AMH and Ovarian.

1. Journal Reading
Evaluation of Female Fertility—AMH
and Ovarian Reserve Testing
Presenter:
Moderator:
Assesor:
DEPARTMENT OF OBSTETRICS AND GYNECOLOGY
FACULTY OF MEDICINE SRIWIJAYA UNIVERSITY / DR. MOHAMMAD HOESIN
GENERAL HOSPITAL PALEMBANG
2023

2. 2

3. INTRODUCTION
3
Infertility
Aneuploidy
Ovarian
Reserve
Antimullerian
hormone
(AMH)

4. 4
Figure 1. Live birth per transfer based on age (Society for Assisted
Reproductive Technology) comparing autologous eggs to donor eggs

5. 5
Figure 2. Percentage of live birth declines with increasing age

6. 6
Figure 3. The occurrence of aneuploidy in human: lessons from the
cytogenetic studies of human oocytes.

7. 7
Figure 4. Individual markers of serumantimüllerian hormone (AMH) across ages

8. Materials and Methods
8
PubMed search was conducted to find recent literature
on measurements and use of serum AMH as a marker
of ovarian reserve and in treatment of infertility.

9. DISCUSSION
Strategies for Diagnosis, Management and Treatment
9
Initial Evaluation of
the Infertile Couple
Couples should begin an evaluation if
they have not conceived after 1
year of active attempts.
Vaginal intercourse, history,
and life style

10. DISCUSSION
10
Symptoms of hypothyroidism, hyperprolactinemia,
hypoestrogenism, or hyperandrogenism.
The first approach to an infertile woman is to characterize the menstrual
Approach to the Subfertile/Infertile Woman
Women undergoing active fertility management, particularly ovarian
stimulation, should have an evaluation of ovarian reserve by serum
AMH and/or ultrasound-guided AFC

11. How to Use Antimüllerian Hormone in
Clinical Management
11
AMH is a predictor of
response to stimulation (IVF
cycle) but does not correlate
with pregnancy success.
Assisted reproductive technology
AMH is used to counsel
regarding the expected
number of oocytes at retrieval,
and to help determine specific
stimulation protocol and
required dosing

12. Ovulatory Dysfunction
12
The 2 most common causes of anovulation are
polycystic ovary syndrome (PCOS):
Irregular cycles, hyperandrogenism, and polycystic-appearing ovaries; and
hypogonadotropic hypogonadism, which can be genetic, functional, or due to
hypothyroidism or hyperprolactinemia
For women with PCOS, screening should exclude dyslipidemia, fatty
liver, and/or impaired glucose tolerance/ diabetes that may require
further assessment, treatment, and/or weight loss before conception.

13. Focus on high
antimüllerian hormone
13
Increasingly a role for AMH in the
pathophysiology of PCOS has been
identified. AMH reduces the progression
of developing follicles into
the recruitable pool.
Polycystic ovary syndrome.
PCOS is the most common
endocrine disorder of
reproductive-aged women.

14. Focus on low
antimüllerian Hormone
14
In cases of severe diminished
ovarian reserve and primary ovarian
insufficiency (POI), AMH levels may
be quite low.
Primary ovarian
insufficiency,
hypogonadotropic
hypogonadism.
Case of hypogonadotropic
hypogonadism, AMH may be falsely
suppressed inaccurately suggesting
poor stimulation capacity

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Figure 5. Relationship betweenantimüllerian hormone (AMH) and
duration of human menopausal gonadotropin (hMG) over 2 cycles.

16. CONCLUSION
16
Assessment of ovarian reserve is critical in the evaluation of an infertile woman.
AMH and AFC both assess the functional ovarian reserve: the capacity for
response to stimulation and the reproductive window
Women with high AMH, and PCOS, are best treated with weight reduction. If this
fails to induce ovulation and/or the individual is older, ovulation induction with
letrozole is indicated.
Women with low AMH and hypogonadotropic hypogonadism should have the
underlying cause corrected if possible: hyperprolactinemia, hypothyroidism, low
body weight, or excessive exercise. The ideal therapy with primary
hypogonadotropic hypogonadism or functional hypothalamic amenorrhea is to
replace the missing hormone with pulsatile GnRH.

