Catford S R, Halliday J, Lewis S, O'Bryan M K, Handelsman D J, Hart R J, McBain J, Rombauts L, Amor D J, Saffery R, McLachlan R I
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Melbourne, Australia.
Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia.
Hum Reprod. 2022 Nov 24;37(12):2908-2920. doi: 10.1093/humrep/deac212.
Is the metabolic health of men conceived using ICSI different to that of IVF and spontaneously conceived (SC) men?
ICSI-conceived men aged 18-24 years, compared with SC controls, showed differences in some metabolic parameters including higher resting diastolic blood pressure (BP) and homeostasis model assessment for insulin resistance (HOMA-IR) scores, although the metabolic parameters of ICSI- and IVF-conceived singleton men were more comparable.
Some studies suggest that IVF-conceived offspring may have poorer cardiovascular and metabolic profiles than SC children. Few studies have examined the metabolic health of ICSI-conceived offspring.
STUDY DESIGN, SIZE, DURATION: This cohort study compared the metabolic health of ICSI-conceived men to IVF-conceived and SC controls who were derived from prior cohorts. Participants included 121 ICSI-conceived men (including 100 singletons), 74 IVF-conceived controls (all singletons) and 688 SC controls (including 662 singletons).
PARTICIPANTS/MATERIALS, SETTING, METHODS: Resting systolic and diastolic BP (measured using an automated sphygmomanometer), height, weight, BMI, body surface area and fasting serum metabolic markers including fasting insulin, glucose, total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol, triglycerides, highly sensitive C-reactive protein (hsCRP) and HOMA-IR were compared between groups. Data were analysed using multivariable linear regression adjusted for various covariates including age and education level.
After adjusting for covariates, compared to 688 SC controls, 121 ICSI-conceived men had higher diastolic BP (β 4.9, 95% CI 1.1-8.7), lower fasting glucose (β -0.7, 95% CI -0.9 to -0.5), higher fasting insulin (ratio 2.2, 95% CI 1.6-3.0), higher HOMA-IR (ratio 1.9, 95% CI 1.4-2.6), higher HDLC (β 0.2, 95% CI 0.07-0.3) and lower hsCRP (ratio 0.4, 95% CI 0.2-0.7) levels. Compared to 74 IVF-conceived singletons, only glucose differed in the ICSI-conceived singleton men (β -0.4, 95% CI -0.7 to -0.1). No differences were seen in the paternal infertility subgroups.
LIMITATIONS, REASONS FOR CAUTION: The recruitment rate of ICSI-conceived men in this study was low and potential for recruitment bias exists. The ICSI-conceived men, the IVF-conceived men and SC controls were from different cohorts with different birth years and different geographical locations. Assessment of study groups and controls was not contemporaneous, and the measurements differed for some outcomes (BP, insulin, glucose, lipids and hsCRP).
These observations require confirmation in a larger study with a focus on potential mechanisms. Further efforts to identify whether health differences are due to parental characteristics and/or factors related to the ICSI procedure are also necessary.
STUDY FUNDING/COMPETING INTEREST(S): This study was funded by an Australian National Health and Medical Research Council Partnership Grant (NHMRC APP1140706) and was partially funded by the Monash IVF Research and Education Foundation. S.R.C. was supported through an Australian Government Research Training Program Scholarship. R.J.H. is supported by an NHMRC project grant (634457), and J.H. and R.I.M. have been supported by the NHMRC as Senior and Principal Research Fellows respectively (J.H. fellowship number: 1021252; R.I.M. fellowship number: 1022327). L.R. is a minority shareholder and the Group Medical Director for Monash IVF Group, and reports personal fees from Monash IVF Group and Ferring Australia, honoraria from Ferring Australia and travel fees from Merck Serono and MSD and Guerbet; R.J.H. is the Medical Director of Fertility Specialists of Western Australia and has equity in Western IVF; R.I.M. is a consultant for and shareholder of Monash IVF Group and S.R.C. reports personal fees from Besins Healthcare and nonfinancial support from Merck outside of the submitted work. The remaining authors have no conflicts of interest to declare.
