title: 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?
abstract: OBJECTIVE
  To assess the capacity of human frozen-thawed ovarian follicles matured in xenografts to form metaphase II (MII) oocytes after xenotransplantation and exogenous stimulation.
  
  
  METHODS
  Prospective controlled animal study.
  
  
  METHODS
  University hospital gynecology research unit.
  
  
  METHODS
  Ovarian fragments were obtained from 17 women with malignant diseases who wished to cryopreserve ovarian tissue for later pregnancy before chemotherapy.
  
  
  METHODS
  Eighty-eight female severe combined immunodeficient (SCID) mice.
  
  
  METHODS
  Cryopreserved human ovarian tissue was grafted into oophorectomized SCID mice. The mice were divided into three groups: Group A received hMG alone every 2 days for a maximum of 24 weeks; group B additionally received nRH agonist (GnRHa) every 4 weeks; and group C was an untreated control group.
  
  
  METHODS
  Follicular density, morphology, proliferation, oocyte maturation, malignant cell contamination.
  
  
  RESULTS
  Follicle survival and development were similar in all three groups. No significant interactions between the stimulation protocols and grafting duration were noted. Three MII oocytes were observed in grafted follicles. Two MII oocytes were harvested without stimulation. None of the mice showed signs of reintroduced malignancy, nor did microscopic evaluation of the grafts raise any suspicion of residual malignant disease.
  
  
  CONCLUSIONS
  After xenotransplantation, human primordial follicles can be matured to MII oocytes even without stimulation. Administering human gonadotropin and GnRHa does not enhance the developmental capacity of xenografted oocytes. The optimal stimulation schedule for grafted tissue remains unknown.
authors.affiliation: Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Lotz
authors.affiliation: Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Schneider
authors.affiliation: Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Hackl
authors.affiliation: Department of Pathology, Erlangen University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Wachter
authors.affiliation: Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Inge
authors.initials: I
authors.lastname: Hoffmann
authors.affiliation: Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Jurgons
authors.affiliation: Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.affiliation: Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany. Electronic address: ralf.dittrich@uk-erlangen.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dittrich
mesh_terms: D000328:Adult; D000818:Animals; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006062:Gonadotropins / Q000494:pharmacology*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009865:Oocytes / Q000187:drug effects / Q000276:immunology; D006080:Ovarian Follicle / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D011446:Prospective Studies; D014183:Transplantation, Heterologous / Q000379:methods; D015854:Up-Regulation / Q000276:immunology; D055815:Young Adult
chemical_list: D006062:Gonadotropins; D007987:Gonadotropin-Releasing Hormone
keywords: Ovarian tissue cryopreservation; gonadotropin stimulation; malignant cell contamination; metaphase II oocyte; xenotransplantation