Human Reproduction, Vol.29, No.1 pp. 184–187, 2014
LETTERS TO THE EDITOR
Anti-Mullerian hormone: reality check
References Broer SL, van Disseldorp J, Broeze KA, Dolleman M, Opmeer BC, Bossuyt P, Eijkemans MJ, Mol BW, Broekmans FJ; IMPORT study group. Added value of ovarian reserve testing on patients characteristics in the prediction of ovarian response and ongoing pregnancy: an individual patient data approach. Hum Reprod Update 2013;19:26 – 36.
& The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: [email protected]
Downloaded from http://humrep.oxfordjournals.org/ at Akdeniz University on December 24, 2014
Sir, Determination of circulating anti-Mu¨llerian hormone (AMH) has become a cornerstone of the infertility workup (Seifer et al., 2011). AMH has been reported to be strongly associated with age, antral follicle count (AFC) and FSH; elevated levels have been associated with polycystic ovarian syndrome (PCOS). It has also been reported to be an indicator of response to ovarian stimulation (Broer et al., 2013), a predictor of pregnancy outcome IVF/ICSI (Khader et al., 2013), and a marker for the onset of menopause (Dolleman et al., 2013). It has been suggested that AMH should be considered a replacement for the ‘gold standard biomarker’ AFC (Usta and Oral, 2012; Nelson, 2013) based upon the contention that AFC is not sufficiently reliable due to variable skills of operators performing the baseline scans. Implicit in all the proposed attributes and uses for AMH, therefore, is the necessity of reliability and reproducibility of AMH detection. Li et al. (2012) recently concluded that age-appropriate ranges should be derived by each laboratory and that AMH levels from different assays are not directly comparable. There have been several commercially available assays for AMH: the Beckman Coulter’s Immunotech (IOT) assay and the Diagnostic Systems Lab assay. These have been gradually replaced by Beckman Coulter’s Gen II assay which has been widely used internationally for almost 3 years (Nelson and La Marca, 2011; Wallace et al., 2011). Several ‘urgent field safety notices’ for this kit have been issued over the past 10 months. They included both a product recall and several contradictory revisions to correct original manufacturer’s instructions. Different notices issued between November 2012 (http://www.imb.ie/images/uploaded/documents/fsn/ FSNDec2012/V16335_FSN.pdf) and July 2013 (http://www.mhra. gov.uk/home/groups/fsn/documents/fieldsafetynotice/con297532. pdf) indicated that the original methodology resulted in potentially (but not definitely) either falsely high or low AMH values, apparently due to complement interference in the assay (Han et al., 2013). This situation naturally raises considerable concern. Should patients be recalled and retested if their AMH levels (measured in the 3 years prior to the product correction notices) fell outside expected age-related ranges? Were patients counseled or treated accordingly? Should those AMH values that, perhaps spuriously, fell within expected age-related ranges be accepted as accurate? Should the Gen II AMH body of work prior to July 2013 be re-analyzed entirely, knowing in hindsight that values generated by the assay and any conclusions drawn may have been unreliable? There is no current standard for AMH measurement although the UK NEQAS has been conducting an international pilot scheme for the past 2 years (Syme et al., 2013). Standardization is a necessary step for the determination of assay accuracy. However, it is concerning that the target
levels in samples distributed to participating labs are established not against a known standard, but by using an all laboratory trimmed mean (ALTM). Labs using the Gen II AMH kit over the last 3 years, therefore, were unknowingly reporting potentially falsely high or low levels, with the possibility of erroneous values actually being incorporated into the calculation of expected values. Use of the ALTM to derive expected values renders standardization of AMH measurement both vulnerable to and unable to detect technical error, especially when laboratories are increasingly relying upon only one assay worldwide. AMH has rather quickly acquired a very significant clinical role in the assessment and treatment of infertility, perhaps before its reliability and utility have been sufficiently and accurately defined. The decline in AMH throughout women’s reproductive years, until it is undetectable by menopause, has been consistently observed, regardless of the assay employed or the demographic studied. However, within each age group, regardless of obstetric history, there is a wide variation in AMH (La Marca et al., 2010, 2012; Seifer et al., 2011). Recently, there have been suggestions that measurement of AMH is less convincing as a superior biomarker for ovarian reserve and its reproducibility is under question (Loh and Maheshwari, 2011; Rustamov et al., 2012; Fitzgerald et al., 2013). Many groups have reported no correlation between AMH and live birth following IVF/ICSI, although they did find low age-appropriate AMH was associated with poor ovarian response (Tremellen and Kolo, 2010; Broer et al., 2013; Li et al., 2013). La Marca et al. (2012) reported that in women with a normal reproductive history, there was no association between AMH level and either miscarriage or pregnancy. In addition, there are reports of intra- and inter-cycle variation among individuals, and even circadian variations among patients with PCOS (Bungum et al., 2013; Hadlow et al., 2013). Conflicting findings as well as the recent technical difficulties indicate a need for caution when evaluating the evolving clinical significance of AMH. It is important for physicians to educate their patients regarding (i) the relative nature of AMH determination; (ii) the absence of a generalized cut-off that either precludes or predicts successful IVF/ICSI outcome; and (iii) the inadvisability of attributing diagnostic or prognostic significance to an absolute AMH value. While AMH has a role to play in the infertility workup, it would be premature to recommend it as a stand-alone measure of ovarian reserve. We believe it should continue to be interpreted in context with all other laboratory, radiologic and clinical findings.
