Repetitive Maturation of Oocytes From Non-Stimulated Xenografted Ovarian Tissue From a Prepubertal Patient Indicating the Independence of Human Ovarian Tissue

Introduction Modern anti-cancer strategies have distinctly increased survival rates; nevertheless, often accompanied by sterility. Currently, the only option for preserving fertility in prepubertal females is to cryopreserve ovarian tissue and re-transplant frozen-thawed tissue to restore fertility after treatment. Our aim was to report the occurrence of repetitive antral follicle formation and oocyte maturation in a prepubescent ovarian tissue xenograft without exogenous hormone stimulation. Material and Methods Frozen-thawed ovarian tissue from a 6-year-old patient suffering from nephroblastoma was xenotransplanted in oophorectomized severe combined immunodeficiency (SCID) mice to evaluate follicle development. Ergebnisse Repetitive follicle development to the antral stage occurred in the same xenograft of prepubertal ovarian tissue without exogenous hormone administration; 37 days after retrieving a maturing oocyte (this first retrieval has been previously published), another, completely mature oocyte was harvested from the xenograft. Subsequent histological evaluation of the grafted tissue showed primordial follicles, nearly all stages of developing follicles, as well as large atretic ones. Many clusters with dormant primordial follicles were also present. Conclusion Xenotransplanted prepubertal ovarian tissue has the potential for repetitive oocyte retrieval cycles without administering exogenous hormones. The results indicate that the human ovarian tissue might be able to synchronize the hypothalamus-hypophysis-axes of the mouse to the physiological human cycle; this should be investigated in future studies.

[1]  S. Schapiro Handbook of Laboratory Animal Science Animal Models , 2018 .

[2]  Alexandra L Rutz,et al.  A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice , 2017, Nature Communications.

[3]  A. Guilmain,et al.  Efficacy of ovarian tissue cryopreservation for fertility preservation: lessons learned from 545 cases , 2017, Human reproduction.

[4]  M. Beckmann,et al.  Surgical Aspects of Ovarian Tissue Removal and Ovarian Tissue Transplantation for Fertility Preservation , 2016, Geburtshilfe und Frauenheilkunde.

[5]  A. Shikanov,et al.  The artificial ovary: current status and future perspectives. , 2016, Future oncology.

[6]  K. Heusinger,et al.  Fertility Protection in Female Oncology Patients: How Should Patients Be Counseled? , 2015, Geburtshilfe und Frauenheilkunde.

[7]  A. Ferster,et al.  Live birth after autograft of ovarian tissue cryopreserved during childhood. , 2015, Human reproduction.

[8]  M. Beckmann,et al.  Xenotransplantation of cryopreserved human ovarian tissue--a systematic review of MII oocyte maturation and discussion of it as a realistic option for restoring fertility after cancer treatment. , 2015, Fertility and sterility.

[9]  M. Beckmann,et al.  Spontaneous antral follicle formation and metaphase II oocyte from a non-stimulated prepubertal ovarian tissue xenotransplant , 2014, Reproductive Biology and Endocrinology.

[10]  M. Beckmann,et al.  Does stimulation with human gonadotropins and gonadotropin-releasing hormone agonist enhance and accelerate the developmental capacity of oocytes in human ovarian tissue xenografted into severe combined immunodeficient mice? , 2014, Fertility and sterility.

[11]  G. Pennings,et al.  Beyond the dichotomy: a tool for distinguishing between experimental, innovative and established treatment. , 2014, Human reproduction.

[12]  Jann Hau,et al.  Handbook of Laboratory Animal Science, Volume III, Third Edition: Animal Models , 2013 .

[13]  J. Donnez,et al.  Evaluation of cryopreserved ovarian tissue from prepubertal patients after long-term xenografting and exogenous stimulation. , 2013, Fertility and sterility.

[14]  E. Telfer,et al.  Ovarian follicle culture: advances and challenges for human and nonhuman primates. , 2013, Fertility and sterility.

[15]  Claus Yding Andersen,et al.  Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue: a review of 60 cases of reimplantation. , 2013, Fertility and sterility.

