Semin Reprod Med 2005; 23(3): 248-256
DOI: 10.1055/s-2005-872453
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Ovarian Reserve

N. S. Macklon1 , B.C.J. M. Fauser2
  • 1Professor, Head Infertility, Department of Gynaecology and Reproductive Medicine, University Medical Centre, Utrecht, The Netherlands
  • 2Professor, Head, Department of Reproductive Medicine, Chair, Division of Perinatology and Gynecology, University Medical Centre, Utrecht, The Netherlands
Further Information

Publication History

Publication Date:
01 August 2005 (online)

ABSTRACT

The tendency to delay childbirth has increased the importance of ovarian reserve as a determinant of infertility treatment outcome. In the context of assisted reproduction technology, effective strategies to overcome the impact of ovarian aging and diminished ovarian reserve on pregnancy chances remain elusive. Markers of ovarian reserve are increasingly used to aid management and counseling of these patients. Proper interpretation of currently applied hormonal markers, ultrasound parameters, and hormone challenge tests requires an understanding of what constitutes and determines ovarian reserve. This article addresses these aspects and highlights recent developments in the field.

REFERENCES

  • 1 Evers J L. Female subfertility.  Lancet. 2002;  360 151-159
  • 2 Baker T C. A quantitative and cytological study of germ cells in human ovaries.  Proc R Soc Lond Br Biol Sci. 1963;  158 417-433
  • 3 Forabasco A, Sforza C, de Pol A, Vizzotto L, Marzona L. Morphometric study of the human neonatal ovary.  Anat Rec. 1991;  231 201-208
  • 4 Himelstein-Braw R, Byskov A G, Peters H, Faber M. Follicular atresia in the infant human ovary.  J Reprod Fertil. 1976;  46 455-459
  • 5 Faddy M J, Gosden R G, Gougeon A, Richardson S J, Nelson J F. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause.  Hum Reprod. 1992;  7 1342-1346
  • 6 Schwartzman R A, Cidlowski J. Apoptosis: the biochemistry and molecular biology of programmed cell death.  Endocr Rev. 1993;  14 133-151
  • 7 Lintern-Moore S, Peters H, Moore G P, Faber M. Follicular development in the infant human ovary.  J Reprod Fertil. 1974;  39 53-64
  • 8 Johnson J, Canning J, Kaneko T, Pru J K, Tilly J L. Germline stem cells and follicular renewal in the postnatal mammalian ovary.  Nature. 2004;  428 145-150
  • 9 Treloar A E. Menstrual cyclicity and the premenopause.  Maturitas. 1981;  3 49-64
  • 10 Scott R T, Toner J P, Muasher S J, Oehninger S, Robinson S, Rosenwaks Z. Follicle-stimulating hormone levels on cycle day 3 are predictive of in vitro fertilization outcome.  Fertil Steril. 1989;  51 651-654
  • 11 Klein N A, Battaglia D E, Fujimoto V Y. Reproductive aging: accelerated ovarian follicular development associated with a monotropic rise in follicle-stimulating hormone rise in normal older women.  J Clin Endocrinol Metab. 1996;  81 1038-1045
  • 12 te Velde E R, Pearson P L. The variability of female reproductive ageing.  Hum Reprod Update. 2002;  8 141-154
  • 13 Piette C, de Mouzon J, Bachelot A, Spira A. In-vitro fertilization: influence of women's age on pregnancy rates.  Hum Reprod. 1990;  5 56-59
  • 14 Tucker M J, Morton P C, Wright G, Ingargiola P E, Jones A E, Sweitzer C L. Factors affecting success with intracytoplasmic sperm injection.  Reprod Fertil Dev. 1995;  7 229-236
  • 15 Ashkenazi J, Orvieto R, Gold-Deutch R et al.. The impact of woman’s age and sperm parameters on fertilization rates in IVF cycles.  Eur J Obstet Gynecol Reprod Biol. 1996;  66 155-159
  • 16 Yie S M, Collins J A, Daya S, Hughes E, Sagle M, Younglie E V. Polyploidy and failed fertilization in in-vitro fertilization are related to patients age and gamete quality.  Hum Reprod. 1996;  11 614-617
  • 17 Cordiero I, Calhaz-Jorge C, Barata M, Leal F, Proenca H, Coelho A M. Repercussao da idade de mulher, de taxa de clivagem e da qualidade embrionaria, na obtencao de graviez por fertilizacao in-vitro.  Acta Med Port. 1995;  8 145-150
  • 18 Hull M G, Fleming C F, Hughes A O, McDermott A. The age related decline in female fecundity: a quantitative controlled study of implanting capacity and survival of individual embryos after in-vitro fertilization.  Fertil Steril. 1996;  65 783-790
