Skip to main content
SpringerLink
Log in

Oogonial Precursor Cell-Derived Autologous Mitochondria Injection to Improve Outcomes in Women With Multiple IVF Failures Due to Low Oocyte Quality: A Clinical Translation

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bentov Y, Yavorska T, Esfandiari N, Jurisicova A, Casper RF. The contribution of mitochondrial function to Reproductive aging. J Assist Reprod Genet. 2011;28(9):773–783.

    Article  Google Scholar 

  2. Keefe DL, Niven-Fairchild T, Powell S, Buradagunta S. Mitochondrial deoxyribonucleic acid deletions in oocytes and reproductive aging in women. Fertil Steril. 1995;64(3):577–583.

    Article  CAS  Google Scholar 

  3. Liu L, Trimarchi JR, Smith PJ, Keefe DL. Mitochondrial dysfunction leads to telomere attrition and genomic instability. Aging Cell. 2002;1(1):40–46.

    Article  CAS  Google Scholar 

  4. Eichenlaub-Ritter U, Wieczorek M, Luke S, Seidel T. Age related changes in mitochondrial function and new approaches to study redox regulation in mammalian oocytes in response to age or maturation conditions. Mitochondrion. 2011;11(5):783–796.

    Article  CAS  Google Scholar 

  5. Tilly JL, Sinclair DA. Germline energetics, aging, and female infertility. Cell Metab. 2013;17(6):838–850.

    Article  CAS  Google Scholar 

  6. Oktay K. Ovarian tissue cryopreservation and transplantation: preliminary findings and implications for cancer patients. Hum Reprod Update. 2001;7(6):526–534.

    Article  CAS  Google Scholar 

  7. Fujioka T, Yasuchika K, Nakamura Y, Nakatsuji N, Suemori H. A simple and efficient cryopreservation method for primate embryonic stem cells. Int J Dev Biol. 2004;48(10):1149–1154.

    Article  Google Scholar 

  8. World Health Organization. Laboratory Manual for the Examination and Processing of Human Semen. 5th ed. Geneva, Switzerland: WHO; 2010.

    Google Scholar 

  9. Henkel R. Sperm preparation: state-of-the-art–physiological aspects and application of advanced sperm preparation methods. Asian J Androl. 2012;14(2):260–269.

    Article  CAS  Google Scholar 

  10. Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004;428(6979):145–150.

    Article  CAS  Google Scholar 

  11. Pacchiarotti J1, Maki C, Ramos T, et al. Differentiation potential of germ line stem cells derived from the postnatal mouse ovary. Differentiation. 2010;79(3):159–170.

    Article  CAS  Google Scholar 

  12. Bukovsky A, Caudle MR, Svetlikova M, Upadhyaya NB. Origin of germ cells and formation of new primary follicles in adult human ovaries. Reprod Biol Endocrinol. 2004;2:20.

    Article  Google Scholar 

  13. Tilly J, Johnson J; Compositions comprising female germline stem cells and methods of use thereof. US patent number US7955846 B2, Jun 7 2011.

  14. Van Blerkom J. Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion. 2011;11(5):797–813.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Molecular Reproduction and Fertility Preservation, Department of Obstetrics and Gynecology, New York Medical College, 10595, Valhalla, New York, NY, USA

    Kutluk Oktay MD, PhD, FACOG, Volkan Turan MD & Fred Moy PhD

  2. Innovation Institute for Fertility Preservation and IVF, New York, NY, USA

    Kutluk Oktay MD, PhD, FACOG & Volkan Turan MD

  3. GenArt Women’s Health and Reproductive Biotechnology Centre, Ankara, Turkey

    Kutluk Oktay MD, PhD, FACOG, Volkan Baltaci MD, Evrim Unsal PhD, Aysun Baltaci MD & Suleyman Aktuna PhD

  4. Department of Obstetrics and Gynecology, Ankara University School of Medicine, Ankara, Turkey

    Murat Sonmezer MD

  5. Deparment of Pathology, New York Medical College, Valhalla, NY, USA

    Fred Moy PhD

Authors
  1. Kutluk Oktay MD, PhD, FACOG
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Volkan Baltaci MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Murat Sonmezer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Volkan Turan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Evrim Unsal PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aysun Baltaci MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Suleyman Aktuna PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fred Moy PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kutluk Oktay MD, PhD, FACOG.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oktay, K., Baltaci, V., Sonmezer, M. et al. Oogonial Precursor Cell-Derived Autologous Mitochondria Injection to Improve Outcomes in Women With Multiple IVF Failures Due to Low Oocyte Quality: A Clinical Translation. Reprod. Sci. 22, 1612–1617 (2015). https://doi.org/10.1177/1933719115612137

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719115612137

Keywords

Search

Navigation