[16]  E. Ernst,et al.  Case report: stimulation of puberty in a girl with chemo- and radiation therapy induced ovarian failure by transplantation of a small part of her frozen/thawed ovarian tissue. , 2013, European journal of cancer.

[17]  M. Andersen,et al.  Cryopreserved ovarian cortex from patients with leukemia in complete remission contains no apparent viable malignant cells. , 2012, Blood.

[18]  C. Hei,et al.  Effects of HMG on revascularization and follicular survival in heterotopic autotransplants of mouse ovarian tissue. , 2012, Reproductive biomedicine online.

[19]  G. Pasquinelli,et al.  Cryopreservation of Ovarian Tissue in Pediatric Patients , 2012, Obstetrics and gynecology international.

[20]  C. Poirot,et al.  Induction of puberty by autograft of cryopreserved ovarian tissue , 2012, The Lancet.

[21]  M. Beckmann,et al.  Live birth after ovarian tissue autotransplantation following overnight transportation before cryopreservation. , 2012, Fertility and sterility.

[22]  E. Telfer,et al.  Strategies to support human oocyte development in vitro. , 2012, The International journal of developmental biology.

[23]  W. Wallace,et al.  Fertility preservation in girls and young women , 2011, Clinical endocrinology.

[24]  M. Beckmann,et al.  Xenotransplantation of cryopreserved ovarian tissue from patients with ovarian tumors into SCID mice--no evidence of malignant cell contamination. , 2011, Fertility and sterility.

[25]  E. Telfer,et al.  In Vitro Development of Ovarian Follicles , 2011, Seminars in reproductive medicine.

[26]  J. Donnez,et al.  Fertility preservation in girls during childhood: is it feasible, efficient and safe and to whom should it be proposed? , 2010, Human reproduction update.

[27]  P. Saussoy,et al.  Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. , 2010, Blood.

[28]  F. Lu,et al.  The future potential of cryopreservation for assisted reproduction. , 2010, Cryobiology.

[29]  R. Van den Broecke,et al.  Xenotransplantation of cryopreserved human ovarian tissue into murine back muscle. , 2010, Human reproduction.

[30]  S. Revel-Vilk,et al.  At what age can human oocytes be obtained? , 2009, Fertility and sterility.

[31]  S. E. Harris,et al.  The in vitro growth and maturation of follicles. , 2008, Reproduction.

[32]  M. Montag,et al.  Cryopreservation of human ovarian tissue: effect of spontaneous and initiated ice formation. , 2008, Reproductive biomedicine online.

[33]  M. Beckmann,et al.  Significant loss of primordial follicles after prolonged gonadotropin stimulation in xenografts of cryopreserved human ovarian tissue in severe combined immunodeficient mice. , 2007, Fertility and sterility.

[34]  T. Maltaris,et al.  Comparison of xenografting in SCID mice and LIVE/DEAD assay as a predictor of the developmental potential of cryopreserved ovarian tissue. , 2006, In vivo.

[35]  Nam-Hyung Kim,et al.  Assessment of the integrity of human oocytes retrieved from cryopreserved ovarian tissue after xenotransplantation. , 2005, Human reproduction.

[36]  D. Gook,et al.  Diagnostic assessment of the developmental potential of human cryopreserved ovarian tissue from multiple patients using xenografting. , 2005, Human reproduction.

[37]  D. Gook,et al.  Oocyte maturation, follicle rupture and luteinization in human cryopreserved ovarian tissue following xenografting. , 2003, Human reproduction.

[38]  T. Colgan,et al.  Preliminary experience with subcutaneous human ovarian cortex transplantation in the NOD-SCID mouse. , 1999, Biology of reproduction.

[39]  A. Gougeon Dynamics of follicular growth in the human: a model from preliminary results. , 1986, Human reproduction.

[40]  H. Peters,et al.  Follicular growth in fetal and prepubertal ovaries of humans and other primates. , 1978, Clinics in endocrinology and metabolism.

[41]  H. Peters,et al.  Follicular development in the infant human ovary. , 1974, Journal of reproduction and fertility.