Understanding follicle growth in vitro: Are we getting closer to obtaining mature oocytes from in vitro‐grown follicles in human?

Abstract

Obtaining and fertilizing mature oocytes from immature follicles that were grown outside the body has conceptually attracted scientists for centuries, with initial attempts first documented in the 19th century. Significant progress has been made since then, due in part to a better understanding of folliculogenesis and improved techniques of in vitro follicle growth. Indeed, in vitro growth is now considered a reasonable approach to preserve or restore fertility when immature follicles and their oocytes need to be grown and matured outside the body. Certain patients would benefit from in vitro follicle growth, particularly those who carry a risk of cancer re-seeding after grafting of frozen-thawed ovarian tissue or who are at the risk of premature ovarian failure due to several intrinsic ovarian defects and genetic mutations that lead to accelerated follicle atresia and early exhaustion of the ovarian reserve. This review provides an update on the current status of in vitro growth of preantral human follicles, from initial efforts to the most recent achievements.

Recent advances: fertility preservation and fertility restoration options for males and females

“…To address this problem, a dynamic multistep culture technique for in vitro growth of oocytes was developed for growing primordial follicles to the stage that can be matured by IVM technique. Dynamic multistep culture mimics follicular development in vivo and is generally composed of three steps: (1) activation of primordial follicles to small preantral follicles, (2) in vitro growth of small preantral follicles to antral follicles where cumulus–oocyte complexes (COCs) can be isolated for (3) IVM 130 – 132 .…”

Technologies for the Production of Fertilizable Mammalian Oocytes

“…A few years later, a two-step method based on the combination of ovarian tissue and 2D culture onto collagen gels allowed obtaining the first viable offspring from IVG activated primordial/primary mouse follicles [44]. Since the development of multistep culture systems better supports each specific developmental stage [67], after several technical improvements, mouse primordial follicles were completely differentiated in vitro. The derived embryos were able to produce a healthy colony formed by 35 females and 37 males that survived to adulthood [68].…”

“…In 2018, Telfer and her collaborators [90] obtained for the first time MII oocytes from human unilaminar follicles by using a four-step culture system. After that, reproducible results have been achieved by several laboratories using fresh and cryopreserved ovarian tissue, and new information about the genes regulating this process is now available (for a review, see [67]).…”

Premature Ovarian Insufficiency: Procreative Management and Preventive Strategies

“…In vitro follicle growth (IVG) is an experimental and exciting new method of growing immature ovarian follicles in vitro, to eliminate the risk of reintroducing cancer cells. It may also be applicable to prepubertal patients for whom hormone stimulation is not an appropriate strategy to obtain viable follicles [28]. The immature (primordial) follicle is isolated and grown in a three-dimensional culture.…”