School of Medicine, University of Glasgow, Level two New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, UK.
Service de Gynecologie Endocrinienne et Medecine de la Reproduction, Hopital Jeanne de Flandre, Centre Hospitalier Regional Universitaire, 2 Avenue Oscar Lambret, 59037 Lille, France.
Hum Reprod. 2017 Aug 1;32(8):1710-1715. doi: 10.1093/humrep/dex219.
Can anti-Müllerian hormone (AMH) automated immunoassays (Elecsys® and Access) be used interchangeably as a companion diagnostic for individualisation of follitropin delta dosing?
The Access assay gives systematically higher AMH values than the Elecsys® assay which results in over 29% of women being misclassified to a different follitropin delta dose.
Follitropin delta is the first gonadotrophin to be licenced with a companion diagnostic, the Roche Elecsys® AMH Plus assay. Alternative automated AMH assays including the Beckman Coulter Access immunoassay are considered to provide similar results, but clarification of their suitability as an off-licence companion diagnostic for follitropin delta is required.
STUDY DESIGN, SIZE, DURATION: We systematically searched the existing literature for studies that had measured AMH using both automated assays in the same cohort of women. Individual paired patient data were acquired from each author and combined with unpublished data.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We identified five eligible prospective published studies and one additional unpublished study. A 100% response from the authors was achieved. We collected paired AMH data on samples from 848 women. Passing-Bablok regression and Bland-Altman plots were used to compare the analytical performance of the two assays. The degree of misclassification to different treatment categories was estimated should the Access AMH be used as a companion diagnostic instead of the Elecsys AMH in determining the dosing of follitropin delta.
The Passing-Bablok regression shows a linear relationship (Access = -0.05 + 1.10 × Elecsys). The Access assay systematically gave higher values by an average of 10% compared with the Elecsys assay (slope = 1.10, 95% CI: 1.09 to 1.12). The average of the difference between the two assays was 2.7 pmol/l. The 95% limits of agreement were -11.7 to 6.3. Overall 253 (29.3%) women would have received an inappropriate follitropin delta dose if the Beckman Coulter Access assay was used. Specifically, a substantial proportion of women (ranging from 49% to 90% depending on the AMH category) would receive a lower dose of follitropin delta based on the Access AMH assay. Up to 10% (ranging from 2.5% to 10%) of women with high ovarian reserve would have been misclassified to a greater dose of follitropin delta based on the Access AMH assay.
We compared the values of the two principal automated assays, extrapolation of our findings to other automated AMH assays would require similar comprehensive examination.
An international standard for the calibration of the automated AMH assays is warranted to facilitate efficient use of AMH as a companion diagnostic. The variable calibration of alternative automated AMH assays may adversely impact on the performance of the follitropin delta dosing algorithm.
STUDY FUNDING/COMPETING INTEREST(S): No formal funding has been received for this study. SI is funded by a UK Medical Research Council skills development fellowship (MR/N015177/1). SMN has received speakers fees, travel to meetings and participated in advisory Boards for Beckman Coulter, IBSA, Ferring Pharmaecuticals, Finox, Merck Serono, Merck and Roche Diagnostics. SMN has received research support from Ansh laboratories, Beckman Coulter, Ferring Pharmaceuticals and Roche Diagnostics.
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抗苗勒氏管激素（AMH）自动化免疫分析（Elecsys®和 Access）能否作为个体化促卵泡激素 delta 剂量的伴随诊断进行互换使用？
Access 检测法给出的 AMH 值系统上高于 Elecsys®检测法，这导致超过 29%的女性被错误分类为不同的促卵泡激素 delta 剂量。
促卵泡激素 delta 是第一个获得伴随诊断许可的促性腺激素，即罗氏 Elecsys® AMH Plus 检测法。其他的自动化 AMH 检测法，包括贝克曼库尔特 Access 免疫分析，被认为提供了相似的结果，但需要澄清它们作为促卵泡激素 delta 的非许可伴随诊断的适用性。
研究设计、规模、持续时间：我们系统地在同一批女性的研究中搜索了同时使用两种自动化检测法测量 AMH 的现有文献。从每位作者那里获取了个体配对患者的数据，并结合了未发表的数据。
参与者/材料、设置、方法：我们确定了五项符合条件的前瞻性已发表研究和一项额外的未发表研究。作者实现了 100%的回复率。我们收集了 848 名女性样本的配对 AMH 数据。采用 Passing-Bablok 回归和 Bland-Altman 图比较了两种检测法的分析性能。如果在确定促卵泡激素 delta 剂量时使用贝克曼库尔特 Access AMH 作为伴随诊断，估计会有多少女性被错误分类到不同的治疗类别。
Passing-Bablok 回归显示出线性关系（Access = -0.05 + 1.10×Elecsys）。Access 检测法平均比 Elecsys 检测法高出 10%（斜率=1.10，95%CI：1.09 至 1.12）。两种检测法之间差值的平均值为 2.7 pmol/l。95%的一致性区间为-11.7 至 6.3。如果使用贝克曼库尔特 Access 检测法，总体上有 253（29.3%）名女性将接受不适当的促卵泡激素 delta 剂量。具体而言，根据 Access AMH 检测法，相当一部分女性（根据 AMH 类别，比例从 49%到 90%不等）将接受较低剂量的促卵泡激素 delta。根据 Access AMH 检测法，多达 10%（范围从 2.5%到 10%）的卵巢储备较高的女性可能会被错误分类为更大剂量的促卵泡激素 delta。
局限性/谨慎原因：我们比较了两种主要的自动化检测法的数值，将我们的发现外推到其他自动化 AMH 检测法需要类似的全面检查。
有必要建立自动化 AMH 检测法的国际校准标准，以促进 AMH 作为伴随诊断的有效使用。替代自动化 AMH 检测法的可变校准可能会对促卵泡激素 delta 剂量算法的性能产生不利影响。
研究资助/利益冲突：这项研究没有收到正式的资助。SI 由英国医学研究理事会技能发展奖学金（MR/N015177/1）资助。SMN 曾获得贝克曼库尔特、IBSA、费森尤斯制药、芬诺克斯、默克雪兰诺、默克和罗氏诊断公司的演讲费、会议差旅费和参与顾问委员会。SMN 从 Ansh 实验室、贝克曼库尔特、费森尤斯制药和罗氏诊断公司获得了研究支持。
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