Polyzos Nikolaos P, Sakkas Evangelos, Vaiarelli Alberto, Poppe Kris, Camus Michel, Tournaye Herman
Center for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium Department of Clinical Medicine, Faculty of Health, University of Aarhus, Incuba/Skejby, bld. 2, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Aarhus, Denmark
Center for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
Hum Reprod. 2015 Jul;30(7):1690-6. doi: 10.1093/humrep/dev089. Epub 2015 May 6.
Is there any association between thyroid autoimmunity (TAI) and diminished ovarian reserve (DOR)?
TAI and hypothyroidism are not associated with low ovarian reserve.
TAI is a common co-existent endocrinopathy in women with primary ovarian insufficiency. Several studies support a potential link between TAI and the reduction in ovarian reserve. However, robust evidence regarding its prevalence in women with DOR is lacking.
STUDY DESIGN, SIZE, DURATION: This study is a large cross-sectional analysis of retrospective data from the Centre for Reproductive Medicine/University Hospital of Brussels. Serum measurements were taken for anti-Mullerian hormone (AMH), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and anti-thyroperoxidase (anti-TPO).
PARTICIPANTS/MATERIALS, SETTING, METHODS: Among 5076 consecutive women, 4894 women had their AMH, FT4, TSH and anti-TPO levels measured on the same day. AMH levels were plotted in relation to age for the whole patients' cohort and age-specific AMH values (per year) were considered in order to categorize women according to the AMH levels of ovarian reserve. There were 3929 women who demonstrated normal reserve, 487 women who had low ovarian reserve and 478 women who demonstrated high ovarian reserve.
Serum FT4 and TSH levels were comparable between different ovarian reserve categories (P = 0.611 and 0.811, respectively). No significant differences were observed in the prevalence of positive anti-TPO antibodies among women with low (12.1%), normal (10.3%) and high (9.8%) ovarian reserve (P = 0.423). Finally, the prevalence of overt or subclinical hypothyroidism was comparable between the groups (4.1% in low, 4.6% in normal and 3.8% in high ovarian reserve women, P = 0.645).Analysis according to the exact cause of low ovarian reserve demonstrated that women with a genetic cause of low ovarian reserve had a significantly higher prevalence of overt hypothyroidism and subclinical hypothyroidism compared with women with unexplained low ovarian reserve for their age (25 versus 3.2%, P = 0.002 and 18.8 versus 1.6%, P = 0.004, respectively). On the contrary, no significant differences were observed in the prevalence of hypothyroidism between genetic causes and iatrogenic causes (P = 0.316) and between iatrogenic and unexplained causes (P = 0.219) of low ovarian reserve.
LIMITATIONS, REASONS FOR CAUTION: This is a cross-sectional analysis based on retrospective data collection. Due to the retrospective design of this study, the presence of biases related to such a study design cannot be excluded. Furthermore, this study assessed only the association of TAI, and not autoimmunity in general, with ovarian reserve.
TAI and hypothyroidism are not associated with low ovarian reserve. Future research should focus on examining underlying mechanisms, other than TAI, which may have an effect on ovarian reserve.
STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. No conflicts of interest are declared.
甲状腺自身免疫（TAI）与卵巢储备功能减退（DOR）之间是否存在关联？
TAI和甲状腺功能减退与低卵巢储备无关。
TAI是原发性卵巢功能不全女性中常见的并存内分泌病。多项研究支持TAI与卵巢储备功能降低之间存在潜在联系。然而，缺乏关于其在DOR女性中患病率的有力证据。
研究设计、规模、持续时间：本研究是对布鲁塞尔大学医院生殖医学中心的回顾性数据进行的大型横断面分析。检测血清中的抗苗勒管激素（AMH）、游离甲状腺素（FT4）、促甲状腺激素（TSH）和抗甲状腺过氧化物酶（抗-TPO）。
参与者/材料、环境、方法：在5076名连续的女性中，4894名女性在同一天检测了AMH、FT4、TSH和抗-TPO水平。针对整个患者队列绘制了AMH水平与年龄的关系图，并考虑了特定年龄的AMH值（每年），以便根据卵巢储备的AMH水平对女性进行分类。有3929名女性显示储备正常，487名女性卵巢储备功能低，478名女性卵巢储备功能高。
不同卵巢储备类别之间的血清FT4和TSH水平相当（P分别为0.611和0.811）。卵巢储备功能低（12.1%）、正常（10.3%）和高（9.8%）的女性中，抗-TPO抗体阳性的患病率无显著差异（P = 0.423）。最后，各组之间显性或亚临床甲状腺功能减退的患病率相当（卵巢储备功能低的女性中为4.1%，正常的为4.6%，高的为3.8%，P = 0.645）。根据卵巢储备功能降低的确切原因进行分析表明，与年龄相符的不明原因卵巢储备功能降低的女性相比，因遗传原因导致卵巢储备功能降低的女性显性甲状腺功能减退和亚临床甲状腺功能减退的患病率显著更高（分别为25%对3.2%；P = 0.002和18.8%对1.6%；P = 0.004）。相反，在遗传原因与医源性原因导致的卵巢储备功能降低之间（P = 0.316）以及医源性与不明原因导致的卵巢储备功能降低之间（P = 0.219），甲状腺功能减退的患病率无显著差异。
局限性、谨慎原因：这是一项基于回顾性数据收集的横断面分析。由于本研究的回顾性设计，不能排除与这种研究设计相关的偏倚。此外，本研究仅评估了TAI与卵巢储备的关联，而非一般自身免疫与卵巢储备的关联。
TAI和甲状腺功能减退与低卵巢储备无关。未来的研究应侧重于研究除TAI之外可能影响卵巢储备的潜在机制。
研究资金/利益冲突：本研究未使用外部资金。未声明存在利益冲突。
