FERTILITY PRESERVATION: Construction and use of artificial ovaries

Abstract

Increasing numbers of patients are now surviving previously fatal malignant diseases, so for women of childbearing age, fertility concerns are paramount once they are cured. However, the treatments themselves, namely chemo- and radiotherapy, can cause considerable damage to endocrine and reproductive functions, often leaving these women unable to conceive. When such gonadotoxic therapy cannot be postponed due to the severity of the disease or for prepubertal girls, the only way to preserve fertility is cryobanking their ovarian tissue for future use. Unfortunately, with some types of cancer, there is a risk of reimplanting malignant cells together with the frozen-thawed tissue, so it is not recommended. A safer approach involves grafting isolated preantral follicles back to their native environment inside a specially created transplantable artificial ovary for their protection. This bioengineered ovary must mimic the natural organ and therefore requires an appropriate scaffold to encapsulate not only isolated follicles, but also autologous ovarian cells, which are needed for follicles to survive and develop. Here we review the indications for use of this artificial ovary and advances in the field that are bringing us ever closer to clinical implementation.

Fertility Preservation: The Challenge of Freezing and Transplanting Ovarian Tissue

“…In view of this risk, various research teams worldwide have been investigating alternative approaches, including: (i) in vitro (ex vivo) culture of follicles [122][123][124], and (ii) in vivo (post-transplantation) growth of isolated preantral follicles inside a transplantable artificial ovary [92,[125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140]. The primary objective of an artificial ovary is to safely transplant ovarian follicles, while ensuring secretion of sex hormones and development of fertilizable mature oocytes.…”

Overview of fertility preservation

“…The risk of reintroduction of malignant cells at the time of auto-transplantation can be minimised by meticulous examination of a representative biopsy in terms of histology, immunohistochemistry, and molecular biology 66 . Optic coherence tomography can also be used to screen malignant cells in the ovarian tissue before transplantation 67 .…”

Time for fertility preservation

“…The risks are most serious with leukemia, some lymphomas, neuroblastoma and any disease that sends metastases to the gonads. Dolmans and Amorim (2019) review in this issue progress for constructing artificial ovaries to avoid this hazard. The ovary is a plastic organ that can be disaggregated to single cells and isolated follicles for eliminating malignancy before recombining the healthy components in molecular scaffolds for transplantation.…”