In Vitro Maturation of Oocytes

ABSTRACT

In vitro maturation of oocytes is a safe and effective treatment offered in some fertility centers for assisted reproduction, where immature oocytes are retrieved from unstimulated ovaries. Therefore, the procedure avoids ovarian stimulation with expensive gonadotropins, side effects of the medications, and risks such as ovarian hyperstimulation syndrome. Added advantages are reduced frequency of monitoring scans and shorter treatment regimen compared with in vitro fertilization. The candidates initially considered were women with polycystic ovaries having multiple antral follicles, but the indications are widening to include women with primarily poor quality embryos in repeated cycles and poor responders to stimulation. The two new applications for in vitro maturation we are now successfully implementing at McGill Reproductive Center are for oocyte donors and for fertility preservation, especially in women with cancer who are undergoing gonadotoxic therapy. In young women without partners needing this treatment for fertility preservation, it is combined with vitrification of the oocytes. We have achieved a 38% clinical pregnancy rate per cycle in women having IVM for infertility treatment up to the age of 35 years, and 50% clinical pregnancy rate per cycle in recipients of IVM egg donation.

KEYWORDS

In vitro maturation (IVM) - oocytes - polycystic ovaries - IVF

REFERENCES

• 1 Steptoe P C, Edwards R G. Birth after the reimplantation of a human embryo.  Lancet. 1978;  2 366
• 2 Tan S L, Maconochie N, Doyle P et al.. Cumulative conception and live-birth rates after in vitro fertilization with and without the use of long, short, and ultrashort regimens of the gonadotropin-releasing hormone agonist buserelin.  Am J Obstet Gynecol. 1994;  171 513-520
• 3 Tan S L, Royston P, Campbell S et al.. Cumulative conception and livebirth rates after in-vitro fertilisation.  Lancet. 1992;  339 1390-1394
• 4 Beerendonk C CM, van Dop P A, Braat D DM, Merkus J MWM. Ovarian hyperstimulation syndrome: facts and fiction.  Obstet Gynecol Surv. 1998;  53 439-449
• 5 MacDougall M J, Tan S L, Balen A, Jacob H S. Controlled study comparing patients with and without polycystic ovaries undergoing in-vitro fertilization.  Hum Reprod. 1993;  8 233-237
• 6 Whittemore A S. The risk of ovarian cancer after treatment for infertility.  N Engl J Med. 1994;  331 805-806
• 7 Pincus G, Enzmann E V. The comparative behavior of mammalian eggs in vivo and in vitro, I. The activation of ovarian eggs.  J Exp Med. 1935;  62 655-675
• 8 Edwards R G. Maturation in vitro of human ovarian oocytes.  Lancet. 1965;  2 926-929
• 9 Edwards R G, Bavister B D, Steptoe P C. Early stages of fertilization in vitro of human oocytes matured in vitro.  Nature. 1969;  221 632-635
• 10 Cha K Y, Koo J J, Ko J J, Choi D H, Han S Y, Yoon T K. 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. 1991;  55 109-113
• 11 Trounson A, Wood C, Kausche A. In vitro maturation and the fertilization and developmental competence of oocytes recovered from untreated polycystic ovarian patients.  Fertil Steril. 1994;  62 353-362
• 12 Cha K Y, Chian R C. Maturation in vitro of immature human oocytes for clinical use.  Hum Reprod Update. 1998;  4 103-120
• 13 Gerhart J, Wu M, Kirschner M. Cell cycle dynamics of an M phase specific cytoplasmic factor in Xenopus laevis oocytes and eggs.  J Cell Biol. 1984;  98 1247-1255
• 14 Hashimoto N, Kishimoto T. Regulation of meiotic metaphase by a cytoplasmic maturation promoting factor during mouse oocyte maturation.  Dev Biol. 1988;  126 242-252
• 15 Shibuya E K, Masui Y. Molecular characteristics of cytostatic factors in amphibian eggs extracts.  Development. 1989;  106 799-808
• 16 Smith L C, Olivera-Angel M, Groome N P et al.. Oocyte quality in small antral follicles in the presence or absence of a large dominant follicle in cattle.  J Reprod Fertil. 1996;  106 193-199
• 17 Mikkelsen A L, Lindenberg S. Impact of estradiol and inhibin A concentrations on pregnancy rate in vitro oocyte maturation.  Hum Reprod. 2000;  15 1685-1690
• 18 Chian R C, Chung J T, Downey B F et al.. Maturational and developmental competence of immature oocytes retrieved from ovaries at different phases of folliculogenesis: bovine model study.  Reprod Biomed Online. 2002;  4 127-132
