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胚胎移植策略的成本效益:一种使用试管婴儿产生的单胎和多胎的长期成本及后果的决策分析模型。

Cost-effectiveness of embryo transfer strategies: a decision analytic model using long-term costs and consequences of singletons and multiples born as a consequence of IVF.

作者信息

van Heesch M M J, van Asselt A D I, Evers J L H, van der Hoeven M A H B M, Dumoulin J C M, van Beijsterveldt C E M, Bonsel G J, Dykgraaf R H M, van Goudoever J B, Koopman-Esseboom C, Nelen W L D M, Steiner K, Tamminga P, Tonch N, Torrance H L, Dirksen C D

机构信息

Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands

Department of Pharmacy, University of Groningen, Deusinglaan 1, 9713 AV Groningen, The Netherlands.

出版信息

Hum Reprod. 2016 Nov;31(11):2527-2540. doi: 10.1093/humrep/dew229. Epub 2016 Oct 6.

Abstract

STUDY QUESTION

What is the cost-effectiveness of elective single embryo transfer (eSET) versus double embryo transfer (DET) strategies from a societal perspective, when applying a time horizon of 1, 5 and 18 years?

SUMMARY ANSWER

From a short-term perspective (1 year) it is cost-effective to replace DET with single embryo transfer; however when intermediate- (5 years) and long-term (18 years) costs and consequences are incorporated, DET becomes the most cost-effective strategy, given a ceiling ratio of €20 000 per quality-adjusted life years (QALY) gained.

WHAT IS ALREADY KNOWN

According to previous cost-effectiveness research into embryo transfer strategies, DET is considered cost-effective if society is willing to pay around €20 000 for an extra live birth. However, interpretation of those studies is complicated, as those studies fail to incorporate long-term costs and outcomes and used live birth as a measure of effectiveness instead of QALYs. With this outcome, both multiple and singletons were valued as one live birth, whereas costs of all children of a multiple were incorporated.

STUDY DESIGN, SIZE, DURATION: A Markov model (cycle length: 1 year; time horizon: 1, 5 and 18 years) was developed comparing a maximum of: (i) three cycles of eSET in all patients; (ii) four cycles of eSET in all patients; (iii) five cycles of eSET in all patients; (iv) three cycles of standard treatment policy (STP), i.e. eSET in women <38 years with a good quality embryo, and DET in all other women; and (v) three cycles of DET in all patients.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Expected life years (LYs), child QALYs and costs were estimated for all comparators. Input parameters were derived from a retrospective cohort study, in which hospital resource data were collected (n=580) and a parental questionnaire was sent out (431 respondents). Probabilistic sensitivity analysis (5000 iterations) was performed.

MAIN RESULTS AND THE ROLE OF CHANCE

With a time horizon of 18 years, DETx3 is most effective (0.54 live births, 10.2 LYs and 9.8 QALYs) and expensive (€37 871) per couple starting IVF. Three cycles of eSET are least effective (0.43 live births, 7.1 LYs and 6.8 QALYs) and expensive (€25 563). We assumed that society is willing to pay €20 000 per QALY gained. With a time horizon of 1 year, eSETx3 was the most cost-effective embryo transfer strategy with a probability of being cost-effective of 99.9%. With a time horizon of 5 or 18 years, DETx3 was most cost-effective, with probabilities of being cost-effective of 77.3 and 93.2%, respectively.

LIMITATIONS, REASONS FOR CAUTION: This is the first study to use QALYs generated by the children in the economic evaluation of embryo transfer strategies. There remains some disagreement on whether QALYs generated by new life should be used in economic evaluations of fertility treatment. A further limitation is that treatment ends when it results in live birth and that only child QALYs were considered as measure of effectiveness. The results for the time horizon of 18 years might be less solid, as the data beyond the age of 8 years are based on extrapolation.

