STUDY QUESTION Is preconception leukocyte telomere length associated with fecundability, pregnancy loss and live birth among women attempting natural conception with a history of 1–2 prior pregnancy losses? SUMMARY ANSWER Preconception leukocyte telomere length is not associated with fecundability, pregnancy loss or live birth. WHAT IS KNOWN ALREADY As women increasingly delay childbearing, accessible preconception biomarkers to predict pregnancy outcomes among women seeking natural conception could improve preconception counseling. Findings of small case–control or cross-sectional studies suggest that telomere attrition is associated with adverse pregnancy outcomes among women undergoing fertility treatment, but prospective studies in non-clinical populations are lacking. STUDY DESIGN, SIZE, DURATION Participants included 1228 women aged 18–40 years with a history of 1–2 prior pregnancy losses who were recruited at four university medical centers (2006–2012). PARTICIPANTS/MATERIALS, SETTING, METHODS Preconception leukocyte telomere length was measured at baseline using PCR and reported as a ratio (T/S) in relation to population-specific standard reference DNA. Women were followed for up to six cycles while attempting to conceive. Associations of telomere length with fecundability, live birth and pregnancy loss were estimated using discrete Cox proportional hazards models and log-binomial models. MAIN RESULTS AND THE ROLE OF CHANCE After adjustment for age, BMI, smoking and other factors, preconception telomere length was not associated with fecundability (Q4 vs Q1 FOR = 1.00; 95% CI = 0.79, 1.27), live birth (Q4 vs Q1 RR = 1.00; 95% CI = 0.85, 1.19), or pregnancy loss (Q4 vs Q1 RR = 1.12; 95% CI = 0.78, 1.62). LIMITATIONS, REASONS FOR CAUTION Telomere length was measured in leukocytes, which is an accessible tissue in women attempting natural conception but may not reflect telomere length in oocytes. Most women were younger than 35 years, limiting our ability to evaluate associations among older women. Participants had a history of 1–2 prior pregnancy losses; therefore, our findings may not be widely generalizable. WIDER IMPLICATIONS OF THE FINDINGS Despite prior research suggesting that telomere length may be associated with pregnancy outcomes among women seeking fertility treatment, our findings suggest that leukocyte telomere length is not a suitable biomarker of pregnancy establishment or maintenance among women attempting natural conception. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Institutes of Health, Bethesda, MD, USA; contract numbers HHSN267200603423, HHSN267200603424 and HHSN267200603426). The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER The trial was registered with ClinicalTrials.gov, number NCT00467363.

中文翻译：

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具有生育能力的女性的孕前白细胞端粒长度和妊娠结局

研究问题 在尝试自然受孕且有 1-2 次流产史的女性中，受孕前白细胞端粒长度是否与生育能力、流产和活产有关？摘要 答案 孕前白细胞端粒长度与生育能力、流产或活产无关。已知情况随着女性越来越多地推迟生育，可利用孕前生物标志物来预测寻求自然受孕的女性的妊娠结局，可以改善孕前咨询。小型病例对照或横断面研究的结果表明，端粒磨损与接受生育治疗的女性的不良妊娠结局相关，但缺乏对非临床人群的前瞻性研究。研究设计，尺寸，持续时间 参与者包括 1228 名年龄在 18-40 岁、有 1-2 次流产史的女性，她们在四所大学医疗中心（2006-2012 年）招募。参与者/材料、设置、方法 使用 PCR 在基线测量孕前白细胞端粒长度，并报告为与人群特异性标准参考 DNA 相关的比率 (T/S)。女性在尝试怀孕时被跟踪长达六个周期。使用离散 Cox 比例风险模型和对数二项式模型估计端粒长度与生育力、活产和流产的关联。主要结果和机会的作用 在调整年龄、BMI、吸烟和其他因素后，孕前端粒长度与生育能力（Q4 vs Q1 FOR = 1.00；95% CI = 0.79, 1.27）、活产（Q4 vs Q1）无关RR = 1.00；95% CI = 0.85, 1.19)，或妊娠丢失 (Q4 vs Q1 RR = 1.12; 95% CI = 0.78, 1.62)。限制和注意的原因 端粒长度是在白细胞中测量的，白细胞是尝试自然受孕的女性可接近的组织，但可能无法反映卵母细胞中的端粒长度。大多数女性的年龄小于 35 岁，这限制了我们评估老年女性之间关联的能力。参与者有 1-2 次流产史；因此，我们的研究结果可能无法广泛推广。研究结果的更广泛意义 尽管先前的研究表明端粒长度可能与寻求生育治疗的女性的妊娠结局相关，但我们的研究结果表明，白细胞端粒长度并不是试图自然受孕的女性建立或维持妊娠的合适生物标志物。研究资金/竞争利益 本研究得到 Eunice Kennedy Shriver 国家儿童健康与人类发展研究所（美国马里兰州贝塞斯达国立卫生研究院；合同号 HHSN267200603423、HHSN267200603424 和 HHSN267200603426）的校内研究计划的支持. 作者没有利益冲突要披露。试验注册号 该试验已在 ClinicalTrials.gov 注册，编号为 NCT00467363。