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自然周期中自发排卵或诱导排卵的冻融胚胎移植:对最佳方案的探索仍在继续。

Frozen-thawed embryo transfers in natural cycles with spontaneous or induced ovulation: the search for the best protocol continues.

作者信息

Montagut M, Santos-Ribeiro S, De Vos M, Polyzos N P, Drakopoulos P, Mackens S, van de Vijver A, van Landuyt L, Verheyen G, Tournaye H, Blockeel C

机构信息

Center for Human Reproduction-IFREARES, Clinique Saint Jean du Languedoc, 20 route de Revel, 31400 Toulouse, France.

Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101-1090 Brussels, Belgium.

出版信息

Hum Reprod. 2016 Dec;31(12):2803-2810. doi: 10.1093/humrep/dew263. Epub 2016 Oct 25.

DOI:10.1093/humrep/dew263
PMID:27798046
Abstract

STUDY QUESTION

Is natural cycle frozen-thawed embryo transfer (NC-FET) associated with better clinical pregnancy rates (CPR) when compared to modified natural cycle frozen-thawed embryo transfer (mNC-FET)?

SUMMARY ANSWER

NC-FET is associated with a higher CPR compared to mNC-FET.

WHAT IS KNOWN ALREADY

There is conflicting evidence regarding the impact of hCG triggering on clinical outcomes after frozen-thawed embryo transfer (FET), and information on the effect of luteal phase support (LPS) is lacking.

STUDY DESIGN, SIZE, DURATION: This retrospective study included all (n = 2353) consecutive cycles with FET of vitrified cleavage and blastocyst stage embryos warmed between January 2010 and April 2015 in a tertiary centre. The FET cycles were grouped by type as follows: NC (n = 501), NC + LPS (n = 828) or mNC + LPS (n = 1024). Artificial cycles were excluded from the analysis.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed mixed-effect multilevel multivariable regression analysis to account for the clustering of FETs using embryos derived from the same patient and/or ovarian stimulation cycle. Adjustment for the following potential confounders was also performed: female age at oocyte retrieval, number of oocytes retrieved, fresh cycle pregnancy outcome, embryo transfer rank, number of embryos transferred, embryo stage and grade and endometrial thickness. Bonferroni adjustment for multiple comparisons was performed whenever indicated.

MAIN RESULTS AND THE ROLE OF CHANCE

The unadjusted CPR per cycle was significantly higher in the NC-FET group (46.9%) when compared with the mNC-FET + LPS groups (29.7%, P < 0.001) but not the NC-FET + LPS group (39.9%, P = 0.069). The lower clinical performance of mNC-FET + LPS remained significant even after adjusting for potential confounders [adjusted odds ratio (95% CI) compared to the NC-FET groups: 2.18 (1.64-2.90) and 1.67 (1.31-2.12) for the NC-FET and NC-FET + LPS groups, respectively]. A sensitivity analysis restricting the sample only to the first FET performed by the couple in our centre was also performed. The predicted CPR in this multivariable logistic regression model remained significantly higher in the NC-FET (53.9%) and NC-FET + LPS (44.9%) groups when compared to mNC-FET + LPS (34.2%, all Bonferroni-adjusted pairwise comparisons with P ≤ 0.01).

LIMITATIONS, REASONS FOR CAUTION: The interpretation of the findings of this study is limited by the retrospective nature of the analysis and the potential for unmeasured confounding.

WIDER IMPLICATIONS OF THE FINDINGS

The use of mNC-FET, using hCG triggering or progesterone supplementation, should be reconsidered in light of the potential negative effect on pregnancy outcome.

STUDY FUNDING/COMPETING INTERESTS: None.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

与改良自然周期冻融胚胎移植(mNC-FET)相比,自然周期冻融胚胎移植(NC-FET)是否具有更高的临床妊娠率(CPR)?

总结答案

与mNC-FET相比,NC-FET具有更高的临床妊娠率。

已知信息

关于人绒毛膜促性腺激素(hCG)触发对冻融胚胎移植(FET)后临床结局的影响,存在相互矛盾的证据,并且缺乏关于黄体期支持(LPS)效果的信息。

研究设计、规模、持续时间:这项回顾性研究纳入了2010年1月至2015年4月在一家三级中心进行的所有(n = 2353)连续周期的FET,这些周期使用的是玻璃化卵裂期和囊胚期胚胎解冻后移植。FET周期按类型分组如下:自然周期(NC,n = 501)、自然周期 + 黄体期支持(NC + LPS,n = 828)或改良自然周期 + 黄体期支持(mNC + LPS,n = 1024)。人工周期被排除在分析之外。

参与者/材料、环境、方法:我们进行了混合效应多级多变量回归分析,以考虑使用来自同一患者和/或卵巢刺激周期的胚胎进行FET的聚类情况。还对以下潜在混杂因素进行了调整:取卵时的女性年龄、取卵数量、新鲜周期妊娠结局、胚胎移植顺序、移植胚胎数量、胚胎阶段和等级以及子宫内膜厚度。必要时进行了Bonferroni多重比较调整。

主要结果及偶然性的作用

与mNC-FET + LPS组(29.7%)相比,NC-FET组每周期未经调整的临床妊娠率显著更高(46.9%,P < 0.001),但与NC-FET + LPS组(39.9%)相比无显著差异(P = 0.069)。即使在调整潜在混杂因素后,mNC-FET + LPS较低的临床效果仍然显著[与NC-FET组相比的调整优势比(95%置信区间):NC-FET组为2.18(1.64 - 2.90),NC-FET + LPS组为1.67(1.31 - 2.12)]。还进行了一项敏感性分析,将样本仅限制为夫妇在本中心进行的首次FET。在该多变量逻辑回归模型中,与mNC-FET + LPS组(34.2%)相比,NC-FET组(53.9%)和NC-FET + LPS组(44.9%)的预测临床妊娠率仍然显著更高(所有Bonferroni调整后的两两比较,P≤0.01)。

局限性、谨慎原因:本研究结果的解释受到分析的回顾性性质以及潜在未测量混杂因素的限制。

研究结果的更广泛影响

鉴于对妊娠结局的潜在负面影响,应重新考虑使用hCG触发或补充孕酮的mNC-FET。

研究资金/利益冲突:无。

试验注册号

无。

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