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Abstract：
OBJECTIVE: Subfertility, a time to pregnancy (TTP) longer than 12 months, is present in 40% of female patients with rheumatoid arthritis (RA) who are actively trying to conceive. Because patients with RA appear to reach menopause at a younger age, diminished ovarian function may explain the reduced fertility. Serum anti-Müllerian hormone (AMH) levels are the best proxy to measure ovarian function. Our objectives were to study AMH levels in female patients with RA and determine the association of preconception serum AMH levels with TTP.
METHODS: A post hoc analysis was performed before conception in patients of the Pregnancy-Induced Amelioration of Rheumatoid Arthritis (PARA) cohort. Serum AMH levels were compared with those in an existing cohort of healthy controls using analysis of covariance. Associations between AMH and TTP were studied using the Cox proportional hazard analysis.
RESULTS: Preconception serum was available in 209 women of the PARA cohort (aged 32.1 ± 3.9 years), of whom 45% were subfertile in the current episode. The median AMH level was 2.5 μg/l (interquartile range: 1.5-4.6). AMH levels were significantly lower compared with those in healthy controls (P < 0.001), with 17% of patients having levels below the age-specific 10th percentile. A multivariable analysis showed a negative association of AMH with the presence of anticitrullinated protein antibodies (ACPAs) (P = 0.009). AMH levels showed no significant association with TTP (P = 0.26).
CONCLUSIONS: Women with RA have lower AMH levels than healthy controls, and AMH levels were lower in ACPA-positive patients. However, because preconception AMH levels were not associated with TTP, the reduced AMH levels do not explain the reduced fertility in patients with RA.
METHODS: A post hoc analysis was performed before conception in patients of the Pregnancy-Induced Amelioration of Rheumatoid Arthritis (PARA) cohort. Serum AMH levels were compared with those in an existing cohort of healthy controls using analysis of covariance. Associations between AMH and TTP were studied using the Cox proportional hazard analysis.
RESULTS: Preconception serum was available in 209 women of the PARA cohort (aged 32.1 ± 3.9 years), of whom 45% were subfertile in the current episode. The median AMH level was 2.5 μg/l (interquartile range: 1.5-4.6). AMH levels were significantly lower compared with those in healthy controls (P < 0.001), with 17% of patients having levels below the age-specific 10th percentile. A multivariable analysis showed a negative association of AMH with the presence of anticitrullinated protein antibodies (ACPAs) (P = 0.009). AMH levels showed no significant association with TTP (P = 0.26).
CONCLUSIONS: Women with RA have lower AMH levels than healthy controls, and AMH levels were lower in ACPA-positive patients. However, because preconception AMH levels were not associated with TTP, the reduced AMH levels do not explain the reduced fertility in patients with RA.
摘要：
目标：不孕不育，怀孕时间（TTP）超过12个月，在积极尝试怀孕的类风湿关节炎（RA）女性患者中，有40％存在。因为RA患者似乎在更年轻的年龄达到更年期，卵巢功能减少可以解释生育能力下降的原因。血清抗苗勒管激素（AMH）水平是衡量卵巢功能的最佳指标。我们的目的是研究女性RA患者的AMH水平，并确定孕前血清AMH水平与TTP的关系。
方法：妊娠诱导类风湿关节炎改善（PARA）队列患者在受孕前进行事后分析。使用协方差分析将血清AMH水平与现有健康对照队列中的水平进行比较。使用Cox比例风险分析研究了AMH和TTP之间的关联。
结果：PARA队列中的209名女性（年龄32.1±3.9岁）可获得孕前血清，其中45%在当前情节中处于低生育能力。AMH水平中位数为2.5μg/l（四分位间距：1.5-4.6）。AMH水平显著低于健康对照组(P<0.001),17%的患者的水平低于特定年龄的第10百分位数。多变量分析显示AMH与抗瓜氨酸蛋白抗体（ACPAs）的存在呈负相关（P=0.009）。AMH水平与TTP无显著相关性(P=0.26)。
结论：RA患者的AMH水平低于健康对照组，ACPA阳性患者的AMH水平较低。然而,因为孕前AMH水平与TTP无关，AMH水平的降低并不能解释RA患者生育能力的降低.
方法：妊娠诱导类风湿关节炎改善（PARA）队列患者在受孕前进行事后分析。使用协方差分析将血清AMH水平与现有健康对照队列中的水平进行比较。使用Cox比例风险分析研究了AMH和TTP之间的关联。
结果：PARA队列中的209名女性（年龄32.1±3.9岁）可获得孕前血清，其中45%在当前情节中处于低生育能力。AMH水平中位数为2.5μg/l（四分位间距：1.5-4.6）。AMH水平显著低于健康对照组(P<0.001),17%的患者的水平低于特定年龄的第10百分位数。多变量分析显示AMH与抗瓜氨酸蛋白抗体（ACPAs）的存在呈负相关（P=0.009）。AMH水平与TTP无显著相关性(P=0.26)。
结论：RA患者的AMH水平低于健康对照组，ACPA阳性患者的AMH水平较低。然而,因为孕前AMH水平与TTP无关，AMH水平的降低并不能解释RA患者生育能力的降低.
