Biomarkers of Ovarian Reserve in Women with Polycystic Ovary Syndrome

 

 Buy Article Permissions and Reprints

Abstract

Recent years have seen an acceleration of research on biomarkers of ovarian reserve, with most inquiries targeted toward what these markers tell us about fertility and the reproductive lifespan. However, in the patient with polycystic ovarian syndrome (PCOS), ovarian reserve markers may provide information about the condition itself. This review will consider the use of common markers of functional ovarian reserve, including antral follicle count, ovarian volume, and anti-Müllerian hormone in the PCOS population for the purposes of diagnosing PCOS, characterizing the PCOS phenotype, and predicting response to fertility treatment.

• References

• 1 Duijkers IJ, Klipping C. Polycystic ovaries, as defined by the 2003 Rotterdam consensus criteria, are found to be very common in young healthy women. Gynecol Endocrinol 2010; 26: 152-160
  CrossrefPubMedGoogle Scholar
• 2 Johnstone EB, Rosen MP, Neril R , et al. The polycystic ovary post-rotterdam: a common, age-dependent finding in ovulatory women without metabolic significance. J Clin Endocrinol Metab 2010; 95: 4965-4972
  CrossrefPubMedGoogle Scholar
• 3 Jonard S, Robert Y, Cortet-Rudelli C , et al. Ultrasound examination of polycystic ovaries: is it worth counting the follicles?. Hum Reprod 2003; 18: 598-603
  CrossrefPubMedGoogle Scholar
• 4 Koivunen R, Laatikainen T, Tomas C , et al. The prevalence of polycystic ovaries in healthy women. Acta Obstet Gynecol Scand 1999; 78: 137-141
  CrossrefPubMedGoogle Scholar
• 5 Kristensen SL, Ramlau-Hansen CH, Ernst E , et al. A very large proportion of young Danish women have polycystic ovaries: is a revision of the Rotterdam criteria needed?. Human Reproduction 2010; 25: 3117-3122
  CrossrefPubMedGoogle Scholar
• 6 Broekmans FJ, Kwee J, Hendriks DJ, Mol BW, Lambalk CB. A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Update 2006; 12 (6) 685-718
  CrossrefPubMedGoogle Scholar
• 7 Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab 1998; 83 (9) 3078-3082
  CrossrefPubMedGoogle Scholar
• 8 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18 (6) 774-800
  CrossrefPubMedGoogle Scholar
• 9 Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999; 84 (1) 165-169
  CrossrefPubMedGoogle Scholar
• 10 Hansen KR, Hodnett GM, Knowlton N, Craig LB. Correlation of ovarian reserve tests with histologically determined primordial follicle number. Fertil Steril 2011; 95 (1) 170-175
  CrossrefPubMedGoogle Scholar
• 11 Rebar R, Judd HL, Yen SS, Rakoff J, Vandenberg G, Naftolin F. Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. J Clin Invest 1976; 57 (5) 1320-1329
  CrossrefPubMedGoogle Scholar
• 12 Lobo RA. Disturbances of androgen secretion and metabolism in polycystic ovary syndrome. Clin Obstet Gynaecol 1985; 12 (3) 633-647
  PubMedGoogle Scholar
• 13 Porter MB. Polycystic ovary syndrome: the controversy of diagnosis by ultrasound. Semin Reprod Med 2008; 26 (3) 241-251
  Article in Thieme ConnectPubMedGoogle Scholar
• 14 Adams J, Franks S, Polson DW , et al. Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet 1985; 2 (8469-70) 1375-1379
  PubMedGoogle Scholar
• 15 Zawadski J, Dunaif A. Diagnostic Criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens J, Haseltine F, , eds. Polycystic Ovary Syndrome. Boston, MA: Blackwell Scientific; 1992: 377-384
  Google Scholar
• 16 Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19 (1) 41-47
  CrossrefPubMedGoogle Scholar
• 17 Balen AH, Laven JS, Tan SL, Dewailly D. Ultrasound assessment of the polycystic ovary: international consensus definitions. Hum Reprod Update 2003; 9 (6) 505-514
  CrossrefPubMedGoogle Scholar
• 18 Dewailly D. Androgen excess in women: not just a cosmetic problem. Ann Endocrinol (Paris) 2010; 71 (1) 1
  CrossrefPubMedGoogle Scholar