  • 19 Sharif K, Elgendy M, Lashen H, Afnan M. Age and basal follicle stimulating hormone as predictors of in vitro fertilization outcome.  Br J Obstet Gynaecol. 1998;  105 107-112
  • 20 Yaron Y, Botchan A, Amit A et al.. Endometrial receptivity: the age related decline in pregnancy rates and the effect of ovarian function.  Fertil Steril. 1993;  60 314-318
  • 21 Roest J, Van Heusden A M, Mous H, Zeilmaker G H, Verhoeff A. The ovarian response as a predictor for successful in vitro fertilization treatment after the age of 40 years.  Fertil Steril. 1996;  66 969-973
  • 22 Widra E A, Botchan A, Amit A, Kogosowaki A, Yovel I, Lessing J B. Endometrial receptivity: the age-related decline in pregnancy rates and the effect of ovarian function.  Fertil Steril. 1996;  65 103-108
  • 23 Legro R S, Shakleworth D P, Moessner J M, Gnatuk C L, Dodson W C. ART in women 40 and over. Is the cost worth it?.  J Reprod Med. 1997;  42 76-82
  • 24 van Noord-Zaadstra B M, Looman C W, Alsbach H, Habbema J D, te Velde E R, Karbaat J. Delaying childbearing: effect of age on fecundity and outcome of pregnancy.  BMJ. 1991;  302 1361-1365
  • 25 Templeton A A, Morris J K, Parslow W. Factors that affect the outcome of in vitro fertilization treatment.  Lancet. 1996;  348 1402-1406
  • 26 Chuang C C, Chen C D, Chao K H, Chen S U, Ho H N, Yang Y S. Age is a better predictor of pregnancy potential than basal follicle-stimulating hormone levels in women undergoing in vitro fertilization.  Fertil Steril. 2003;  79 63-68
  • 27 Fauser B CJM, Macklon N S. Medical approaches to ovarian stimulation for infertility. In: Strauss JF, Barbieri RL Yen and Jaffe's Reproductive Endocrinology. 5th ed. Philadelphia, PA; Elsevier Saunders 2004: 965-1012
  • 28 de Boer E J, den Tonkelaar I, te Velde E R, Burger C W, Klip H, van Leeuwen F E. A low number of retrieved oocytes at in vitro fertilization treatment is predictive of early menopause.  Fertil Steril. 2002;  77 978-985
  • 29 Nikolaou D, Lavery S, Turner C, Margara R, Trew G. Is there a link between an extremely poor response to ovarian hyperstimulation and early ovarian failure?.  Hum Reprod. 2002;  17 1106-1111
  • 30 Lawson R, El-Toukhy T, Kassab A et al.. Poor response to ovulation induction is a stronger predictor of early menopause than elevated basal FSH: a life table analysis.  Hum Reprod. 2003;  18 527-533
  • 31 Tarlatzis B C, Zepiridis L, Grimbizis G, Bontis J. Clinical management of low ovarian response to stimulation for IVF: a systematic review.  Hum Reprod Update. 2003;  9 61-76
  • 32 Van Hooff M H, Alberda A T, Huisman G J, Zeilmaker G H, Leerentveld R A. Doubling the human menopausal gonadotrophin dose in the course of an in-vitro fertilization treatment cycle in low responders: a randomized study.  Hum Reprod. 1993;  8 369-373
  • 33 Out H J, Braat D D, Lintsen B M et al.. Increasing the daily dose of recombinant follicle stimulating hormone (Puregon) does not compensate for the age-related decline in retrievable oocytes after ovarian stimulation.  Hum Reprod. 2000;  15 29-35
  • 34 Keny S. The poor responed. In: Macklon N NF in One Medically Complicated Patient: A Guide to Management London; Taylor and Francis 2005: 205-219
  • 35 Muasher S J, Oehninger S, Simonetti S et al.. The value of basal and/or stimulated serum gonadotropin levels in prediction of stimulation response and in vitro fertilization outcome.  Fertil Steril. 1988;  50 298-307
  • 36 Toner J P, Philput C B, Jones G S, Muasher S J. Basal follicle-stimulating hormone level is a better predictor of in vitro fertilization performance than age.  Fertil Steril. 1991;  55 784-791
  • 37 Akande V A, Fleming C F, Hunt L P, Keay S D, Jenkins J M. Biological versus chronological ageing in oocytes, distinguishable by raised FSH levels in relation to the success of IVF treatment.  Hum Reprod. 2002;  17 2003-2008
  • 38 van Rooij I A, Bancsi L F, Broekmans F J, Looman C W, Habbema J D, te Velde E R. Women older than 40 years of age and those with elevated follicle-stimulating hormone levels differ in poor response rate and embryo quality in in vitro fertilization.  Fertil Steril. 2003;  79 482-488
  • 39 Toner J P. Modest follicle-stimulating hormone elevations in younger women: warn but don’t disqualify.  Fertil Steril. 2004;  81 1493-1495
