Only a fraction of oocytes present in the ovaries at birth are ever ovulated during the lifetime of a female mammal. In vitro maturation (IVM) offers the possibility to exploit what is a largely untapped biological resource. Although IVM is used routinely for the in vitro production of embryos in domestic species, especially cattle, its clinical use in human-assisted reproduction is still evolving. The successful recapitulation in vitro of the events associated with successful oocyte maturation is not always achieved, with the majority of immature oocytes typically failing to develop to the blastocyst stage. Evidence suggests that although culture conditions throughout in vitro embryo production may have a modest influence on the developmental potential of the early embryo, the quality of the oocyte at the start of the process is the key factor determining the proportion of oocytes developing to the blastocyst stage.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Baker TG. 1.  1963. A quantitative and cytological study of germ cells in human ovaries. Proc. R. Soc. Lond. B Biol. Sci. 158:417–33 [Google Scholar]
  2. Erickson BH. 2.  1966. Development and senescence of the postnatal bovine ovary. J. Anim. Sci. 25:800–5 [Google Scholar]
  3. Gougeon A. 3.  1996. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr. Rev. 17:121–55 [Google Scholar]
  4. Crowe MA, Diskin MG, Williams EJ. 4.  2014. Parturition to resumption of ovarian cyclicity: comparative aspects of beef and dairy cows. Animal 8:Suppl. 140–53 [Google Scholar]
  5. Kruip TA, Pieterse MC, van Beneden TH, Vos PL, Wurth YA, Taverne MA. 5.  1991. A new method for bovine embryo production: a potential alternative to superovulation. Vet. Rec. 128:208–10 [Google Scholar]
  6. Pieterse MC, Vos PL, Kruip TA, Wurth YA, van Beneden TH. 6.  et al. 1991. Transvaginal ultrasound guided follicular aspiration of bovine oocytes. Theriogenology 35:857–62 [Google Scholar]
  7. Perry G. 7.  2014. 2013 statistics of embryo collection and transfer in domestic farm animals. Embryo Transf. Newsl. 32:14–26 [Google Scholar]
  8. Gordon I. 8.  2003. Laboratory Production of Cattle Embryos Wallingford, UK: CABI Publ. [Google Scholar]
  9. Amiridis GS, Cseh S. 9.  2012. Assisted reproductive technologies in the reproductive management of small ruminants. Anim. Reprod. Sci. 130:152–61 [Google Scholar]
  10. Gil MA, Cuello C, Parrilla I, Vazquez JM, Roca J, Martinez EA. 10.  2010. Advances in swine in vitro embryo production technologies. Reprod. Domest. Anim. 45:Suppl. 240–48 [Google Scholar]
  11. Grupen CG. 11.  2014. The evolution of porcine embryo in vitro production. Theriogenology 81:24–37 [Google Scholar]
  12. Hinrichs K. 12.  2012. Assisted reproduction techniques in the horse. Reprod. Fertil. Dev. 25:80–93 [Google Scholar]
  13. Hinrichs K. 13.  2010. In vitro production of equine embryos: state of the art. Reprod. Domest. Anim. 45:Suppl. 23–8 [Google Scholar]
  14. Fair T, Hyttel P, Greve T. 14.  1995. Bovine oocyte diameter in relation to maturational competence and transcriptional activity. Mol. Reprod. Dev. 42:437–42 [Google Scholar]
  15. Pincus G, Enzmann EV. 15.  1935. The comparative behavior of mammalian eggs in vivo and in vitro: I. The activation of ovarian eggs. J. Exp. Med. 62:665–75 [Google Scholar]
  16. Hyttel P, Greve T, Callesen H. 16.  1989. Ultrastructural aspects of oocyte maturation and fertilization in cattle. J. Reprod. Fertil. Suppl. 38:35–47 [Google Scholar]
  17. Hyttel P, Xu KP, Smith S, Greve T. 17.  1986. Ultrastructure of in-vitro oocyte maturation in cattle. J. Reprod. Fertil. 78:615–25 [Google Scholar]
  18. Rizos D, Ward F, Duffy P, Boland MP, Lonergan P. 18.  2002. Consequences of bovine oocyte maturation, fertilization or early embryo development in vitro versus in vivo: implications for blastocyst yield and blastocyst quality. Mol. Reprod. Dev. 61:234–48 [Google Scholar]
