Age Group-specific Reference Intervals for the Elecsys Anti-Müllerian Hormone Assay in Healthy Korean Women: a Nationwide Population-based Study

다국어 초록 (Multilingual Abstract)

Background: Anti-Müllerian hormone (AMH) is one of the most reliable markers of ovarian reserve. Automated AMH assays are widely used in clinical laboratories, but reference intervals for the Elecsys AMH assay for Asian populations have not yet been determined.
We aimed to determine reference intervals in healthy Korean women.
Methods: The study included 1,450 women aged 19 to 54 years who participated in the Korea National Health and Nutrition Examination Survey between 2013 and 2016. The study participants were divided into seven 5-year age groups. AMH and progesterone concentrations were measured using Roche Elecsys assays, and bone morphogenetic protein-15 (BMP15) was genotyped for the detection of major variants. Age group-specific reference intervals for AMH were established as recommended by the CLSI EP28-A3c guidelines.
Results: The mean age was 37.4 years. AMH concentrations decreased with increasing age, especially after 40 years, with the median AMH decreasing from 30.9 pmol/L in participants of 19–24 years to 0.071 pmol/L in participants of 50–54 years. The mid-95 percentile AMH reference intervals decreased from 7.93–81.21 pmol/L in participants of 19– 24 years to 0.07–3.86 pmol/L in participants of 50–54 years. Disease-associated BMP15 variants were not detected.
Conclusions: We determined Elecsys AMH assay reference intervals in healthy Korean women. The results may provide basic information for the interpretation of AMH concentrations and assessment of ovarian reserve in Korean women.

참고문헌 (Reference)

1 이지은 ; 박동수 ; 김미라 ; 윤보성 ; 송태종 ; 김미경 ; 성석주 ; 김영주, "규칙적인 생리주기를 갖는 2,879명의 한국 여성에서의 나이에 따른 anti-Müllerian hormone 수치 분포에 관한 연구" 대한산부인과학회 55 (55): 920-928, 2012

2 Nelson SM, "Two new automated, compared with two enzyme-linked immunosorbent, antimüllerian hormone assays" 104 : 1016-1021, 2015

3 Dewailly D, "The physiology and clinical utility of anti-Mullerian hormone in women" 20 : 370-385, 2014

4 Rustamov O, "The measurement of anti-Müllerian hormone : a critical appraisal" 99 : 723-732, 2014

5 Kim Y, "The Korea National Health and Nutrition Examination Survey(KNHANES) : current status and challenges" 36 : e2014002-, 2014

6 Podfigurna A, "Testing ovarian reserve in pre-menopausal women: why, whom and how?" 109 : 112-117, 2018

7 Kim Sollip ; Lee Kyunghoon ; Park Hyung-Doo ; Lee Yong-Wha ; Chun Sail ; Min Won-Ki, "Schemes and Performance Evaluation Criteria of Korean Association of External Quality Assessment (KEQAS) for Improving Laboratory Testing" 대한진단검사의학회 41 (41): 230-239, 2021

8 이중엽 ; 안소연 ; 이정렬 ; 지병철 ; 김청현 ; 서소연 ; 서창석 ; 김석현, "Reference Values for the Revised Anti-Müllerian Hormone Generation II Assay: Infertile Population-based Study" 대한의학회 32 (32): 825-829, 2017

9 Zou Yutong ; Wang Danchen ; Cheng Xinqi ; Ma Chaochao ; Lin Songbai ; Hu Yingying ; Yu Songlin ; Xia Liangyu ; Li Honglei ; Yin Yicong ; Liu Huaicheng ; Zhang Dianxi ; Zhang Kui ; Lian Xiaolan ; Xu Tengda ; Qiu Ling, "Reference Intervals for Thyroid-Associated Hormones and the Prevalence of Thyroid Diseases in the Chinese Population" 대한진단검사의학회 41 (41): 77-85, 2021

10 Shin HY, "Recent trends in the prevalence of underweight, overweight, and obesity in Korean adults: the Korean National Health and Nutrition Examination Survey from 1998 to 2014" 27 : 413-419, 2017

11 Bleil ME, "Race/ethnic disparities in reproductive age: an examination of ovarian reserve estimates across four race/ethnic groups of healthy, regularly cycling women" 101 : 199-207, 2014

12 van Helden J, "Performance of the two new fully automated anti-Müllerian hormone immunoassays compared with the clinical standard assay" 30 : 1918-1926, 2015