17. REFERENCE
1. Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil
Steril. 2013;99(1):63.
2. MatthewsTJ, Hamilton BE. First births to older women continue to rise. NCHS Data Brief. 2014;(152):1-8.
3. Society for Assisted Reproductive Technology (SART). Final National Summary Report for 2014. 2014. Accessed November 9, 2021.
https://www.sartcorsonline.com/rptCSR_ PublicMultYear.aspx?reportingYear=2014
4. World Health Organization. Infertility definitions and terminology. 2020. Accessed October 2021.
http://www.who.int/reproductivehealth/topics/infertility/definitions/en/
5. Fischer R, Baukloh V. Commentary: managementstrategies for POSEIDON Groups 3 and 4. Front Endocrinol (Lausanne).
2020;11:34.
6. Pellestor F, Andreo B, Anahory T, Hamamah S. The occurrence of aneuploidy in human: lessons from the cytogenetic studies of human oocytes. Eur J Med
Genet. 2006;49(2):103-116.
7. 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.
8. Rosen MP, Johnstone E, McCulloch CE, et al. A characterizationof the relationship of ovarian reserve markers with age. Fertil Steril. 2012;97(1):238-243.
9. Cramer DW, Xu H, Harlow BL. Family history as a predictorof early menopause. Fertil Steril. 1995;64(4):740-745.
10. de Bruin JP, Bovenhuis H, van Noord PA, et al. The role of genetic factors in age at natural menopause. Hum Reprod.
2001;16(9):2014-2018.
11. Murabito JM, Yang Q, Fox C, Wilson PW, Cupples LA. Heritability of age at natural menopause in the Framingham Heart Study. J Clin Endocrinol Metab.
2005;90(6):3427-3430.
12. Rosen MP, Sternfeld B, Schuh-Huerta SM, Reijo Pera RA, McCulloch CE, Cedars MI. Antral follicle count: absence of significant midlife decline. Fertil
Steril. 2010;94(6):2182-2185.
13. Bentzen JG, Forman JL, Larsen EC, et al. Maternal menopause
as a predictor of anti-Mullerianhormone level and antral follicle count in daughters during reproductive age. Hum Reprod. 2013;28(1):247-255.
14. Moolhuijsen LME, Visser JA. Anti-müllerian hormone and ovarian reserve: update on assessing ovarian function. J Clin Endocrinol Metab.
2020;105(11):3361-3373.
15. 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
17

18. 18
16. Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinology and Infertility.
Optimizing natural fertility: a committeeopinion. Fertil Steril. 2017;107(1):52-58.
17. Ethics Committee of the American Society for Reproductive Medicine. Disposition of abandoned embryos: a committee opinion. Fertil Steril.
2013;99(7):1848-1849.
18. Harris BS, Steiner AZ, Jukic AM. Ovarian reserve biomarkers and menstrual cycle length in a prospective cohort study. J Clin Endocrinol Metab.
2021;106(9):e3748-e3759.
19. Vassena R, Vidal R, Coll O, Vernaeve V. Menstrual cycle length in reproductive age women is an indicator of oocyte quality and a candidate marker of ovarian
reserve. Eur J Obstet Gynecol Reprod Biol. 2014;177:130-134.
20. Younis JS, Iskander R, Fauser BCJM, Izhaki I. Does an association exist between menstrual cycle length within the normal range and ovarian reserve
biomarkers during the reproductive years? a systematic review and meta-analysis. Hum Reprod Update. 2020;26(6):904-928.
21. Mersereau JE, Pergament E, Zhang X, Milad MP. Preimplantation genetic screening to improve in vitro fertilization pregnancy rates: a prospective
randomized controlledtrial. Fertil Steril. 2008;90(4):1287-1289.
22. Pal L, Zhang K, Zeitlian G, Santoro N. Characterizing the reproductive hormone milieu in infertile women with diminished ovarian reserve. Fertil Steril.
2010;93(4):1074-1079.
23. Pfister A, Crawford NM, Steiner AZ. Association betweendiminished ovarian reserve and luteal phase deficiency. Fertil Steril. 2019;112(2):378-386.
24. Broekmans FJM, de Ziegler D, Howles CM, Gougeon A, Trew G, Olivennes F. The antral follicle count: practical recommendations for better standardization.
Fertil Steril. 2010;94(3):1044-1051.
25. von Wolff M, Roumet M, Stute P, Liebenthron J. Serum antiMullerian hormone (AMH) concentration has limited prognostic value for density of primordial
and primary follicles, questioning it as an accurate parameter for the ovarian reserve. Maturitas. 2020;134:34-40.
26. Streuli I, Fraisse T, Pillet C, Ibecheole V, Bischof P, de Ziegler D. Serum antimüllerian hormone levels remain stable throughout the menstrual cycle and after
oral or vaginal administrationof synthetic sex steroids. Fertil Steril. 2008;90(2):395-400.
27. Steiner AZ, Pritchard D, Stanczyk FZ, et al. Association between biomarkers of ovarian reserve and infertility among older women of reproductive age.
JAMA. 2017;318(14):1367-1376.
28. Zarek SM, Mitchell EM, Sjaarda LA, et al. Is anti-Müllerian hormone associated with fecundability? findings from the EAGeR trial. J Clin Endocrinol Metab.
2015;100(11):4215-4221.
29. Depmann M, Broer SL, Eijkemans MJC, et al. Anti-Müllerian hormone does not predict time to pregnancy: results of a prospective cohort study. Gynecol
Endocrinol. 2017;33(8):644-648.
30. Broer SL, Mol BW, Dólleman M, Fauser BC, Broekmans FJM. The role of anti-Müllerian hormone assessment in assisted reproductive technology outcome.
Curr Opin Obstet Gynecol. 2010;22(3):193-201.