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通过卵胞浆内单精子注射(ICSI)受孕的男性的代谢健康状况与通过体外受精(IVF)受孕的男性以及自然受孕(SC)的男性是否不同?
与SC对照组相比,18 - 24岁通过ICSI受孕的男性在一些代谢参数上存在差异,包括静息舒张压(BP)较高和胰岛素抵抗稳态模型评估(HOMA - IR)得分较高,不过通过ICSI和IVF受孕的单胎男性的代谢参数更具可比性。
一些研究表明,与自然受孕的儿童相比,通过IVF受孕的后代可能具有较差的心血管和代谢状况。很少有研究考察通过ICSI受孕的后代的代谢健康情况。
研究设计、规模、持续时间:这项队列研究比较了通过ICSI受孕的男性与来自先前队列的IVF受孕和SC对照组的代谢健康状况。参与者包括121名通过ICSI受孕的男性(包括100名单胎)、74名IVF受孕对照组(均为单胎)和688名SC对照组(包括662名单胎)。
参与者/材料、设置、方法:比较了各组之间的静息收缩压和舒张压(使用自动血压计测量)、身高、体重、体重指数(BMI)、体表面积以及空腹血清代谢标志物,包括空腹胰岛素、血糖、总胆固醇、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇、甘油三酯、高敏C反应蛋白(hsCRP)和HOMA - IR。使用多变量线性回归分析数据,并对包括年龄和教育水平在内的各种协变量进行了调整。
在对协变量进行调整后,与688名SC对照组相比,121名通过ICSI受孕的男性舒张压较高(β 4.9,95%置信区间1.1 - 8.7)、空腹血糖较低(β -0.7,95%置信区间 -0.9至 -0.5)、空腹胰岛素较高(比值2.2,95%置信区间1.6 - 3.0)、HOMA - IR较高(比值1.9,95%置信区间1.4 - 2.6)、HDLC较高(β 0.2,95%置信区间0.07 - 0.3)且hsCRP较低(比值0.4,95%置信区间0.2 - 0.7)。与74名IVF受孕的单胎相比,通过ICSI受孕的单胎男性中只有血糖存在差异(β -0.4,95%置信区间 -0.7至 -0.1)。在父亲不育亚组中未观察到差异。
局限性、谨慎的原因:本研究中通过ICSI受孕的男性的招募率较低,存在招募偏倚的可能性。通过ICSI受孕的男性、通过IVF受孕的男性和SC对照组来自不同队列,出生年份不同且地理位置不同。对研究组和对照组的评估并非同期进行,并且某些结果(血压、胰岛素、血糖、血脂和hsCRP)的测量方法存在差异。
这些观察结果需要在一项更大型的研究中得到证实,该研究应关注潜在机制。进一步努力确定健康差异是否归因于父母特征和/或与ICSI程序相关的因素也很有必要。
研究资金/利益冲突:本研究由澳大利亚国家卫生与医学研究委员会合作基金(NHMRC APP1140706)资助,并部分由莫纳什IVF研究与教育基金会资助。S.R.C.获得了澳大利亚政府研究培训计划奖学金的支持。R.J.H.获得了NHMRC项目基金(634457)的支持,J.H.和R.I.M.分别获得了NHMRC的高级和首席研究员资助(J.H.资助编号:1021252;R.I.M.资助编号:1022327)。L.R.是莫纳什IVF集团的少数股东和集团医学总监,报告了来自莫纳什IVF集团和澳大利亚辉凌的个人费用、来自澳大利亚辉凌的酬金以及来自默克雪兰诺、默克和加柏的差旅费;R.J.H.是西澳大利亚生育专家的医学总监,在西澳大利亚IVF拥有股份;R.I.M.是莫纳什IVF集团的顾问和股东,S.R.C.报告了来自贝西尼斯医疗保健公司的个人费用以及在提交工作之外从默克获得的非财务支持。其余作者声明无利益冲突。
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