  19. Dieleman SJ, Hendriksen PJ, Viuff D, Thomsen PD, Hyttel P. 19.  et al. 2002. Effects of in vivo prematuration and in vivo final maturation on developmental capacity and quality of pre-implantation embryos. Theriogenology 57:5–20 [Google Scholar]
  20. Tesfaye D, Lonergan P, Hoelker M, Rings F, Nganvongpanit K. 20.  et al. 2007. Suppression of connexin 43 and E-cadherin transcripts in in vitro derived bovine embryos following culture in vitro or in vivo in the homologous bovine oviduct. Mol. Reprod. Dev. 74:978–88 [Google Scholar]
  21. Gad A, Schellander K, Hoelker M, Tesfaye D. 21.  2012. Transcriptome profile of early mammalian embryos in response to culture environment. Anim. Reprod. Sci. 134:76–83 [Google Scholar]
  22. Lonergan P, Fair T. 22.  2008. In vitro-produced bovine embryos: dealing with the warts. Theriogenology 69:17–22 [Google Scholar]
  23. Farin PW, Piedrahita JA, Farin CE. 23.  2006. Errors in development of fetuses and placentas from in vitro-produced bovine embryos. Theriogenology 65:178–91 [Google Scholar]
  24. Kruip ThAM, den Daas JHG. 24.  1997. In vitro produced and cloned embryos: effects on pregnancy, parturition and offspring. Theriogenology 47:43–52 [Google Scholar]
  25. Hill JR. 25.  2014. Incidence of abnormal offspring from cloning and other assisted reproductive technologies. Annu. Rev. Anim. Biosci. 2:307–21 [Google Scholar]
  26. Ireland JJ, Mihm M, Austin E, Diskin MG, Roche JF. 26.  2000. Historical perspective of turnover of dominant follicles during the bovine estrous cycle: key concepts, studies, advancements, and terms. J. Dairy Sci. 83:1648–58 [Google Scholar]
  27. Roche JF. 27.  1996. Control and regulation of folliculogenesis—a symposium in perspective. Rev. Reprod. 119–27 [Google Scholar]
  28. Norris RP, Ratzan WJ, Freudzon M, Mehlmann LM, Krall J. 28.  et al. 2009. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development 136:1869–78 [Google Scholar]
  29. Vaccari S, Weeks JL 2nd, Hsieh M, Menniti FS, Conti M. 29.  2009. Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. Biol. Reprod. 81:595–604 [Google Scholar]
  30. Dieleman SJ, Bevers MM, Poortman J, van Tol HT. 30.  1983. Steroid and pituitary hormone concentrations in the fluid of preovulatory bovine follicles relative to the peak of LH in the peripheral blood. J. Reprod. Fertil. 69:641–49 [Google Scholar]
  31. Li Q, Jimenez-Krassel F, Bettegowda A, Ireland JJ, Smith GW. 31.  2007. Evidence that the preovulatory rise in intrafollicular progesterone may not be required for ovulation in cattle. J. Endocrinol. 192:473–83 [Google Scholar]
  32. Lonergan P, Forde N. 32.  2014. Maternal-embryo interaction leading up to the initiation of implantation of pregnancy in cattle. Animal 8:Suppl. 164–69 [Google Scholar]
  33. Fair T, Lonergan P. 33.  2012. The role of progesterone in oocyte acquisition of developmental competence. Reprod. Domest. Anim. 47:Suppl. 4142–47 [Google Scholar]
  34. Aparicio IM, Garcia-Herreros M, O'Shea LC, Hensey C, Lonergan P, Fair T. 34.  2011. Expression, regulation, and function of progesterone receptors in bovine cumulus oocyte complexes during in vitro maturation. Biol. Reprod. 84:910–21 [Google Scholar]
  35. Hardy K, Wright CS, Franks S, Winston RM. 35.  2000. In vitro maturation of oocytes. Br. Med. Bull. 56:588–602 [Google Scholar]
  36. Mehta JG. 36.  2015. In vitro maturation. Fertil. Sci. Res. 1:7–15 [Google Scholar]
  37. Sauerbrun-Cutler MT, Vega M, Keltz M, McGovern PG. 37.  2015. In vitro maturation and its role in clinical assisted reproductive technology. Obstet. Gynecol. Surv. 70:45–57 [Google Scholar]
  38. Smitz JE, Thompson JG, Gilchrist RB. 38.  2011. The promise of in vitro maturation in assisted reproduction and fertility preservation. Semin. Reprod. Med. 29:24–37 [Google Scholar]
  39. Cha KY, Koo JJ, Ko JJ, Choi DH, Han SY, Yoon TK. 39.  1991. 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. Fertil. Steril. 55:109–13 [Google Scholar]
