Fertility preservation in girls and young women

Division of Reproductive and Developmental Science, MRC Centre for Reproductive Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Clinical Endocrinology (Impact Factor: 3.46). 05/2011; 75(4):409-19. DOI: 10.1111/j.1365-2265.2011.04100.x
Source: PubMed


There is increasing interest and experience in the options available to preserve fertility in those about to undergo potentially gonadotoxic chemotherapy or radiation therapy, usually related to treatment for cancer. Recent years have seen the development of methods for prepubertal girls, female adolescents and adult women, although these remain less established than sperm cryopreservation for men. At present, the options for prepubertal boys remain experimental. Embryo cryopreservation following ovarian stimulation and IVF is a routine procedure technically and its success in the management of infertility is established. However, there are no data on uptake or success rates in the context of fertility preservation in women with cancer. Oocyte cryopreservation is technically challenging and requires ovarian stimulation, thus potentially resulting in a delay in cancer treatment. Oocyte vitrification offers increased success rates in comparison with slow freezing; however, this approach is also limited by the number of oocytes that can be obtained. The third possibility, ovarian tissue cryopreservation, can be performed without significant delay and is the only option for prepubertal girls. Worldwide, a small number of children have been born following reimplantation of frozen/thawed ovarian tissue. It is clear that fertility preservation is important for some girls and young women facing treatments that will compromise their fertility, but the availability of all approaches varies widely. Effective approaches for prepubertal boys are also required.

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Available from: Richard A Anderson, Oct 09, 2015
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    • " It has become a mantra in articles and conferences on fertility preservation: the only option to preserve the fertility of prepubertal girls undergoing gonadotoxic treatment is ovarian tissue cryopreservation (Jadoul et al, 2010; Smitz et al, 2010; Revel & Revel-Vilk, 2010; Anderson & Wallace, 2011; Fabbri et al, 2012; Rodriguez-Wallberg & Oktay, 2012; Chung et al, 2013; Mintziori et al, 2014). The first healthy live birth after autotransplantation of ovarian tissue harvested during childhood (although not prepubertal) reported in this issue and thus proof of principle is likely to reinforce this dogma even further (Demeestere et al, 2015). "
    Human Reproduction 07/2015; 30(9). DOI:10.1093/humrep/dev176 · 4.57 Impact Factor
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    • "Additionally, even though embryo cryopreservation for breast cancer patients has been successfully used for fertility preservation without specific side effects, the theoretical risk for increasing cancer recurrence exists [9]. Ovarian tissue can be cryopreserved and orthotopically transplanted, this option remains experimental and few successful births have been reported [10,11]. Additionally, ovarian tissue removal and transplantation requires repeated operations, which may be a significant physical and financial burden for patients. "
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    ABSTRACT: IVM refers to the maturation of immature oocytes in culture after their recovery from small antral follicles at the stage prior to selection and dominance. IVM requires little or no FSH in vivo and has been proposed as an alternative to conventional IVF, since it reduces the primary adverse effects caused by controlled ovarian stimulation, including the ovarian hyperstimulation syndrome. Moreover, IVM is a promising option for cases for which no standard protocol is suitable, such as FSH resistance, contraindications for ovarian stimulatory drugs, and the need for urgent fertility preservation. Recently, IVM has been used in women with regular cycles and normal ovaries. However, the pregnancy rate following IVM is suboptimal compared with that of conventional IVF, indicating that further studies to optimize the protocol and the culture conditions are warranted.
    Clinical and Experimental Reproductive Medicine 06/2014; 41(2):41-6. DOI:10.5653/cerm.2014.41.2.41
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    • "These results have implications for young children and adolescents who have had ovarian tissue collected for fertility preservation purposes prior to reaching sexual maturity. Currently, removal and cryopreservation of cortical tissue is the only option for pre-pubertal children facing loss of fertility through chemo/radiotherapy with later reimplantation of this tissue (Anderson and Wallace, 2011). In some patients tissue reimplantation is not desirable due to the risk of reintroducing malignant cells present in the stored tissue back into the cured patient (Dolmans et al., 2010; Rosendahl et al., 2010). "
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    ABSTRACT: Do the ovarian follicles of children and adolescents differ in their morphology and in vitro growth potential from those of adults? Pre-pubertal ovaries contained a high proportion of morphologically abnormal non-growing follicles, and follicles showed reduced capacity for in vitro growth. The pre-pubertal ovary is known to contain follicles at the early growing stages. How this changes over childhood and through puberty is unknown, and there are no previous data on the in vitro growth potential of follicles from pre-pubertal and pubertal girls. Ovarian biopsies from five pre-pubertal and seven pubertal girls and 19 adult women were analysed histologically, cultured in vitro for 6 days, with growing follicles then isolated and cultured for a further 6 days. Ovarian biopsies were obtained from girls undergoing ovarian tissue cryopreservation for fertility preservation, and compared with biopsies from adult women. Follicle stage and morphology were classified. After 6 days in culture, follicle growth initiation was assessed. The growth of isolated secondary follicles was assessed over a further 6 days, including analysis of oocyte growth. Pre-pubertal ovaries contained a high proportion of abnormal non-growing follicles (19.4 versus 4.85% in pubertal ovaries; 4004 follicles analysed; P = 0.02) characterized by indistinct germinal vesicle membrane and absent nucleolus. Follicles with this abnormal morphology were not seen in the adult ovary. During 6 days culture, follicle growth initiation was observed at all ages; in pre-pubertal samples there was very little development to secondary stages, while pubertal samples showed similar growth activation to that seen in adult tissue (pubertal group: P = 0.02 versus pre-pubertal, ns versus adult). Isolated secondary follicles were cultured for a further 6 days. Those from pre-pubertal ovary showed limited growth (P < 0.05 versus both pubertal and adult follicles) and no change in oocyte diameter over that period. Follicles from pubertal ovaries showed increased growth; this was still reduced compared with follicles from adult women (P < 0.05) but oocyte growth was proportionate to follicle size. These data derive from only a small number of ovarian biopsies, although large numbers of follicles were analysed. It is unclear whether the differences between groups are related to puberty, or just age. These findings show that follicles from girls of all ages can be induced to grow in vitro, which has important implications for some patients who are at high risk of malignant contamination of their ovarian tissue. The reduced growth of isolated follicles indicates that there are true intrafollicular differences in addition to potential differences in their local environment, and that there are maturational processes occurring in the ovary through childhood and adolescence, which involve the loss of abnormal follicles, and increasing follicle developmental competence. Funded by MRC grants G0901839 and G1100357. No competing interests.
    Human Reproduction 10/2013; 29(1). DOI:10.1093/humrep/det388 · 4.57 Impact Factor
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