• 19 Azziz R. Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: the Rotterdam criteria are premature. J Clin Endocrinol Metab 2006; 91 (3) 781-785
  CrossrefPubMedGoogle Scholar
• 20 Johnstone EB, Rosen MP, Neril R , et al. The polycystic ovary post-Rotterdam: a common, age-dependent finding in ovulatory women without metabolic significance. J Clin Endocrinol Metab 2010; 95 (11) 4965-4972
  CrossrefPubMedGoogle Scholar
• 21 Lujan ME, Jarrett BY, Brooks ED , et al. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Hum Reprod 2013; 28 (5) 1361-1368
  CrossrefPubMedGoogle Scholar
• 22 Duijkers IJ, Klipping C. Polycystic ovaries, as defined by the 2003 Rotterdam consensus criteria, are found to be very common in young healthy women. Gynecol Endocrinol 2010; 26 (3) 152-160
  CrossrefPubMedGoogle Scholar
• 23 Koivunen R, Laatikainen T, Tomás C, Huhtaniemi I, Tapanainen J, Martikainen H. The prevalence of polycystic ovaries in healthy women. Acta Obstet Gynecol Scand 1999; 78 (2) 137-141
  CrossrefPubMedGoogle Scholar
• 24 Kristensen SL, Ramlau-Hansen CH, Ernst E , et al. A very large proportion of young Danish women have polycystic ovaries: is a revision of the Rotterdam criteria needed?. Hum Reprod 2010; 25 (12) 3117-3122
  CrossrefPubMedGoogle Scholar
• 25 Dewailly D, Gronier H, Poncelet E , et al. Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries. Hum Reprod 2011; 26 (11) 3123-3129
  CrossrefPubMedGoogle Scholar
• 26 Johnstone EB, Davis G, Zane LT, Cedars MI, Huddleston HG. Age-related differences in the reproductive and metabolic implications of polycystic ovarian syndrome: findings in an obese, United States population. Gynecol Endocrinol 2012; 28 (10) 819-822
  CrossrefPubMedGoogle Scholar
• 27 Alsamarai S, Adams JM, Murphy MK , et al. Criteria for polycystic ovarian morphology in polycystic ovary syndrome as a function of age. J Clin Endocrinol Metab 2009; 94 (12) 4961-4970
  CrossrefPubMedGoogle Scholar
• 28 Rosen MP, Johnstone E, McCulloch CE , et al. A characterization of the relationship of ovarian reserve markers with age. Fertil Steril 2012; 97 (1) 238-243
  CrossrefPubMedGoogle Scholar
• 29 Bili H, Laven J, Imani B, Eijkemans MJ, Fauser BC. Age-related differences in features associated with polycystic ovary syndrome in normogonadotrophic oligo-amenorrhoeic infertile women of reproductive years. Eur J Endocrinol 2001; 145 (6) 749-755
  CrossrefPubMedGoogle Scholar
• 30 Elting MW, Kwee J, Korsen TJ, Rekers-Mombarg LT, Schoemaker J. Aging women with polycystic ovary syndrome who achieve regular menstrual cycles have a smaller follicle cohort than those who continue to have irregular cycles. Fertil Steril 2003; 79 (5) 1154-1160
  CrossrefPubMedGoogle Scholar
• 31 Pigny P, Jonard S, Robert Y, Dewailly D. Serum anti-Mullerian hormone as a surrogate for antral follicle count for definition of the polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91 (3) 941-945
  CrossrefPubMedGoogle Scholar
• 32 Dewailly D, Catteau-Jonard S, Reyss AC, Maunoury-Lefebvre C, Poncelet E, Pigny P. The excess in 2-5 mm follicles seen at ovarian ultrasonography is tightly associated to the follicular arrest of the polycystic ovary syndrome. Hum Reprod 2007; 22 (6) 1562-1566
  CrossrefPubMedGoogle Scholar
• 33 Hahn S, Bering van Halteren W, Roesler S , et al. The combination of increased ovarian volume and follicle number is associated with more severe hyperandrogenism in German women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2006; 114 (4) 175-181
  Article in Thieme ConnectPubMedGoogle Scholar
• 34 Pache TD, de Jong FH, Hop WC, Fauser BC. Association between ovarian changes assessed by transvaginal sonography and clinical and endocrine signs of the polycystic ovary syndrome. Fertil Steril 1993; 59 (3) 544-549
  PubMedGoogle Scholar
