目的:在冷冻胚胎移植(FET)后出生的婴儿中观察到与冷冻技术或子宫内膜准备方案相关的大胎龄(LGA)吗?
结论:人工周期与较高的LGA风险相关,两种冷冻技术(玻璃化与缓慢冷冻)或胚胎阶段(分裂胚胎与胚泡)之间的速率没有差异。
背景:一些研究比较了新鲜胚胎移植(ET)和FET后的新生儿结局,并表明FET与改善的新生儿结局有关,包括降低早产风险,低出生体重,小于胎龄(SGA),与新鲜ET相比。然而,这些研究还显示FET后LGA的风险增加.这种风险增加的潜在病理生理学仍不清楚;父母不孕症,实验室程序(包括胚胎培养条件和冻融过程),和子宫内膜准备治疗可能涉及。
方法:通过回顾性分析2014年至2018年法国国家IVF注册的标准化个人临床记录,进行了多中心流行病学数据研究,包括在生育中心前瞻性收集的新鲜ET或FET导致的单次分娩。补充数据是从参与的生育中心收集的,包括玻璃化培养基和装置,和子宫内膜准备方案。
方法:数据来自35个法国ART中心,导致总共包含72.789个新鲜ET,10.602慢速冻结FET,和39.062玻璃化FET。根据移植胚胎的来源(新鲜,缓慢冷冻,或玻璃化胚胎)和子宫内膜准备FET(排卵或人工周期),比较五个不同的组(新鲜,缓慢的冷冻-排卵周期,慢速冷冻-人工循环,玻璃化-排卵周期,和玻璃化-人工循环)。根据胎龄和特定性别的体重百分位数分布,在活产的单胎中定义胎儿生长障碍:如果<第10和≥第90百分位数,则为SGA和LGA。分别。使用ART中心作为随机效应的线性混合模型进行分析。
结果:转移导致,分别,19.006、1798和9195交付,对应于每次转移的交付率为26.1%,17.0%,新鲜ET后23.5%,慢速冷冻FET,和玻璃化FET,分别。FET周期在排卵周期(n=21.704)或人工周期(n=34.237)中进行,导致5910和10.322怀孕,分别,每次转移的妊娠率为31.6%和33.3%。与排卵周期相比,在人工周期中观察到明显更高的自发性流产率(33.3%对21.4%,P<0.001,在缓慢冷冻组中,分别为31.6%和21.8%,玻璃化组P<0.001)。因此,与缓慢冷冻和玻璃化组的排卵周期相比,人工周期的每次转移的分娩率较低(15.5%对18.9%,P<0.001和22.8%对24.9%,分别为P<0.001)。在26.585名活出生的单身人士中,16.413婴儿从新鲜的ET出生,1644来自慢速冷冻FET,和8528来自玻璃化FET。FET组的出生体重明显高于新鲜ET组,两种冷冻技术没有区别。同样,无论使用何种方法冷冻胚胎,与新鲜ET组相比,FET组的LGA率更高,SGA率更低。在多变量分析中,与排卵周期相比,人工FET后LGA的风险显著增加.相比之下,LGA的风险与冷冻程序(玻璃化冷冻与缓慢冷冻)或冷冻时的胚胎阶段(切割胚胎与胚泡)无关.关于玻璃化方法,LGA的风险与所用的玻璃化培养基或胚胎阶段无关.
结论:没有关于产妇背景的数据,比如奇偶校验,BMI,不孕的原因,或母体合并症,在法国国家数据库中。特别是,我们不能排除在FET人工循环后观察到的LGA风险增加可能,至少部分地,与一些母亲因素的混杂效应有关。没有关于胚胎培养和孵育条件的信息。大多数玻璃化技术是使用相同的设备和两种主要的玻璃化介质进行的。根据使用的设备或玻璃化介质限制LGA风险比较的有效性。
结论:我们的结果似乎令人放心,因为与缓慢冷冻相比,胚胎玻璃化后没有观察到潜在的胎儿生长障碍。即使涉及其他因素,子宫内膜准备治疗似乎对FET后的LGA风险影响最大.排卵周期中的FET可以将胎儿生长障碍的风险降至最低。
背景:这项工作已获得法国生物医学机构的资助(批准号:19AMP002)。没有任何作者有任何利益冲突声明。
背景:不适用。
OBJECTIVE: Is large for gestational age (LGA) observed in babies born after frozen embryo transfer (FET) associated with either the freezing technique or the endometrial preparation protocol?