185
Letters to the Editor
Wallace AM, Faye SA, Fleming R, Nelson SM. A multicentre evaluation of the new Beckman Coulter anti-Mu¨llerian hormone immunoassay (AMH Gen II). Ann Clin Biochem 2011;48:370 – 373. Christine A. Clark1,*, Carl A. Laskin2 and Kenneth Cadesky3 Mt. Sinai Hospital and LifeQuest Centre for Reproductive Medicine, Toronto, ON, Canada 2 University of Toronto and LifeQuest Centre for Reproductive Medicine, Toronto, ON, Canada 3 LifeQuest Centre for Reproductive Medicine, Toronto, ON, Canada 1
*Correspondence address. E-mail: [email protected] doi:10.1093/humrep/det413 Advanced Access publication on November 13, 2013
Time-lapse parameters could not predict pregnancy: a hasty conclusion? Sir, Kirkegaard et al.’s (2013) prospective study provides additional evidence that timing of early cleavage events can predict blastocyst development, first established using cryopreserved, donated embryos (Wong et al., 2010) and recently validated in a large-scale multi-center prospective study with 1233 embryos from 160 patients (Conaghan et al., 2013). Three specific time-lapse parameters: duration of (i) first cytokinesis, (ii) 2-cell stage and (iii) 3-cell stage were identified in retrospective studies and prospective trials as enhancing blastocyst prediction (Conaghan et al., 2013; Kirkegaard et al., 2013). Although Kirkegaard et al.’s model used direct cleavage (DC) to 3-cell instead of duration of 2-cell stage, the authors acknowledged DC as ‘derived from duration of the 2-cell stage’ and concluded that duration of 2-cell stage ‘holds predictive value’. Since reproducibility is a cornerstone of scientific and clinical research, these prospective studies demonstrate consistency in the predictive value of early time-lapse parameters for blastocyst development. However, I wish to discuss several limitations and other conclusions from Kirkegaard et al.’s study. The authors tested whether these timing parameters differed between implanted and non-implanted embryos concluding that ‘time-lapse parameters could not predict pregnancy’. I believe this conclusion is premature. First, the authors state that their sample size (n ¼ 84) is ‘sufficiently large to test up to five parameters using the targeted logistic regression approach’; an overstated assertion since they failed to consider the low prevalence of a positive outcome (n ¼ 26 implanted embryos; 31%). According to the wellestablished 1-in-10 rule (Harrell et al., 1996), at least 50 implanted embryos are needed to test five parameters. In contrast, blastocyst prediction analyses were based on a sample size of 571 embryos with 140 high-quality blastocysts. Since the authors conclude that time-lapse parameters cannot predict pregnancy from an absence of statistical significance, one must consider type II statistical error (i.e. failure to identify a difference when one exists). While the authors identified small sample size as a key study limitation, this does not justify their overstated conclusion. The emphasis in both the title and in the discussion on
Downloaded from http://humrep.oxfordjournals.org/ at Akdeniz University on December 24, 2014