  40. De Vos M, Smitz J, Woodruff TK. 40.  2014. Fertility preservation in women with cancer. Lancet 384:1302–10 [Google Scholar]
  41. Downs SM. 41.  2015. Nutrient pathways regulating the nuclear maturation of mammalian oocytes. Reprod. Fertil. Dev. 27:572–82 [Google Scholar]
  42. Regassa A, Rings F, Hoelker M, Cinar U, Tholen E. 42.  et al. 2011. Transcriptome dynamics and molecular cross-talk between bovine oocyte and its companion cumulus cells. BMC Genomics 12:57 [Google Scholar]
  43. Tesfaye D, Ghanem N, Carter F, Fair T, Sirard MA. 43.  et al. 2009. Gene expression profile of cumulus cells derived from cumulus-oocyte complexes matured either in vivo or in vitro. Reprod. Fertil. Dev. 21:451–61 [Google Scholar]
  44. Matoba S, Bender K, Fahey AG, Mamo S, Brennan L. 44.  et al. 2014. Predictive value of bovine follicular components as markers of oocyte developmental potential. Reprod. Fertil. Dev. 26:337–45 [Google Scholar]
  45. Assidi M, Montag M, Sirard MA. 45.  2015. Use of both cumulus cells' transcriptomic markers and zona pellucida birefringence to select developmentally competent oocytes in human assisted reproductive technologies. BMC Genom. 16:Suppl. 1S9 [Google Scholar]
  46. Bunel A, Jorssen EP, Merckx E, Leroy JL, Bols PE, Sirard MA. 46.  2015. Individual bovine in vitro embryo production and cumulus cell transcriptomic analysis to distinguish cumulus-oocyte complexes with high or low developmental potential. Theriogenology 83:228–37 [Google Scholar]
  47. Fair T, Hyttel P, Greve T, Boland M. 47.  1996. Nucleus structure and transcriptional activity in relation to oocyte diameter in cattle. Mol. Reprod. Dev. 43:503–12 [Google Scholar]
  48. Lonergan P, Monaghan P, Rizos D, Boland MP, Gordon I. 48.  1994. Effect of follicle size on bovine oocyte quality and developmental competence following maturation, fertilization, and culture in vitro. Mol. Reprod. Dev. 37:48–53 [Google Scholar]
  49. Hendriksen PJ, Steenweg WN, Harkema JC, Merton JS, Bevers MM. 49.  et al. 2004. Effect of different stages of the follicular wave on in vitro developmental competence of bovine oocytes. Theriogenology 61:909–20 [Google Scholar]
  50. Machatkova M, Krausova K, Jokesova E, Tomanek M. 50.  2004. Developmental competence of bovine oocytes: effects of follicle size and the phase of follicular wave on in vitro embryo production. Theriogenology 61:329–35 [Google Scholar]
  51. van de Leemput EE, Vos PL, Zeinstra EC, Bevers MM, van der Weijden GC, Dieleman SJ. 51.  1999. Improved in vitro embryo development using in vivo matured oocytes from heifers superovulated with a controlled preovulatory LH surge. Theriogenology 52:335–49 [Google Scholar]
  52. Leibfried-Rutledge ML, Critser ES, Eyestone WH, Northey DL, First NL. 52.  1987. Development potential of bovine oocytes matured in vitro or in vivo. Biol. Reprod. 36:376–83 [Google Scholar]
  53. Blondin P, Guilbault LA, Sirard MA. 53.  1997. The time interval between FSH-P administration and slaughter can influence the developmental competence of beef heifer oocytes. Theriogenology 48:803–13 [Google Scholar]
  54. Blondin P, Coenen K, Guilbault LA, Sirard MA. 54.  1997. In vitro production of bovine embryos: Developmental competence is acquired before maturation. Theriogenology 47:1061–75 [Google Scholar]
  55. Blondin P, Bousquet D, Twagiramungu H, Barnes F, Sirard MA. 55.  2002. Manipulation of follicular development to produce developmentally competent bovine oocytes. Biol. Reprod. 66:38–43 [Google Scholar]
  56. Nivet AL, Bunel A, Labrecque R, Belanger J, Vigneault C. 56.  et al. 2012. FSH withdrawal improves developmental competence of oocytes in the bovine model. Reproduction 143:165–71 [Google Scholar]
  57. Durocher J, Morin N, Blondin P. 57.  2006. Effect of hormonal stimulation on bovine follicular response and oocyte developmental competence in a commercial operation. Theriogenology 65:102–15 [Google Scholar]
