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.

Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system

“…Given the widespread adoption of ovarian tissue cryopreservation for cancer patients (Anderson et al, 2017), our results make plausible the utilization of in vitro generated mature human oocytes for embryo production and thus an alternative to autologous transplantation particularly where there is a threat of tumour reintroduction as a result of grafting. Whether the multi-step model will be useful for other applications such as screening for potentially gonadotoxic therapies or environmental toxins is not yet known but these are becoming realistic prospects for future applications.…”

Systematic review of fertility preservation patient decision aids for cancer patients

“…Methods of fertility preservation for female cancer patients include oocyte and embryo cryopreservation, ovarian transportation, conservative gynaecological surgery, ovarian suppression, or cryopreservation of ovarian tissue . With the increasing success of ovarian cryopreservation and transplantation techniques, this option is more recently being considered as standard practice, especially in prepubertal patients . Cryopreservation of spermatozoa is the only established method of fertility preservation for male patients, with cryopreservation of testicular tissue recommended only when as part of a clinical trial or experimental protocol .…”

Future developments: In vitro growth (IVG) of human ovarian follicles

“…The most significant clinical application of IVG of human oocytes is in fertility preservation given the widespread adoption of ovarian tissue cryopreservation for cancer patients . It is clear that making a good egg is not an easy or straightforward process .…”

“…The ability to develop human immature oocytes in vitro would have many potential applications but would be of particular relevance to fertility preservation. Ovarian tissue cryopreservation is now an option for women with cancer prior to undergoing gonadotoxic treatments . Re‐implantation of cryo‐preserved tissue is currently the only option to use stored tissue, but in many cases, particularly for women with leukemia, malignant cells are present in the ovary and therefore re‐implantation is not an option; however, the oocytes within this tissue could potentially be grown in vitro .…”