OBJECTIVES:To investigate the association between anti-Müllerian hormone (AMH), a well-established marker of the ovarian reserve, and time-to-pregnancy (TTP) in natural conceptions, and to assess changes in serum-AMH in early pregnancy. STUDY DESIGN:A cross sectional study comprising 279 women aged 21-42 years with a natural conception recruited during 2012-2014. AMH was measured in gestational week 10-19. AMH z-scores (z-AMH) adjusted for gestational week at blood sampling were categorised in the 1st, 2nd-4th (reference), and 5th quintile. Data were analysed by discrete-time survival-analysis and results presented as odds ratios (OR), 95% confidence interval (CI); OR <1 indicating a longer TTP and OR >1 indicating a shorter TTP. RESULTS:The median AMH-level was 23.0 (range:<3.0;144.0)pmol/l, and serum-AMH decreased by 7.5% (95% CI:-12.0%;-2.8%) per gestational week. Mean±SD female age was 30.9±3.6years. The median TTP was 2 (range: 1-32) months. After adjustment for possible confounders including total sperm count, TTP was unrelated to female age (aOR:1.0, 95% CI:0.9;1.0) and continuous z-AMH (aOR:0.8, 95% CI:0.7;1.0), but women in the low z-AMH group had a shorter TTP than the reference group (aOR:1.7, 95% CI:1.1;2.7). TTP was prolonged in preconception oral contraceptive (OC) users (aOR:0.7, 95% CI:0.5;1.0, p=0.04). Compared with women having used OC <2 years, TTP was significantly longer in women having used OC for 2-12 years (aOR:0.5, 95% CI:0.2;1.0, p=0.048) and >12 years (aOR:0.4, 95% CI:0.2;0.9, p=0.022) after age-adjustment. CONCLUSIONS:TTP was unrelated with z-AMH when modelled as a continuous covariate. Unexpectedly, TTP was shorter in the low z-AMH group. Natural conception was observed in women with a wide range of AMH-levels including women with undetectable serum-AMH. A continuous decrease in serum-AMH was observed during first and second trimester. Preconception OC-use was identified as an independent predictor of a prolonged TTP, and the duration of OC-use appeared to influence the delay in conception. Although this is presently one of the largest studies investigating the association between AMH and fecundability in fertile women, the study has some limitation including a relatively low participation rate and a risk of selection bias in addition to AMH assessment in pregnancy and a retrospective collection of TTP and OC-use associated with a risk of recall bias. These limitations may explain the unexpected finding of a shorter TTP in the low z-AMH group.

译文

目的:研究公认的卵巢储备标志物抗苗勒氏激素(AMH)与自然受孕时间(TTP)之间的关联,并评估早孕期血清AMH的变化。
研究设计:一项横断面研究,由279名年龄在21-42岁之间的女性组成,他们在2012-2014年期间招募了一个自然受孕的女性。在孕10-19周测量AMH。在采血时调整孕周的AMH z得分(z-AMH)分为第一,第二,第四(参考)和第五个五分位数。数据通过离散时间生存分析进行分析,结果以比值比(OR),95%置信区间(CI)表示; OR <1表示较长的TTP,OR> 1表示较短的TTP。
结果:孕周平均AMH水平为23.0(范围:<3.0; 144.0)pmol / l,血清AMH下降了7.5%(95%CI:-12.0%;-2.8%)。女性的平均±SD年龄为30.9±3.6岁。 TTP的中位数为2(范围:1-32)个月。在对可能的混杂因素(包括精子总数)进行调整后,TTP与女性年龄(aOR:1.0,95%CI:0.9; 1.0)和持续性z-AMH(aOR:0.8,95%CI:0.7; 1.0)无关,但是女性低z-AMH组中的TTP比参考组短(aOR:1.7,95%CI:1.1; 2.7)。孕前口服避孕药(OC)使用者的TTP延长(aOR:0.7,95%CI:0.5; 1.0,p = 0.04)。与使用OC <2年的女性相比,使用OC 2至12年的女性(aOR:0.5,95%CI:0.2; 1.0,p = 0.048)和> 12岁(aOR:0.4, 95%CI:0.2; 0.9,p = 0.022)。
结论:当以连续协变量建模时,TTP与z-AMH不相关。出乎意料的是,低z-AMH组的TTP较短。在具有广泛AMH水平的女性中观察到自然受孕,包括血清AMH不可检测的女性。在孕早期和孕中期观察到血清AMH持续下降。避孕前使用OC被确定为TTP延长的独立预测因素,并且OC使用的持续时间似乎会影响受孕的延迟。尽管这是目前调查AMH与可育妇女生育力之间关系的最大研究之一,但该研究存在一些局限性,包括相对较低的参与率和除妊娠期AMH评估和TTP回顾性收集外还有选择偏见的风险。 OC使用会带来召回偏见风险。这些局限性可能解释了在低z-AMH组中意外发现更短的TTP的原因。

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