Aberdeen Fertility Centre, NHS Grampian, Aberdeen, UK.
Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
Hum Reprod. 2021 Oct 18;36(11):2891-2903. doi: 10.1093/humrep/deab207.
What are couples' preferences for fresh embryo transfer versus freezing of all embryos followed by frozen embryo transfer and the associated clinical outcomes that may differentiate them?
Couples' preferences are driven by anticipated chances of live birth, miscarriage, neonatal complications, and costs but not by the differences in the treatment process (including delay of embryo transfer linked to frozen embryo transfer and risk of ovarian hyperstimulation syndrome (OHSS) associated with fresh embryo transfer).
A policy of freezing all embryos followed by transfer of frozen embryos results in livebirth rates which are similar to or higher than those following the transfer of fresh embryos while reducing the risk of OHSS and small for gestational age babies: it can, however, increase the risk of pre-eclampsia and large for gestational age offspring. Hence, the controversy continues over whether to do fresh embryo transfer or freeze all embryos followed by frozen embryo transfer.
STUDY DESIGN, SIZE, DURATION: We used a discrete choice experiment (DCE) technique to survey infertile couples between August 2018 and January 2019.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We asked IVF naïve couples attending a tertiary referral centre to independently complete a questionnaire with nine hypothetical choice tasks between fresh and frozen embryo transfer. The alternatives varied across the choice occurrences on several attributes including efficacy (live birth rate), safety (miscarriage rate, neonatal complication rate), and cost of treatment. We assumed that a freeze-all strategy prolonged treatment but reduced the risk of OHSS. An error components mixed logit model was used to estimate the relative value (utility) that couples placed on the alternative treatment approaches and the attributes used to describe them. Willingness to pay and marginal rates of substitution between the non-cost attributes were calculated. A total of 360 individual questionnaires were given to 180 couples who fulfilled the inclusion criteria, of which 212 were completed and returned Our study population included 3 same sex couples (2 females and 1 male) and 101 heterosexual couples. Four questionnaires were filled by one partner only. The response rate was 58.8%.
Couples preferred both fresh and frozen embryo transfer (odds ratio 27.93 and 28.06, respectively) compared with no IVF treatment, with no strong preference for fresh over frozen. Couples strongly preferred any IVF technique that offered an increase in live birth rates by 5% (P = 0.006) and 15% (P < 0.0001), reduced miscarriage by 18% (P < 0.0001) and diminished neonatal complications by 10% (P < 0.0001). Respondents were willing to pay an additional £2451 (95% CI 604 - 4299) and £761 (95% CI 5056-9265) for a 5 and 15% increase in the chance of live birth, respectively, regardless of whether this involved fresh or frozen embryos. They required compensation of £5230 (95% CI 3320 - 7141) and £13 245 (95% CI 10 110-16 380) to accept a 10 and 25% increase in the risk of neonatal complications, respectively (P < 0.001). Results indicated that couples would be willing to accept a 1.26% (95% CI 1.001 - 1.706) reduction in the live birth rate for a 1% reduction in the risk of neonatal complications per live birth. Older couples appeared to place less emphasis on the risk of neonatal complications than younger couples.
LIMITATIONS, REASONS FOR CAUTION: DCEs can elicit intentions which may not reflect actual behaviour. The external validity of this study is limited by the fact that it was conducted in a single centre with generous public funding for IVF. We cannot rule out the potential for selection or responder bias.
If a strategy of freeze all was to be implemented it would appear to be acceptable to patients, if either success rates can be improved or neonatal complications reduced. Live birth rates, neonatal complication rates, miscarriage rates, and cost are more likely to drive their preferences than a slight delay in the treatment process. The results of this study have important implications for future economic evaluations of IVF, as they suggest that the appropriate balance needs to be struck between success and safety. A holistic approach incorporating patient preferences for expected clinical outcomes and risks should be taken into consideration for individualized care.
STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought for this study. A.M. is the chief investigator of the randomized controlled trial 'Freeze all'. S.B. is an Editor in Chief of Human Reproduction Open. The other co-authors have no conflicts of interest to declare. Graham Scotland reports non-financial support from Merck KGaA, Darmstadt, Germany, outside the submitted work.
