Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology

 

Abstract

Background

Recent advances in cell culture media have led to a shift in IVF practice from early cleavage embryo transfer to blastocyst stage transfer. The rationale for blastocyst culture is to improve both uterine and embryonic synchronicity and self selection of viable embryos thus resulting in higher implantation rates.

Objectives

To determine if blastocyst stage embryo transfers (ETs) affect live birth rate and associated outcomes compared with cleavage stage ETs and to investigate what factors may influence this.

Search methods

Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and Bio extracts. The last search date was January 2007.

Selection criteria

Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers.

Data collection and analysis

Of the 50 trials that were identified, 18 randomised controlled trials (RCTs) met the inclusion criteria and were reviewed. The primary outcome was rate of live birth. Secondary outcomes were rates per couple of clinical pregnancy, multiple pregnancy, high order pregnancy, miscarriage, failure to transfer embryos and cryopreservation. Quality assessment, data extraction and meta-analysis were performed following Cochrane guidelines.

Main results

Evidence of a significant difference in live-birth rate per couple between the two treatment groups was detected in favour of blastocyst culture (9 RCTs; OR 1.35, 95% CI 1.05 to 1.74 (Day 2/3: 29.4% versus Day 5/6: 36.0%)). This was particularly for trials with good prognosis patients, equal number of embryos transferred (including single embryo transfer) and those in which the randomisation took place on Day 3. Rates of embryo freezing per couple was significantly higher in Day 2 to 3 transfers (9 RCTs; OR 0.45, 95% CI 0.36 to 0.56). Failure to transfer any embryos per couple was significantly higher in the Day 5 to 6 group (16 RCTs; OR 2.85, 95% CI 1.97 to 4.11 (Day 2/3: 2.8% versus Day 5/6: 8.9%)) but was not significantly different for good prognosis patients (9 RCTs; OR 1.50, 95% CI 0.79 to 2.84).

Authors' conclusions

This review provides evidence that there is a significant difference in pregnancy and live birth rates in favour of blastocyst transfer with good prognosis patients with high numbers of eight-cell embryos on Day three being the most favoured in subgroup for whom there is no difference in cycle cancellation. There is emerging evidence to suggest that in selected patients, blastocyst culture maybe applicable for single embryo transfer.

 

Plain language summary

Cleavage stage versus blastocyst stage embryo transfer in assisted conception

Keeping embryos a few days longer in the laboratory before transfer leads to more pregnancies than regular IVF.
In vitro fertilisation (IVF) is fertilisation (egg and sperm creating an embryo) in a laboratory (in a 'test tube'). With regular IVF, embryos are transferred into the woman's uterus two to three days after fertilisation (at the cleavage stage). An alternative technique delays transferal until five to six days after fertilisation (at blastocyst stage). This may be better timing and allow choice of more viable embryos. The review of trials found evidence that more women will have a pregnancy and baby with blastocyst transfer than with regular IVF. There was however, a higher risk that a women would have fewer embryos to freeze and no embryos available for transfer.

 

摘要

背景

在人工受孕當中，卵裂期與囊胚階段的胚胎移植之比較

因為細胞培養媒介方面的最近發展，使得體外受精操作方法發生了變化由早期卵裂階段的胚胞移植，改成在囊胚階段的移植。會選擇囊胚培養的理由，就是針對子宮與胚胎方面的同步化，以及可用的胚胎本身之選擇，2方面都要追求改善，因此才能夠得到較高的著床比率。

目標

跟卵裂期的胚胎移植(ETs)比較起來，囊胚階段的胚胎移植，是否會影響到產下活胎的比率，以及相關預後果，要針對這些進行確認，並且探討哪些因素可能會影響這樣的情況。

搜尋策略

如果這些試驗都有經過隨機化，而且針對早期卵裂相較於囊胚階段的移植，曾經比較過它們的功效，那麼這些試驗就會被收集在內。

選擇標準

搜尋Cochrane Menstrual Disorders以及Subfertility Group 隨機對照試驗專科登錄中心、Cochrane Controlled Trials Register (CENTRAL) (Cochrane Library) 、MEDLINE、EMBASE 以及Bio extracts。最後一次搜尋日期為2007年1月。

資料收集與分析

當中共有50份試驗獲得了確認，有18份隨機對照試驗(RTCs)符合了收集的標準，而且都經過了檢視。主要的結果是產下活胎的比率。接下來的次要結果為臨床上懷孕的每對夫妻、懷有多胞胎、懷有更多胎數的妊娠、流產、胚胎移植失敗，以及冷凍保存等方面的比率。品質評估、資料擷取，以及統合分析，都是按照Cochrane的指導方法來完成的。

主要結論

在這2個治療組別之間，針對每1對夫妻產下活胎的比率方面，有證據指出了某種明顯的差異，而這樣的證據是在贊成使用囊胚培養的條件中所測量出來(9 RCTs；OR 1.35， 95% CI 1.05到1.74(天數2/3：29.4% 相對於天數5/6：36.0%))。這樣的結果特別適用於試驗中曾受到良好診斷的病患、胚胎移植的數目相同(包括了單1胚胎移植)，以及那些在第3天時進行了隨機化的試驗。在第2天到第3天的移植當中，每1對夫妻的胚胎冷凍比率都明顯地比較高(9 RCTs；OR 0.45，95% CI 0.36到0.56)。每1對夫妻當中，無法移植任何胚胎的比率，在第5天到第6天這個群組當中會明顯地提高(16 RCTs；OR 2.85，95% CI 1.97到4.11(天數2/3：2.8% 相較於天數5/6：8.9%))，但是對於預測起來情況良好的患者而言，卻沒有明顯的差異(9 RCTs；OR 1.50，95% CI 0.79到2.84)。

作者結論

本篇回顧提供的證據顯示，對於在偏好於採用囊胚移植的那組當中，而且又被預測為良好的患者而言，在懷孕與產下活胎的比率當中，有很明顯的差異，至於在第3天時，我們發現8細胞之胚胎數量很高的情況，會是次群組中最受到喜好的，而她們卻在取消誘導排卵方面沒有任何差異。目前還新增了很多的證據顯示，在經過挑選的患者當中，囊胚培養或許可以適用於單1個胚胎移植。

翻譯人

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

在人工受孕當中，卵裂期與囊胚階段的胚胎移植之比較。跟正常的體外受精比較起來，在移植之前，若是將實驗室當中的胚胎再多保留個幾天，已經證實不會造成更多的懷孕數目。體外受精(IVF)指的是在某間實驗室當中(在某根「試管」當中)所進行的受精行為(卵子與精子形成了1顆胚胎)。若是進行常規的體外授精，就會在受精的2到3天之後(在卵裂的階段)，將這些胚胎移植到該名婦女的子宮裡面。另外1種可供選擇的技術，則是將移植的程序延後，直到受精的5到6天之後(在囊胚的階段)。這或許會是更好的時機，並且為更多可用的胚胎提供了選擇。本篇試驗的回顧發現，跟正常的體外受精比較起來，採取囊胚移植的時候，會有更多的婦女們能夠懷孕並且擁有寶寶。然而，卻存在著某種較高的風險，那就是婦女們能夠用來冷凍的胚胎會變得比較少，而沒有任何胚胎可進行移植。