Drakopoulos Panagiotis, van de Vijver Arne, Parra Jose, Anckaert Ellen, Schiettecatte Johan, Blockeel Christophe, Hund Martin, Verhagen-Kamerbeek Wilma D J, He Ying, Tournaye Herman, Polyzos Nikolaos P
Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Front Endocrinol (Lausanne). 2019 Feb 26;10:115. doi: 10.3389/fendo.2019.00115. eCollection 2019.
What is the effect of gonadotropin-releasing hormone (GnRH)-agonist treatment on serum anti-Müllerian hormone (AMH)? This prospective cohort study conducted in a tertiary university hospital comprised patients ( = 52) who self-administered daily triptorelin (0.1 mg/0.1 mL) subcutaneously for 14 days from menstrual cycle day 21 ± 3, between July 2015 and March 2016. Enrolled women were 18-43 years old, considered normal ovarian responders, with a planned GnRH agonist controlled ovarian stimulation protocol. The primary endpoint was to evaluate the effect of GnRH agonist on serum AMH levels after 7 and 14 days of treatment. Under GnRH agonist treatment, serum AMH was significantly decreased vs. baseline on day 7 (mean change from baseline: -0.265 ng/mL; 95% confidence interval [CI], -0.395 to -0.135 ng/mL; < 0.001). On day 14, serum AMH was significantly increased (mean change from baseline: 0.289 ng/mL; 95% CI, 0.140-0.439 ng/mL; < 0.001). Although the median change in AMH from baseline was only -14.9% on day 7 and +17.4% on day 14, from day 7 to 14 AMH significantly increased by 0.55 ng/mL (43.8%; < 0.001), which is of paramount clinical importance. A linear, mixed-effect model demonstrated that GnRH agonist treatment for 7 and 14 days had a highly significant effect on serum AMH concentration after adjustment for confounding factors (age, body mass index, baseline antral follicle count, and visit). AMH assay precision was excellent (four aliquots/sample); coefficient of variation was 1.2-1.4%. GnRH agonist treatment had a clinically significant effect on serum AMH, dependent on treatment duration. The clear V-shaped response of AMH level to daily GnRH agonist treatment has important clinical implications for assessing ovarian reserve and predicting ovarian response, thus AMH measurements under GnRH agonist downregulation should be interpreted with great caution.
促性腺激素释放激素(GnRH)激动剂治疗对血清抗苗勒管激素(AMH)有何影响?这项前瞻性队列研究在一家三级大学医院开展,研究对象为2015年7月至2016年3月期间从月经周期第21±3天开始连续14天每日皮下自行注射曲普瑞林(0.1 mg/0.1 mL)的52例患者。入选女性年龄在18至43岁之间,被认为是正常卵巢反应者,采用计划的GnRH激动剂控制性卵巢刺激方案。主要终点是评估GnRH激动剂治疗7天和14天后对血清AMH水平的影响。在GnRH激动剂治疗下,第7天时血清AMH较基线水平显著降低(相对于基线的平均变化:-0.265 ng/mL;95%置信区间[CI],-0.395至-0.135 ng/mL;P<0.001)。第14天时,血清AMH显著升高(相对于基线的平均变化:0.289 ng/mL;95%CI,0.140 - 0.439 ng/mL;P<0.001)。尽管第7天时AMH相对于基线的中位数变化仅为-14.9%,第14天时为+17.4%,但从第7天到第14天AMH显著升高了0.55 ng/mL(43.8%;P<0.001),这具有至关重要的临床意义。线性混合效应模型表明,在调整混杂因素(年龄、体重指数、基线窦卵泡计数和就诊情况)后,GnRH激动剂治疗7天和14天对血清AMH浓度有高度显著影响。AMH检测精密度极佳(每个样本4份等分试样);变异系数为1.2 - 1.4%。GnRH激动剂治疗对血清AMH有临床显著影响,这取决于治疗持续时间。AMH水平对每日GnRH激动剂治疗呈现明显的V形反应,这对于评估卵巢储备和预测卵巢反应具有重要临床意义,因此在GnRH激动剂下调情况下进行AMH测量时应极其谨慎地解读。