目的:辅助孵化是否会增加反复植入失败的低生育能力夫妇的累积活产率?
结论:这项研究没有证据表明辅助孵化在反复植入失败的低生育能力夫妇中是一种附加效应。
背景:辅助孵化的功效,在随机试验或荟萃分析中,活产率尚未得到令人信服的证明。建议尽管预后特别差的妇女,例如,反复植入失败的女性,可能会从辅助孵化中受益最大。
方法:该研究设计为双盲,多中心随机对照优势试验。为了证明辅助孵化后,活产率在统计上显着绝对增加了10%,每个治疗臂需要包括294名参与者,总共有588对不生育的夫妇。参与者从2012年11月至2017年11月被纳入并随机分配,297人被分配到研究的辅助孵化臂,295人被分配到对照臂。对20名参与者进行分组随机化,并对参与者隐瞒随机化,治疗医生,和参与胚胎移植程序的实验室人员。卵巢过度刺激,取卵,实验室程序,移植和冷冻保存的胚胎选择,转移本身,和黄体支持根据当地方案进行,除了辅助孵化程序仅在干预组中进行外,干预组和对照组均相同.执行辅助孵化程序的实验室人员不参与胚胎移植本身。
方法:参与者在接受了至少两个连续的新鲜IVF或ICSI胚胎移植后,有资格被纳入研究。包括转移源自这些新鲜周期的冷冻和解冻胚胎,并且没有导致怀孕,或者已经进行了至少一次新鲜IVF或ICSI移植和至少两次冷冻胚胎移植,其中胚胎来自该新鲜周期,但没有导致怀孕。这项研究是在荷兰的三家三级转诊医院和两家大学医学中心的实验室进行的。
结果:每个开始周期的累积活产率,包括新鲜和后续冷冻/解冻胚胎的转移,如果适用,辅助孵化组有77例活产(n=297,25.9%),对照组有68例活产(n=295,23.1%)。这在统计学上没有显着差异(相对风险:1.125,95%CI:0.847至1.494,P=0.416)。
结论:有一小群未生育的夫妇在未达到持续妊娠后,在试验结束时仍有冷冻保存的胚胎,即最后一次随机化后1年。不能排除这些冷冻/解冻胚胎的未来转移会增加任一或两个研究组的累积活产率。接下来,在这项研究开始时,关于反复植入失败的定义没有国际共识。因此,不能排除辅助孵化可能对高阶重复植入失败有效.
结论:这项研究没有证据表明,在反复植入失败的低生育夫妇中,通过增加活产率,对辅助孵化没有统计学意义。即夫妻,基于荟萃分析,建议从辅助孵化中受益最大。因此,建议仅在提供有关无效果证据的信息时,才应提供辅助孵化。在没有额外费用的情况下,最好仅在考虑成本效益的临床试验中。
背景:无。
背景:荷兰试验注册(NTR3387,NL3235,https://www。临床试验登记。nl/nl/试验/26138)。
■2012年4月6日。
■2012年11月28日。
Does assisted hatching increase the cumulative live birth rate in subfertile couples with repeated implantation failure?
This study showed no evidence of effect for assisted hatching as an add-on in subfertile couples with repeated implantation failure.
The efficacy of assisted hatching, with regard to the live birth rate has not been convincingly demonstrated in randomized trials nor meta-analyses. It is suggested though that especially poor prognosis women, e.g. women with repeated implantation failure, might benefit most from assisted hatching.
The study was designed as a double-blinded, multicentre randomized controlled superiority trial. In order to demonstrate a statistically significant absolute increase in live birth rate of 10% after assisted hatching, 294 participants needed to be included per treatment arm, being a total of 588 subfertile couples. Participants were included and randomized from November 2012 until November 2017, 297 were allocated to the assisted hatching arm of the study and 295 to the control arm. Block randomization in blocks of 20 participants was applied and randomization was concealed from participants, treating physicians, and laboratory staff involved in the embryo transfer procedure. Ovarian hyperstimulation, oocyte retrieval, laboratory procedures, embryo selection for transfer and cryopreservation, the transfer itself, and luteal support were performed according to local protocols and were identical in both the intervention and control arm of the study with the exception of the assisted hatching procedure which was only performed in the intervention group. The laboratory staff performing the assisted hatching procedure was not involved in the embryo transfer itself.
Participants were eligible for inclusion in the study after having had either at least two consecutive fresh IVF or ICSI embryo transfers, including the transfer of frozen and thawed embryos originating from those fresh cycles, and which did not result in a pregnancy or as having had at least one fresh IVF or ICSI transfer and at least two frozen embryo transfers with embryos originating from that fresh cycle which did not result in a pregnancy. The study was performed at the laboratory sites of three tertiary referral hospitals and two university medical centres in the Netherlands.
The cumulative live birth rate per started cycle, including the transfer of fresh and subsequent frozen/thawed embryos if applicable, resulted in 77 live births in the assisted hatching group (n = 297, 25.9%) and 68 live births in the control group (n = 295, 23.1%). This proved to be statistically not significantly different (relative risk: 1.125, 95% CI: 0.847 to 1.494, P = 0.416).
There was a small cohort of subfertile couples that after not achieving an ongoing pregnancy, still had cryopreserved embryos in storage at the endpoint of the trial, i.e. 1 year after the last randomization. It cannot be excluded that the future transfer of these frozen/thawed embryos increases the cumulative live birth rate in either or both study arms. Next, at the start of this study, there was no international consensus on the definition of repeated implantation failure. Therefore, it cannot be excluded that assisted hatching might be effective in higher order repeated implantation failures.
This study demonstrated no evidence of a statistically significant effect for assisted hatching by increasing live birth rates in subfertile couples with repeated implantation failure, i.e. the couples which, based on meta-analyses, are suggested to benefit most from assisted hatching. It is therefore suggested that assisted hatching should only be offered if information on the absence of evidence of effect is provided, at no extra costs and preferably only in the setting of a clinical trial taking cost-effectiveness into account.
None.
Netherlands Trial Register (NTR 3387, NL 3235, https://www.clinicaltrialregister.nl/nl/trial/26138).
6 April 2012.
28 November 2012.