  58. Ward F, Enright B, Rizos D, Boland M, Lonergan P. 58.  2002. Optimization of in vitro bovine embryo production: effect of duration of maturation, length of gamete co-incubation, sperm concentration and sire. Theriogenology 57:2105–17 [Google Scholar]
  59. Bilodeau-Goeseels S. 59.  2012. Bovine oocyte meiotic inhibition before in vitro maturation and its value to in vitro embryo production: Does it improve developmental competence?. Reprod. Domest. Anim. 47:687–93 [Google Scholar]
  60. Romero-Arredondo A, Seidel GE Jr. 60.  1996. Effects of follicular fluid during in vitro maturation of bovine oocytes on in vitro fertilization and early embryonic development. Biol. Reprod 55:51012–16 [Google Scholar]
  61. Assey RJ, Hyttel P, Greve T, Purwantara B. 61.  1994. Oocyte morphology in dominant and subordinate follicles. Mol. Reprod. Dev. 37:335–44 [Google Scholar]
  62. Albuz FK, Sasseville M, Lane M, Armstrong DT, Thompson JG, Gilchrist RB. 62.  2010. Simulated physiological oocyte maturation (SPOM): a novel in vitro maturation system that substantially improves embryo yield and pregnancy outcomes. Hum. Reprod. 25:2999–3011 [Google Scholar]
  63. Gilchrist RB. 63.  2011. Recent insights into oocyte–follicle cell interactions provide opportunities for the development of new approaches to in vitro maturation. Reprod. Fertil. Dev. 23:23–31 [Google Scholar]
  64. Guimaraes AL, Pereira SA, Leme LO, Dode MA. 64.  2015. Evaluation of the simulated physiological oocyte maturation system for improving bovine in vitro embryo production. Theriogenology 83:52–57 [Google Scholar]
  65. Gilchrist RB, Zeng HT, Wang X, Richani D, Smitz J, Thompson JG. 65.  2015. Reevaluation and evolution of the simulated physiological oocyte maturation system. Theriogenology 84:4656–57 doi: 10.1016/j.theriogenology.2015.03.032 [Google Scholar]
  66. Carolan C, Lonergan P, Khatir H, Mermillod P. 66.  1996. In vitro production of bovine embryos using individual oocytes. Mol. Reprod. Dev. 45:145–50 [Google Scholar]
  67. Ward FA, Lonergan P, Enright BP, Boland MP. 67.  2000. Factors affecting recovery and quality of oocytes for bovine embryo production in vitro using ovum pick-up technology. Theriogenology 54:433–46 [Google Scholar]
  68. Matoba S, Fair T, Lonergan P. 68.  2010. Maturation, fertilisation and culture of bovine oocytes and embryos in an individually identifiable manner: a tool for studying oocyte developmental competence. Reprod. Fertil. Dev. 22:839–51 [Google Scholar]
  69. Bender K, Walsh S, Evans AC, Fair T, Brennan L. 69.  2010. Metabolite concentrations in follicular fluid may explain differences in fertility between heifers and lactating cows. Reproduction 139:1047–55 [Google Scholar]
  70. Leroy JL, Vanholder T, Mateusen B, Christophe A, Opsomer G. 70.  et al. 2005. Non-esterified fatty acids in follicular fluid of dairy cows and their effect on developmental capacity of bovine oocytes in vitro. Reproduction 130:485–95 [Google Scholar]
  71. Holm P, Walker SK, Seamark RF. 71.  1996. Embryo viability, duration of gestation and birth weight in sheep after transfer of in vitro matured and in vitro fertilized zygotes cultured in vitro or in vivo. J. Reprod. Fertil. 107:175–81 [Google Scholar]
  72. Banwell KM, Thompson JG. 72.  2008. In vitro maturation of mammalian oocytes: outcomes and consequences. Semin. Reprod. Med. 26:162–74 [Google Scholar]
  73. Chian RC, Cao YX. 73.  2014. In vitro maturation of immature human oocytes for clinical application. Methods Mol. Biol. 1154:271–88 [Google Scholar]
  74. Buckett WM, Chian RC, Holzer H, Dean N, Usher R, Tan SL. 74.  2007. Obstetric outcomes and congenital abnormalities after in vitro maturation, in vitro fertilization, and intracytoplasmic sperm injection. Obstet. Gynecol. 110:885–91 [Google Scholar]
  75. Mikkelsen AL. 75.  2005. Strategies in human in-vitro maturation and their clinical outcome. Reprod. Biomed. Online 10:593–99 [Google Scholar]
