Hum. Reprod. Advance Access originally published online on July 29, 2009
Human Reproduction 2009 24(11):2845-2855; doi:10.1093/humrep/dep274
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Ovarian endocrine profile and long-term vascular patency following heterotopic autotransplantation of cryopreserved whole ovine ovaries
1 Division of Animal Sciences, School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, Leicestershire LE12 5RD, UK 2 Division of Obstetrics and Gynaecology, School of Human Development, University of Nottingham, Queens Medical Centre, Nottingham, Nottinghamshire NG7 2UH, UK 3 Human Reproductive Sciences Unit, Medical Research Council, University of Edinburgh Centre for Reproductive Biology, Edinburgh EH16 4SB, UK
4 Correspondence address. Tel: +44-115-8230674; E-mail: vicki.onions{at}nottingham.ac.uk
BACKGROUND: This study examined the ability of cryopreserved whole ovine ovaries to resume function in vivo following autotransplantation.
METHODS: Swaledale ewes had their left ovaries removed and either perfused but not cryopreserved (n = 4; control), or perfused and cryopreserved (n = 8; cryopreserved) before autotransplantation sub-cutaneously to the neck by microvascular anastomosis. Right ovaries were removed and fixed as non-grafted controls. Weekly jugular venous blood samples were analysed for plasma FSH, LH, inhibin A and progesterone levels, grafts were scanned transdermally and oestrus was detected. Vascular patency was assessed post-mortem and follicle populations were measured in recovered tissue.
RESULTS: Immediate vascular patency was achieved in all ewes and maintained in 7/8 cryopreserved and 3/4 control grafts. Functional corpora lutea were identified in three ewes (one control; two cryopreserved) 18–25 weeks after grafting. Inhibin A levels indicated resumption of follicular development in four cryopreserved and one control ewes, however, castrate gonadotrophin levels persisted in five cryopreserved and two control ewes. Primordial follicle density was reduced following grafting in both cryopreserved and non-frozen ovaries (P < 0.001).
CONCLUSIONS: In conclusion, these results demonstrate successful partial restoration of ovarian function following cryopreservation of the whole ovary and vascular pedicle in a large monovulatory species. The inability to restore full ovarian function was related to loss of primordial follicles rather than vascular patency in both frozen and fresh tissue, suggesting that factors associated with cannulation and perfusion may contribute to this depletion. Further work is therefore needed to elucidate these factors before the procedure could be considered a viable option for fertility preservation.
Key words: cryopreservation/whole ovary/follicle survival/vascular patency/ovarian graft
Submitted on March 9, 2009; resubmitted on June 24, 2009; accepted on July 2, 2009.
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