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夫妇对新鲜胚胎移植与冷冻所有胚胎后进行冷冻胚胎移植的偏好是什么，以及可能导致他们产生偏好的相关临床结局有哪些？
夫妇的偏好取决于他们对活产、流产、新生儿并发症和成本的预期几率，但不取决于治疗过程的差异（包括与冷冻胚胎移植相关的胚胎转移延迟和与新鲜胚胎移植相关的卵巢过度刺激综合征（OHSS）风险）。
冷冻所有胚胎后进行胚胎移植的策略可以产生与新鲜胚胎移植相似或更高的活产率，同时降低 OHSS 和小于胎龄儿的风险，但会增加子痫前期和大于胎龄儿的风险。因此，是否进行新鲜胚胎移植或冷冻所有胚胎后进行冷冻胚胎移植的争议仍在继续。
研究设计、规模、持续时间：我们使用离散选择实验（DCE）技术，于 2018 年 8 月至 2019 年 1 月期间对不孕夫妇进行了调查。
参与者/材料、地点、方法：我们要求在三级转诊中心就诊的 IVF 初治夫妇独立完成一份包含九个假设选择任务的问卷，这些任务涉及新鲜胚胎移植和冷冻胚胎移植之间的各种属性，包括功效（活产率）、安全性（流产率、新生儿并发症率）和治疗成本。我们假设冷冻所有胚胎的策略会延长治疗时间，但会降低 OHSS 的风险。我们使用错误成分混合对数模型来估计夫妇对替代治疗方法的相对价值（效用），以及用于描述这些方法的属性。还计算了非成本属性之间的意愿支付和边际替代率。我们总共向符合纳入标准的 180 对夫妇发放了 360 份个人问卷，其中 212 份完成并返回。我们的研究人群包括 3 对同性伴侣（2 名女性和 1 名男性）和 101 对异性伴侣。4 份问卷由一名伴侣填写。回复率为 58.8%。
与没有 IVF 治疗相比，夫妇更喜欢新鲜胚胎移植和冷冻胚胎移植（优势比分别为 27.93 和 28.06），但对新鲜胚胎移植并没有明显偏好。夫妇强烈偏好任何能提高活产率 5%（P=0.006）和 15%（P<0.0001）、降低流产率 18%（P<0.0001）和减少新生儿并发症率 10%（P<0.0001）的 IVF 技术。无论涉及新鲜胚胎还是冷冻胚胎，受访者都愿意额外支付 2451 英镑（95%CI 604-4299）和 761 英镑（95%CI 5056-9265），以获得 5%和 15%的活产率提高，而不管这是否涉及新鲜胚胎或冷冻胚胎。他们需要补偿 5230 英镑（95%CI 3320-7141）和 13245 英镑（95%CI 10110-16380），才能接受新生儿并发症风险增加 10%和 25%（P<0.001）。结果表明，夫妇愿意接受活产率降低 1.26%（95%CI 1.001-1.706），以换取新生儿并发症风险降低 1%。年龄较大的夫妇似乎比年龄较小的夫妇对新生儿并发症的风险不太重视。
局限性、谨慎的原因：DCE 可以引出可能不符合实际行为的意图。由于该研究是在一个拥有大量公共资金支持 IVF 的单一中心进行的，因此该研究的外部有效性受到限制。我们不能排除选择或应答者偏倚的可能性。
研究结果对 IVF 的未来经济评估具有重要意义，因为这表明，如果成功率能够提高或新生儿并发症减少，这种策略对患者来说是可以接受的。活产率、新生儿并发症率、流产率和成本比治疗过程的轻微延迟更有可能影响他们的偏好。本研究的结果对未来的 IVF 经济评估具有重要意义，因为这表明需要在成功和安全性之间取得适当的平衡。应该考虑采用包含患者对预期临床结果和风险的偏好的整体方法，以进行个体化治疗。
研究资金/利益冲突：本研究未寻求外部资金。A.M. 是“冷冻所有”随机对照试验的首席研究员。S.B. 是 Human Reproduction Open 的主编。其他合著者没有利益冲突需要申报。Graham Scotland 报告说，他从默克公司（德国达姆施塔特）获得了非财务支持，这与提交的工作无关。
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