Higher Doses of FSH Used for Superovulation Do Not Adversely Affect Embryonic Ploidy: A Randomized Controlled Trial (STimulation Resulting in Embryonic Aneuploidy using Menopur (STREAM) Trial)

A. Shyamsunder, T. Hardy, A. Yazdani, A. Polyakov, R. Norman, R. Hart, F. Agresta, L. Rombauts, C. Boothroyd, M. Chapman, Prudence Sweeten, Eleanor Somerville, Rachel Jose, H. Wand, W. Ledger
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Abstract

Research Question: Does the dose of gonadotropin used for superovulation in IVF affect the proportion of euploid blastocysts obtained after fertilization? Study Design: Multicentre randomized controlled trial recruiting 57 women who were treated with ovarian stimulation using either 150 or 300 IU Menopur per day. Both groups received GnRH antagonist from day 5 of ovarian stimulation and final oocyte maturation was induced using a leuprolide GnRH (gonadotropin releasing hormone) agonist trigger when three or more follicles reached 17 mm diameter. Oocyte collection was scheduled 36–38 hours post trigger. In vitro fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) were performed according to individual unit protocol and embryos were cultured to blastocyst stage. A trophectoderm biopsy was performed on day 5 of embryo culture and used for preimplantation genetic testing for aneuploidy. Euploid embryos were transferred in subsequent frozen embryo transfer cycles with appropriate endometrial preparation. Results: The number of oocytes obtained from women randomized to 150 IU Menopur was between 3 and 17 (mean = 9), whereas the number of oocytes obtained from women randomized to 300 IU Menopur was between 3 and 24 (mean = 11). There was a positive linear relationship between serum AMH concentration and oocyte yield in both the 150 and 300 IU Menopur groups ([Formula: see text] = 0.3359, [Formula: see text] = 0.1129 and [Formula: see text] = 0.3741, [Formula: see text] = 0.1399). The percentage of euploid to aneuploid embryos in the 150 IU Menopur group was 63% and in the 300 IU Menopur group, the proportion was 75%, which was not significantly different ([Formula: see text] = 0.17). Conclusion: The higher dose ovarian stimulation protocol did not significantly increase the number of oocytes retrieved, nor did the higher dose protocol reduce the proportion of euploid embryos created. This study does not support the hypothesis that use of higher doses of gonadotropin for ovarian stimulation results in a reduction in the proportion of euploid embryos obtained after IVF.
高剂量卵泡刺激素用于超排卵不会对胚胎倍性产生不利影响:一项随机对照试验(使用绝经(STREAM)试验刺激导致胚胎非整倍体)
研究问题:体外受精中用于超排卵的促性腺激素的剂量是否影响受精后获得整倍体囊胚的比例?研究设计:多中心随机对照试验,招募57名妇女,每天使用150或300 IU的绝经治疗卵巢刺激。两组从卵巢刺激的第5天开始使用GnRH拮抗剂,当三个或更多卵泡达到17mm直径时,使用leuprolide GnRH(促性腺激素释放激素)激动剂触发最终诱导卵母细胞成熟。卵母细胞采集计划在触发后36-38小时进行。采用体外受精(IVF)或卵浆内单精子注射(ICSI),将胚胎培养至囊胚期。在胚胎培养第5天进行滋养外胚层活检,并用于着床前非整倍体基因检测。在随后的冷冻胚胎移植周期中移植整倍体胚胎,并进行适当的子宫内膜准备。结果:从随机分配到150 IU绝经组的妇女中获得的卵母细胞数量为3 ~ 17个(平均= 9),而从随机分配到300 IU绝经组的妇女中获得的卵母细胞数量为3 ~ 24个(平均= 11)。在150和300 IU绝经组,血清AMH浓度与卵母细胞产量呈线性正相关([公式:见文]= 0.3359,[公式:见文]= 0.1129,[公式:见文]= 0.3741,[公式:见文]= 0.1399)。在150 IU绝经组中,整倍体到非整倍体的比例为63%,在300 IU绝经组中,这一比例为75%,差异不显著([公式:见文]= 0.17)。结论:高剂量卵巢刺激方案并没有显著增加卵母细胞的数量,也没有降低整倍体胚胎的形成比例。本研究不支持使用高剂量促性腺激素刺激卵巢导致体外受精后获得的整倍体胚胎比例减少的假设。
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