Bungum L, Franssohn F, Bungum M, Humaidan P, Givercman A. The circadian variation in anti-Mu¨llerian hormone in patients with polycystic ovary syndrome differs significantly from normally ovulating women. PLoS One 2013;9:e68223. Dolleman M, Faddy MJ, van Disseldorp J, van der Schouw TY, Messow CM, Leader B, Peeters PH, McConnachie A, Nelson SM, Broekmans FJ. The relationship between anti-Mu¨llerian hormone in women receiving fertility assessments and age at menopause in subfertile women: evidence from large population studies. J Clin Enodocrinol Metab 2013;98:1946 – 1953. Fitzgerald C, Rustamov O, Pemberton P, Smith A, Yates A, Krishnan M, Russel R, Nardo L, Roberts S. AMH Assays: a review of the literature on assay method comparability. Hum Reprod 2013;28(Suppl 1): 0 – 184. Hadlow N, Longhurst K, McClements A, Natalwala J, Brown SJ, Matson PL. Variation in anti-Mu¨llerian hormone concentration during the menstrual cycle may change the clinical classification of the ovarian response. Fertil Steril 2013;99:1791 – 1797. Han X, McShane M, Sahertian R, White C, Ledger W. Pre-mixing samples with assay buffer is an essential pre-requisite for reproducible anti-Mu¨llerian hormone (AMH) measurement using the Beckman Coulter Gen II assay (Gen II). Hum Reprod 2013;28(Suppl 1):0– 185. Khader A, Lloyd SM, McConnaichie A, Fleming R, Grisendi V, La Marca A, Nelson SM. External validation of anti-Mu¨llerian hormone based prediction of live birth in assisted conception. J Ovarian Res 2013;6:3. La Marca A, Sighinolfi G, Siulini S, Traglia M, Argento C, Sala C, Masciullo C, Volpe A, Toniolo D. Normal serum concentrations of anti-Mu¨llerian hormone in women with regular menstrual cycles. Reprod BioMed Online 2010;21:463 – 469. La Marca A, Spada E, Grisendi V, Argento C, Papale E, Milani S, Volpe A. Normal serum anti-Mu¨llerian hormone levels in the general female population and the relationship with reproductive history. Eur J Obstet Gynecol Reprod Biol 2012;163:180 – 184. Li HW, Ng EH, Wong BP, Anderson RA, Ho PC, Yeung WS. Correlation between three assay systems for anti-Mu¨llerian hormone (AMH) determination. J Assist Reprod Genet 2012;29:1443 –1446. Li HW, Lee VC, Lau EY, Yeung WS, Ho PC, Ng EH. Role of baseline antral follicle count and anti-Mu¨llerian hormone in prediction of cumulative live birth in the first in vitro fertilization cycle: a retrospective cohort analysis. PLoS One 2013;8:e61095. Loh JS, Maheshwari A. Anti-Mu¨llerian hormone is it a crystal ball for predicting ovarian aging? Hum Reprod 2011;26:2925 – 2932. Nelson SM. Anti-Mu¨llerian hormone: is the writing on the wall for antral follicle count [letter]? Fertil Steril 2013;99:1563 – 1564. Nelson SM, La Marca A. The journey from the old to the new AMH assay: how to avoid getting lost in the values. Reprod Biomed Online 2011;23:411 – 420. Rustamov O, Smith A, Roberts SA, Yates AP, Firzgearld C, Krishnan M, Nardo LG, Pemberon PW. Anti-Mu¨llerian hormone: poor assay reproducibility in a large cohort of subjects suggests sample instability. Hum Reprod 2012;27:3085 – 3091. Seifer DB, Baker VL, Leader B. Age-specific serum anti-Mu¨llerian hormone values for 17,120 women presenting to fertility centers within the United states. Fertil Steril 2011;95:747 –750. Syme NR, Al-Sadie R, Sturgeon C. Is performance for anti-Mu¨llerian hormone improving? Evidence from UK NEQAS. Ann Clin Biochem 2013;50(Suppl 1):37– 38. Tremellen K, Kolo M. Serum anti-Mu¨llerian hormone is a useful measure of quantitative ovarian reserve but does not predict the chances of live-birth pregnancy. Aust N Z J Obstet Gynecol 2010;50:568 – 572. Usta T, Oral I. Is the measurement of anti-Mu¨llerian hormone essential? Curr Opin Obstet Gynecol 2012;24:151 – 157.
