Blastocyst trophectoderm biopsy and preimplantation genetic diagnosis for familial monogenic disorders and chromosomal translocations
Blastocyst trophectoderm biopsy and preimplantation genetic diagnosis for familial monogenic disorders and chromosomal translocations
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DOI：
10.1002/pd.1924
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发表时间：
2008-05-01
影响因子：
3
通讯作者：
Jansen, R. P. S.
中科院分区：
文献类型：
--
作者：
McArthur, S. J.;Leigh, D.;Jansen, R. P. S.
目的现代体外受精技术包括将胚胎移植为囊胚，此时胚胎的合成代谢已建立良好，在单次移植胚胎的同时可以维持妊娠率，以避免多胎妊娠。然而，植入前遗传学诊断(PGD)的胚胎活检通常在第3天进行，此时胚胎只有6到8个细胞，其中1到2个被取出进行检测，种植率和临床妊娠率保持在相对较低的水平，并且不排除这种早期胚胎失去1个或多个细胞的有害影响。方法我们对接受PGD的患者进行了399次取卵和1879次胚胎活检，以避免严重的单基因疾病或染色体不平衡易位。我们比较了在第3天(卵裂期活检)和推迟到第5天或第6天的活检后的着床和成活妊娠率，当时胚胎是胚泡，可以从滋养外胚层中提取5个或更多细胞，而胎儿发育的内部细胞团保持完好。结果囊胚率为3.6%，卵裂期为6.6%，囊胚期和卵裂期分别为43.4%和25.6%(P(I)0.01)，继续妊娠和活产妊娠率分别为34.2%(平均移植次数1.1)和25.5%(移植次数1.6)。排除单基因疾病的多胎妊娠率从16.7%下降到2%(P=0.04，单尾)。结论排除遗传病，第5-6天囊胚期活检比第3天进行PGD后更有可能发生植入和单胎出生。版权所有(C)2008 John Wiley&Sons，Ltd.
Objective Modem in vitro fertilization practices involve transfer of embryos as blastocysts, when anabolic metabolism is well established and pregnancy rates can be maintained while transferring embryos singly to avoid multiple pregnancies. Embryo biopsy for preimplantation genetic diagnosis (PGD), however, is generally performed on day 3, when the embryo comprises just 6 to 8 cells, one or two of which are removed for testing, Implantation rates and clinical pregnancy rates have remained relatively low and a harmful effect from losing one or more cells from such early embryos has not been excluded.Methods We performed a sequential study involving 399 egg retrievals and 1879 embryo biopsies for patients undergoing PGD to avoid a serious monogenic disease or an unbalanced chromosomal translocation. We compared implantation and viable pregnancy rates after biopsies taken on day 3 (cleavage-stage biopsy) with biopsies delayed until day 5 or 6, when the embryo is a blastocyst and 5 or more cells can be sampled from the trophectoderm while the inner cell mass, from which the fetus develops, remains intact. All embryos were transferred as blastocysts.Results Despite fewer blastocysts than cleavage embryos biopsied and tested (3.6 compared to 6.6), implantation rates per embryo transferred were 43.4% if biopsied at the blastocyst stage and 25.6% if biopsied at the cleavage stage (P (i) 0.01), with ongoing or live-birth pregnancy rates per egg retrieval of 34.2% (average transfer number 1.1) for blastocyst biopsies and 25.5 % (transfer number 1.6) for cleavage stage biopsies (P (i) 0.05, 1-tailed). The multiple pregnancy rate for monogenic disease exclusion fell from 16.7% to 2% (P = 0.04, 1-tailed).Conclusions For exclusion of genetic disease, day 5-6 blastocyst-stage biopsies are more likely to be followed by implantation and singleton births than is the case after PGD performed on day 3. Copyright (c) 2008 John Wiley & Sons, Ltd.