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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^[1]. They showed maturation occurs in isolation from normal follicular environment^[1]. In 1965 Edwards then continued IVM studies in mouse, sheep, cow, pig, rhesus monkey and human^[2]^[3]. By 1991, the first pregnancy was recorded using IVM followed by IVF^[4], 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^[5].

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^[6]. 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 ^[6]. Of these primordial follicles, only around 400 mature oocytes are released and could be potentially fertilised, with the rest undergoing atresia^[7].

‘Maturation’ of an oocyte is the process by which an ‘oocyte attains the competence to be fertilised and undergo embryogenesis’ ^[8].

Folliculogenesis is the mechanism by which the ovarian follicles mature. This can take many months in vivo and involves primordial follicle growth and differentiation^[8].

Primordial follicles containing the primary oocyte, arrested at prophase of meiosis I^[8], 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^[6]. 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^[3]. 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^[7].

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.

^ ^a ^b Pincus, Gregory; Enzmann, E. V. (1935-11-01). "The Comparative Behavior of Mammalian Eggs in Vivo and in Vitro". Journal of Experimental Medicine. 62 (5): 665–675. doi:10.1084/jem.62.5.665. ISSN 0022-1007. PMID 19870440.
^ Edwards (1965). "Maturation in vitro of mouse, sheep, cow, pig, rhesus monkey and human ovarian oocytes". Nature. 208(5008): 349–351.
^ ^a ^b Edwards, R. G. (1965-11-06). "Maturation in vitro of human ovarian oöcytes". Lancet (London, England). 2 (7419): 926–929. ISSN 0140-6736. PMID 4165802.
^ Cha, K. Y.; Koo, J. J.; Ko, J. J.; Choi, D. H.; Han, S. Y.; Yoon, T. K. (1991-01-01). "Pregnancy after in vitro fertilization of human follicular oocytes collected from nonstimulated cycles, their culture in vitro and their transfer in a donor oocyte program". Fertility and Sterility. 55 (1): 109–113. ISSN 0015-0282. PMID 1986950.
^ Trounson, Alan; Wood, Carl; Kausche, Annette (1994-08-01). "In vitro maturation and the fertilization and developmental competence of oocytes recovered from untreated polycystic ovarian patients*". Fertility and Sterility. 62 (2): 353–362. doi:10.1016/S0015-0282(16)56891-5.
^ ^a ^b ^c Dunlop, Cheryl E.; Anderson, Richard A. (2014-08-01). "The regulation and assessment of follicular growth". Scandinavian Journal of Clinical and Laboratory Investigation. 74 (sup244): 13–17. doi:10.3109/00365513.2014.936674. ISSN 0036-5513.
^ ^a ^b Chian, Ri-Cheng; Lim, Jin-Ho; Tan, Seang-Lin (2004-06-01). "State of the art in in-vitro oocyte maturation". Current Opinion in Obstetrics & Gynecology. 16 (3): 211–219. ISSN 1040-872X. PMID 15129050.
^ ^a ^b ^c Hardy, Wright, Franks, Winston (2000). "In vitro maturation of oocytes". British medical bulletin. 56(3): 588-602.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[:0-1] Pincus, Gregory; Enzmann, E. V. (1935-11-01). "The Comparative Behavior of Mammalian Eggs in Vivo and in Vitro". Journal of Experimental Medicine. 62 (5): 665–675. doi:10.1084/jem.62.5.665. ISSN 0022-1007. PMID 19870440.

[2] Edwards (1965). "Maturation in vitro of mouse, sheep, cow, pig, rhesus monkey and human ovarian oocytes". Nature. 208(5008): 349–351.

[:1-3] Edwards, R. G. (1965-11-06). "Maturation in vitro of human ovarian oöcytes". Lancet (London, England). 2 (7419): 926–929. ISSN 0140-6736. PMID 4165802.

[4] Cha, K. Y.; Koo, J. J.; Ko, J. J.; Choi, D. H.; Han, S. Y.; Yoon, T. K. (1991-01-01). "Pregnancy after in vitro fertilization of human follicular oocytes collected from nonstimulated cycles, their culture in vitro and their transfer in a donor oocyte program". Fertility and Sterility. 55 (1): 109–113. ISSN 0015-0282. PMID 1986950.

[5] Trounson, Alan; Wood, Carl; Kausche, Annette (1994-08-01). "In vitro maturation and the fertilization and developmental competence of oocytes recovered from untreated polycystic ovarian patients*". Fertility and Sterility. 62 (2): 353–362. doi:10.1016/S0015-0282(16)56891-5.

[:2-6] Dunlop, Cheryl E.; Anderson, Richard A. (2014-08-01). "The regulation and assessment of follicular growth". Scandinavian Journal of Clinical and Laboratory Investigation. 74 (sup244): 13–17. doi:10.3109/00365513.2014.936674. ISSN 0036-5513.

[:3-7] Chian, Ri-Cheng; Lim, Jin-Ho; Tan, Seang-Lin (2004-06-01). "State of the art in in-vitro oocyte maturation". Current Opinion in Obstetrics & Gynecology. 16 (3): 211–219. ISSN 1040-872X. PMID 15129050.

[:4-8] Hardy, Wright, Franks, Winston (2000). "In vitro maturation of oocytes". British medical bulletin. 56(3): 588-602.{{cite journal}}: CS1 maint: multiple names: authors list (link)

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