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Allogeneic ovarian transplantation using immunomodulator preimplantation factor (PIF) as monotherapy restored ovarian function in olive baboon

  • Fertility Preservation
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Abstract

Purpose

Allogeneic ovarian transplantation may be an alternative in the future to oocyte donation in women with premature ovarian failure. The objectives of this study were to (a) evaluate allotransplantation feasibility for restoration of ovarian function and (b) assess efficacy of synthetic preimplantation factor (PIF) monotherapy as sole immune-acceptance regimen.

Methods

This is an experimental animal study using non-human primates (Papio anubis). Allogeneic orthotopic ovarian tissue transplantation was performed in two female olive baboons. PIF was administered as a monotherapy to prevent immune rejection and achieve transplant maintenance and function. Subjects underwent bilateral oophorectomy followed by cross-transplantation of prepared ovarian cortex. Postoperatively, subjects were monitored for clinical and biochemical signs of graft rejection and return of function. Weekly blood samples were obtained to monitor graft acceptance and endocrine function restoration.

Results

Postoperatively, there were no clinical signs of rejection. Laboratory parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine) did not indicate organ rejection at any stage of the experiment. Initially, significant loss of follicles was noticed after grafting and serum follicle-stimulating hormone (FSH) and E2 levels were consistent with ovarian failure. Seven months after transplantation, one animal exhibited recurrence of ovarian endocrine function (perineal swelling, E2 rise, FSH decrease, and return of menstruation).

Conclusions

Organ rejection after allogeneic ovarian transplantation was prevented using PIF as monotherapy for the first time and no side effects were recorded. The study suggests the clinical feasibility of ovarian allotransplantation to obtain ovarian function.

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Acknowledgements

The present study was presented at the late-breaking abstract session of the ASRM annual meeting in Salt-Lake City, October 19th 2016. The authors wish to thank Ms. Sharon Chepkwony and Mr. Nicholas Kiulia for their organizational help at the Institute of Primate Research (IPR), Karen, Kenya, and Dr. David Erikson for hormonal assays at the Oregon National Primate Research Center, OR, Portland. In addition, we appreciate Amy Carter and Stephanie Zinn for editorial assistance.

Funding

This study was funded by the Medical Scientific Fund of the Mayor of Vienna (Nr.:14063), the Wunschbaby Institut Feichtinger, by an unrestricted grant from BioIncept and by private funds of M.F. and S.S.K.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Division of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria

    Michael Feichtinger

  2. Wunschbaby Institut Feichtinger, Vienna, Austria

    Michael Feichtinger

  3. BioIncept, LLC, Cherry Hill, NJ, 08003, USA

    Eytan R. Barnea

  4. SIEP, Society for the Investigation of Early Pregnancy, Cherry Hill, NJ, 08003, USA

    Eytan R. Barnea

  5. Institute of Primate Research, Karen, Kenya

    Atunga Nyachieo

  6. Department of Obstetrics and Gynecology, University of Gothenburg, Gothenburg, Sweden

    Mats Brännström

  7. Stockholm IVF, Stockholm, Sweden

    Mats Brännström

  8. University of Kansas, Kansas City, KS, USA

    S. Samuel Kim

  9. American-Sino Women’s and Children’s Hospital, 155 Songyuan Rd., Shanghai, China

    S. Samuel Kim

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  1. Michael Feichtinger
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  2. Eytan R. Barnea
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Correspondence to S. Samuel Kim.

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The study was approved by the Institutional Animal Care and Use Committee (IACUC) of the Institute of Primate Research (IPR), Karen, Kenya (Ref.: IRC/10/14).

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Feichtinger, M., Barnea, E.R., Nyachieo, A. et al. Allogeneic ovarian transplantation using immunomodulator preimplantation factor (PIF) as monotherapy restored ovarian function in olive baboon. J Assist Reprod Genet 35, 81–89 (2018). https://doi.org/10.1007/s10815-017-1051-y

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