LETTERS TO THE EDITOR
Anti-Mullerian hormone: reality check
References Broer SL, van Disseldorp J, Broeze KA, Dolleman M, Opmeer BC, Bossuyt P, Eijkemans MJ, Mol BW, Broekmans FJ; IMPORT study group. Added value of ovarian reserve testing on patients characteristics in the prediction of ovarian response and ongoing pregnancy: an individual patient data approach. Hum Reprod Update 2013;19:26 – 36.
& The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: [email protected]
Downloaded from http://humrep.oxfordjournals.org/ at Akdeniz University on December 24, 2014
Sir, Determination of circulating anti-Mu¨llerian hormone (AMH) has become a cornerstone of the infertility workup (Seifer et al., 2011). AMH has been reported to be strongly associated with age, antral follicle count (AFC) and FSH; elevated levels have been associated with polycystic ovarian syndrome (PCOS). It has also been reported to be an indicator of response to ovarian stimulation (Broer et al., 2013), a predictor of pregnancy outcome IVF/ICSI (Khader et al., 2013), and a marker for the onset of menopause (Dolleman et al., 2013). It has been suggested that AMH should be considered a replacement for the ‘gold standard biomarker’ AFC (Usta and Oral, 2012; Nelson, 2013) based upon the contention that AFC is not sufficiently reliable due to variable skills of operators performing the baseline scans. Implicit in all the proposed attributes and uses for AMH, therefore, is the necessity of reliability and reproducibility of AMH detection. Li et al. (2012) recently concluded that age-appropriate ranges should be derived by each laboratory and that AMH levels from different assays are not directly comparable. There have been several commercially available assays for AMH: the Beckman Coulter’s Immunotech (IOT) assay and the Diagnostic Systems Lab assay. These have been gradually replaced by Beckman Coulter’s Gen II assay which has been widely used internationally for almost 3 years (Nelson and La Marca, 2011; Wallace et al., 2011). Several ‘urgent field safety notices’ for this kit have been issued over the past 10 months. They included both a product recall and several contradictory revisions to correct original manufacturer’s instructions. Different notices issued between November 2012 (http://www.imb.ie/images/uploaded/documents/fsn/ FSNDec2012/V16335_FSN.pdf) and July 2013 (http://www.mhra. gov.uk/home/groups/fsn/documents/fieldsafetynotice/con297532. pdf) indicated that the original methodology resulted in potentially (but not definitely) either falsely high or low AMH values, apparently due to complement interference in the assay (Han et al., 2013). This situation naturally raises considerable concern. Should patients be recalled and retested if their AMH levels (measured in the 3 years prior to the product correction notices) fell outside expected age-related ranges? Were patients counseled or treated accordingly? Should those AMH values that, perhaps spuriously, fell within expected age-related ranges be accepted as accurate? Should the Gen II AMH body of work prior to July 2013 be re-analyzed entirely, knowing in hindsight that values generated by the assay and any conclusions drawn may have been unreliable? There is no current standard for AMH measurement although the UK NEQAS has been conducting an international pilot scheme for the past 2 years (Syme et al., 2013). Standardization is a necessary step for the determination of assay accuracy. However, it is concerning that the target
levels in samples distributed to participating labs are established not against a known standard, but by using an all laboratory trimmed mean (ALTM). Labs using the Gen II AMH kit over the last 3 years, therefore, were unknowingly reporting potentially falsely high or low levels, with the possibility of erroneous values actually being incorporated into the calculation of expected values. Use of the ALTM to derive expected values renders standardization of AMH measurement both vulnerable to and unable to detect technical error, especially when laboratories are increasingly relying upon only one assay worldwide. AMH has rather quickly acquired a very significant clinical role in the assessment and treatment of infertility, perhaps before its reliability and utility have been sufficiently and accurately defined. The decline in AMH throughout women’s reproductive years, until it is undetectable by menopause, has been consistently observed, regardless of the assay employed or the demographic studied. However, within each age group, regardless of obstetric history, there is a wide variation in AMH (La Marca et al., 2010, 2012; Seifer et al., 2011). Recently, there have been suggestions that measurement of AMH is less convincing as a superior biomarker for ovarian reserve and its reproducibility is under question (Loh and Maheshwari, 2011; Rustamov et al., 2012; Fitzgerald et al., 2013). Many groups have reported no correlation between AMH and live birth following IVF/ICSI, although they did find low age-appropriate AMH was associated with poor ovarian response (Tremellen and Kolo, 2010; Broer et al., 2013; Li et al., 2013). La Marca et al. (2012) reported that in women with a normal reproductive history, there was no association between AMH level and either miscarriage or pregnancy. In addition, there are reports of intra- and inter-cycle variation among individuals, and even circadian variations among patients with PCOS (Bungum et al., 2013; Hadlow et al., 2013). Conflicting findings as well as the recent technical difficulties indicate a need for caution when evaluating the evolving clinical significance of AMH. It is important for physicians to educate their patients regarding (i) the relative nature of AMH determination; (ii) the absence of a generalized cut-off that either precludes or predicts successful IVF/ICSI outcome; and (iii) the inadvisability of attributing diagnostic or prognostic significance to an absolute AMH value. While AMH has a role to play in the infertility workup, it would be premature to recommend it as a stand-alone measure of ovarian reserve. We believe it should continue to be interpreted in context with all other laboratory, radiologic and clinical findings.