19. 19
31. Broer SL, van Disseldorp J, Broeze KA, et al. 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.
32. Iliodromiti S, Kelsey TW, Wu O, Anderson RA, Nelson SM. The predictive accuracy of anti-Müllerian hormone for live birth after assisted conception: a
systematic review and meta-analysis of the literature. Hum Reprod Update. 2014;20(4):560-570. 33. Granger E, Tal R. Anti-Müllerian hormone and its
predictive utility in assisted reproductive technologiesoutcomes. Clin Obstet Gynecol. 2019;62(2):238-256.
34. La Marca A, Papaleo E, Grisendi V, Argento C, Giulini S, Volpe A. Development of a nomogram based on markers of ovarian reserve for the
individualisation of the follicle-stimulatinghormone starting dose in in vitro fertilisationcycles. BJOG. 2012;119(10):1171-1179.
35. Hendriks DJ, Mol BW, Bancsi LFJMM, Te Velde ER, Broekmans FJM. Antral follicle count in the prediction of poor ovarian response and pregnancy after in
vitro fertilization: a metaanalysis and comparison with basal follicle-stimulatinghormone level. Fertil Steril. 2005;83(2):291-301.
36. Iliodromiti S, Anderson RA, Nelson SM. Technical and performance characteristics of anti-Müllerian hormone and antral follicle count as biomarkers of
ovarian response. Hum Reprod Update. 2015;21(6):698-710.
37. 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.
38. Polyzos NP, Tournaye H, Guzman L, Camus M, Nelson SM. Predictors of ovarian response in women treated with corifollitropin alfa for in vitro
fertilization/intracytoplasmicsperm injection. Fertil Steril. 2013;100(2):430-437.
39. Neves AR, Blockeel C, Griesinger G, et al. The performance of the Elecsys anti-Müllerian hormone assay in predicting extremes of ovarian response to
corifollitropinalfa. Reprod Biomed Online. 2020;41(1):29-36.
40. Esteves SC, Yarali H, Vuong LN, et al. Antral follicle count and anti-Müllerian hormone to classify low-prognosis women under the POSEIDON criteria: a
classificationagreement study of over 9000 patients. Hum Reprod. 2021;36(6):1530-1541.
41. Tomas C, Nuojua-Huttunen S, Martikainen H. Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in
in-vitro fertilization.Hum Reprod. 1997;12(2):220-223.
42. Chang MY, Chiang CH, Hsieh TT, Soong YK, Hsu KH. Use of the antral follicle count to predict the outcome of assisted reproductive technologies. Fertil
Steril. 1998;69(3):505-510.
43. Hsu A, Arny M, Knee AB, et al. Antral follicle count in clinicalpractice:analyzing clinicalrelevance. Fertil Steril. 2011;95(2):474-479.
44. Tsakos E, Tolikas A, Daniilidis A, Asimakopoulos B. Predictive value of anti-müllerian hormone, follicle-stimulating hormone and antral follicle count
on the outcome of ovarian stimulationin women following GnRH-antagonist protocol for IVF/ET. Arch Gynecol Obstet. 2014;290(6):1249-1253.
45. Blazar AS, Lambert-Messerlian G, Hackett R, Krotz S, Carson SA, Robins JC. Use of in-cycle antimüllerian hormone levels to predict cycle outcome. Am J
Obstet Gynecol. 2011;205(3):223.e1- 223.e5