• 35 Legro RS, Chiu P, Kunselman AR, Bentley CM, Dodson WC, Dunaif A. Polycystic ovaries are common in women with hyperandrogenic chronic anovulation but do not predict metabolic or reproductive phenotype. J Clin Endocrinol Metab 2005; 90 (5) 2571-2579
  CrossrefPubMedGoogle Scholar
• 36 Pittenger SR, Kao CN, Pasch LA , et al. Ovarian morphology is associated with insulin resistance: can ovarian volume identify women with metabolic risk in polycystic ovary syndrome?. Fertil Steril 2012; 98: S84
  PubMedGoogle Scholar
• 37 Broer SL, Dólleman M, Opmeer BC, Fauser BC, Mol BW, Broekmans FJ. AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Hum Reprod Update 2011; 17 (1) 46-54
  CrossrefPubMedGoogle Scholar
• 38 Fulghesu AM, Ciampelli M, Belosi C, Apa R, Pavone V, Lanzone A. A new ultrasound criterion for the diagnosis of polycystic ovary syndrome: the ovarian stroma/total area ratio. Fertil Steril 2001; 76 (2) 326-331
  CrossrefPubMedGoogle Scholar
• 39 Jonard S, Robert Y, Dewailly D. Revisiting the ovarian volume as a diagnostic criterion for polycystic ovaries. Hum Reprod 2005; 20 (10) 2893-2898
  CrossrefPubMedGoogle Scholar
• 40 Lujan ME, Jarrett BY, Brooks ED , et al. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Hum Reprod 2013; 28 (5) 1361-1368
  CrossrefPubMedGoogle Scholar
• 41 Chen Y, Li L, Chen X , et al. Ovarian volume and follicle number in the diagnosis of polycystic ovary syndrome in Chinese women. Ultrasound Obstet Gynecol 2008; 32 (5) 700-703
  CrossrefPubMedGoogle Scholar
• 42 Carmina E, Orio F, Palomba S, Longo RA, Lombardi G, Lobo RA. Ovarian size and blood flow in women with polycystic ovary syndrome and their correlations with endocrine parameters. Fertil Steril 2005; 84 (2) 413-419
  CrossrefPubMedGoogle Scholar
• 43 Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC. Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab 1999; 84 (5) 1617-1622
  CrossrefPubMedGoogle Scholar
• 44 Nyboe Andersen A, Balen AH, Platteau P, Pettersson G, Arce JC. Prestimulation parameters predicting live birth in anovulatory WHO Group II patients undergoing ovulation induction with gonadotrophins. Hum Reprod 2010; 25 (8) 1988-1995
  CrossrefPubMedGoogle Scholar
• 45 Zhang H, Legro RS, Zhang J , et al; Reproductive Medicine Network. Decision trees for identifying predictors of treatment effectiveness in clinical trials and its application to ovulation in a study of women with polycystic ovary syndrome. Hum Reprod 2010; 25 (10) 2612-2621
  CrossrefPubMedGoogle Scholar
• 46 Picard JY, Belville C. Genetics and molecular pathology of anti-Mullerian hormone and its receptor [in French]. J Soc Biol 2002; 196 (3) 217-221
  PubMedGoogle Scholar
• 47 Weenen C, Laven JS, Von Bergh AR , et al. Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 2004; 10 (2) 77-83
  CrossrefPubMedGoogle Scholar
• 48 Laven JS, Mulders AG, Visser JA, Themmen AP, De Jong FH, Fauser BC. Anti-Müllerian hormone serum concentrations in normoovulatory and anovulatory women of reproductive age. J Clin Endocrinol Metab 2004; 89 (1) 318-323
  CrossrefPubMedGoogle Scholar
• 49 van Rooij IA, Broekmans FJ, te Velde ER , et al. Serum anti-Müllerian hormone levels: a novel measure of ovarian reserve. Hum Reprod 2002; 17 (12) 3065-3071
  CrossrefPubMedGoogle Scholar
• 50 Nelson SM, Anderson RA, Broekmans FJ, Raine-Fenning N, Fleming R, La Marca A. Anti-Müllerian hormone: clairvoyance or crystal clear?. Hum Reprod 2012; 27 (3) 631-636
  CrossrefPubMedGoogle Scholar
• 51 Aksglaede L, Sørensen K, Boas M , et al. Changes in anti-Müllerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years. J Clin Endocrinol Metab 2010; 95 (12) 5357-5364
  CrossrefPubMedGoogle Scholar
• 52 Bentzen JG, Forman JL, Johannsen TH, Pinborg A, Larsen EC, Andersen AN. Ovarian antral follicle subclasses and anti-mullerian hormone during normal reproductive aging. J Clin Endocrinol Metab 2013; 98 (4) 1602-1611