  • 40 Scott Jr R T, Hofmann G E. Prognostic assessment of ovarian reserve.  Fertil Steril. 1995;  63 1-11
  • 41 Bancsi L F, Broekmans F J, Mol B W, Habbema J D, te Velde E R. Performance of basal follicle-stimulating hormone in the prediction of poor ovarian response and failure to become pregnant after in vitro fertilization: a meta-analysis.  Fertil Steril. 2003;  79 1091-1100
  • 42 van Rooij I AJ, de Jong E, Broekmans F JM et al.. High follicle-stimulating hormone levels should not necessarily lead to the exclusion of subfertile patients from treatment.  Fertil Steril. 2004;  81 1478-1485
  • 43 Schipper I, de Jong F H, Fauser BCJM. Lack of correlation between maximum early follicular phase serum follicle-stimulating hormone levels and menstrual cycle characteristics in women under the age of 35.  Hum Reprod. 1998;  13 1442-1448
  • 44 Martin JSB, Nisker J A, Tummon I S et al.. Future in vitro fertilization pregnancy potential of women with variable elevated day 3 follicle-stimulating hormone levels.  Fertil Steril. 1996;  65 1238-1240
  • 45 Scott R T, Hofmann G E, Oehninger S C, Muasher S J. Intercycle variability of day 3 follicle-stimulating hormone levels and its effect on stimulation quality in in vitro fertilization.  Fertil Steril. 1990;  54 297-302
  • 46 Evers J L, Slaats P, Land J A, Dumoulin J C, Dunselman G A. Elevated levels of basal estradiol-17 beta predict poor response in patients with normal basal levels of follicle-stimulating hormone undergoing in vitro fertilization.  Fertil Steril. 1998;  69 1010-1014
  • 47 Lockwood G M. Prognostic tests of ovarian reserve. In: Gardner DK, Weissman A, Howles CM, Shoham Z Textbook of Assisted Reproductive Techniques. 2nd ed. London; Taylor and Francis 2004: 781-787
  • 48 Groome N P, Illingworth P J, O'Brien M et al.. Measurement of dimeric inhibin B throughout the human menstrual cycle.  J Clin Endocrinol Metab. 1996;  81 1401-1405
  • 49 Creus M, Penarrubia J, Fabregues F et al.. Day 3 serum inhibin B and FSH and age as predictors of assisted reproduction treatment outcome.  Hum Reprod. 2000;  15 2341-2346
  • 50 Yong P Y, Baird D T, Thong K J, McNeilly A S, Anderson R A. Prospective analysis of the relationships between the ovarian follicle cohort and basal FSH concentration, the inhibin response to exogenous FSH and ovarian follicle number at different stages of the normal menstrual cycle and after pituitary down-regulation.  Hum Reprod. 2003;  18 35-44
  • 51 Klein N A, Illingworth P J, Groome N P, McNeilly A S, Battaglia D E, Soules M R. Decreased inhibin B secretion is associated with the monotropic FSH rise in older, ovulatory women: a study of serum and follicular fluid levels of dimeric inhibin A and B in spontaneous menstrual cycles.  J Clin Endocrinol Metab. 1996;  81 2742-2745
  • 52 Seifer D B, Lambert-Messerlian G, Hogan J W, Gardiner A C, Blazar A S, Berk C A. Day 3 serum inhibin-B is predictive of assisted reproductive technologies outcome.  Fertil Steril. 1997;  67 110-114
  • 53 Seifer D B, Scott Jr R T, Bergh P A et al.. Women with declining ovarian reserve may demonstrate a decrease in day 3 serum inhibin B before a rise in day 3 follicle-stimulating hormone.  Fertil Steril. 1999;  72 63-65
  • 54 Hall J E, Welt C K, Cramer D W. Inhibin A and inhibin B reflect ovarian function in assisted reproduction but are less useful at predicting outcome.  Hum Reprod. 1999;  14 409-415
  • 55 Corson S L, Gutmann J, Batzer F R, Wallace H, Klein N, Soules M R. Inhibin-B as a test of ovarian reserve for infertile women.  Hum Reprod. 1999;  14 2818-2821
  • 56 Penarrubia J, Balasch J, Fabregues F et al.. Day 5 inhibin B serum concentrations as predictors of assisted reproductive technology outcome in cycles stimulated with gonadotrophin-releasing hormone agonist-gonadotrophin treatment.  Hum Reprod. 2000;  15 1499-1504
  • 57 Fawzy M, Lambert A, Harrison R F et al.. Day 5 inhibin B levels in a treatment cycle are predictive of IVF outcome.  Hum Reprod. 2002;  17 1535-1543
  • 58 Bancsi L F, Broekmans F J, Eijkemans M J, de Jong F H, Habbema J D, te Velde E R. Predictors of poor ovarian response in in vitro fertilization: a prospective study comparing basal markers of ovarian reserve.  Fertil Steril. 2002;  77 328-336
