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睡眠特征与 IVF/ICSI 治疗结局的关系:一项前瞻性队列研究。

Associations of sleep characteristics with outcomes of IVF/ICSI treatment: a prospective cohort study.

机构信息

Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.

出版信息

Hum Reprod. 2022 May 30;37(6):1297-1310. doi: 10.1093/humrep/deac040.

Abstract

STUDY QUESTION

Are sleep characteristics associated with outcomes of IVF/ICSI treatment?

SUMMARY ANSWER

Nocturnal sleep <7 h/night and disturbed sleep are related to impaired oocyte and embryo yield, while longer nocturnal sleep might reduce the chance of a successful pregnancy, and the associations between nocturnal sleep duration and IVF/ICSI outcomes are modified by maternal age and subjective sleep quality.

WHAT IS KNOWN ALREADY

Disturbed sleep and circadian rhythm contribute to impaired fecundity in the general population, but the effects of sleep characteristics on IVF/ICSI outcomes are largely unknown.

STUDY DESIGN, SIZE, DURATION: This study was conducted among 1276 women undergoing IVF/ICSI treatment between December 2018 and September 2019 based on the Tongji Reproductive and Environmental cohort. Owing to the limited number of multiple cycles, we included only the outcomes of their first IVF/ICSI cycle in the current analysis.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on sleep characteristics were collected via questionnaires on the day of oocyte retrieval. IVF/ICSI outcomes were abstracted from medical records. Quasi-Poisson, quasi-binomial or logistic regression models were used to assess the relations between sleep characteristics and reproductive outcomes after adjusting for relevant confounders. We also performed stratified analyses by subjective sleep quality (good versus poor) and maternal age (≤30 versus >30 years).

MAIN RESULTS AND THE ROLE OF CHANCE

Compared with women who slept 7 to <8 h/night, those who slept <7 h/night exhibited decreases in the number of retrieved and mature oocytes of 11.5% (95% CI: -21.3%, -0.48%) and 11.9% (95% CI: -22.4%, -0.03%), respectively. A mid-sleep time (MST) earlier than 2:21 a.m. (<2:21 a.m.) or later than 3:00 a.m. (≥3:00 a.m.) and poor subjective sleep quality were inversely associated with the fertilization rate. Women who had trouble falling asleep more than three times per week had a lower number of mature oocytes (-10.5%, 95% CI: -18.6%, -1.6%), normal fertilized oocytes (-14.8%, 95% CI: -23.7%, -4.8%) and good-quality embryos (-15.1%, 95% CI: -25.4%, -3.5%) than those who had no such trouble. In addition, women who slept 9 to <10 h/night had a lower chance of clinical pregnancy compared to women who slept 7 to <8 h/night (odds ratio = 0.65, 95% CI: 0.44, 0.98). In the stratified analyses, the positive associations of nocturnal sleep duration with the number of good-quality embryos and fertilization rate existed only among the women with poor subjective sleep quality (P for interaction = 0.02 and 0.03, respectively). Additionally, we found that the positive associations of nocturnal sleep duration with implantation or clinical pregnancy only existed among women aged over 30 years (P for interaction = 0.04 and 0.01, respectively).

LIMITATIONS, REASONS FOR CAUTION: Sleep characteristics are self-reported, which may lead to misclassification. MST serves as a proxy of chronotype and may be non-differentially misclassified resulting in an underestimate of the association of interest. Measuring sleep characteristics on the day of oocyte retrieval may lead to bias. Chance findings cannot be excluded because of the limited number of women with <7 h or ≥10 h nocturnal sleep and multiple testing. Our results may be biased by other confounders and may not be generalizable to women of other ethnicities.

WIDER IMPLICATIONS OF THE FINDINGS

Unhealthy sleep characteristics, including short nocturnal sleep, inappropriate sleep time, poor subjective sleep quality and having trouble falling asleep, may impair oocyte quantity and its potential to mature or be fertilized. Long nocturnal sleep might reduce the chance of clinical pregnancy among infertile females, especially women younger than 30 years old. Prolonged nocturnal sleep duration may be a potential beneficial behavior for improving IVF/ICSI outcomes for women aged over 30 years and women with poor subjective sleep quality, which requires further investigation.

STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (81771654) and the National Key R&D Program of China (No. 2018YFC1004201). There are no conflicts of interest to declare.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

睡眠特征与体外受精/卵胞浆内单精子注射(IVF/ICSI)治疗结局有关吗?

总结答案

夜间睡眠<7 小时/夜和睡眠障碍与卵母细胞和胚胎产量受损有关,而夜间睡眠时间较长可能降低成功妊娠的机会,夜间睡眠时间与 IVF/ICSI 结局之间的关联受产妇年龄和主观睡眠质量的影响。

已知事实

睡眠障碍和昼夜节律紊乱会导致普通人群生育能力下降,但睡眠特征对 IVF/ICSI 结局的影响在很大程度上尚不清楚。

研究设计、规模、持续时间:本研究基于同济生殖与环境队列,于 2018 年 12 月至 2019 年 9 月期间纳入了 1276 名接受 IVF/ICSI 治疗的女性。由于多次周期的数量有限,我们仅将其首次 IVF/ICSI 周期的结果纳入了当前分析。

参与者/材料、设置、方法:在取卵日通过问卷收集睡眠特征数据。从病历中提取 IVF/ICSI 结局。在调整了相关混杂因素后,使用拟泊松回归、拟二项式回归或逻辑回归模型评估睡眠特征与生殖结局之间的关系。我们还根据主观睡眠质量(好与差)和产妇年龄(≤30 岁与>30 岁)进行了分层分析。

主要结果和机遇的作用

与夜间睡眠 7 至<8 小时/夜的女性相比,夜间睡眠<7 小时/夜的女性的获卵数和成熟卵母细胞数分别减少了 11.5%(95%CI:-21.3%,-0.48%)和 11.9%(95%CI:-22.4%,-0.03%)。中睡眠时间(MST)早于凌晨 2:21(<2:21 a.m.)或晚于凌晨 3:00(≥3:00 a.m.)和主观睡眠质量差与受精率呈负相关。每周入睡困难超过三次的女性,其成熟卵母细胞数量(-10.5%,95%CI:-18.6%,-1.6%)、正常受精卵母细胞(-14.8%,95%CI:-23.7%,-4.8%)和优质胚胎(-15.1%,95%CI:-25.4%,-3.5%)减少。此外,与夜间睡眠 7 至<8 小时/夜的女性相比,夜间睡眠 9 至<10 小时/夜的女性的临床妊娠率较低(优势比=0.65,95%CI:0.44,0.98)。在分层分析中,仅在主观睡眠质量差的女性中,夜间睡眠时间与优质胚胎数量和受精率呈正相关(交互作用 P 值分别为 0.02 和 0.03)。此外,我们还发现,夜间睡眠时间与着床或临床妊娠的正相关仅存在于年龄>30 岁的女性中(交互作用 P 值分别为 0.04 和 0.01)。

局限性、谨慎的原因:睡眠特征是自我报告的,可能导致分类错误。MST 作为昼夜节律的替代指标,可能存在非差异性错误分类,从而低估了感兴趣的关联。在取卵日测量睡眠特征可能会导致偏差。由于夜间睡眠<7 小时或≥10 小时的女性数量有限且进行了多次检验,因此不能排除偶然发现的可能性。我们的结果可能受到其他混杂因素的影响,并且可能不适用于其他种族的女性。

研究结果的更广泛意义

不健康的睡眠特征,包括夜间睡眠<7 小时、睡眠时间不合适、主观睡眠质量差和入睡困难,可能会损害卵母细胞的数量及其成熟或受精的潜力。夜间睡眠时间较长可能降低不孕女性的临床妊娠机会,尤其是年龄<30 岁的女性。对于年龄>30 岁和主观睡眠质量差的女性,延长夜间睡眠时间可能是改善 IVF/ICSI 结局的一种潜在有益行为,这需要进一步研究。

研究资助/利益冲突:本工作得到了国家自然科学基金(81771654)和国家重点研发计划(2018YFC1004201)的支持。没有利益冲突声明。

临床试验注册号

无。

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