutations.
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The egg is the most important element of the first days of life. Not only does it carry the genetic contribution (DNA) of the mother, but it also contains in its cytoplasm reserves of materials (eg RNA, proteins, energy reserves and organelles) vital for the development of the embryo. Poor egg quality is a major contributing factor to female infertility, for which no effective treatment has been developed. The problem is characterized by repeated failure of egg fertilization and/or defective embryonic development. Currently, the only strategy available for patients who produce poor quality eggs is to undergo fertilization treatments. in vitro (IVF) using donated eggs or embryos. This approach can help patients achieve pregnancy, but excludes them from contributing genetically to their child.
Maternal spindle transfer is an advanced laboratory technique that belongs to the family of methods known collectively as mitochondrial replacement therapies (MRTs). These techniques were originally proposed to prevent the transmission of mitochondrial diseases and their application for this clinical purpose is already authorized in some countries, such as the United Kingdom and Australia. The method involves replacing the cytoplasm of the patient’s egg with cytoplasm from a donated young egg, while retaining the patient’s nuclear genetic material. Mounting evidence suggests that this process can solve some of the problems associated with an egg’s inability to support fertilization and embryonic development, while allowing patients to produce genetically related children.
This exploratory pilot study was conducted in Greece after receiving approval from theNational Assisted Reproduction Authority. The research team aimed to explore, for the first time, the clinical feasibility of the maternal spindle transfer technique in the context of infertility treatment. The pilot study began in 2018 et was limited to a cohort of 25 infertile couples who were carefully selected based on their long history of unsuccessful IVF treatments associated with poor egg quality. Patients had undergone between 3 and 11 previous IVF attempts (an average of 6.4 per patient) without success. Study results included the usual measures of IVF success, as well as other parameters specifically related to the technique, and pediatric follow-up to assess the general health of children born following the procedure.
The data obtained during the study is unique and suggests that the maternal spindle transfer technique may have the potential to help a class of infertile patients who have been extremely difficult to treat with conventional methods. The patients included in the study had already undergone 159 IVF treatments, during which 423 mature eggs had been collected, but no pregnancy had been obtained. A total of 28 maternal spindle transfer attempts were made and resulted in the birth of six babies. The state of health and development of the children (some of whom are almost 4 years old today) is not remarkable, which reassures about the harmlessness of the method.
The scientific team monitored the amount of mitochondrial DNA (mtDNA) transferred into the donor egg with the patient’s spindle and showed that more than 99% of the mtDNA in the embryos produced came from the donor of egg. However, in a child born after the procedure, the patient’s mitochondria expanded significantly during development, and at the time of birth, they comprised about 50% of the child’s total cells. This is the first time that this phenomenon, known as “inversion”, has been reported in human embryos. Although none of the patients in the study were carriers of mitochondrial disease, the possibility that the small number of mitochondria, inevitably transferred to the donor egg along with the patient’s DNA, could proliferate from disproportionately has implications for the use of MRTs to prevent the transmission of such disorders. The severity of mtDNA disorders is related to the proportion of mitochondria from the affected patient. The resurgence of a patient’s mitochondria, after they were initially reduced to a tiny population, suggests that some of these treatments may not be 100% effective.
While the data obtained is encouraging and has the potential to create a new therapy for previously untreatable types of infertility, the researchers would like to emphasize that this was a pilot study, and that , therefore, its size and range were limited. A definitive evaluation of the clinical value of the technique must await future larger randomized controlled trials.
Item ID: DOI : https://doi.org/10.1016/j.fertnstert.2023.02.008.
Auteurs : Nuno Costa-Borges, PhD; Eros Nikitos, MSc; Katharina Späth, PhD; Irene Miguel-EscaladaPhD ; Hong MaPhD ; Klaus Rink, PhD; Clement Coudereau, PhD; Hayley Darby; Amy KoskiMSc ; Crystal Van DykenPhD ; Henry MestresPhD ; Evmorfia PapakyriakouMSc ; Dominique DeZieglerMD ; George KontopoulosMD ; Themistoklis MantzavinosMD ; Ioannis VasilopoulosMD ; Stylianos GrigorakisMD ; Thomas ProkopakisMD ; Konstantinos DimitropoulosMD ; Panagiotis PolyzosMD ; Nikolaοs Vlachos, MD ; Konstantinos Kostaras, MD; Shoukhrat Mitalipov, PhD ; Gloria Calderón, PhD ; Panagiotis PsathasMD ; Dagan Wells*, PhD.
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