185
Letters to the Editor
Wallace AM, Faye SA, Fleming R, Nelson SM. A multicentre evaluation of the new Beckman Coulter anti-Mu¨llerian hormone immunoassay (AMH Gen II). Ann Clin Biochem 2011;48:370 – 373. Christine A. Clark1,*, Carl A. Laskin2 and Kenneth Cadesky3 Mt. Sinai Hospital and LifeQuest Centre for Reproductive Medicine, Toronto, ON, Canada 2 University of Toronto and LifeQuest Centre for Reproductive Medicine, Toronto, ON, Canada 3 LifeQuest Centre for Reproductive Medicine, Toronto, ON, Canada 1
*Correspondence address. E-mail: [email protected] doi:10.1093/humrep/det413 Advanced Access publication on November 13, 2013
Time-lapse parameters could not predict pregnancy: a hasty conclusion? Sir, Kirkegaard et al.’s (2013) prospective study provides additional evidence that timing of early cleavage events can predict blastocyst development, first established using cryopreserved, donated embryos (Wong et al., 2010) and recently validated in a large-scale multi-center prospective study with 1233 embryos from 160 patients (Conaghan et al., 2013). Three specific time-lapse parameters: duration of (i) first cytokinesis, (ii) 2-cell stage and (iii) 3-cell stage were identified in retrospective studies and prospective trials as enhancing blastocyst prediction (Conaghan et al., 2013; Kirkegaard et al., 2013). Although Kirkegaard et al.’s model used direct cleavage (DC) to 3-cell instead of duration of 2-cell stage, the authors acknowledged DC as ‘derived from duration of the 2-cell stage’ and concluded that duration of 2-cell stage ‘holds predictive value’. Since reproducibility is a cornerstone of scientific and clinical research, these prospective studies demonstrate consistency in the predictive value of early time-lapse parameters for blastocyst development. However, I wish to discuss several limitations and other conclusions from Kirkegaard et al.’s study. The authors tested whether these timing parameters differed between implanted and non-implanted embryos concluding that ‘time-lapse parameters could not predict pregnancy’. I believe this conclusion is premature. First, the authors state that their sample size (n ¼ 84) is ‘sufficiently large to test up to five parameters using the targeted logistic regression approach’; an overstated assertion since they failed to consider the low prevalence of a positive outcome (n ¼ 26 implanted embryos; 31%). According to the wellestablished 1-in-10 rule (Harrell et al., 1996), at least 50 implanted embryos are needed to test five parameters. In contrast, blastocyst prediction analyses were based on a sample size of 571 embryos with 140 high-quality blastocysts. Since the authors conclude that time-lapse parameters cannot predict pregnancy from an absence of statistical significance, one must consider type II statistical error (i.e. failure to identify a difference when one exists). While the authors identified small sample size as a key study limitation, this does not justify their overstated conclusion. The emphasis in both the title and in the discussion on
Downloaded from http://humrep.oxfordjournals.org/ at Akdeniz University on December 24, 2014
