Department of Gynecology and Obstetrics, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Hum Reprod. 2014 Mar;29(3):518-24. doi: 10.1093/humrep/det468. Epub 2014 Jan 12.
Do parameters which are involved in pathogenesis of polycystic ovarian syndrome (PCOS) predict the dosage of recombinant FSH required to achieve monofollicular development for ovulation induction?
Anti-Mullerian hormone (AMH) appeared to be an independent predictor of the required dosage of FSH to achieve monofollicular development for ovulation induction in a study sample of clomiphene-resistant PCOS patients.
AMH plays a key role in the pathogenesis of PCOS. This is the first study that has evaluated the association between AMH and the required FSH dosage to achieve the development of a large follicle of at least 18 mm, in the presence of additional predictors of ovarian responsiveness. In the few studies to date which have evaluated predictors of ovarian responsiveness in PCOS patients, fasting insulin has been shown to be a significant predictor.
STUDY DESIGN, SIZE, DURATION: A total of 48 infertile PCOS patients aged 18-43 years were enrolled in this prospective, observational study between 2009 and 2013. Study participants received between one and six cycles of ovarian stimulation with recombinant FSH using a step-up protocol. The mean total FSH dosage per cycle for reaching a monofollicular development for ovulation induction was evaluated to investigate its association with AMH, LH, FSH, LH/FSH-ratio, sex hormone-binding globulin (SHBG), androstendione, testosterone, free testosterone index, antral follicle count, ovarian volume, body mass index (BMI) and the age of patients.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We used AMH-Gen-II ELISA (Beckman Coulter, Immunotech, Webster, TX, USA) for the assessment of AMH levels. Crude and multiple linear regression models were fitted to explore potential predictors of the required FSH dosage.
An interquartile range (IQR) increase in AMH was associated with a 51.4% [95% confidence interval (CI): 24.7-79.0%; P = 0.0003] increase in the mean total FSH dosage per cycle (in IU) in a crude regression model, corresponding to a 7.2% increase in the mean total FSH dosage per cycle per ng/ml AMH. Adjustment for BMI augmented the effect of AMH, with a 58.3% (95% CI: 33.2-84.2%; P = 1.8 × 10(-5)) increase in FSH dosage per IQR AMH (corresponding to an 8.2% increase per ng/ml AMH) and a 46.2% (95% CI: 16.5-76.6%; P = 0.003) increase per IQR BMI (corresponding to a 3.7% increase per kg/m(2)). AMH was the only independent variable for which the effect on FSH dosage was statistically significant in the crude regression model as well as after adjustment for other promising predictors. The association of BMI with FSH dosage was statistically significant while adjusted for AMH, but not in the crude model.
LIMITATIONS, REASONS FOR CAUTION: The impact of metabolic parameters such as insulin resistance on the reported association between AMH and FSH dosage was not assessed.
Knowledge about the predictors of ovarian sensitivity to FSH can facilitate a physician's decision-making in providing the optimal infertility therapy for PCOS patients.
STUDY FUNDING/COMPETING INTERESTS: Funding was provided by the University Hospital of Essen.
参与多囊卵巢综合征（PCOS）发病机制的参数是否可以预测重组 FSH 达到排卵诱导所需的剂量？
在抗苗勒管激素（AMH）的研究样本中，对于氯米酚耐药的 PCOS 患者，AMH 似乎是预测达到排卵诱导所需的 FSH 剂量的独立预测因子。
AMH 在 PCOS 的发病机制中起关键作用。这是第一项评估 AMH 与达到至少 18mm 大卵泡发育所需的 FSH 剂量之间关联的研究，同时考虑了其他卵巢反应性预测因子。迄今为止，评估 PCOS 患者卵巢反应性的少数研究表明，空腹胰岛素是一个重要的预测因子。
研究设计、大小和持续时间：2009 年至 2013 年期间，共纳入 48 名年龄在 18-43 岁之间的不孕 PCOS 患者进行了这项前瞻性、观察性研究。研究参与者接受了重组 FSH 的卵巢刺激，使用逐步递增方案进行了 1-6 个周期。评估每个周期达到排卵诱导所需的单卵泡发育所需的平均总 FSH 剂量，以研究其与 AMH、LH、FSH、LH/FSH 比值、性激素结合球蛋白（SHBG）、雄烯二酮、睾酮、游离睾酮指数、窦卵泡计数、卵巢体积、体重指数（BMI）和患者年龄的关系。
参与者/材料、设置、方法：我们使用 AMH-Gen-II ELISA（Beckman Coulter，Immunotech，Webster，TX，USA）评估 AMH 水平。使用粗回归模型和多元线性回归模型来探索潜在的 FSH 剂量预测因子。
AMH 的一个四分位距（IQR）增加与每个周期平均总 FSH 剂量（IU）的 51.4%（95%置信区间（CI）：24.7-79.0%；P=0.0003）增加相关，对应于每个周期每 ng/ml AMH 增加 7.2%的 FSH 剂量。调整 BMI 增强了 AMH 的作用，AMH 的 IQR 增加 58.3%（95%CI：33.2-84.2%；P=1.8×10(-5)），每个 IQR AMH 增加 8.2%的 FSH 剂量（对应于每 ng/ml AMH 增加 3.7%），BMI 的 IQR 增加 46.2%（95%CI：16.5-76.6%；P=0.003），对应于每 kg/m(2)增加 3.7%的 FSH 剂量。在粗回归模型和调整其他有希望的预测因子后，AMH 是唯一对 FSH 剂量有统计学意义的独立变量。BMI 与 FSH 剂量的关联在调整 AMH 后具有统计学意义，但在粗模型中则没有。
局限性、谨慎的原因：未评估代谢参数（如胰岛素抵抗）对 AMH 和 FSH 剂量之间报告关联的影响。
了解卵巢对 FSH 敏感性的预测因子可以帮助医生在为 PCOS 患者提供最佳的不孕治疗方案时做出决策。
研究资金/利益冲突：该研究由埃森大学医院提供资金。
