title: Oogonial Precursor Cell-Derived Autologous Mitochondria Injection to Improve Outcomes in Women With Multiple IVF Failures Due to Low Oocyte Quality: A Clinical Translation.
abstract: BACKGROUND
  Mitochondrial dysfunction has been suggested as a major cause of age-induced decline in oocyte quality. In the past, donor oocyte cytoplasmic transfer showed some success but was abandoned due to the concerns with heteroplasmy. Recent studies indicated presence of oogonial precursor cells (OPCs) in the human ovary, which could be an autologous source of "healthy mitochondria." We sought to investigate the clinical efficacy of OPC-derived autologous mitochondrial injection (AMI) to improve oocyte quality in women with multiple in vitro fertilization (IVF) failures.
  
  
  METHODS
  The OPCs were isolated from laparoscopically obtained ovarian cortical pieces by cell sorting using a monoclonal anti-vasa homolog (anti-DDX) antibody. They were then disrupted and mitochondria were isolated. Reconstituted mitochondria were injected into each oocyte during intracytoplasmic sperm injection. Paired comparisons were made between the first failed cycles and the post-AMI cycles.
  
  
  RESULTS
  Of the 15 women undergoing ovarian stimulation, 2 were canceled and 3 decided to pool oocytes for later AMI. In remaining 10 (mean age 34.7 ± 4.1), AMI significantly improved fertilization rates (49.7 ± 31.3 vs 78.3 ± 18.9; P = .03) with a trend for better embryo grades (2.3 ± 0.3 vs 3.1 ± 0.7; P = .08). Four of 10 women conceived after single frozen embryo transfer and 3 after confirmation of diploidy via array comparative genomic hybridization (aCGH) (clinical pregnancy/embryo transfer = 4/10).
  
  
  CONCLUSIONS
  These data show encouraging results for AMI in comparison to previous failed IVF cycles.
authors.affiliation: Laboratory of Molecular Reproduction and Fertility Preservation, Department of Obstetrics and Gynecology, New York Medical College, New York, NY, USA Innovation Institute for Fertility Preservation and IVF, New York, NY, USA GenArt Women's Health and Reproductive Biotechnology Centre, Ankara, Turkey koktay@fertilitypreservation.org.
authors.forename: Kutluk
authors.initials: K
authors.lastname: Oktay
authors.affiliation: GenArt Women's Health and Reproductive Biotechnology Centre, Ankara, Turkey.
authors.forename: Volkan
authors.initials: V
authors.lastname: Baltaci
authors.affiliation: Department of Obstetrics and Gynecology, Ankara University School of Medicine, Ankara, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Sonmezer
authors.affiliation: Laboratory of Molecular Reproduction and Fertility Preservation, Department of Obstetrics and Gynecology, New York Medical College, New York, NY, USA Innovation Institute for Fertility Preservation and IVF, New York, NY, USA.
authors.forename: Volkan
authors.initials: V
authors.lastname: Turan
authors.affiliation: GenArt Women's Health and Reproductive Biotechnology Centre, Ankara, Turkey.
authors.forename: Evrim
authors.initials: E
authors.lastname: Unsal
authors.affiliation: GenArt Women's Health and Reproductive Biotechnology Centre, Ankara, Turkey.
authors.forename: Aysun
authors.initials: A
authors.lastname: Baltaci
authors.affiliation: GenArt Women's Health and Reproductive Biotechnology Centre, Ankara, Turkey.
authors.forename: Suleyman
authors.initials: S
authors.lastname: Aktuna
authors.affiliation: Laboratory of Molecular Reproduction and Fertility Preservation, Department of Obstetrics and Gynecology, New York Medical College, New York, NY, USA Deparment of Pathology, New York Medical College, Valhalla, NY, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Moy
mesh_terms: D000328:Adult; D001755:Blastocyst / Q000473:pathology; D055028:Comparative Genomic Hybridization; D005260:Female; D005298:Fertility; D005307:Fertilization in Vitro; D005820:Genetic Testing; D006801:Humans; D007246:Infertility / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D008928:Mitochondria / Q000637:transplantation*; D009865:Oocytes / Q000473:pathology*; D000072977:Oogonial Stem Cells / Q000637:transplantation*; D011247:Pregnancy; D018873:Pregnancy Rate; D011296:Prenatal Diagnosis / Q000379:methods; D056826:Single Embryo Transfer; D020554:Sperm Injections, Intracytoplasmic; D014182:Transplantation, Autologous; D017211:Treatment Failure
keywords: IVF; embryo transfer; mitochondria; oocyte quality; oogonial precursor cells; pregnancy