Department of Epidemiology, HPC FA40, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands.
Hum Reprod. 2013 Dec;28(12):3236-46. doi: 10.1093/humrep/det386. Epub 2013 Oct 27.
Can modified natural cycle IVF or ICSI (MNC) be a cost-effective alternative for controlled ovarian hyperstimulation IVF or ICSI (COH)?
The comparison of simulated scenarios indicates that a strategy of three to six cycles of MNC with minimized medication is a cost-effective alternative for one cycle of COH with strict application of single embryo transfer (SET).
MNC is cheaper per cycle than COH but also less effective in terms of live birth rate (LBR). However, strict application of SET in COH cycles reduces effectiveness and up to three MNC cycles can be performed at the same costs as one COH cycle.
STUDY DESIGN, SIZE, DURATION: The cost-effectiveness of MNC versus COH was evaluated in three simulated treatment scenarios: three cycles of MNC versus one cycle of COH with SET or double embryo transfer (DET) and subsequent transfer of cryopreserved embryos (Scenario 1); six cycles of MNC versus one cycle of COH with strictly SET and subsequent transfer of cryopreserved embryos (Scenario 2); six cycles of MNC with minimized medication (hCG ovulation trigger only) versus one cycle of COH with SET or DET and subsequent transfer of cryopreserved embryos (Scenario 3). We used baseline data obtained from two retrospective cohorts of consecutive patients (2005-2008) undergoing MNC in the University Medical Center Groningen (n = 499, maximum six cycles per patient) or their first COH cycle with subsequent transfer of cryopreserved embryos in the Academic Medical Center Amsterdam (n = 392).
PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 1994 MNC cycles (958 MNC-IVF and 1036 MNC-ICSI) and 392 fresh COH cycles (one per patient, 196 COH-IVF and 196 COH-ICSI) with subsequent transfer of cryopreserved embryos (n = 72 and n = 94 in MNC and COH cycles, respectively) in ovulatory, subfertile women <36 years of age served as baseline for the three simulated scenarios. To compare the scenarios, the incremental cost-effectiveness ratio (ICER) was calculated, defined as the ratio of the difference in IVF costs up to 6 weeks postpartum to the difference in LBR. Live birth was the primary outcome measure and was defined as the birth of at least one living child after a gestation of ≥25 weeks.
In the baseline data, MNC was not cost-effective, as COH dominated MNC with a higher cumulative LBR (27.0 versus 24.0%) and lower cost per patient (€3694 versus €5254). The simulations showed that in scenario 1 three instead of six cycles lowered the costs of MNC to below the level of COH (€3390 versus €3694, respectively), but also lowered the LBR per patient (from 24.0 to 16.2%, respectively); Scenario 2: COH with strict SET was less effective than six cycles MNC (LBR 17.5 versus 24.0%, respectively), but also less expensive per patient (€2908) than MNC (€5254); Scenario 3: improved the cost-effectiveness of MNC but COH still dominated MNC when medication was minimized in terms of costs, i.e. €855 difference in favor of COH and 3% difference in LBR in favor of COH (ICER: €855/-3.0%).
LIMITATIONS, REASONS FOR CAUTION: Owing to the retrospective nature of the study, the analyses required some assumptions, for example regarding the costs of pregnancy and delivery, which had to be based on the literature rather than on individual data. Furthermore, costs of IVF treatment were based on tariffs and not on actual costs. Although this may limit the external generalizability of the results, the limitations will influence both treatments equally, and would therefore not bias the comparison of MNC versus COH.
The combined results suggest that MNC with minimized medication might be a cost-effective alternative for COH with strict SET. The scenarios reflect realistic alternatives for daily clinical practice. A preference for MNC depends on the willingness to trade off effectiveness in terms of LBR against the benefits of a milder stimulation regimen, including a very low rate of multiple pregnancies and hyperstimulation syndrome and ensuing lower costs per live birth.
STUDY FUNDING/COMPETING INTEREST(S): The study was supported by research grants from Merck Serono and Ferring Pharmaceuticals. The authors declare no conflicts of interest.