CONCLUSIONS: Artificial cycles are associated with a higher risk of LGA, with no difference in rate between the two freezing techniques (vitrification versus slow freezing) or embryo stage (cleaved embryo versus blastocyst).
BACKGROUND: Several studies have compared neonatal outcomes after fresh embryo transfer (ET) and FET and shown that FET is associated with improved neonatal outcomes, including reduced risks of preterm birth, low birthweight, and small for gestational age (SGA), when compared with fresh ET. However, these studies also revealed an increased risk of LGA after FET. The underlying pathophysiology of this increased risk remains unclear; parental infertility, laboratory procedures (including embryo culture conditions and freezing-thawing processes), and endometrial preparation treatments might be involved.
METHODS: A multicentre epidemiological data study was performed through a retrospective analysis of the standardized individual clinical records of the French national register of IVF from 2014 to 2018, including single deliveries resulting from fresh ET or FET that were prospectively collected in fertility centres. Complementary data were collected from the participating fertility centres and included the vitrification media and devices, and the endometrial preparation protocols.
METHODS: Data were collected from 35 French ART centres, leading to the inclusion of a total of 72 789 fresh ET, 10 602 slow-freezing FET, and 39 062 vitrification FET. Main clinical outcomes were presented according to origin of the transferred embryos (fresh, slow frozen, or vitrified embryos) and endometrial preparations for FET (ovulatory or artificial cycles), comparing five different groups (fresh, slow freezing-ovulatory cycle, slow freezing-artificial cycle, vitrification-ovulatory cycle, and vitrification-artificial cycle). Foetal growth disorders were defined in live-born singletons according to gestational age and sex-specific weight percentile distribution: SGA and LGA if <10th and ≥90th percentiles, respectively. Analyses were performed using linear mixed models with the ART centres as random effect.
RESULTS: Transfers led to, respectively, 19 006, 1798, and 9195 deliveries corresponding to delivery rates per transfer of 26.1%, 17.0%, and 23.5% after fresh ET, slow-freezing FET, and vitrification FET, respectively. FET cycles were performed in either ovulatory cycles (n = 21 704) or artificial cycles (n = 34 237), leading to 5910 and 10 322 pregnancies, respectively, and corresponding to pregnancy rates per transfer of 31.6% and 33.3%. A significantly higher rate of spontaneous miscarriage was observed in artificial cycles when compared with ovulatory cycles (33.3% versus 21.4%, P < 0.001, in slow freezing groups and 31.6% versus 21.8%, P < 0.001 in vitrification groups). Consequently, a lower delivery rate per transfer was observed in artificial cycles compared with ovulatory cycles both in slow freezing and vitrification groups (15.5% versus 18.9%, P < 0.001 and 22.8% versus 24.9%, P < 0.001, respectively). Among a total of 26 585 live-born singletons, 16 413 babies were born from fresh ET, 1644 from slow-freezing FET, and 8528 from vitrification FET. Birthweight was significantly higher in the FET groups than in the fresh ET group, with no difference between the two freezing techniques. Likewise, LGA rates were higher and SGA rates were lower in the FET groups compared with the fresh ET group whatever the method used for embryo freezing. In a multivariable analysis, the risk of LGA following FET was significantly increased in artificial compared with ovulatory cycles. In contrast, the risk of LGA was not associated with either the freezing procedure (vitrification versus slow freezing) or the embryo stage (cleaved embryo versus blastocyst) at freezing. Regarding the vitrification method, the risk of LGA was not associated with either the vitrification medium used or the embryo stage.
CONCLUSIONS: No data were available on maternal context, such as parity, BMI, infertility cause, or maternal comorbidities, in the French national database. In particular, we cannot exclude that the increased risk of LGA observed following FET with artificial cycles may, at least partially, be associated with a confounding effect of some maternal factors. No information about embryo culture and incubation conditions was available. Most of the vitrification techniques were performed using the same device and with two main vitrification media, limiting the validity of a comparison of risk for LGA according to the device or vitrification media used.
CONCLUSIONS: Our results seem reassuring, since no potential foetal growth disorders following embryo vitrification in comparison with slow freezing were observed. Even if other factors are involved, the endometrial preparation treatment seems to have the greatest impact on LGA risk following FET. FET during ovulatory cycles could minimize the risk for foetal growth disorders.
BACKGROUND: This work has received funding from the French Biomedicine Agency (Grant number: 19AMP002). None of the authors has any conflict of interest to declare.
BACKGROUND: N/A.