新冠疫情后优先考虑 IVF 治疗：基于英国国家数据的预测模型研究。

Prioritizing IVF treatment in the post-COVID 19 era: a predictive modelling study based on UK national data.

机构信息

School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, UK.

Centre for Reproductive Medicine, Academic Medical Centre University of Amsterdam, Amsterdam, Netherlands.

出版信息

Hum Reprod. 2021 Feb 18;36(3):666-675. doi: 10.1093/humrep/deaa339.

DOI:10.1093/humrep/deaa339

PMID:33226080

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7717242/

Abstract

STUDY QUESTION

Can we use prediction modelling to estimate the impact of coronavirus disease 2019 (COVID 19) related delay in starting IVF or ICSI in different groups of women?

SUMMARY ANSWER

Yes, using a combination of three different models we can predict the impact of delaying access to treatment by 6 and 12 months on the probability of conception leading to live birth in women of different age groups with different categories of infertility.

WHAT IS KNOWN ALREADY

Increased age and duration of infertility can prejudice the chances of success following IVF, but couples with unexplained infertility have a chance of conceiving naturally without treatment whilst waiting for IVF. The worldwide suspension of IVF could lead to worse outcomes in couples awaiting treatment, but it is unclear to what extent this could affect individual couples based on age and cause of infertility.

STUDY DESIGN, SIZE, DURATION: A population-based cohort study based on national data from all licensed clinics in the UK obtained from the Human Fertilisation and Embryology Authority Register. Linked data from 9589 women who underwent their first IVF or ICSI treatment in 2017 and consented to the use of their data for research were used to predict livebirth.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Three prediction models were used to estimate the chances of livebirth associated with immediate treatment versus a delay of 6 and 12 months in couples about to embark on IVF or ICSI.

MAIN RESULTS AND THE ROLE OF CHANCE

We estimated that a 6-month delay would reduce IVF livebirths by 0.4%, 2.4%, 5.6%, 9.5% and 11.8% in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively, while corresponding values associated with a delay of 12 months were 0.9%, 4.9%, 11.9%, 18.8% and 22.4%, respectively. In women with known causes of infertility, worst case (best case) predicted chances of livebirth after a delay of 6 months followed by one complete IVF cycle in women aged <30, 30-35, 36-37, 38-39 and 40-42 years varied between 31.6% (35.0%), 29.0% (31.6%), 23.1% (25.2%), 17.2% (19.4%) and 10.3% (12.3%) for tubal infertility and 34.3% (39.2%), 31.6% (35.3%) 25.2% (28.5%) 18.3% (21.3%) and 11.3% (14.1%) for male factor infertility. The corresponding values in those treated immediately were 31.7%, 29.8%, 24.5%, 19.0% and 11.7% for tubal factor and 34.4%, 32.4%, 26.7%, 20.2% and 12.8% in male factor infertility. In women with unexplained infertility the predicted chances of livebirth after a delay of 6 months followed by one complete IVF cycle were 41.0%, 36.6%, 29.4%, 22.4% and 15.1% in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively, compared to 34.9%, 32.5%, 26.9%, 20.7% and 13.2% in similar groups of women treated without any delay. The additional waiting period, which provided more time for spontaneous conception, was predicted to increase the relative number of babies born by 17.5%, 12.6%, 9.1%, 8.4% and 13.8%, in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively. A 12-month delay showed a similar pattern in all subgroups.

LIMITATIONS, REASONS FOR CAUTION: Major sources of uncertainty include the use of prediction models generated in different populations and the need for a number of assumptions. Although the models are validated and the bases for the assumptions are robust, it is impossible to eliminate the possibility of imprecision in our predictions. Therefore, our predicted live birth rates need to be validated in prospective studies to confirm their accuracy.

WIDER IMPLICATIONS OF THE FINDINGS

A delay in starting IVF reduces success rates in all couples. For the first time, we have shown that while this results in fewer babies in older women and those with a known cause of infertility, it has a less detrimental effect on couples with unexplained infertility, some of whom conceive naturally whilst waiting for treatment. Post-COVID 19, clinics planning a phased return to normal clinical services should prioritize older women and those with a known cause of infertility.

STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this study. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy work for ObsEva, Merck, Merck KGaA, Guerbet and iGenomics. S.B. is Editor-in-Chief of Human Reproduction Open. None of the other authors declare any conflicts of interest.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

我们能否使用预测模型来估计新冠肺炎（COVID-19）相关延迟对不同年龄段女性开始进行体外受精（IVF）或卵胞浆内单精子注射（ICSI）治疗的影响？

总结答案

是的，我们可以使用三种不同的模型组合，预测在延迟 6 个月和 12 个月后接受治疗对不同年龄组不孕女性的受孕并导致活产的概率的影响。

已知情况

年龄增加和不孕时间延长会影响 IVF 的成功率，但不明原因不孕的夫妇有机会在等待 IVF 的同时自然受孕而无需治疗。全球暂停 IVF 可能会导致正在等待治疗的夫妇的结局恶化，但尚不清楚这在多大程度上会根据年龄和不孕原因影响个别夫妇。

研究设计、规模、持续时间：这是一项基于英国人类受精与胚胎管理局注册中心从英国所有持牌诊所获得的全国数据的基于人群的队列研究。使用了 2017 年首次接受 IVF 或 ICSI 治疗并同意将其数据用于研究的 9589 名女性的链接数据来预测活产。

参与者/材料、设置、方法：使用三种预测模型来估计在即将进行 IVF 或 ICSI 的夫妇中，立即治疗与延迟 6 个月和 12 个月的活产机会。

主要结果和机会的作用

我们估计，6 个月的延迟将使<30 岁、30-35 岁、36-37 岁、38-39 岁和 40-42 岁的女性的 IVF 活产率分别降低 0.4%、2.4%、5.6%、9.5%和 11.8%，而相应的 12 个月延迟值分别为 0.9%、4.9%、11.9%、18.8%和 22.4%。在已知不孕原因的女性中，在延迟 6 个月后紧接着进行一个完整的 IVF 周期，在<30 岁、30-35 岁、36-37 岁、38-39 岁和 40-42 岁的女性中，最差情况下（最佳情况）预测活产率在<30 岁、30-35 岁、36-37 岁、38-39 岁和 40-42 岁的女性中分别为 31.6%（35.0%）、29.0%（31.6%）、23.1%（25.2%）、17.2%（19.4%）和 10.3%（12.3%）（输卵管不孕）和 34.3%（39.2%）、31.6%（35.3%）、25.2%（28.5%）、18.3%（21.3%）和 11.3%（14.1%）（男性因素不孕）。立即治疗的相应值分别为 31.7%、29.8%、24.5%、19.0%和 11.7%（输卵管因素）和 34.4%、32.4%、26.7%、20.2%和 12.8%（男性因素不孕）。在不明原因不孕的女性中，在延迟 6 个月后紧接着进行一个完整的 IVF 周期，<30 岁、30-35 岁、36-37 岁、38-39 岁和 40-42 岁的女性的预测活产率分别为 41.0%、36.6%、29.4%、22.4%和 15.1%，而在类似的无延迟治疗组中，这些女性的预测活产率分别为 34.9%、32.5%、26.9%、20.7%和 13.2%。额外的等待期为自然受孕提供了更多的时间，预计会使婴儿数量增加 17.5%、12.6%、9.1%、8.4%和 13.8%，在<30 岁、30-35 岁、36-37 岁、38-39 岁和 40-42 岁的女性中。12 个月的延迟在所有亚组中显示出类似的模式。

局限性、谨慎的原因：主要的不确定性来源包括使用不同人群中生成的预测模型以及需要进行许多假设。尽管这些模型经过验证，并且假设的基础是可靠的，但我们的预测仍然不可能没有不精确的可能性。因此，我们预测的活产率需要在前瞻性研究中进行验证，以确认其准确性。

研究结果的更广泛意义

延迟开始 IVF 会降低所有夫妇的成功率。这首次表明，在老年女性和已知不孕原因的女性中，这会导致婴儿数量减少，但对不明原因不孕的夫妇影响较小，其中一些女性在等待治疗时自然受孕。新冠肺炎疫情后，计划分阶段恢复正常临床服务的诊所应优先考虑老年女性和已知不孕原因的女性。

研究资金/利益冲突：本研究无外部资金支持。B.W.M. 得到了 NHMRC 从业者奖学金（GNT1082548）的支持，并报告了为 ObsEva、Merck、Merck KGaA、Guerbet 和 iGenomics 提供的咨询工作。S.B. 是 Human Reproduction Open 的主编。其他作者均无利益冲突。