Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Department of Community Medicine and Global Health, Institute of Health and Society, University of Oslo, Oslo, Norway.
Hum Reprod. 2022 Jan 28;37(2):322-332. doi: 10.1093/humrep/deab252.
Is fecundability associated with miscarriage history and future miscarriage risk?
Prior miscarriage was associated with lower fecundability, and participants with a history of subfertility (time-to-pregnancy (TTP) ≥12 months) were at a higher risk of subsequent miscarriage.
Although miscarriage and low fecundability share common risk factors, prior studies have reported both lower and higher fecundability after miscarriage.
STUDY DESIGN, SIZE, DURATION: In this study, we examined two related associations: one, between miscarriage history and subsequent fecundability and, two, between fecundability and miscarriage risk in the subsequent pregnancy. The study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). In addition, the outcome of the pregnancy after the MoBa index pregnancy was obtained by linking information from three national health registries: the Medical Birth Registry of Norway, the Norwegian Patient Registry and the general practice database.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We examined the association between number of prior miscarriages and fecundability in 48 537 naturally conceived, planned pregnancies in participants with at least one prior pregnancy. We estimated fecundability ratios (FRs) and 95% CIs using proportional probability regression. We further estimated the relative risk (RR) of miscarriage in the subsequent pregnancy as a function of TTP in the MoBa index pregnancy for 7889 pregnancies using log-binomial regression. Multivariable analyses adjusted for maternal age, pre-pregnancy maternal BMI, smoking status, cycle regularity, income level and highest completed or ongoing education.
Fecundability decreased as the number of prior miscarriages increased. The adjusted FRs among women with one, two and three or more prior miscarriages were 0.83 (95% CI: 0.80-0.85), 0.79 (95% CI: 0.74-0.83) and 0.74 (95% CI: 0.67-0.82), respectively, compared with women with no prior miscarriages. Compared to women with a TTP of <3 months, the adjusted RR of miscarriage in the subsequent pregnancy was 1.16 (0.99-1.35) with TTP of 3-6 months, 1.18 (0.93-1.49) with TTP of 7-11 months and 1.43 (1.13-1.81) with TTP of 12 or more months.
LIMITATIONS, REASONS FOR CAUTION: Information on TTP and prior miscarriages was obtained retrospectively, and TTP was self-reported. MoBa is a pregnancy cohort, and findings may not be generalizable to all women. We were unable to examine the effect of changing partners between pregnancies, as well as other paternal factors such as seminal parameters. We also did not know what proportion of our participants had changed partners between their prior pregnancies and the index pregnancy. Furthermore, it is likely that many early miscarriages are not recognized.
The association between miscarriage and fecundability may reflect a contribution of occult pregnancy losses to TTP, as well as shared underlying causes for reduced fecundability and miscarriage.
STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Research Council of Norway through its Medical Student Research Program funding scheme (project number 271555/F20), its Centres of Excellence funding scheme (project number 262700) and through the project 'Women's fertility - an essential component of health and well-being' (project number 320656). M.C.M. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement number 947684). A.J.W. is supported by the Intramural Program of the National Institute of Environmental Health Sciences at the National Institutes of Health, USA. The authors report no competing interests.
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生育力与流产史和未来流产风险相关吗？
既往流产与较低的生育力相关，而具有不孕史（时间到怀孕（TTP）≥12 个月）的参与者随后发生流产的风险更高。
虽然流产和低生育力有共同的风险因素，但之前的研究报告了流产后生育力较低和较高的情况。
研究设计、规模、持续时间：在这项研究中，我们研究了两个相关的关联：一是流产史与随后的生育力之间的关系，二是生育力与随后妊娠中流产风险之间的关系。该研究基于挪威母婴父亲和儿童队列研究（MoBa）。此外，通过链接来自三个国家健康登记处的信息获得了 MoBa 指数妊娠后的妊娠结局：挪威医学出生登记处、挪威患者登记处和一般实践数据库。
参与者/材料、设置、方法：我们研究了至少有一次既往妊娠的参与者中，既往流产次数与生育力之间的关系。我们使用比例概率回归估计生育力比值（FR）和 95%置信区间（CI）。我们进一步使用对数二项式回归，根据 MoBa 指数妊娠中 TTP 估计了随后妊娠中流产的相对风险（RR）。多变量分析调整了母亲年龄、孕前母亲 BMI、吸烟状况、周期规律性、收入水平和最高完成或正在接受的教育。
生育力随着既往流产次数的增加而降低。有一次、两次和三次或更多次既往流产的女性的调整后 FR 分别为 0.83（95%CI：0.80-0.85）、0.79（95%CI：0.74-0.83）和 0.74（95%CI：0.67-0.82），与无既往流产的女性相比。与 TTP<3 个月的女性相比，TTP 为 3-6 个月、7-11 个月和 12 个月或更长时间的女性随后发生流产的调整 RR 分别为 1.16（0.99-1.35）、1.18（0.93-1.49）和 1.43（1.13-1.81）。
局限性、谨慎的原因：TTP 和既往流产的信息是回顾性获得的，TTP 是自我报告的。MoBa 是一个妊娠队列，研究结果可能不适用于所有女性。我们无法检查妊娠之间伴侣变化的影响，以及其他父亲因素，如精液参数。我们也不知道我们的参与者中有多少人在既往妊娠和指数妊娠之间改变了伴侣。此外，许多早期流产可能没有被发现。
流产和生育力之间的关联可能反映了隐性妊娠丢失对 TTP 的贡献，以及生育力下降和流产的共同潜在原因。
研究资金/竞争利益：该研究由挪威研究理事会通过其医学学生研究计划资助计划（项目编号 271555/F20）、卓越中心资助计划（项目编号 262700）以及通过“妇女生育能力-健康和幸福的重要组成部分”项目（项目编号 320656）提供资金。M.C.M. 收到了欧洲研究理事会（ERC）的资助，该理事会通过欧盟地平线 2020 研究和创新计划（拨款协议号 947684）。A.J.W. 得到了美国国立卫生研究院国家环境健康科学研究所内部计划的支持。作者没有报告任何利益冲突。
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