Kutluk Oktay1, Volkan Baltaci2, Murat Sonmezer3, Volkan Turan4, Evrim Unsal2, Aysun Baltaci2, Suleyman Aktuna2, Fred Moy5. 1. 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. 2. GenArt Women's Health and Reproductive Biotechnology Centre, Ankara, Turkey. 3. Department of Obstetrics and Gynecology, Ankara University School of Medicine, Ankara, Turkey. 4. 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. 5. 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.
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). CONCLUSION: These data show encouraging results for AMI in comparison to previous failed IVF cycles.
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). CONCLUSION: These data show encouraging results for AMI in comparison to previous failed IVF cycles.
Authors: Julie A MacDonald; Yasushi Takai; Osamu Ishihara; Hiroyuki Seki; Dori C Woods; Jonathan L Tilly Journal: Fertil Steril Date: 2019-03-11 Impact factor: 7.329
Authors: Marcos R Chiaratti; Bruna M Garcia; Karen F Carvalho; Carolina H Macabelli; Fernanda Karina da Silva Ribeiro; Amanda F Zangirolamo; Fabiana D Sarapião; Marcelo M Seneda; Flávio V Meirelles; Francisco E G Guimarães; Thiago S Machado Journal: Anim Reprod Date: 2018-08-17 Impact factor: 1.807