Amsterdam UMC, University of Amsterdam, Centre for Reproductive Medicine, Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands.
Department of Obstetrics and Gynaecology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands.
Hum Reprod. 2021 Mar 18;36(4):998-1006. doi: 10.1093/humrep/deaa305.
Is IVF with frozen-thawed blastocyst transfer (freeze-all strategy) more effective than IVF with fresh and frozen-thawed blastocyst transfer (conventional strategy)?
The freeze-all strategy was inferior to the conventional strategy in terms of cumulative ongoing pregnancy rate per woman.
IVF without transfer of fresh embryos, thus with frozen-thawed embryo transfer only (freeze-all strategy), is increasingly being used in clinical practice because of a presumed benefit. It is still unknown whether this new IVF strategy increases IVF efficacy.
STUDY DESIGN, SIZE, DURATION: A single-centre, open label, two arm, parallel group, randomised controlled superiority trial was conducted. The trial was conducted between January 2013 and July 2015 in the Netherlands. The intervention was one IVF cycle with frozen-thawed blastocyst transfer(s) versus one IVF cycle with fresh and frozen-thawed blastocyst transfer(s). The primary outcome was cumulative ongoing pregnancy resulting from one IVF cycle within 12 months after randomisation. Couples were allocated in a 1:1 ratio to the freeze-all strategy or the conventional strategy with an online randomisation programme just before the start of down-regulation.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were subfertile couples with any indication for IVF undergoing their first IVF cycle, with a female age between 18 and 43 years. Differences in cumulative ongoing pregnancy rates were expressed as relative risks (RR) with 95% CI. All outcomes were analysed following the intention-to-treat principle.
Two-hundred-and-five couples were randomly assigned to the freeze-all strategy (n = 102) or to the conventional strategy (n = 102). The cumulative ongoing pregnancy rate per woman was significantly lower in women allocated to the freeze-all strategy (19/102 (19%)) compared to women allocated to the conventional strategy (32/102 (31%); RR 0.59; 95% CI 0.36-0.98).
LIMITATIONS, REASONS FOR CAUTION: As this was a single-centre study, we were unable to study differences in study protocols and clinic performance. This, and the limited sample size, should make one cautious in using the results as the basis for definitive policy. All patients undergoing IVF, including those with a poor prognosis, were included; therefore, the outcome could differ in women with a good prognosis of IVF treatment success.
Our results indicate that there might be no benefit of a freeze-all strategy in terms of cumulative ongoing pregnancy rates. The efficacy of the freeze-all strategy in subgroups of patients, different stages of embryo development, and different freezing protocols needs to be further established and balanced against potential benefits and harms for mothers and children.
STUDY FUNDING/COMPETING INTEREST(S): The Netherlands Organisation for Health Research and Development (ZonMW grant 171101007). S.M., F.M. and M.v.W. stated they are authors of the Cochrane review 'Fresh versus frozen embryo transfers in assisted reproduction'.
Dutch Trial Register, NTR3187.
9 December 2011.
DATE OF FIRST PATIENT’S ENROLMENT: 8 January 2013.
与新鲜胚胎和冷冻胚胎移植（常规策略）相比，体外受精（IVF）联合冷冻-解冻囊胚移植（冷冻-全部策略）是否更有效？
就每位女性的累积持续妊娠率而言，冷冻-全部策略劣于常规策略。
由于推测存在益处，因此越来越多地在临床实践中使用不转移新鲜胚胎的 IVF 治疗，从而仅进行冷冻-解冻胚胎移植（冷冻-全部策略）。目前仍不清楚这种新的 IVF 策略是否会增加 IVF 的疗效。
研究设计、大小、持续时间：这是一项单中心、开放标签、两臂、平行组、随机对照优势试验。该试验于 2013 年 1 月至 2015 年 7 月在荷兰进行。干预措施是一次 IVF 周期联合冷冻-解冻囊胚移植与一次 IVF 周期联合新鲜和冷冻-解冻囊胚移植。主要结局是随机分组后 12 个月内单次 IVF 周期的累积持续妊娠。在下调开始前，通过在线随机化程序以 1:1 的比例将夫妇分配到冷冻-全部策略或常规策略。
参与者/材料、设置、方法：接受 IVF 的生育力低下的夫妇首次接受 IVF 周期，女性年龄在 18 至 43 岁之间。累积持续妊娠率的差异用相对风险（RR）和 95%置信区间（CI）表示。所有结局均按照意向治疗原则进行分析。
205 对夫妇被随机分配到冷冻-全部策略（n=102）或常规策略（n=102）。与接受常规策略的女性（32/102（31%））相比，接受冷冻-全部策略的女性的累积持续妊娠率明显较低（19/102（19%）；RR 0.59；95%CI 0.36-0.98）。
局限性、谨慎的原因：由于这是一项单中心研究，我们无法研究研究方案和临床操作的差异。这一点以及有限的样本量，应该使人们在将结果用作明确政策的基础时谨慎行事。所有接受 IVF 的患者，包括预后较差的患者，都被纳入；因此，在 IVF 治疗成功预后良好的女性中，结果可能会有所不同。
我们的研究结果表明，在累积持续妊娠率方面，冷冻-全部策略可能没有益处。需要进一步确定冷冻-全部策略在患者亚组、胚胎发育不同阶段和不同冷冻方案中的疗效，并平衡对母亲和儿童的潜在益处和危害。
研究资金/竞争利益：荷兰健康研究与发展组织（ZonMW 资助 171101007）。S.M.、F.M.和 M.v.W.表示他们是 Cochrane 综述“新鲜胚胎与冷冻胚胎移植在辅助生殖中的比较”的作者。
荷兰试验注册处，NTR3187。
2011 年 12 月 9 日。
2013 年 1 月 8 日。
