Restoration of fertility
Follicle culture
Any culture strategy designed to support the complete IVG of oocytes and follicles from cryopreserved tissues must mimic the sequence of events and cellular checkpoints that the follicles and oocytes would normally be exposed to in vivo. The growth rates, cell–cell signalling and metabolic turnover of follicles and oocytes grown in vitro must correspond to the parameters of similar cells grown to maturity in the body nolvadex canada. During their extended growth phase, oocytes progressively synthesize and accumulate the payload of proteins and acids (RNAs), which are required to support production of a fertile gamete and the preimplantation development of the early embryo. Furthermore, there are stage-specific changes in genomic imprinting during oocyte growth in vivo that must be replicated in oocytes grown in vitro.
Despite these stringent biological requirements, significant advances have been made in IVG technologies. Encouraging results have been obtained in laboratory species. In contrast, progress in IVG in large animals and humans is far slower than that observed in rodents, as ruminant and human oocytes are much larger eggs, which take many months to acquire their fertile potential. Nevertheless, in both sheep and humans it is now possible to: initiate and maintain primordial follicle growth over extended periods; induce antral cavity formation in preantral follicles; induce appropriate levels of steroid biosynthesis after provision of suitable substrates. Importantly, extensive validation studies carried out on isolated sheep follicles have revealed that IVG can be achieved with equal efficiency using both fresh and cryopreserved tissue. Electron microscopy has also shown that the in vitro-grown cells have a similar morphology to oocytes and follicles grown in vivo. Further advances in IVG technology will soon enable us to determine if the oocytes derived following cryopreservation and IVG of human ovarian cortex are healthy and fertile.
Loss of ovarian function and reduction of fertile potential in young patients can be combated by the development of strategies to quantify the risk of ovarian damage, to protect the gonads from the destructive effects of medical treatments and, in extreme cases, to cryopreserve fertility. Advances in fertility preservation methods for young patients will inevitably be dependent on the development of an improved understanding of the effects on the ovary of contemporary treatments, as exposure to cytotoxic agents is frequently unavoidable prior to a window of safety being available for oocyte and ovarian tissue harvesting. Furthermore, the development of a safe clinical strategy to preserve the fertility of all young patients, irrespective of diagnosis, has to be based around high-quality basic research into the biology and technology of oocyte and ovarian tissue cryopreservation and its safe and cheap viagra canada online and efficient use to restore fertility. Future research topics are therefore likely to include: development of new diagnostics to test the gonadotoxicity of treatments such as those offered to cancer patients; development of accurate methods to predict the lifespan of autografts; determination of the optimum location of autografts; assessment of the impact of patient age on the efficiency of the freezing, thawing and grafting or IVG processes; quantification of the consequences of prior exposure to chemo- or radiotherapies; and evaluation of the normality of uterine function and the contribution of the uterus to implantation post-treatment.
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