  • 59 Reuss M L, Kline J, Santos R. Age and the ovarian follicle pool assessed with transvaginal ultrasonography.  Am J Obstet Gynecol. 1996;  174 624-627
  • 60 Fratterelli J L, Levi A J, Miller B T, Segars J H. A prospective assessment of the predictive value of basal antral follicles in in vitro fertilization cycles.  Fertil Steril. 2003;  80 350-355
  • 61 Andolf A, Jorgensen C, Svalenius E et al.. Ultrasound measurement of the ovarian volume.  Acta Obstet Gynecol Scand. 1987;  66 387-389
  • 62 Syrop C H, Willhoite A, van Voorhuis B J. Ovarian volume: a novel outcome predictor for assisted reproduction.  Fertil Steril. 1995;  64 1167-1171
  • 63 Lass A, Skull J, McVeigh E, Margara R, Winston R M. Measurement of ovarian volume by transvaginal sonography before ovulation induction with human menopausal gonadotrophin for in-vitro fertilization can predict poor response.  Hum Reprod. 1997;  12 294-297
  • 64 Syrop C H, Dawson J D, Husman K J et al.. Ovarian volume may predict assisted reproductive outcomes better than follicle stimulating hormone concentration on day 3.  Hum Reprod. 1999;  14 1752-1756
  • 65 Navot D, Rosenwaks Z, Mergalioth E J. Prognostic assessment of female fecundity.  Lancet. 1987;  2 645-647
  • 66 Bukman A, Heineman M J. Ovarian reserve testing and the use of prognostic models in patients with subfertility.  Hum Reprod Update. 2001;  7 581-590
  • 67 Sharara F I, Scott R T, Seifer D B. The detection of diminished ovarian reserve in infertile women.  Am J Obstet Gynecol. 1998;  179 804-812
  • 68 Jain T, Soules M R, Collins J. Comparison of basal follicle-stimulating hormone versus the clomiphene citrate challenge test for ovarian reserve screening.  Fertil Steril. 2004;  82 180-185
  • 69 Fanchin R, de Ziegler D, Olivennes F et al.. Exogenous follicle stimulating hormone ovarian reserve test (EFORT): a simple and reliable screening test for detecting ‘poor responders’ in in-vitro fertilization.  Hum Reprod. 1994;  9 1607-1611
  • 70 Kwee J, Schats R, McDonnell J, Lambalk C B, Schoemaker J. Intercycle variability of ovarian reserve tests: results of a prospective randomized study.  Hum Reprod. 2004;  19 590-595
  • 71 Padilla S L, Bayati J, Garcia J E. Prognostic value of the early serum estradiol response to leuprolide acetate in in vitro fertilization.  Fertil Steril. 1990;  53 288-294
  • 72 De Vet A, Laven J S, de Jong F H, Themmen A P, Fauser B C. Anti-mullerian hormone serum hormone levels: a putative marker for ovarian aging.  Fertil Steril. 2002;  77 357-362
  • 73 Fanchin R, Schonauer L M, Righini C, Guibourdenche J, Frydman R, Taieb J. Serum anti-mullerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3.  Hum Reprod. 2003;  18 323-327
  • 74 Seifer D B, MacLaughlin D T, Christian B P, Feng B, Shelden R M. Early follicular serum mullerian-inhibiting levels are associated with ovarian response during assisted reproductive technology cycles.  Fertil Steril. 2002;  77 468-471
  • 75 van Rooij I A, Broekmans F J, te Velde E R et al.. Serum anti-mullerian hormone levels: a novel measure of ovarian reserve.  Hum Reprod. 2002;  17 3065-3071
  • 76 Beckers N G, Macklon N S, Eijkemans M J, Fauser B C. Women with regular menstrual cycles and a poor response to ovarian hyperstimulation for in vitro fertilization exhibit follicular phase characteristics suggestive of ovarian aging.  Fertil Steril. 2002;  78 291-297
  • 77 Hohmann F P, Macklon N S, Fauser B C. A randomized comparison of two ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) cotreatment for in vitro fertilization commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the standard longGnRH agonist protocol.  J Clin Endocrinol Metab. 2003;  88 166-173
  • 78 Bath L E, Wallace W H, Shaw M P, Fitzpatrick C, Anderson R A. Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-mullerian hormone, inhibin B and ovarian ultrasound.  Hum Reprod. 2003;  18 2368-2374

 Prof.
N. S Macklon

Department of Gynecology and Reproductive Medicine, University Medical Centre

Utrecht, Heidelberglaan 100

3584 CX Utrecht, The Netherlands

Email: n.macklon@umcutrecht

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