Biomarkers of Ovarian Reserve as Predictors of Reproductive Potential

Anne Z. Steiner

doi:10.1055/s-0033-1356479

Seminars in Reproductive Medicine, Table of Contents

Semin Reprod Med 2013; 31(06): 437-442
DOI: 10.1055/s-0033-1356479

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Biomarkers of Ovarian Reserve as Predictors of Reproductive Potential

Anne Z. Steiner

¹Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina

› Author Affiliations

Abstract

The size of the oocyte pool, the ovarian reserve, can determine a woman's reproductive stage. Chronologic age, anti-Müllerian hormone (AMH) levels, early follicular phase follicle-stimulating hormone levels, and early follicular phase inhibin B levels are correlated with ovarian reserve. Therefore, these biomarkers of ovarian reserve should serve as predictors of reproductive potential. Clinical and epidemiologic studies suggest that historical and laboratory biomarkers of ovarian reserve are associated with natural and treatment-related fertility. However, controversy remains as to their ability to predict reproductive potential. For infertile women undergoing assisted reproductive technology treatment, these biomarkers tend to be highly specific but not sensitive for cycle failure (nonpregnancy). While these biomarkers are being used as “fertility tests” in the general population, their value as predictors of unassisted fertility is still uncertain. Among laboratory biomarkers, AMH appears to have the most promise; however, further studies are needed to refine cutoff values and to determine test characteristics in the prediction of natural fertility or infertility in the general population.