20. 20
46. 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.
47. La Marca A, Argento C, Sighinolfi G, et al. Possibilities and limits of ovarian reserve testing in ART. Curr Pharm Biotechnol.
2012;13(3):398-408.
48. Oudshoorn SC, van Tilborg TC, Eijkemans MJC, et al; OPTIMIST Study Group. Individualized versus standard FSH dosing in women starting
IVF/ICSI: an RCT. Part 2: the predicted hyper responder. Hum Reprod. 2017;32(12):2506-2514.
49. Sopa N, Larsen EC, Westring Hvidman H, Andersen AN. An AMHbased FSH dosing algorithm for OHSS risk reduction in first cycle
antagonist protocol for IVF/ICSI. Eur J Obstet Gynecol Reprod Biol. 2019;237:42-47.
50. Broer SL, Dólleman M, Opmeer BC, Fauser BC, Mol BW, Broekmans FJM. AMH and AFC as predictors of excessive response in controlled
ovarian hyperstimulation: a meta-analysis. Hum Reprod Update. 2011;17(1):46-54.
51. Allegra A, Marino A, Volpes A, et al. A randomized controlled trial investigating the use of a predictive nomogram for the selection of the
FSH starting dose in IVF/ICSI cycles. Reprod Biomed Online. 2017;34(4):429-438.
52. Galindo A, Bodri D, Guillén JJ, Colodrón M, Vernaeve V, Coll O. Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte
donation cycles: a randomised clinical trial. Gynecol Endocrinol. 2009;25(1):60-66.
53. Youssef MAFM, Van der Veen F, Al-Inany HG, et al. Gonadotropinreleasing hormone agonist versus HCG for oocyte triggering in
antagonist-assisted reproductive technology. Cochrane Database Syst Rev. 2014(10):CD008046.
54. Burks HR, Ross L, Opper N, Paulson E, Stanczyk FZ, Chung K. Can highly sensitive antimüllerian hormone testing predict failed response
to ovarian stimulation? Fertil Steril. 2015;104(3):643-648.
55. Morin SJ, Patounakis G, Juneau CR, Neal SA, Scott RT Jr, Seli E. Diminished ovarian reserve and poor response to stimulation in patients <
38 years old: a quantitative but not qualitative reduction in performance. Hum Reprod. 2018;33(8):1489-1498.
56. Jaswa EG, McCulloch CE, Simbulan R, Cedars MI, Rosen MP. Diminished ovarian reserve is associated with reduced euploid rates via
preimplantation genetic testing for aneuploidy independently from age: evidence for concomitant reduction in oocyte quality with quantity.
Fertil Steril. 2021;115(4):966-973. 57. Haahr T, Dosouto C, Alviggi C, Esteves SC, Humaidan P. Management strategies for POSEIDON
groups 3 and 4. Front Endocrinol (Lausanne). 2019;10:614.
58. Tal R, Seifer DB, Tal R, Granger E, Wantman E, Tal O. AMH highly correlates with cumulative live birth rate in women with diminished
ovarian reserve independent of age. J Clin Endocrinol Metab. 2021;106(9):2754-2766. 59. Legro RS, Brzyski RG, Diamond MP, et al.
Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119-129.
60. Balen AH, Morley LC, Misso M, et al. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis

21. 21
61. Tranoulis A, Laios A, Pampanos A, Yannoukakos D, Loutradis D, Michala L. Efficacy and safety of pulsatile gonadotropin-releasing hormone therapy
among patients with idiopathic and functional hypothalamic amenorrhea: a systematic review of the literature and a meta-analysis. Fertil Steril.
2018;109(4):708-719.e8.
62. Dumont A, Dewailly D, Plouvier P, Catteau-Jonard S, Robin G. Comparison between pulsatile GnRH therapy and gonadotropins for ovulation induction
in women with both functional hypothalamic amenorrhea and polycystic ovarian morphology. Gynecol Endocrinol. 2016;32(12):999-1004. 63. Bozdag G,
Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-
analysis. Hum Reprod. 2016;31(12):2841-2855.
64. 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. Blackwell Scientific; 1992:377-384. 65. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus
on diagnostic criteriaand longterm health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19-25.
66. Teede HJ, Misso ML, Costello MF, et al; International PCOS Network. Recommendations from the international evidence-based guideline for the
assessment and management of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2018;89(3):251-268. 67. 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.
68. 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.
69. 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.
70. Lauritsen MP, Bentzen JG, Pinborg A, et al. The prevalence of polycystic ovary syndrome in a normal population according to the Rotterdam criteria
versus revised criteriaincluding anti-Mullerianhormone. Hum Reprod. 2014;29(4):791-801.
71. Quinn MM, Kao CN, Ahmad AK, et al; NIH/NICHD Reproductive Medicine Network. Age-stratified thresholds of antiMüllerian hormone improve
prediction of polycystic ovary syndrome over a population-based threshold. Clin Endocrinol (Oxf). 2017;87(6):733-740. 72. Teede HJ, Misso ML,
Costello MF, et al; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management
of polycystic ovary syndrome. Fertil Steril. 2018;110(3):364-379. 73. Mumford SL, Legro RS, Diamond MP, et al. Baseline AMH level associated with
ovulation following ovulation induction in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2016;101(9):3288-3296.
74. Zarek SM, Mitchell EM, Sjaarda LA, et al. Antimüllerian hormone and pregnancy loss from the Effects of Aspirin in Gestation and Reproduction trial. Fertil
Steril. 2016;105(4):946-952.e2.
75. Dólleman M, Verschuren WMM, Eijkemans MJC, Broekmans FJM, van der Schouw YT. Added value of anti-Müllerian hormone in prediction of
menopause: results from a large prospective cohort study. Hum Reprod. 2015;30(8):1974-1981

