Yang Zhihong, Liu Jiaen, Collins Gary S, Salem Shala A, Liu Xiaohong, Lyle Sarah S, Peck Alison C, Sills E Scott, Salem Rifaat D
Division of Reproductive Endocrinology Research, Pacific Reproductive Center, Torrance, CA, 90505, USA.
Mol Cytogenet. 2012 May 2;5(1):24. doi: 10.1186/1755-8166-5-24.
Single embryo transfer (SET) remains underutilized as a strategy to reduce multiple gestation risk in IVF, and its overall lower pregnancy rate underscores the need for improved techniques to select one embryo for fresh transfer. This study explored use of comprehensive chromosomal screening by array CGH (aCGH) to provide this advantage and improve pregnancy rate from SET.
First-time IVF patients with a good prognosis (age <35, no prior miscarriage) and normal karyotype seeking elective SET were prospectively randomized into two groups: In Group A, embryos were selected on the basis of morphology and comprehensive chromosomal screening via aCGH (from d5 trophectoderm biopsy) while Group B embryos were assessed by morphology only. All patients had a single fresh blastocyst transferred on d6. Laboratory parameters and clinical pregnancy rates were compared between the two groups.
For patients in Group A (n = 55), 425 blastocysts were biopsied and analyzed via aCGH (7.7 blastocysts/patient). Aneuploidy was detected in 191/425 (44.9%) of blastocysts in this group. For patients in Group B (n = 48), 389 blastocysts were microscopically examined (8.1 blastocysts/patient). Clinical pregnancy rate was significantly higher in the morphology + aCGH group compared to the morphology-only group (70.9 and 45.8%, respectively; p = 0.017); ongoing pregnancy rate for Groups A and B were 69.1 vs. 41.7%, respectively (p = 0.009). There were no twin pregnancies.
Although aCGH followed by frozen embryo transfer has been used to screen at risk embryos (e.g., known parental chromosomal translocation or history of recurrent pregnancy loss), this is the first description of aCGH fully integrated with a clinical IVF program to select single blastocysts for fresh SET in good prognosis patients. The observed aneuploidy rate (44.9%) among biopsied blastocysts highlights the inherent imprecision of SET when conventional morphology is used alone. Embryos randomized to the aCGH group implanted with greater efficiency, resulted in clinical pregnancy more often, and yielded a lower miscarriage rate than those selected without aCGH. Additional studies are needed to verify our pilot data and confirm a role for on-site, rapid aCGH for IVF patients contemplating fresh SET.
单胚胎移植(SET)作为一种降低体外受精(IVF)中多胎妊娠风险的策略,其应用仍未得到充分利用,且其总体较低的妊娠率凸显了改进技术以选择单个胚胎进行新鲜移植的必要性。本研究探讨了使用阵列比较基因组杂交(aCGH)进行全面染色体筛查,以提供这一优势并提高SET的妊娠率。
将首次接受IVF且预后良好(年龄<35岁,无既往流产史)且核型正常、寻求选择性SET的患者前瞻性随机分为两组:A组根据形态学和通过aCGH(来自第5天滋养外胚层活检)进行的全面染色体筛查来选择胚胎,而B组胚胎仅通过形态学进行评估。所有患者均在第6天移植单个新鲜囊胚。比较两组的实验室参数和临床妊娠率。
A组患者(n = 55)中,425个囊胚进行了活检并通过aCGH分析(每位患者7.7个囊胚)。该组中191/425(44.9%)的囊胚检测到非整倍体。B组患者(n = 48)中,389个囊胚进行了显微镜检查(每位患者8.1个囊胚)。形态学+aCGH组的临床妊娠率显著高于仅形态学组(分别为70.9%和45.8%;p = 0.017);A组和B组的持续妊娠率分别为69.1%和41.7%(p = 0.009)。无双胎妊娠。
尽管aCGH联合冻融胚胎移植已用于筛查有风险的胚胎(例如,已知父母染色体易位或反复妊娠丢失史),但这是首次描述将aCGH完全整合到临床IVF程序中,为预后良好的患者选择单个囊胚进行新鲜SET。活检囊胚中观察到的非整倍体率(44.9%)突出了单独使用传统形态学时SET固有的不精确性。随机分配到aCGH组的胚胎着床效率更高,临床妊娠更频繁,流产率低于未进行aCGH选择的胚胎。需要进一步研究来验证我们的初步数据,并确认现场快速aCGH在考虑新鲜SET的IVF患者中的作用。