目的:心血管疾病(CVD)危险因素是否与女性和男性的不孕风险相关?
结论:我们发现证据支持女性开始吸烟和不孕史之间的因果关系。
背景:几种CVD危险因素与不孕症病史相关。先前使用孟德尔随机化(MR)的研究进一步支持BMI与女性不孕症之间的因果关系。
■我们使用了挪威Trøndelag健康研究(HUNT)的数据,一项基于人群的前瞻性队列研究,包括在1995-1997年(HUNT2)参加三项调查的26.811名妇女和15.598名男子,2006-2008(HUNT3),和2017-2019(HUNT4)。
方法:我们的结果是女性自我报告的不孕史,定义为曾尝试受孕12个月或更长时间或曾使用ART。我们将女性报告的不孕症病史分配给男性伴侣;因此,不孕症的衡量标准是夫妻水平。我们使用常规多变量分析和单样本MR分析来评估女性和男性CVD危险因素之间的关联(包括BMI,血压,脂质分布测量,和吸烟行为)以及男女不孕史,分开。
结果:共有4702名女性(18%)和2508名男性(16%)被归类为不孕史。我们发现,在多变量和MR分析中,女性吸烟者的不孕风险高于非吸烟者(多变量分析中的比值比(OR),1.20;95%CI,1.12-1.28;MR分析中的OR,1.13;CI,1.02-1.26),并可能用于较高的BMI(多变量分析中的OR,1.13;CI,1.09-1.18;或在MR分析中,1.11,CI,0.92-1.34)。在女性的多变量分析中,我们还发现了甘油三酯水平之间关联的证据,高密度脂蛋白胆固醇,终身吸烟指数,和吸烟强度与较高的不孕风险。然而,这些结果在MR分析中不一致.我们发现男性CVD危险因素与不育症之间没有强烈或一致的关联。
结论:我们的主要限制是所测量的心血管疾病危险因素可能无法充分捕捉到夫妇试图怀孕的相关时间段。此外,我们没有关于女性或男性不孕症原因的信息。
结论:患有不孕症的女性可能具有更差的CVD危险因素,因此旨在减少某些CVD危险因素的影响的公共卫生干预措施。比如吸烟和BMI,可以减轻不孕症的负担。然而,用更大的样本量对CVD危险因素和不孕症之间的关系进行更多的MR研究是有价值的.
背景:该研究得到了欧盟“地平线2020”研究与创新计划下欧洲研究理事会的资助(资助协议编号:947684)。这项研究还得到了挪威研究理事会通过其卓越中心资助计划的支持(项目编号:262700),部分由挪威研究理事会资助,项目:妇女的生育能力-健康和福祉的重要组成部分(项目编号320656)。D.A.L.和A.F.在布里斯托尔大学和英国医学研究理事会(MC_UU_00011/6)的支持下工作。D.A.L.对本文的贡献得到了欧洲研究理事会(101021566)的支持,英国心脏基金会(CH/F/20/90003和AA/18/7/34219)。S.B.\对文章的贡献得到了惠康信托基金(225790/Z/22/Z)的支持。由教育联络委员会资助,挪威中部的研究和创新;以及圣奥拉夫斯医院和医学与健康科学学院之间的联合研究委员会,NTNU。HUNT的基因分型由国家卫生研究所(NIH)资助;密歇根大学;挪威研究委员会;教育联络委员会,挪威中部的研究和创新;以及圣奥拉夫斯医院和医学与健康科学学院之间的联合研究委员会,NTNU。没有资助组织影响研究设计,reporting,或对结果的解释。本文表达的观点是作者的观点,不一定是任何公认的资助组织的观点。D.A.L.报告了MedtronicLtd和RocheDiagnostics在提交工作之外的授权。其他作者没有利益冲突。
背景:不适用。
OBJECTIVE: Are cardiovascular disease (CVD) risk factors causally associated with higher risk of infertility among women and men?
CONCLUSIONS: We found evidence to support a causal relationship between smoking initiation and history of infertility in women.
BACKGROUND: Several CVD risk factors are associated with history of infertility. Previous studies using Mendelian randomization (MR) further support a causal relationship between BMI and infertility in women.
UNASSIGNED: We used data from the Trøndelag Health
Study (HUNT) in Norway, a prospective population-based cohort
study, including 26 811 women and 15 598 men participating in three survey collections in 1995-1997 (HUNT2), 2006-2008 (HUNT3), and 2017-2019 (HUNT4).
METHODS: Our outcome was women\'s self-reported history of infertility, defined as ever having tried to conceive for 12 months or more or having used ART. We assigned the history of infertility reported by women to their male partners; therefore, the measure of
infertility was on the couple level. We used both conventional multivariable analyses and one-sample MR analyses to evaluate the association between female and male CVD risk factors (including BMI, blood pressure, lipid profile measurements, and smoking behaviours) and history of infertility in women and men, separately.
RESULTS: A total of 4702 women (18%) and 2508 men (16%) were classified with a history of infertility. We found a higher risk of infertility among female smokers compared to non-smokers in both multivariable and MR analyses (odds ratio (OR) in multivariable analysis, 1.20; 95% CI, 1.12-1.28; OR in MR analysis, 1.13; CI, 1.02-1.26), and potentially for higher BMI (OR in multivariable analysis, 1.13; CI, 1.09-1.18; OR in MR analysis, 1.11, CI, 0.92-1.34). In multivariable analysis in women, we also found evidence of associations between triglyceride levels, high-density lipoprotein cholesterol, lifetime smoking index, and smoking intensity with higher risk of infertility. However, these results were not consistent in MR analyses. We found no robust or consistent associations between male CVD risk factors and infertility.
CONCLUSIONS: Our main limitation was that the CVD risk factors measured might not adequately capture the relevant time periods for when couples were trying to conceive. Additionally, we did not have information on causes of infertility in either women or men.
CONCLUSIONS: Women with infertility could have a worse CVD risk factor profile and thus public health interventions aimed at reducing the impact of some CVD risk factors, such as smoking and BMI, could reduce the burden of infertility. However, additional MR studies of the relationship between CVD risk factors and infertility with a larger sample size would be of value.
BACKGROUND: The
study was supported by a grant from the European Research Council under the European Union\'s Horizon 2020 research and innovation program (grant agreements no. 947684). This research was also supported by the Research Council of Norway through its Centres of Excellence funding scheme (project no. 262700) and partly funded by the Research Council of Norway, project: Women\'s fertility-an essential component of health and well-being (project no. 320656). D.A.L. and A.F. work in a unit that is supported by the University of Bristol and the UK Medical Research Council (MC_UU_00011/6). D.A.L.\'s contribution to the article is supported by the European Research Council (101021566), the British Heart Foundation (CH/F/20/90003 and AA/18/7/34219). S.B.\'s contribution to the article is supported by the Wellcome Trust (225790/Z/22/Z). B.M.B. is funded by The Liaison Committee for education, research and innovation in Central Norway; and the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. The genotyping in HUNT was financed by the National Institute of Health (NIH); University of Michigan; The Research Council of Norway; The Liaison Committee for education, research and innovation in Central Norway; and the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. None of the funding organizations influenced the
study design, reporting, or interpretation of results. The views expressed in the present article are those of the authors and not necessarily any acknowledged funding organization. D.A.L. reports grants from Medtronic Ltd and Roche Diagnostics outside the submitted work. The other authors have no conflicts of interest.
BACKGROUND: N/A.