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      Orthotopic and heterotopic ovarian tissue transplantation

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          Abstract

          BACKGROUND

          Transplantation of ovarian tissue is, at present, the only clinical option available to restore fertility using cryopreserved ovarian tissue. More than 30 transplantations of cryopreserved tissue have been reported, and six babies have been born, worldwide, following this procedure. Despite these encouraging results, it is essential to optimize the procedure by improving the follicular survival, confirming safety and developing alternatives. Here, we review the different factors affecting follicular survival and growth after grafting.

          METHODS

          Relevant studies were identified by searching Pubmed up to January 2009 with English language limitation. The following key words were used: (ovarian tissue or whole ovary) AND (transplantation) AND (cryopreservation or pregnancy). Using the literature and personal experience, we examined relevant data on the different exogenous and clinical factors affecting follicular development after grafting.

          RESULTS

          Clinical factors such as the patient's age and the transplantation sites influenced the lifespan of the graft. A heterotopic transplantation site is not optimal but offers some advantages and it may also promote the hormonal environment after a combined heterotopic and orthotopic transplantation. Exogenous factors such as antioxidants, growth factors or hormones were tested to improve follicular survival; however, their efficiency regarding further follicular development and fertility potential remains to be established.

          CONCLUSION

          Additional evidence is required to define optimal conditions for ovarian tissue transplantation. Alternatives such as whole ovary or isolated follicles transplantations require further investigation but are likely to be successful in humans in the future.

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          Most cited references172

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          Livebirth after orthotopic transplantation of cryopreserved ovarian tissue.

          The lifesaving treatment endured by cancer patients leads, in many women, to early menopause and subsequent infertility. In clinical situations for which chemotherapy needs to be started, ovarian tissue cryopreservation looks to be a promising option to restore fertility. In 1997, biopsy samples of ovarian cortex were taken from a woman with stage IV Hodgkin's lymphoma and cryopreserved before chemotherapy was initiated. After her cancer treatment, the patient had premature ovarian failure. In 2003, after freeze-thawing, orthotopic autotransplantation of ovarian cortical tissue was done by laparoscopy. 5 months after reimplantation, basal body temperature, menstrual cycles, vaginal ultrasonography, and hormone concentrations indicated recovery of regular ovulatory cycles. Laparoscopy at 5 months confirmed the ultrasonographic data and showed the presence of a follicle at the site of reimplantation, clearly situated outside the ovaries, both of which appeared atrophic. From 5 to 9 months, the patient had menstrual bleeding and development of a follicle or corpus luteum with every cycle. 11 months after reimplantation, human chorionic gonadotrophin concentrations and vaginal echography confirmed a viable intrauterine pregnancy, which has resulted in a livebirth. We have described a livebirth after orthotopic autotransplantation of cryopreserved ovarian tissue. Our findings suggest that cryopreservation of ovarian tissue should be offered to all young women diagnosed with cancer.
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            The effects of radiotherapy and chemotherapy on female reproduction.

            High dose chemotherapy and radiotherapy have radically increased long-term survival of young cancer patients, but major side effects of these treatments are ovarian failure and infertility. Knowledge of the risks and probabilities of ovarian failure caused by treatment is crucial for patients and physicians in order to make informed choices that will best serve patients' interests. This review presents data on ovarian damage and failure following exposure to radiotherapy, chemotherapy and ablative therapy. The risk is evaluated from the published literature according to patient's age, treatment protocol and also according to the diagnosis of some common malignancies. Many of these patients will not be sterilized immediately following treatment, but will suffer from premature menopause. In order to prevent sterilization, ovarian transposition before pelvic irradiation is mandatory. Besides cryopreservation of ovarian tissue and embryos before administration of chemotherapy, the possible protective effect of pituitary-ovarian down-regulation is discussed. The mechanism of primordial follicles damage induced by radio/chemotherapy is presented as well as the role of apoptosis signalling pathways underlying destruction. Increased knowledge of these mechanisms could help to identify potential effective inhibitors that can block the path of primordial follicles destruction and reduce ovarian failure rate.
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              Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy.

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                Author and article information

                Journal
                Hum Reprod Update
                humupd
                humupd
                Human Reproduction Update
                Oxford University Press
                1355-4786
                1460-2369
                Nov-Dec 2009
                27 May 2009
                27 May 2009
                : 15
                : 6
                : 649-665
                Affiliations
                [1 ]Research Laboratory on Human Reproduction, Medicine Faculty, simpleUniversité Libre de Bruxelles (ULB), Erasme Hospital , 808 Route de Lennik, 1070 Brussels, Belgium
                [2 ]Fertility Clinic, Department of Gynaecology and Obstetrics, simpleUniversité Libre de Bruxelles (ULB), Erasme Hospital , 808 Route de Lennik, 1070 Brussels, Belgium
                Author notes
                [3 ]Correspondence address. Tel: +32-2-5556358; Fax: +32-2-5556205; E-mail: idemeest@ 123456ulb.ac.be
                Article
                dmp021
                10.1093/humupd/dmp021
                2759329
                19474206
                31ee8bf8-8cd1-4cda-9517-af4df67bc819
                © The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

                The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

                History
                : 15 January 2009
                : 20 April 2009
                : 24 April 2009
                Categories
                Reviews

                Human biology
                transplantation,vascularization,sites,pregnancy,ovarian tissue
                Human biology
                transplantation, vascularization, sites, pregnancy, ovarian tissue

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