Bungum L, Franssohn F, Bungum M, Humaidan P, Givercman A. The circadian variation in anti-Mu¨llerian hormone in patients with polycystic ovary syndrome differs significantly from normally ovulating women. PLoS One 2013;9:e68223. Dolleman M, Faddy MJ, van Disseldorp J, van der Schouw TY, Messow CM, Leader B, Peeters PH, McConnachie A, Nelson SM, Broekmans FJ. The relationship between anti-Mu¨llerian hormone in women receiving fertility assessments and age at menopause in subfertile women: evidence from large population studies. J Clin Enodocrinol Metab 2013;98:1946 – 1953. Fitzgerald C, Rustamov O, Pemberton P, Smith A, Yates A, Krishnan M, Russel R, Nardo L, Roberts S. AMH Assays: a review of the literature on assay method comparability. Hum Reprod 2013;28(Suppl 1): 0 – 184. Hadlow N, Longhurst K, McClements A, Natalwala J, Brown SJ, Matson PL. Variation in anti-Mu¨llerian hormone concentration during the menstrual cycle may change the clinical classification of the ovarian response. Fertil Steril 2013;99:1791 – 1797. Han X, McShane M, Sahertian R, White C, Ledger W. Pre-mixing samples with assay buffer is an essential pre-requisite for reproducible anti-Mu¨llerian hormone (AMH) measurement using the Beckman Coulter Gen II assay (Gen II). Hum Reprod 2013;28(Suppl 1):0– 185. Khader A, Lloyd SM, McConnaichie A, Fleming R, Grisendi V, La Marca A, Nelson SM. External validation of anti-Mu¨llerian hormone based prediction of live birth in assisted conception. J Ovarian Res 2013;6:3. La Marca A, Sighinolfi G, Siulini S, Traglia M, Argento C, Sala C, Masciullo C, Volpe A, Toniolo D. Normal serum concentrations of anti-Mu¨llerian hormone in women with regular menstrual cycles. Reprod BioMed Online 2010;21:463 – 469. La Marca A, Spada E, Grisendi V, Argento C, Papale E, Milani S, Volpe A. Normal serum anti-Mu¨llerian hormone levels in the general female population and the relationship with reproductive history. Eur J Obstet Gynecol Reprod Biol 2012;163:180 – 184. Li HW, Ng EH, Wong BP, Anderson RA, Ho PC, Yeung WS. Correlation between three assay systems for anti-Mu¨llerian hormone (AMH) determination. J Assist Reprod Genet 2012;29:1443 –1446. Li HW, Lee VC, Lau EY, Yeung WS, Ho PC, Ng EH. Role of baseline antral follicle count and anti-Mu¨llerian hormone in prediction of cumulative live birth in the first in vitro fertilization cycle: a retrospective cohort analysis. PLoS One 2013;8:e61095. Loh JS, Maheshwari A. Anti-Mu¨llerian hormone is it a crystal ball for predicting ovarian aging? Hum Reprod 2011;26:2925 – 2932. Nelson SM. Anti-Mu¨llerian hormone: is the writing on the wall for antral follicle count [letter]? Fertil Steril 2013;99:1563 – 1564. Nelson SM, La Marca A. The journey from the old to the new AMH assay: how to avoid getting lost in the values. Reprod Biomed Online 2011;23:411 – 420. Rustamov O, Smith A, Roberts SA, Yates AP, Firzgearld C, Krishnan M, Nardo LG, Pemberon PW. Anti-Mu¨llerian hormone: poor assay reproducibility in a large cohort of subjects suggests sample instability. Hum Reprod 2012;27:3085 – 3091. Seifer DB, Baker VL, Leader B. Age-specific serum anti-Mu¨llerian hormone values for 17,120 women presenting to fertility centers within the United states. Fertil Steril 2011;95:747 –750. Syme NR, Al-Sadie R, Sturgeon C. Is performance for anti-Mu¨llerian hormone improving? Evidence from UK NEQAS. Ann Clin Biochem 2013;50(Suppl 1):37– 38. Tremellen K, Kolo M. Serum anti-Mu¨llerian hormone is a useful measure of quantitative ovarian reserve but does not predict the chances of live-birth pregnancy. Aust N Z J Obstet Gynecol 2010;50:568 – 572. Usta T, Oral I. Is the measurement of anti-Mu¨llerian hormone essential? Curr Opin Obstet Gynecol 2012;24:151 – 157.