  CrossrefPubMedGoogle Scholar
• 53 La Marca A, Sighinolfi G, Radi D , et al. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update 2010; 16 (2) 113-130
  CrossrefPubMedGoogle Scholar
• 54 Gleicher N, Weghofer A, Barad DH. Anti-Müllerian hormone (AMH) defines, independent of age, low versus good live-birth chances in women with severely diminished ovarian reserve. Fertil Steril 2010; 94 (7) 2824-2827
  CrossrefPubMedGoogle Scholar
• 55 Fallat ME, Siow Y, Marra M, Cook C, Carrillo A. Müllerian-inhibiting substance in follicular fluid and serum: a comparison of patients with tubal factor infertility, polycystic ovary syndrome, and endometriosis. Fertil Steril 1997; 67 (5) 962-965
  CrossrefPubMedGoogle Scholar
• 56 Nardo LG, Yates AP, Roberts SA, Pemberton P, Laing I. The relationships between AMH, androgens, insulin resistance and basal ovarian follicular status in non-obese subfertile women with and without polycystic ovary syndrome. Hum Reprod 2009; 24 (11) 2917-2923
  CrossrefPubMedGoogle Scholar
• 57 Pellatt L, Hanna L, Brincat M , et al. Granulosa cell production of anti-Müllerian hormone is increased in polycystic ovaries. J Clin Endocrinol Metab 2007; 92 (1) 240-245
  CrossrefPubMedGoogle Scholar
• 58 Catteau-Jonard S, Jamin SP, Leclerc A, Gonzalès J, Dewailly D, di Clemente N. Anti-Mullerian hormone, its receptor, FSH receptor, and androgen receptor genes are overexpressed by granulosa cells from stimulated follicles in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93 (11) 4456-4461
  CrossrefPubMedGoogle Scholar
• 59 di Clemente N, Josso N, Gouédard L, Belville C. Components of the anti-Müllerian hormone signaling pathway in gonads. Mol Cell Endocrinol 2003; 211 (1–2) 9-14
  CrossrefPubMedGoogle Scholar
• 60 Pigny P, Merlen E, Robert Y , et al. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab 2003; 88 (12) 5957-5962
  CrossrefPubMedGoogle Scholar
• 61 Carlsen SM, Vanky E, Fleming R. Anti-Müllerian hormone concentrations in androgen-suppressed women with polycystic ovary syndrome. Hum Reprod 2009; 24 (7) 1732-1738
  CrossrefPubMedGoogle Scholar
• 62 La Marca A, Orvieto R, Giulini S, Jasonni VM, Volpe A, De Leo V. Mullerian-inhibiting substance in women with polycystic ovary syndrome: relationship with hormonal and metabolic characteristics. Fertil Steril 2004; 82 (4) 970-972
  CrossrefPubMedGoogle Scholar
• 63 Fleming R, Harborne L, MacLaughlin DT , et al. Metformin reduces serum mullerian-inhibiting substance levels in women with polycystic ovary syndrome after protracted treatment. Fertil Steril 2005; 83 (1) 130-136
  CrossrefPubMedGoogle Scholar
• 64 Bayrak A, Terbell H, Urwitz-Lane R, Mor E, Stanczyk FZ, Paulson RJ. Acute effects of metformin therapy include improvement of insulin resistance and ovarian morphology. Fertil Steril 2007; 87 (4) 870-875
  CrossrefPubMedGoogle Scholar
• 65 Eilertsen TB, Vanky E, Carlsen SM. Anti-Mullerian hormone in the diagnosis of polycystic ovary syndrome: can morphologic description be replaced?. Hum Reprod 2012; 27 (8) 2494-2502
  CrossrefPubMedGoogle Scholar
• 66 Homburg R, Ray A, Bhide P , et al. The relationship of serum anti-Mullerian hormone with polycystic ovarian morphology and polycystic ovary syndrome: a prospective cohort study. Hum Reprod 2013; 28 (4) 1077-1083
  CrossrefPubMedGoogle Scholar
• 67 Piouka A, Farmakiotis D, Katsikis I , et al; Anti-Mullerian hormone levels reflect severity of PCOS but are negatively influenced by obestity: relationship with increased luteinizing hormone levels. Am J Physiol Endocrinol Metab 2009; 296: E238-243
  PubMedGoogle Scholar
• 68 Hart R, Doherty DA, Norman RJ , et al. Serum antimullerian hormone (AMH) levels are elevated in adolescent girls with polycystic ovaries and the polycystic ovarian syndrome (PCOS). Fertil Steril 2010; 94 (3) 1118-1121
  CrossrefPubMedGoogle Scholar