  76. Söderström-Anttila V, Salokorpi T, Pihlaja M, Serenius-Sirve S, Suikkari AM. 76.  2006. Obstetric and perinatal outcome and preliminary results of development of children born after in vitro maturation of oocytes. Hum. Reprod. 21:1508–13 [Google Scholar]
  77. Watkins AJ, Wilkins A, Cunningham C, Perry VH, Seet MJ. 77.  et al. 2008. Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. J. Physiol. 586:2231–44 [Google Scholar]
  78. Eppig JJ, O'Brien MJ, Wigglesworth K, Nicholson A, Zhang W, King BA. 78.  2009. Effect of in vitro maturation of mouse oocytes on the health and lifespan of adult offspring. Hum. Reprod. 24:922–28 [Google Scholar]
  79. Denomme MM, Mann MR. 79.  2012. Genomic imprints as a model for the analysis of epigenetic stability during assisted reproductive technologies. Reproduction 144:393–409 [Google Scholar]
  80. Anckaert E, De Rycke M, Smitz J. 80.  2013. Culture of oocytes and risk of imprinting defects. Hum. Reprod. Update 19:52–66 [Google Scholar]
  81. Anckaert E, Fair T. 81.  2015. DNA methylation reprogramming during oogenesis and interference by reproductive technologies: studies in mouse and bovine models. Reprod. Fertil. Dev. 27:739–54 [Google Scholar]
  82. Heinzmann J, Hansmann T, Herrmann D, Wrenzycki C, Zechner U. 82.  et al. 2011. Epigenetic profile of developmentally important genes in bovine oocytes. Mol. Reprod. Dev. 78:188–201 [Google Scholar]
  83. Colosimo A, Di Rocco G, Curini V, Russo V, Capacchietti G. 83.  et al. 2009. Characterization of the methylation status of five imprinted genes in sheep gametes. Anim. Genet. 40:900–8 [Google Scholar]
  84. Fleming AD, Salgado R, Kuehl TJ. 84.  1985. Maturation of baboon or cow oocytes transplanted into a surrogate dominant follicle in vivo. Theriogenology 23:193 [Google Scholar]
  85. Bergfelt DR, Brogliatti GM, Adams GP. 85.  1998. Gamete recovery and follicular transfer (graft) using transvaginal ultrasonography in cattle. Theriogenology 50:15–25 [Google Scholar]
  86. Carnevale EM, Ginther OJ. 86.  1993. Use of a linear ultrasonic transducer for the transvaginal aspiration and transfer of oocytes in the mare. J. Equine Vet. Sci. 13:331–33 [Google Scholar]
  87. Deleuze S, Goudet G, Caillaud M, Lahuec C, Duchamp G. 87.  2009. Efficiency of embryonic development after intrafollicular and intraoviductal transfer of in vitro and in vivo matured horse oocytes. Theriogenology 72:203–9 [Google Scholar]
  88. Goudet G, Bezard J, Duchamp G, Palmer E. 88.  1997. Transfer of immature oocytes to a preovulatory follicle: An alternative to in vitro maturation in the mare?. Equine Vet. J. Suppl. 29:54–59 [Google Scholar]
  89. Hinrichs K, DiGiorgio LM. 89.  1991. Embryonic development after intra-follicular transfer of horse oocytes. J. Reprod. Fertil. Suppl. 44:369–74 [Google Scholar]
  90. Werner-von der Burg W, Coordes I, Hatzmann W. 90.  1993. Pregnancy following intrafollicular gamete transfer. Hum. Reprod. 8:771–74 [Google Scholar]
  91. Rizos D, Lonergan P, Boland MP, Arroyo-Garcia R, Pintado B. 91.  et al. 2002. Analysis of differential messenger RNA expression between bovine blastocysts produced in different culture systems: implications for blastocyst quality. Biol. Reprod. 66:589–95 [Google Scholar]
  92. Besenfelder U, Havlicek V, Brem G. 92.  2012. Role of the oviduct in early embryo development. Reprod. Domest. Anim. 47:Suppl. 4156–63 [Google Scholar]
  93. Besenfelder U, Havlicek V, Kuzmany A, Brem G. 93.  2010. Endoscopic approaches to manage in vitro and in vivo embryo development: use of the bovine oviduct. Theriogenology 73:768–76 [Google Scholar]
  94. Kassens A, Held E, Salilew-Wondim D, Sieme H, Wrenzycki C. 94.  et al. 2015. Intrafollicular oocyte transfer (IFOT) of abattoir-derived and in vitro-matured oocytes results in viable blastocysts and birth of healthy calves. Biol. Reprod. 92:150 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error