• 19 Abdul Jalil A K, Rezaei N, Chung J T et al.. Effects of vitamins during oocyte maturation on subsequent embryonic development in vitro. Abstract presented at: 48th Annual Meeting of Canadian Fertility and Andrology Society 2002 Charlevoix, Quebec; TP 24
• 20 Chian R C, Buckett W M, Too L et al.. Pregnancies resulting from in vitro matured oocytes retrieved from patients with polycystic ovary syndrome after priming with human chorionic gonadotropin.  Fertil Steril. 1999;  72 639-642
• 21 Chian R C, Abdul Jalil A K, Child T J et al.. Is ICSI essential for in vitro matured human oocytes retrieved from unstimulated women with polycystic ovaries?. Paper presented at: 16th Annual Meeting of the European Society for Human Reproduction and Embryology June 25-28, 2000 Bologna, Italy;
• 22 Child T J, Abdul Jalil A K, Gulekli B, Tan S L. In vitro maturation and fertilization of oocytes from unstimulated normal ovaries, polycystic ovaries and women with polycystic ovary syndrome.  Fertil Steril. 2001;  76 936-942
• 23 Mikkelsen A L, Lindenberg S. Morphology of in vitro matured oocytes: impact on fertility potential and embryo quality.  Hum Reprod. 2001;  16 1714-1718
• 24 Yoon H G, Yoon S H, Son W Y et al.. Pregnancies resulting from in vitro matured oocytes collected from women with regular menstrual cycle.  J Assist Reprod Genet. 2001;  18 325-329
• 25 Tan S L, Child T J, Gulekli B. In vitro maturation and fertilization of oocytes from unstimulated ovaries: predicting the number of immature oocytes retrieved by early follicular phase ultrasonography.  Am J Obstet Gynecol. 2002;  186 684-689
• 26 Mikkelsen A L, Smith S D, Lindenberg S. In vitro maturation of human oocytes from regularly menstruating women may be successful without follicle stimulating hormone priming.  Hum Reprod. 1999;  14 1847-1851
• 27 Trounson A, Anderiesz C, Jones G. Maturation of human oocytes in vitro and their developmental competence.  Reproduction. 2001;  121 51-75
• 28 Paulson R J, Sauer M V, Francis M M et al.. Factors affecting pregnancy success of human in vitro fertilization in unstimulated cycles.  Hum Reprod. 1994;  9 1571-1575
• 29 Thornton M H, Francis M M, Paulson R J. Immature oocyte retrieval: lessons from unstimulated IVF cycles.  Fertil Steril. 1998;  70 647-650
• 30 Chian R C, Buckett W M, Tulandi T et al.. Prospective randomized study of human chorionic gonadotropin priming before immature oocyte retrieval from unstimulated women with polycystic ovarian syndrome.  Hum Reprod. 2000;  15 165-170
• 31 Son W Y, Yoon S H, Lee S W et al.. Blastocyst development and pregnancies after in vitro fertilization of immature oocytes retrieved from unstimulated patients with PCOS after in vitro hCG priming.  Hum Reprod. 2002;  17 134-136
• 32 Albertini D F, Sanfins A, Combelles C. Origins and manifestations of oocyte maturation competencies.  Reprod Biomed Online. 2003;  6 410-415
• 33 Fauser B CJ, Bouchard P, Coelingh J T et al.. Alternative approaches of IVF.  Hum Reprod Update. 2002;  8 1-9
• 34 Mikkelsen A L, Andersson A-M, Skakkebaek N E, Lindenberg S. Basal concentrations of estradiol may predict the outcome of in vitro maturation in regularly menstruating women.  Hum Reprod. 2001;  16 862-876
• 35 Cha K Y, Han S Y, Chung H M et al.. Pregnancies and deliveries after in vitro maturation culture followed by in vitro fertilization and embryo transfer without stimulation in women with polycystic ovary syndrome.  Fertil Steril. 2000;  73 978-983
• 36 Clyde J, Gosden R G, Rutherford A J, Picton H M. Demonstration of a mechanism of aneuploidy in human oocytes using Multifluor fluorescence in situ hybridization.  Fertil Steril. 2001;  76 837-840
• 37 Marquez C, Cohen J, Munne S. Chromosomal identification in human oocytes and polar bodies by spectral karyotyping.  Cytogenet Cell Genet. 1998;  81 254-258
• 38 Janssens R M, Lambalk C B, Vermeiden J P, Schats R, Schoemaker J. In-vitro fertilization in a spontaneous cycle: easy, cheap and realistic.  Hum Reprod. 2000;  15 314-318
• 39 Nargund G, Waterstone J, Bland J, Philips Z, Parsons J, Campbell S. Cumulative conception and live birth rates in natural (unstimulated) IVF cycles.  Hum Reprod. 2001;  16 259-262
• 40 Child T J, Gulekli B, Abdul Jalil A K, Tan S L. In vitro maturation (IVM) of oocytes from unstimulated normal ovaries of women with a previous poor response to IVF.  Fertil Steril. 2000;  74(3 suppl) S45
• 41 Rao G D, Chian R C, Son W S, Gilbert L, Tan S L. Fertility preservation in women undergoing cancer treatment [letter to the editor].  Lancet. 2004;  363-1829