13 Demirdjian G, "Performance characteristics of the Access AMH assay for the quantitative determination of anti-Müllerian hormone(AMH)levels on the Access* family of automated immunoassay systems" 49 : 1267-1273, 2016

14 Tal R, "Ovarian reserve testing : a user’s guide" 217 : 129-140, 2017

15 Cho SY, "Opening of the national biobank of Korea as the infrastructure of future biomedical science in Korea" 3 : 177-184, 2012

16 남가은 ; 김양현 ; 한경도 ; 정진형 ; 이은정 ; 이성수 ; 김대중 ; 이관우 ; 이원영 ; the Taskforce Team of the Obesity Fact Sheet of the Korean Society for the Study of Obesity, "Obesity Fact Sheet in Korea, 2019: Prevalence of Obesity and Abdominal Obesity from 2009 to 2018 and Social Factors" 대한비만학회 29 (29): 124-132, 2020

17 Iliodromiti S, "Non-equivalence of anti-Müllerian hormone automated assays-clinical implications for use as a companion diagnostic for individualised gonadotrophin dosing" 32 : 1710-1715, 2017

18 El-Attar EA, "Nomogram of age-specific anti-Müllerian hormone levels in healthy Egyptian females" 16 : e0254858-, 2021

19 Anckaert E, "Multicenter analytical performance evaluation of a fully automated anti-Müllerian hormone assay and reference interval determination" 49 : 260-267, 2016

20 Dixit H, "Missense mutations in the BMP15 gene are associated with ovarian failure" 119 : 408-415, 2006

21 The International Consortium for Harmonization of Clinical Laboratory Results, "Measurands"

22 Moslehi N, "Is ovarian reserve associated with body mass index and obesity in reproductive aged women? A meta-analysis" 25 : 1046-1055, 2018

23 Di Pasquale E, "Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure" 91 : 1976-1979, 2006

24 Di Pasquale E, "Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15(BMP15)gene" 75 : 106-111, 2004

25 Ghazal Khaldoun ; Brabant Severine ; Prie Dominique ; Piketty Marie-Liesse, "Hormone Immunoassay Interference: A 2021 Update" 대한진단검사의학회 42 (42): 3-23, 2022

26 WHO, "Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity"

27 Pu D, "Gene variation and premature ovarian failure : a meta-analysis" 182 : 226-237, 2014

28 Gassner D, "First fully automated immunoassay for anti-Müllerian hormone" 52 : 1143-1152, 2014

29 Tukey JW, "Exploratory data analysis" Addison-Wesley Publishing Company 1977

30 Kotlyar AM, "Ethnicity/race and age-specific variations of serum AMH in women-A review" 11 : 593216-, 2021

31 Nelson SM, "Ethnic discordance in serum anti-Müllerian hormone in healthy women : a population study from China and Europe" 40 : 461-467, 2020

32 Cheng X, "Establishing age-specific reference intervals for anti-Müllerian hormone in adult Chinese women based on a multicenter population" 474 : 70-75, 2017

33 CLSI, "Defining, establishing, and verifying reference intervals in the Clinical Laboratory; approved guideline" Clinical and Laboratory Standards Institute 2010

34 Kweon S, "Data resource profile : the Korea National Health and Nutrition Examination Survey(KNHANES)" 43 : 69-77, 2014

35 Han Aera ; Suh Borum ; Yi Gwang ; Lee Yoo Jin ; Kim Sung Eun, "Comparison of the Automated Fluorescent Immunoassay System With Roche Elecsys and Beckman Coulter Access 2 Assays for Anti-Müllerian Hormone Measurement" 대한진단검사의학회 42 (42): 47-53, 2022

36 Rossetti R, "BMP15 mutations associated with primary ovarian insufficiency cause a defective production of bioactive protein" 30 : 804-810, 2009

37 Broer SL, "Anti-Müllerian hormone : ovarian reserve testing and its potential clinical implications" 20 : 688-701, 2014

38 Shahrokhi SZ, "Anti-Mullerian hormone : genetic and environmental effects" 476 : 123-129, 2018

39 Ji Hee Yoo ; Hye Ok Kim ; 차선화 ; Chan Woo Park ; Kwang Moon Yang ; In Ok Song ; Mi Kyoung Koong ; Inn Soo Kang, "Age specific serum anti-Müllerian hormone levels in 1,298 Korean women with regular menstruation" 대한생식의학회 38 (38): 93-97, 2011