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History of IVM:
In 1935 Pincus & Enzmann, did the first experiment on immature rabbit oocyte, showing in vitro spontaneous maturation and fertilization. They showed maturation occurs in isolation from normal follicular environment. In 1965 Edwards then continued IVM studies in mouse, sheep, cow, pig, rhesus monkey and human. By 1991, the first pregnancy was recorded using IVM followed by IVF, and in 1994 the first birth using IVM oocytes from polycystic ovarian syndrome patients was recorded highlighting that PCOS patient’s oocytes are capable of maturation.



Background
Oogenesis takes place during fetal life, in which primordial germ cells undergo mitosis until a few weeks prior to birth, forming oogonia. These then begin meiosis to form the oocyte within the primordial follicle. This follicle consists of the oocyte surrounded by flattened pregranulosa cells. Babies are born with 1-2 million primordial follicles, and by puberty have around 300,000. Of these primordial follicles, only around 400 mature oocytes are released and could be potentially fertilised, with the rest undergoing atresia.

‘Maturation’ of an oocyte is the process by which an ‘oocyte attains the competence to be fertilised and undergo embryogenesis’.

Folliculogenesis is the mechanism by which the ovarian follicles mature. This can take many months in vivo and involves primordial follicle growth and differentiation.

Primordial follicles containing the primary oocyte, arrested at prophase of meiosis I, develop into primary follicle containing cuboidal granulosa cells. A secondary follicle is formed with a few granulosa cell layers, as well as a theca layer. Finally before ovulation, a tertiary follicle is formed containing a follicular-fluid filled antrum. Of these small antral follicles, 1 will become dominant and ovulate (in monoovulatory species). During ovulation, the primary oocyte will resume meiosis in response to signals, arresting in metaphase meiosis II, ready for fertilization. The dominant follicle contains the mature oocyte. Follicular development is directly under gonadotropins control, LH and FSH. These use cAMP as an intracellular second messenger, with growth factors and cytokines also influencing their development in vivo.

Through in vitro maturation, folliculogenesis and latter parts of oogenesis are being mimicked outside of the ovaries- trying to recreate the conditions for these processes.