• 69 Li L, Chen X, Mo Y, Chen Y, Wenig M, Yang D. Elevated serum anti-mullerian hormone in adolescent and young adult Chinese patients with polycystic ovary syndrome. Wien Klin Wochenschr 2010; 122 (17–18) 519-524
  CrossrefPubMedGoogle Scholar
• 70 Pawelczak M, Kenigsberg L, Milla S, Liu YH, Shah B. Elevated serum anti-Müllerian hormone in adolescents with polycystic ovary syndrome: relationship to ultrasound features. J Pediatr Endocrinol Metab 2012; 25 (9-10) 983-989
  PubMedGoogle Scholar
• 71 Lie Fong S, Visser JA, Welt CK , et al. Serum anti-müllerian hormone levels in healthy females: a nomogram ranging from infancy to adulthood. J Clin Endocrinol Metab 2012; 97 (12) 4650-4655
  CrossrefPubMedGoogle Scholar
• 72 Kelsey TW, Wright P, Nelson SM, Anderson RA, Wallace WH. A validated model of serum anti-müllerian hormone from conception to menopause. PLoS ONE 2011; 6 (7) e22024
  CrossrefPubMedGoogle Scholar
• 73 Piouka A, Farmakiotis D, Katsikis I, Macut D, Gerou S, Panidis D. Anti-Mullerian hormone levels reflect severity of PCOS but are negatively influenced by obesity: relationship with increased luteinizing hormone levels. Am J Physiol Endocrinol Metab 2009; 296 (2) E238-E243
  PubMedGoogle Scholar
• 74 Lamb JD, Johnstone EB, Rousseau JA , et al. Physical activity in women with polycystic ovary syndrome: prevalence, predictors, and positive health associations. Am J Obstet Gynecol 2011; 204 (4) e1-e6
  PubMedGoogle Scholar
• 75 Norman RJ, Homan G, Moran L, Noakes M. Lifestyle choices, diet, and insulin sensitizers in polycystic ovary syndrome. Endocrine 2006; 30 (1) 35-43
  CrossrefPubMedGoogle Scholar
• 76 Moran LJ, Noakes M, Clifton PM, Norman RJ. The use of anti-mullerian hormone in predicting menstrual response after weight loss in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab 2007; 92 (10) 3796-3802
  CrossrefPubMedGoogle Scholar
• 77 Thomson RL, Buckley JD, Moran LJ , et al. The effect of weight loss on anti-Müllerian hormone levels in overweight and obese women with polycystic ovary syndrome and reproductive impairment. Hum Reprod 2009; 24 (8) 1976-1981
  CrossrefPubMedGoogle Scholar
• 78 Yates AP, Roberts SA, Nardo LG. Anti-Müllerian hormone-tailored stimulation protocols improve outcomes whilst reducing adverse effects and costs of IVF. Hum Reprod 2012; 27 (2) 629
  CrossrefPubMedGoogle Scholar
• 79 Wang JG, Douglas NC, Nakhuda GS , et al. The association between anti-Müllerian hormone and IVF pregnancy outcomes is influenced by age. Reprod Biomed Online 2010; 21 (6) 757-761
  CrossrefPubMedGoogle Scholar
• 80 Bhide P, Gudi A, Shah A, Timms P, Grayson K, Homburg R. Anti-Müllerian hormone as a predictor of pregnancy following IVF. Reprod Biomed Online 2013; 26 (3) 247-252
  CrossrefPubMedGoogle Scholar
• 81 Xi W, Gong F, Lu G. Correlation of serum Anti-Müllerian hormone concentrations on day 3 of the in vitro fertilization stimulation cycle with assisted reproduction outcome in polycystic ovary syndrome patients. J Assist Reprod Genet 2012; 29 (5) 397-402
  CrossrefPubMedGoogle Scholar
• 82 Kaya C, Pabuccu R, Satıroglu H. Serum antimüllerian hormone concentrations on day 3 of the in vitro fertilization stimulation cycle are predictive of the fertilization, implantation, and pregnancy in polycystic ovary syndrome patients undergoing assisted reproduction. Fertil Steril 2010; 94 (6) 2202-2207
  CrossrefPubMedGoogle Scholar
• 83 Lee TH, Liu CH, Huang CC , et al. Serum anti-Müllerian hormone and estradiol levels as predictors of ovarian hyperstimulation syndrome in assisted reproduction technology cycles. Hum Reprod 2008; 23 (1) 160-167
  CrossrefPubMedGoogle Scholar
• 84 Nelson SM, Yates RW, Fleming R. Serum anti-Müllerian hormone and FSH: prediction of live birth and extremes of response in stimulated cycles—implications for individualization of therapy. Hum Reprod 2007; 22 (9) 2414-2421
  CrossrefPubMedGoogle Scholar