Allogeneic ovarian transplantation using immunomodulator preimplantation factor (PIF) as monotherapy restored ovarian function in olive baboon
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.
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.
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).
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.
KeywordsPIF Ovarian graft Fertility preservation Ovary Transplantation Preimplantation factor Allotransplantation POF Premature ovarian failure Premature ovarian insufficiency POI Baboon
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.
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.
Compliance with ethical standards
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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