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

Capsule:
After xenotransplantation, human primordial follicles can be matured to metaphase II oocytes even without stimulation. Administering human gonadotropin and GnRH agonist does not enhance the developmental capacity of oocytes in xenografts.

Authors:
Laura Lotz, Heike Schneider, Janina Hackl, M.D., David Wachter, M.D., Inge Hoffmann, M.D., Roland Jurgons, M.D., Matthias W. Beckmann, M.D., Ralf Dittrich, Ph.D.

Volume 101, Issue 5, Pages 1477–1484.e3

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.

Design:
Prospective controlled animal study.

Setting:
University hospital gynecology research unit.

Patient(s):
Ovarian fragments were obtained from 17 women with malignant diseases who wished to cryopreserve ovarian tissue for later pregnancy before chemotherapy.

Animal(s):
Eighty-eight female severe combined immunodeficient (SCID) mice.

Intervention(s):
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.

Main Outcome Measure(s):
Follicular density, morphology, proliferation, oocyte maturation, malignant cell contamination.

Result(s):
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.

Conclusion(s):
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.

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