Not applicable.
改良自然周期 IVF 或 ICSI（MNC）是否可以作为控制性卵巢过度刺激 IVF 或 ICSI（COH）的一种具有成本效益的替代方案？
模拟方案的比较表明，对于严格应用单胚胎移植（SET）的 COH 周期，三到六个周期的 MNC 加上最小化药物治疗是一种具有成本效益的替代方案。
MNC 每周期比 COH 便宜，但活产率（LBR）也较低。然而，在 COH 周期中严格应用 SET 会降低效果，最多可以进行三个 MNC 周期，其成本与一个 COH 周期相同。
研究设计、规模、持续时间：在三种模拟治疗方案中评估了 MNC 与 COH 的成本效益：三个 MNC 周期与一个具有 SET 或双胚胎移植（DET）和随后冷冻胚胎转移的 COH 周期相比（方案 1）；六个 MNC 周期与一个严格 SET 且随后冷冻胚胎转移的 COH 周期相比（方案 2）；六个 MNC 周期，药物治疗最小化（仅使用 hCG 排卵触发）与一个具有 SET 或 DET 和随后冷冻胚胎转移的 COH 周期相比（方案 3）。我们使用了两项连续患者回顾性队列研究的基线数据（2005-2008 年），这些患者在格罗宁根大学医学中心接受 MNC（n = 499，每个患者最多六个周期）或在阿姆斯特丹学术医学中心接受他们的第一个 COH 周期，并随后转移冷冻胚胎（n = 72 和 n = 94 在 MNC 和 COH 周期中）。
参与者/材料、设置、方法：1994 年 MNC 周期（958 个 MNC-IVF 和 1036 个 MNC-ICSI）和 392 个新鲜 COH 周期（每个患者一个周期，196 个 COH-IVF 和 196 个 COH-ICSI）的数据，以及随后转移冷冻胚胎（n = 72 和 n = 94 在 MNC 和 COH 周期中）作为三种模拟方案的基线。为了比较方案，计算了增量成本效益比（ICER），定义为产后 6 周内 IVF 成本差异与活产率（LBR）差异的比值。活产被定义为至少有一个活产儿出生，妊娠≥25 周。
在基线数据中，COH 主导了 MNC，因为 COH 具有更高的累积 LBR（27.0 与 24.0%）和更低的每个患者成本（€3694 与 €5254），因此 MNC 没有成本效益。模拟显示，在方案 1 中，三个周期而不是六个周期将 MNC 的成本降低到低于 COH 的水平（€3390 与 €3694 分别），但每个患者的 LBR 也降低了（从 24.0%降至 16.2%）；方案 2：COH 严格应用 SET 比六个周期的 MNC 更有效（LBR 17.5 与 24.0%），但每个患者的成本也更低（€2908 与 €5254）；方案 3：改善了 MNC 的成本效益，但在药物最小化方面，COH 仍然主导了 MNC，即 COH 有 €855 的优势，COH 的 LBR 有 3%的优势（ICER：€855/-3.0%）。
局限性、谨慎的原因：由于研究的回顾性性质，分析需要进行一些假设，例如妊娠和分娩的成本，这必须基于文献而不是个人数据。此外，IVF 治疗的成本基于关税，而不是实际成本。虽然这可能限制了结果的外部普遍性，但这些限制将平等地影响两种治疗方法，因此不会对 MNC 与 COH 的比较产生偏差。
综合结果表明，MNC 加上最小化药物治疗可能是 COH 严格应用 SET 的一种具有成本效益的替代方案。方案反映了日常临床实践的现实替代方案。对 MNC 的偏好取决于是否愿意在活产率（LBR）方面权衡效果，以换取刺激方案的益处，包括极低的多胎妊娠和卵巢过度刺激综合征的发生率，以及每个活产的成本更低。
研究资金/利益冲突：该研究得到了默克雪兰诺和费森尤斯制药公司的研究资助。作者声明没有利益冲突。
不适用。
