Abstract
Development of early follicles, especially the activation of primordial follicles, is strictly modulated by a network of signaling pathways. Recent advance in ovarian physiology has been allowed the development of several therapies to improve reproductive outcomes by manipulating early folliculogenesis. Among these, in vitro activation (IVA) has been recently developed to extend the possibility of achieving genetically related offspring for patients with premature ovarian insufficiency and ovarian dysfunction. This method was established based on basic science studies of the intraovarian signaling pathways: the phosphoinositide 3-kinase (PI3K)/Akt and the Hippo signaling pathways. These two pathways were found to play crucial roles in folliculogenesis from the primordial follicle to the early antral follicle. Following the results of rodent experiments, IVA was implemented in clinical practice. There have been multiple recorded live births and ongoing pregnancies. Further investigations are essential to confirm the efficacy and safety of IVA before used widely in clinics. This review aimed to summarize the published literature on IVA and provide future perspectives for its improvement.
Highlights
The majority of achievements in medical science practice are based on basic scientific research
As the timing of follicle growth in this system is highly irregular, the finding has yet to be repeated [37]. These findings suggested that the primordial follicles (PFs) could be suppressed under the physiological environment, or there are in vitro factors stimulating the PF activation [9]
The loss of mTORC1 signaling in oocytes stimulates the phosphoinositide 3-kinase (PI3K) signaling cascade to maintain normal follicular growth [54,56]. These results suggested that mTORC1 signaling is an independent pathway that controls follicular activation
Summary
The majority of achievements in medical science practice are based on basic scientific research. Due to innovations in oncological treatment, the number of cancer survivors at the reproductive age has been increasing, leading to a higher prevalence of premature ovarian insufficiency (POI) [4]. To expand reproductive possibilities to DOR and POI patients, considerable efforts to investigate molecular mechanisms underlying folliculogenesis, leading to a variety of new approaches including follicle regeneration, rejuvenation, and activation [5]. IVA has been recently introduced and gradually implemented in clinical practice This innovation was established from numerous animal experiments, including genetic manipulation studies illustrating the molecular mechanism of two involving signaling pathways in folliculogenesis. To provide a full overview of basic science related to IVA to the scientific community, this review summarized published works from basic scientific studies to clinical reports illustrating the molecular mechanisms and recorded outcomes of this treatment
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