22. 22
76. de Kat AC, van der Schouw YT, Eijkemans MJC, Verschuren WMM, Broekmans FJM. Can menopause prediction be improved with multiple
AMH measurements? results from the prospective Doetinchem Cohort Study. J Clin Endocrinol Metab. 2019;104(11):5024-5031. 77.
Finkelstein JS, Lee H, Karlamangla A, et al. Antimullerian hormone and impending menopause in late reproductive age: the Study of
Women’s Health Across the Nation. J Clin Endocrinol Metab. 2020;105(4):e1862-e1871.
78. Skillern A, Rajkovic A. Recent developments in identifying genetic determinants of premature ovarian failure. Sex Dev. 2008;2(4-
5):228-243. 79. Bilgin EM, Kovanci E. Genetics of premature ovarian failure. Curr Opin Obstet Gynecol. 2015;27(3):167-174.
80. Mersereau JE, Evans ML, Moore DH, et al. Luteal phase estrogen is decreased in regularly menstruating older women compared with a
reference population of younger women. Menopause. 2008;15(3):482-486.
81. Tran ND, Cedars MI, Rosen MP. The role of anti-müllerian hormone (AMH) in assessing ovarian reserve. J Clin Endocrinol Metab.
2011;96(12):3609-3614. 82. Bry-Gauillard H, Larrat-Ledoux F, Levaillant JM, et al. AntiMüllerian hormone and ovarian morphology in
women with isolated hypogonadotropic hypogonadism/Kallmann syndrome: effects of recombinant human FSH. J Clin Endocrinol Metab
2017;102(4):1102-1111.
83. Kallio S, Puurunen J, Ruokonen A, Vaskivuo T, Piltonen T, Tapanainen JS. Antimüllerian hormone levels decrease in women using
combined contraception independently of administration route. Fertil Steril. 2013;99(5):1305-1310.
84. Birch Petersen K, Hvidman HW, Forman JL, et al. Ovarian reserve assessment in users of oral contraception seeking fertility advice on
their reproductive lifespan. Hum Reprod. 2015;30(10):2364-2375.
85. Amer SAKS, James C, Al-Hussaini TK, Mohamed AA. Assessment of circulating anti-Müllerian hormone in women using hormonal
contraception: a systematic review. J Womens Health (Larchmt). 2020;29(1):100-110.
86. Bernardi LA, Weiss MS, Waldo A, et al. Duration, recency, and type of hormonal contraceptive use and antimüllerian hormone levels. Fertil
Steril. 2021;116(1):208-217. 87. Landersoe SK, Birch Petersen K, Sørensen AL, et al. Ovarian reserve markers after discontinuing long-term
use of combined oral contraceptives. Reprod Biomed Online. 2020;40(1):176-186
88. Letourneau JM, Sinha N, Wald K, et al. Random start ovarian stimulation for fertility preservation appears unlikely to delay initiation of
neoadjuvant chemotherapy for breast cancer. Hum Reprod. 2017;32(10):2123-2129.
89. Steiner AZ, Stanczyk FZ, Patel S, Edelman A. Antimullerian hormone and obesity: insights in oral contraceptive users. Contraception.
2010;81(3):245-248.
90. Moslehi N, Shab-Bidar S, Ramezani Tehrani F, Mirmiran P, Azizi F. Is ovarian reserve associated with body mass index and obesity in
reproductive aged women? a meta-analysis. Menopause. 2018;25(9):1046-1055.
91. Jaswa EG, Rios JS, Cedars MI, et al. Increased body mass index is associated with a nondilutional reduction in antimüllerian hormone. J Clin

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