Keywords

biomarkers - ovarian reserve - fertility

Full Text

References

References
1 Hansen KR, Craig LB, Zavy MT, Klein NA, Soules MR. Ovarian primordial and nongrowing follicle counts according to the Stages of Reproductive Aging Workshop (STRAW) staging system. Menopause 2012; 19 (2) 164-171
2 Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod 1992; 7 (10) 1342-1346
3 Gracia CR, Sammel MD, Freeman EW , et al. Defining menopause status: creation of a new definition to identify the early changes of the menopausal transition. Menopause 2005; 12 (2) 128-135
4 Randolph Jr JF, Sowers M, Bondarenko IV, Harlow SD, Luborsky JL, Little RJ. Change in estradiol and follicle-stimulating hormone across the early menopausal transition: effects of ethnicity and age. J Clin Endocrinol Metab 2004; 89 (4) 1555-1561
5 Gnoth C, Schuring AN, Friol K, Tigges J, Mallmann P, Godehardt E. Relevance of anti-Mullerian hormone measurement in a routine IVF program. Hum Reprod 2008; 23 (6) 1359-1365
6 Broer SL, van Disseldorp J, Broeze KA , et al; IMPORT study group. Added value of ovarian reserve testing on patient characteristics in the prediction of ovarian response and ongoing pregnancy: an individual patient data approach. Hum Reprod Update 2013; 19 (1) 26-36
7 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
8 Tremellen KP, Kolo M, Gilmore A, Lekamge DN. Anti-mullerian hormone as a marker of ovarian reserve. Aust N Z J Obstet Gynaecol 2005; 45 (1) 20-24
9 Hansen KR, Knowlton NS, Thyer AC, Charleston JS, Soules MR, Klein NA. A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause. Hum Reprod 2008; 23 (3) 699-708
10 van Rooij IA, Broekmans FJ, Scheffer GJ , et al. Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study. Fertil Steril 2005; 83 (4) 979-987
11 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
12 Gold EB, Bromberger J, Crawford S , et al. Factors associated with age at natural menopause in a multiethnic sample of midlife women. Am J Epidemiol 2001; 153 (9) 865-874
13 Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. 2010 Assisted Reproductive Technology Fertility Clinic Success Rates Report. Atlanta: Department of Health and Human Services; 2012
14 La Marca A, Nelson SM, Sighinolfi G , et al. Anti-Müllerian hormone-based prediction model for a live birth in assisted reproduction. Reprod Biomed Online 2011; 22 (4) 341-349 (Reproductive Healthcare Limited)
15 Jayaprakasan K, Campbell B, Hopkisson J, Johnson I, Raine-Fenning N. A prospective, comparative analysis of anti-Müllerian hormone, inhibin-B, and three-dimensional ultrasound determinants of ovarian reserve in the prediction of poor response to controlled ovarian stimulation. Fertil Steril 2010; 93 (3) 855-864
16 Creus M, Peñarrubia J, Fábregues F , et al. Day 3 serum inhibin B and FSH and age as predictors of assisted reproduction treatment outcome. Hum Reprod 2000; 15 (11) 2341-2346
17 Schwartz D, Mayaux MJ. Female fecundity as a function of age: results of artificial insemination in 2193 nulliparous women with azoospermic husbands. Federation CECOS. N Engl J Med 1982; 306 (7) 404-406
18 Gnoth C, Godehardt D, Godehardt E, Frank-Herrmann P, Freundl G. Time to pregnancy: results of the German prospective study and impact on the management of infertility. Hum Reprod 2003; 18 (9) 1959-1966
19 Abma JC, Chandra A, Mosher WD, Peterson LS, Piccinino LJ. Fertility, family planning, and women's health: new data from the 1995 National Survey of Family Growth. Vital Health Stat 23 1997; 23 (19) 1-114
20 Rothman KJ, Wise LA, Sørensen HT, Riis AH, Mikkelsen EM, Hatch EE. Volitional determinants and age-related decline in fecundability: a general population prospective cohort study in Denmark. Fertil Steril 2013; 99 (7) 1958-1964
21 Wise LA, Mikkelsen EM, Rothman KJ , et al. A prospective cohort study of menstrual characteristics and time to pregnancy. Am J Epidemiol 2011; 174 (6) 701-709
22 van der Steeg JW, Steures P, Eijkemans MJ , et al. Predictive value and clinical impact of Basal follicle-stimulating hormone in subfertile, ovulatory women. J Clin Endocrinol Metab 2007; 92 (6) 2163-2168
23 Brodin T, Bergh T, Berglund L, Hadziosmanovic N, Holte J. Menstrual cycle length is an age-independent marker of female fertility: results from 6271 treatment cycles of in vitro fertilization. Fertil Steril 2008; 90 (5) 1656-1661
24 Fiçicioğlu C, Kutlu T, Demirbaşoğlu S, Mulayim B. The role of inhibin B as a basal determinant of ovarian reserve. Gynecol Endocrinol 2003; 17 (4) 287-293
25 Eldar-Geva T, Margalioth EJ, Ben-Chetrit A , et al. Serum inhibin B levels measured early during FSH administration for IVF may be of value in predicting the number of oocytes to be retrieved in normal and low responders. Hum Reprod 2002; 17 (9) 2331-2337
26 Hall JE, Welt CK, Cramer DW. Inhibin A and inhibin B reflect ovarian function in assisted reproduction but are less useful at predicting outcome. Hum Reprod 1999; 14 (2) 409-415
27 Seifer DB, Scott Jr RT, Bergh PA , 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 (1) 63-65
28 Haadsma ML, Groen H, Fidler V , et al. The predictive value of ovarian reserve tests for spontaneous pregnancy in subfertile ovulatory women. Hum Reprod 2008; 23 (8) 1800-1807
29 Steiner AZ, Herring AH, Kesner JS , et al. Antimüllerian hormone as a predictor of natural fecundability in women aged 30-42 years. Obstet Gynecol 2011; 117 (4) 798-804
30 Jain T, Soules MR, Collins JA. Comparison of basal follicle-stimulating hormone versus the clomiphene citrate challenge test for ovarian reserve screening. Fertil Steril 2004; 82 (1) 180-185
31 Steiner AZ, Long DL, Herring AH, Kesner JS, Meadows JW, Baird DD. Urinary follicle-stimulating hormone as a measure of natural fertility in a community cohort. Reprod Sci 2013; 20 (5) 549-556
32 McDade TW, Woodruff TK, Huang YY , et al. Quantification of anti-Müllerian hormone (AMH) in dried blood spots: validation of a minimally invasive method for assessing ovarian reserve. Hum Reprod 2012; 27 (8) 2503-2508
33 Lee T-H, Liu CH, Huang CC, Hsieh KC, Lin PM, Lee MS. Impact of female age and male infertility on ovarian reserve markers to predict outcome of assisted reproduction technology cycles. Reprod Biol Endocrinol 2009; 7 (1) 100
34 Lukaszuk K, Kunicki M, Liss J, Lukaszuk M, Jakiel G. Use of ovarian reserve parameters for predicting live births in women undergoing in vitro fertilization. Eur J Obstet Gynecol Reprod Biol 2013; 168 (2) 173-177
35 Brodin T, Hadziosmanovic N, Berglund L, Olovsson M, Holte J. Antimüllerian hormone levels are strongly associated with live-birth rates after assisted reproduction. J Clin Endocrinol Metab 2013; 98 (3) 1107-1114
36 Kunt C, Ozaksit G, Keskin Kurt R , et al. Anti-Mullerian hormone is a better marker than inhibin B, follicle stimulating hormone, estradiol or antral follicle count in predicting the outcome of in vitro fertilization. Arch Gynecol Obstet 2011; 283 (6) 1415-1421
37 Kwee J, Schats R, McDonnell J, Themmen A, de Jong F, Lambalk C. Evaluation of anti-Müllerian hormone as a test for the prediction of ovarian reserve. Fertil Steril 2008; 90 (3) 737-743
38 Hagen CP, Vestergaard S, Juul A , et al. Low concentration of circulating antimüllerian hormone is not predictive of reduced fecundability in young healthy women: a prospective cohort study. Fertil Steril 2012; 98 (6) 1602-1608 , e2
39 van Disseldorp J, Lambalk CB, Kwee J , et al. Comparison of inter- and intra-cycle variability of anti-Mullerian hormone and antral follicle counts. Hum Reprod 2010; 25 (1) 221-227
40 Peñarrubia J, Fábregues F, Manau D , et al. Initial analysis of variability among basal hormone biomarkers of ovarian reserve. Reprod Biomed Online 2004; 8 (2) 191-195
41 Jain T, Klein NA, Lee DM, Sluss PM, Soules MR. Endocrine assessment of relative reproductive age in normal eumenorrheic younger and older women across multiple cycles. Am J Obstet Gynecol 2003; 189 (4) 1080-1084
42 Buyalos RP, Ghosh K, Daneshmand ST. Infertile women of advanced reproductive age. Variability of day 3 FSH and E2 levels. J Reprod Med 1998; 43 (12) 1023-1026
43 Scott Jr RT, Hofmann GE, Oehninger S, Muasher SJ. Intercycle variability of day 3 follicle-stimulating hormone levels and its effect on stimulation quality in in vitro fertilization. Fertil Steril 1990; 54 (2) 297-302
44 Abdalla H, Thum MY. Repeated testing of basal FSH levels has no predictive value for IVF outcome in women with elevated basal FSH. Hum Reprod 2006; 21 (1) 171-174