WIDER IMPLICATIONS OF THE FINDINGS

The current Markov model indicates that when child QALYs are used as measure of outcome it is not cost-effective on the long term to replace DET with single embryo transfer strategies. However, for a balanced approach, a family-planning perspective would be preferable, including additional treatment cycles for couples who wish to have another child. Furthermore, the analysis should be extended to include QALYs of family members.

STUDY FUNDING/COMPETING INTERESTS: This study was supported by a research grant (grant number 80-82310-98-09094) from the Netherlands Organization for Health Research and Development (ZonMw). There are no conflicts of interest in connection with this article.

TRIAL REGISTRATION NUMBER

Not applicable.

摘要

研究问题

从社会角度来看,在1年、5年和18年的时间范围内,选择性单胚胎移植(eSET)与双胚胎移植(DET)策略的成本效益如何?

总结答案

从短期(1年)角度来看,用单胚胎移植替代双胚胎移植具有成本效益;然而,当纳入中期(5年)和长期(18年)的成本和后果时,在每获得一个质量调整生命年(QALY)的成本上限为20000欧元的情况下,双胚胎移植成为最具成本效益的策略。

已知信息

根据先前对胚胎移植策略的成本效益研究,如果社会愿意为额外的一次活产支付约20000欧元,那么双胚胎移植被认为具有成本效益。然而,这些研究的解读较为复杂,因为它们没有纳入长期成本和结果,而是使用活产作为有效性的衡量标准,而不是QALY。在这种结果中,多胎和单胎都被视为一次活产,而多胎所有孩子的成本都被纳入其中。

研究设计、规模、持续时间:开发了一个马尔可夫模型(周期长度:1年;时间范围:1年、5年和18年),比较最多以下几种情况:(i)所有患者进行三个周期的eSET;(ii)所有患者进行四个周期的eSET;(iii)所有患者进行五个周期的eSET;(iv)三个周期的标准治疗策略(STP),即38岁以下且胚胎质量良好的女性进行eSET,其他所有女性进行DET;(v)所有患者进行三个周期的DET。

参与者/材料、设置、方法:估计了所有比较组的预期生命年(LYs)、儿童QALY和成本。输入参数来自一项回顾性队列研究,其中收集了医院资源数据(n = 580)并发放了家长问卷(431名受访者)。进行了概率敏感性分析(5000次迭代)。

主要结果及机遇的作用

在18年的时间范围内,对于每对开始进行体外受精的夫妇,三个周期的DET最有效(0.54次活产、10.2个生命年和9.8个QALY)且成本最高(37871欧元)。三个周期的eSET最无效(0.43次活产、7.1个生命年和6.8个QALY)且成本较高(25563欧元)。我们假设社会愿意为每获得一个QALY支付20000欧元。在1年的时间范围内,三个周期的eSET是最具成本效益的胚胎移植策略,具有成本效益的概率为99.9%。在5年或18年的时间范围内,三个周期的DET最具成本效益,具有成本效益的概率分别为77.3%和93.2%。

局限性、谨慎原因:这是第一项在胚胎移植策略的经济评估中使用儿童产生的QALY的研究。对于新生生命产生的QALY是否应在生育治疗的经济评估中使用,仍存在一些分歧。另一个局限性是,治疗在导致活产时结束,并且仅将儿童QALY视为有效性的衡量标准。18年时间范围的结果可能不太可靠,因为8岁以后的数据是基于外推法得出的。

研究结果的更广泛影响

当前的马尔可夫模型表明,当将儿童QALY用作结果衡量标准时,从长期来看,用单胚胎移植策略替代双胚胎移植并不具有成本效益。然而,为了采取平衡的方法,计划生育的观点可能更可取,包括为希望再要一个孩子的夫妇增加治疗周期。此外,分析应扩展到包括家庭成员的QALY。

研究资金/利益冲突:本研究得到了荷兰卫生研究与发展组织(ZonMw)的研究资助(资助编号80 - 82310 - 98 - 09094)。与本文相关不存在利益冲突。

试验注册号

不适用。

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