ovary as shown by ultrasound monitoring. these follicles secrete low levels of oestrogen but are resistant to exogenous follicle stimulating hormone treatment so cannot develop to maturity. like patients with poi, ros patients can respond to incision of the ovarian cortex to cause hippo signalling disruption. additionally, laparoscopic ovarian incision (loi) can be performed in vivo to successfully promote follicle growth without removing tissue outside of the body. post-cancer treatment oocyte cryopreservation is widely used to protect primordial follicles from gonadotoxic treatment but some patients are not eligible for this, iva could be a beneficial option for fertility preservation in cancer patients. the iva approach could maximise the number of secondary oocytes in infertile woman since transplanting ovarian tissue successfully activates the dormant follicle pool. the iva method focuses on the short term goal of generating a large number of activated follicles immediately following transplantation of tissue back into the body. this means that the iva method has a reduced graft lifespan compared to the 4-5 years that can be offered in the cryopreservation method. the graft lifespan relates to the length of time following transplantation back into he body that pregnancies can occur within. this is because iva promotes loss of dormant follicles to activation so fewer dormant follicles will remain in the graft. this, as a result, reduces graft lifespan. however, this can be beneficial in patients looking for immediate outcomes or to improve her chance of conceiving as fast as possible due to advancing age. so far, there have been no reported live births but progress is being made in in-vitro research. surgically removing ovaries patients are usually treated with synthetic oestrogen and progesterone for at least a month in order to suppress their gonadotrophin levels which has been shown to promote ovulation. a laparoscopic approach is used to remove the ovary. the outer part of the ovary (the cortex) is removed using scissors as this minimises any damage to the sensitive inner ovarian tissue. this tissue is then analysed to assess the presence of existing follicles before further manipulation. artificial ovaries artificial ovaries can be used to provide follicles for artificial activation. follicles from these synthetic ovaries have been shown to support successful pregnancies in mouse models and show promise for potential for future treatments in humans. ovarian fragmentation and hippo signalling disruption the hippo signalling pathway is an essential pathway involving several components that regulate cell growth, survival and stem cell renewal. for this reason, the hippo signalling pathway has been implicated in the maintenance and control of organ size in organisms. in recent years, ovarian fragmentation has surfaced as an effective strategy to promote ovarian follicular activation and growth. studies undertaken on cultured human ovarian cortical fragments have demonstrated that the mechanical damage resulting from ovarian tissue fragmentation disrupts the hippo signalling pathway. this has been found to accelerate follicle activation. mechanical damage to the ovaries through fragmentation have been found to induce a transient elevation in actin polymerisation - a process where small actin molecules (proteins) combine to form a large, chain-like structure with repeating actin units. mechanical damage to the ovaries has also decreased phosphorylation of yes-associated protein (yap), an essential compound in the hippo signalling pathway. phosphorylation refers to the addition of phosphate groups to molecules. consequently, this leads to an increase in the levels of yap in the nucleus. this in turn triggers a downstream ripple effect to increase the expression of growth factors and apoptosis inhibitors, therefore promoting cell growth and survival. ovarian fragmentation and hippo signalling pathway pi3k/akt/mtor signalling pathway activation another key pathway in ovarian follicle activation is the pi3k-pten-akt-foxo3 pathway. the pi3k-pten-akt-foxo3 pathway is a complex signal transduction pathway involving a cascade of several molecules. this pathway is involved in promoting growth, survival and proliferation of cells in response to certain factors. the pathway is therefore implicated in the activation of ovarian primordial follicles. in in vitro activation of ovarian follicles, drugs such as inhibitors of pten or activators of pi3k can be administered to stimulate follicle activation. in vitro activation (iva) stimulation of the atk pathway activates dormant primordial follicles. the hippo signalling pathway regulates growth by inhibiting cell proliferation and promoting apoptosis, disrupting this pathway stimulates cell growth and proliferation. in vitro activation (iva) consists of the combination of disrupting the hippo signalling pathway and stimulation of akt signalling to activate ovarian follicle growth and maturation.atk pathway activation can be artificially induced by atk stimulating drugs such as pten inhibitors and pi3k activators and hippo signalling disruption is achieved through fragmentation of ovarian cortex via various methods. growth of follicles can be seen in subsequent autografts, mature eggs can be retrieved and ivf carried out making it a good candidate for fertility preservation. drug free iva may alternatively be used. this is the same as iva however no drugs are used to stimulate the atk pathway, only ovarian cortex fragmentation is used.