STUDY QUESTION:Are maternal preconception lipid levels associated with fecundability? SUMMARY ANSWER:Fecundability was reduced for all abnormal female lipid levels including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total triglyceride levels. WHAT IS KNOWN ALREADY:Subfecundity affects 7-15% of the population and lipid disorders are hypothesized to play a role since cholesterol acts as a substrate for the synthesis of steroid hormones. Evidence illustrating this relationship at the mechanistic level is mounting but few studies in humans have explored the role of preconception lipids in fecundity. STUDY DESIGN, SIZE, DURATION:A secondary analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (2007-2011), a block-randomized, double-blind, placebo-controlled trial. PARTICIPANTS/MATERIALS, SETTING, METHODS:A total of 1228 women, with 1-2 prior pregnancy losses and without a diagnosis of infertility, attempting pregnancy for up to six menstrual cycles were recruited from clinical sites in Utah, New York, PA and Colorado. Time to pregnancy was the number of menstrual cycles to pregnancy as determined by positive hCG test or ultrasound. Individual preconception lipoproteins were measured at baseline, prior to treatment randomization and dichotomized based on clinically accepted cut-points as total cholesterol ≥200 mg/dl, LDL-C ≥130 mg/dl, HDL-C <50 mg/dl and triglycerides ≥150 mg/dl. MAIN RESULTS AND THE ROLE OF CHANCE:There were 148 (12.3%) women with elevated total cholesterol, 94 (7.9%) with elevated LDL-C, 280 (23.2%) with elevated triglycerides and 606 (50.7%) with low HDL-C. The fecundability odds ratio (FOR) was reduced for all abnormal lipids before and after confounder adjustment, indicating reduced fecundability. Total cholesterol ≥200 mg/dl was associated with 24% (FOR: 0.76, 95% CI: 0.59, 0.97) and 29% (FOR: 0.71, 95% CI: 0.55, 0.93) reduced fecundability for hCG-detected and ultrasound-confirmed pregnancy, respectively, compared with total cholesterol <200 mg/dl. There was a 19-36% decrease in the probability of conception per cycle for women with abnormal lipoprotein levels, though additional adjustment for central adiposity and BMI attenuated observed associations. LIMITATIONS, REASONS FOR CAUTION:Although the FOR is a measure of couple fecundability, we had only measures of female lipid levels and can therefore not confirm the findings from a previous study indicating the independent role of male lipids in fecundity. The attenuated estimates and decreased precision after adjustment for central adiposity and obesity indicate the complexity of potential causal lipid pathways, suggesting other factors related to obesity besides dyslipidemia likely contribute to reduced fecundability. WIDER IMPLICATIONS OF THE FINDINGS:Our results are consistent with one other study relating preconception lipid concentrations to fecundity and expand these findings by adding critically important information about individual lipoproteins. As lipid levels are modifiable they may offer an inexpensive target to improve female fecundability. STUDY FUNDING AND COMPETING INTEREST(S):This study was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have declared that no conflicts of interest exist. TRIAL REGISTRATION NUMBER:#NCT00467363.

译文

研究问题:孕产妇的孕前血脂水平是否与生育能力有关?
总结答案:所有异常女性脂质水平,包括总胆固醇,低密度脂蛋白胆固醇(LDL-C),高密度脂蛋白胆固醇(HDL-C)和总甘油三酸酯水平的可育性均降低。
已经知道的是:亚生育力影响了7-15%的人口,并且由于胆固醇是类固醇激素合成的底物,脂质障碍被认为发挥了作用。在机械水平上说明这种关系的证据越来越多,但是在人类中很少有研究探讨先孕脂质在生殖力中的作用。
研究设计,大小,时间:阿司匹林在妊娠和生殖中的作用的二次分析(EAGeR)试验(2007-2011年),该试验是一项区块随机,双盲,安慰剂对照试验。
参与者/材料,背景,方法:从犹他州,纽约州,宾夕法尼亚州和科罗拉多州的临床地点招募了总共1228名女性,这些女性有1-2例先兆流产且没有诊断出不育症,并尝试了长达六个月经的尝试怀孕。 。怀孕时间是通过hCG测试阳性或超声确定的怀孕月经周期数。在治疗随机化之前,在基线时测量各个受孕前的脂蛋白,并根据临床可接受的切分标准将其二分为二,因为总胆固醇≥200 mg / dl,LDL-C≥130mg / dl,HDL-C <50 mg / dl和甘油三酯≥ 150毫克/分升。
主要结果和机会:总胆固醇升高的女性有148位(12.3%),低密度脂蛋白胆固醇升高的女性有94位(7.9%),甘油三酸酯升高的女性有280位(23.2%),高密度脂蛋白低的女性606位(50.7%)。 C。混杂因素调整前后,所有异常脂质的生育能力比值比(FOR)均降低,表明生育力降低。总胆固醇≥200mg / dl与24%(FOR:0.76,95%CI:0.59,0.97)和29%(FOR:0.71,95%CI:0.55,0.93)降低了hCG检测和超声检查的生育能力。确认怀孕的总胆固醇分别低于200 mg / dl。脂蛋白水平异常的女性,每个周期受孕的可能性降低了19-36%,尽管对中央肥胖和BMI的进一步调整减弱了观察到的关联。
局限性,注意事项的原因:尽管FOR是衡量夫妇生育能力的指标,但我们仅能测量雌性脂质水平,因此无法证实以前的研究结果表明雄性脂质在生育力中的独立作用。对中心性肥胖和肥胖症进行调整后,估计值的降低和准确性下降表明潜在的因果性脂质途径的复杂性,表明除血脂异常外,与肥胖症相关的其他因素也可能导致生育能力降低。
研究结果的进一步暗示:我们的结果与另一项有关将先孕期血脂浓度与生育力相关的研究一致,并通过添加有关单个脂蛋白的至关重要的信息扩大了这些发现。由于脂质水平是可调节的,因此它们可以提供廉价的靶标来提高女性的受精能力。
研究资助和竞争兴趣:这项研究由Eunice Kennedy Shriver国家儿童健康与人类发展研究所的内部研究计划资助。作者宣称没有利益冲突。
试用注册号:#NCT00467363。

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