Ovarian tissue cryopreservation for fertility preservation: clinical and research perspectives

Abstract

Background: Small case series have reported successful live births after ovarian tissue cryopreservation and orthotopic transplantation, demonstrating that it can be of value in increasing the chance of successful pregnancy after treatment for cancer and other fertility-impacting diseases in adult women.

Objective and rationale: This review is intended to set out the current clinical issues in the field of ovarian tissue cryopreservation, and elucidate the status of laboratory studies to address these.

Search methods: We reviewed the English-language literature on ovarian tissue cryopreservation and in vitro maturation (IVM) of ovarian follicles.

Outcomes: Ovarian tissue cryopreservation is increasingly used for fertility preservation and, whilst areas for development remain (optimal patient selection, minimizing risk of contamination by malignant cells and IVM protocols), there are emerging data as to its efficacy. We review the current status of ovarian tissue cryopreservation in girls and young women facing loss of fertility from treatment of cancer and other serious diseases. Increasingly large cohort studies are reporting on success rates from ovarian tissue cryopreservation giving an indication of likely success rates. Patient selection is necessary to ensure the safety and effectiveness of this approach, especially in the very experimental situation of its application to prepubertal girls. There are continuing developments in supporting follicle development in vitro.

Limitations reasons for caution: The evidence base consists largely of case series and cohort studies, thus there is the possibility of bias in key outcomes. In vitro development of human ovarian follicles remains some way from clinical application.

Wider implications of the findings: Ovarian tissue cryopreservation is becoming established as a valuable approach to the preservation of fertility in women. Its application in prepubertal girls may be of particular value, as it offers the only approach in this patient group. For both girls and young women, more accurate data are needed on the likelihood of successful childbirth after this procedure and the factors that underpin successful application of this approach, which will lead to its more effective use.

Study funding/competing interests: The author's work in this field is supported by Medical Research Grant (MRC) grants G0901839 and MR/L00299X/1 and partially undertaken in the MRC Centre for Reproductive Health which is funded by MRC Centre grant MR/N022556/1. The authors declare that there is no conflict of interest that could prejudice the impartiality of the present research.

Keywords: cryopreservation; fertility preservation; gonadotoxicity; ivm: artificial ovary; tissue culture.

Figure 1

Ovarian tissue cryopreservation within the wider context of fertility preservation for girls and women. Cryo: cryopreservation. Adapted from Anderson et al. (2015).

Figure 2

Biopsy of ovary from a girl with Ewing's sarcoma in a vertebra. A 12-year-old with Ewing's sarcoma localized to the T7 vertebra and no evidence of metastatic disease underwent ovarian biopsy for fertility preservation. A biopsy sent for pathological examination showed presumed malignant contamination, with CD99 positive cells present consistent with metastatic Ewing's sarcoma. Left panel, solid arrow indicates area of CD99 positive cells in a haematoxylin and eosin stained section, open arrow indicates primordial follicles in cortex of ovary. Right panel: CD99 (brown stain) immunohistochemistry result.

Figure 3

Multistep culture system for activation of human primordial follicles and subsequent follicle/oocyte development. Primordial follicles can be activated or held dormant within ovarian cortical tissue (a). Once activated preantral stages can be isolated (b), they are grown individually to antral stages (c). These can be further grown, for example, within an alginate bead (d) to obtain fully grown oocytes (e), then competence to undergo maturation and fertilization is tested.