Female fertility preservation: past, present and future

Abstract

Anti-cancer therapy, particularly chemotherapy, damages ovarian follicles and promotes ovarian failure. The only pharmacological means for protecting the ovaries from chemotherapy-induced injury is gonadotrophin-releasing hormone agonist, but its efficiency remains controversial; ovarian transposition is used to shield the ovary from radiation when indicated. Until the late 1990s, the only option for fertility preservation and restoration in women with cancer was embryo cryopreservation. The development of other assisted reproductive technologies such as mature oocyte cryopreservation and maturation of oocytes has contributed to fertility preservation. Treatment regimens to obtain mature oocytes/embryos have been modified to overcome various limitations of conventional ovarian stimulation protocols. In the last decades, several centres have begun cryopreserving ovarian samples containing primordial follicles from young patients before anti-cancer therapy. The first live birth following implantation of cryopreserved-thawed ovarian tissue was reported in 2004; since then, the number has risen to more than 130. Nowadays, ovarian tissue cryopreservation can be combined with maturation and vitrification of oocytes. The use of cryopreserved oocytes eliminates the risk posed by ovarian implantation of reseeding the cancer. Novel methods for enhancing follicular survival after implantation are presently being studied. In addition, researchers are currently investigating agents for ovarian protection. It is expected that the risk of reimplantation of malignant cells with ovarian grafts will be overcome with the putative development of an artificial ovary and an efficient follicle class- and species-dependent system for culturing primordial follicles.

AMH prevents primordial ovarian follicle loss and fertility alteration in cyclophosphamide‐treated mice

“…Currently, in the field of oncofertility, efforts are constantly made to improve existing fertility preservation techniques and to develop new strategies suitable for patients of whatever age and ovarian reserve status (43). Thus, several "fertoprotectant" molecules, such as rapamycin or melatonin, have been developed and studied to limit chemotherapyinduced ovarian damages in mice (18,19,30,44,45). However, these treatments are involved in cell-death mechanism or in ubiquitous signaling pathways, and they could therefore interfere with the efficacy of treatment or other physiologic mechanisms (19).…”

“…A recent review focused on the current and future indications and techniques of fertility preservation (17). Preventing chemotherapy-induced ovarian dysfunction might represent an interesting option for preserving optimal chances of natural or medically assisted conceptions after healing (18)(19)(20)(21).…”

A new possibility in fertility preservation: The artificial ovary

“…To date, various efforts have been made to preserve ovarian function and fertility, for example, administration of gonadotropin‐releasing hormone agonist prior to the initiation of chemotherapy, cryopreservation of embryos, mature oocytes, or ovarian tissue (Pereira et al, ). Although means of ovarian protections (Abir, Fisch, Raz, Nitke, & Ben‐Rafael, ) were attempted to prevent or decrease the loss of fertility before the chemotherapy or radiotherapy (Fisch & Abir, ), current treatments are still highly toxic to gonads such as ovary and testis. When chemotherapy impairs ovarian function, patients present reduced antral follicle counts and low anti‐Müllerian hormone levels that are indicative of a low reproductive potential (Wenners et al, ).…”

“…Another group suggested that the artificial ovary contain isolated follicles in a biomaterial and thus is able to preserve fertility and replace hormonal functions of the ovary with a significantly decreased risk of introducing malignant cells back into patients (Soares et al, ). A recent review described the artificial ovary that contains primordial follicles embedded in a matrix, as one of the promising future FP techniques (Fisch & Abir, ).…”

“…Although means of ovarian protections (Abir, Fisch, Raz, Nitke, & Ben-Rafael, 1998) were attempted to prevent or decrease the loss of fertility before the chemotherapy or radiotherapy Eun Cho and Yoon Young Kim contributed equally to this work. (Fisch & Abir, 2018), current treatments are still highly toxic to gonads such as ovary and testis. When chemotherapy impairs ovarian function, patients present reduced antral follicle counts and low anti-Müllerian hormone levels that are indicative of a low reproductive potential (Wenners et al, 2017).…”