TY - JOUR
T1 - First pilot study of maternal spindle transfer for the treatment of repeated in vitro fertilization failures in couples with idiopathic infertility
AU - Costa-Borges, Nuno
AU - Nikitos, Eros
AU - Späth, Katharina
AU - Miguel-Escalada, Irene
AU - Ma, Hong
AU - Rink, Klaus
AU - Coudereau, Clement
AU - Darby, Hayley
AU - Koski, Amy
AU - Van Dyken, Crystal
AU - Mestres, Enric
AU - Papakyriakou, Evmorfia
AU - De Ziegler, Dominique
AU - Kontopoulos, George
AU - Mantzavinos, Themistoklis
AU - Vasilopoulos, Ioannis
AU - Grigorakis, Stylianos
AU - Prokopakis, Thomas
AU - Dimitropoulos, Konstantinos
AU - Polyzos, Panagiotis
AU - Vlachos, Nikolas
AU - Kostaras, Konstantinos
AU - Mitalipov, Shoukhrat
AU - Calderón, Gloria
AU - Psathas, Panagiotis
AU - Wells, Dagan
N1 - Publisher Copyright:
© 2023
PY - 2023/6
Y1 - 2023/6
N2 - Objectives: To gain insights into the technical feasibility of maternal spindle transfer (MST) applied in the context of repeated in vitro fertilization (IVF) failures for the treatment of idiopathic infertility. Design: A prospective pilot study. Setting: IVF center. Patient(s): Twenty-five infertile couples with multiple previous unsuccessful IVF cycles (range, 3–11), no previous pregnancy, and no history of mitochondrial DNA (mtDNA) disease participated. The study focused on women <40 years, with previous IVF attempts characterized by a pattern of low fertilization rates and/or impaired embryo development. Couples with severe male-factor infertility were not eligible. Oocyte donors with previous successful IVF outcomes were matched with patients according to standard practice. Intervention(s): We performed MST by transferring metaphase II spindles from the patients’ oocytes into the previously enucleated donor oocytes, followed by intracytoplasmic sperm injection, in vitro embryo culture, blastocyst biopsy, and vitrification. Only euploid blastocysts were considered for embryo transfer. Main Outcome Measure(s): Outcome measures included oocyte fertilization, blastocyst development, clinical pregnancy and live birth, incidence of mitochondrial carryover and potential mtDNA reversal, as well as general health of the children born. Result(s): Twenty-eight MST cycles produced 6 children (19 embryo transfers, 7 clinical pregnancies). Pediatric follow-up of the children, performed at intervals from birth to 12–24 months of age, revealed their development to be unremarkable. DNA fingerprinting confirmed that the nuclear DNA of MST children was inherited from both parents, without any contribution from the oocyte donor. For 5 of the children, mtDNA was derived almost exclusively (>99%) from the donor. However, 1 child, who had similarly low mtDNA carryover (0.8%) at the blastocyst stage, showed an increase in the maternal mtDNA haplotype, accounting for 30% to 60% of the total at birth. Conclusion(s): This pilot study provides the first insights into the feasibility of applying MST for patients with idiopathic infertility and repeated IVF failures. Reconstructed oocytes produced embryos capable of implanting, developing to term and producing apparently healthy newborns/children. However, claims concerning the efficacy of MST with respect to infertility treatment would be premature considering the limitations of this study. Importantly, mtDNA reversal was detected in one child born after MST, a finding with possible implications for mitochondrial replacement therapies. Clinical Trial Registration Number: Pilot trial registry number, ISRCTN11455145. The date of registration: 20/02/2018. The date of enrolment of the first patients: 18/03/2018.
AB - Objectives: To gain insights into the technical feasibility of maternal spindle transfer (MST) applied in the context of repeated in vitro fertilization (IVF) failures for the treatment of idiopathic infertility. Design: A prospective pilot study. Setting: IVF center. Patient(s): Twenty-five infertile couples with multiple previous unsuccessful IVF cycles (range, 3–11), no previous pregnancy, and no history of mitochondrial DNA (mtDNA) disease participated. The study focused on women <40 years, with previous IVF attempts characterized by a pattern of low fertilization rates and/or impaired embryo development. Couples with severe male-factor infertility were not eligible. Oocyte donors with previous successful IVF outcomes were matched with patients according to standard practice. Intervention(s): We performed MST by transferring metaphase II spindles from the patients’ oocytes into the previously enucleated donor oocytes, followed by intracytoplasmic sperm injection, in vitro embryo culture, blastocyst biopsy, and vitrification. Only euploid blastocysts were considered for embryo transfer. Main Outcome Measure(s): Outcome measures included oocyte fertilization, blastocyst development, clinical pregnancy and live birth, incidence of mitochondrial carryover and potential mtDNA reversal, as well as general health of the children born. Result(s): Twenty-eight MST cycles produced 6 children (19 embryo transfers, 7 clinical pregnancies). Pediatric follow-up of the children, performed at intervals from birth to 12–24 months of age, revealed their development to be unremarkable. DNA fingerprinting confirmed that the nuclear DNA of MST children was inherited from both parents, without any contribution from the oocyte donor. For 5 of the children, mtDNA was derived almost exclusively (>99%) from the donor. However, 1 child, who had similarly low mtDNA carryover (0.8%) at the blastocyst stage, showed an increase in the maternal mtDNA haplotype, accounting for 30% to 60% of the total at birth. Conclusion(s): This pilot study provides the first insights into the feasibility of applying MST for patients with idiopathic infertility and repeated IVF failures. Reconstructed oocytes produced embryos capable of implanting, developing to term and producing apparently healthy newborns/children. However, claims concerning the efficacy of MST with respect to infertility treatment would be premature considering the limitations of this study. Importantly, mtDNA reversal was detected in one child born after MST, a finding with possible implications for mitochondrial replacement therapies. Clinical Trial Registration Number: Pilot trial registry number, ISRCTN11455145. The date of registration: 20/02/2018. The date of enrolment of the first patients: 18/03/2018.
KW - Maternal spindle transfer
KW - infertility
KW - mitochondrial replacement therapies
KW - mtDNA reversal
UR - http://www.scopus.com/inward/record.url?scp=85151404798&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85151404798&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2023.02.008
DO - 10.1016/j.fertnstert.2023.02.008
M3 - Article
C2 - 36787873
AN - SCOPUS:85151404798
SN - 0015-0282
VL - 119
SP - 964
EP - 973
JO - Fertility and sterility
JF - Fertility and sterility
IS - 6
ER -