Smitz Johan, Picton Helen-Mary, Platteau Peter, Rutherford Anthony, Cortvrindt Rita, Clyde Julie, Nogueira Daniela, Devroey Paul, Lyby Karsten, Gröndahl Christian
Center for Reproductive Medicine, Academisch Ziekenhuis, Vrije Universiteit Brussel, Brussels, Belgium.
Fertil Steril. 2007 Apr;87(4):949-64. doi: 10.1016/j.fertnstert.2006.10.009. Epub 2007 Jan 2.
To evaluate the safety of applying follicular-fluid meiosis-activating sterol (FF-MAS) in vitro to immature human oocytes.
Phase I bicenter, randomized, parallel-group, controlled, partially blinded trial.
Third-level referral academic centers, including reproductive biology and genetics laboratories.
Endocrinologically normal women with a medical indication for IVF or intracytoplasmic sperm injection, or healthy volunteers.
INTERVENTION(S): Subjects were randomized at a ratio 1 to 6 into either conventional GnRH-agonist and recombinant FSH stimulation (IVO) for oocyte retrieval, or minimally stimulated in vitro maturation (IVM) with the use of recombinant FSH. Retrieved immature oocyte cumulus complexes were cultured for 30 or 36 hours in one of six IVM culture conditions containing FF-MAS (range, 0.1-20 microM). Polar body-extruded oocytes from the IVO and IVM groups were processed for chromosomal analysis.
MAIN OUTCOME MEASURE(S): The primary endpoint was the incidence of metaphase II stage oocytes with numeric chromosomal abnormalities, using full (spectral karyotyping) or partial (fluorescent in situ hybridization with seven probes) karyotyping or Giemsa count. A secondary objective was to document the frequency of metaphase II oocytes after IVM with FF-MAS supplements.
RESULT(S): Oocyte cumulus complexes obtained from the IVO (mean, 8.9) and IVM (mean, 6.2) groups had equal maturation rates. Compared to IVO, exposure of germinal-vesicle oocytes for a maturation period of 30 hours did not increase aneuploidy. An exposure period of 36 hours doubled the aneuploidy rate, but this was significant only for the 20-muM dose of FF-MAS.
Inclusion of 1-10 microM FF-MAS in a 30-hour IVM protocol is safe.
评估体外应用卵泡液减数分裂激活甾醇（FF-MAS）于未成熟人卵母细胞的安全性。
I期双中心、随机、平行组、对照、部分盲法试验。
三级转诊学术中心，包括生殖生物学和遗传学实验室。
有IVF或卵胞浆内单精子注射医学指征的内分泌正常女性，或健康志愿者。
受试者按1:6的比例随机分为两组，一组采用传统促性腺激素释放激素激动剂和重组促卵泡素刺激（IVO）进行卵母细胞采集，另一组采用重组促卵泡素进行最小刺激体外成熟（IVM）。采集的未成熟卵母细胞-卵丘复合体在含FF-MAS（范围为0.1-20μM）的六种IVM培养条件之一中培养30或36小时。IVO组和IVM组排出极体的卵母细胞进行染色体分析。
主要终点是使用全（光谱核型分析）或部分（用七种探针进行荧光原位杂交）核型分析或吉姆萨计数法检测的中期II期卵母细胞出现数字染色体异常的发生率。次要目标是记录添加FF-MAS的IVM后中期II期卵母细胞的频率。
IVO组（平均8.9个）和IVM组（平均6.2个）获得的卵母细胞-卵丘复合体成熟率相同。与IVO相比，生发泡卵母细胞暴露30小时的成熟时间并未增加非整倍体率。暴露36小时使非整倍体率加倍，但仅在20μM剂量的FF-MAS时具有统计学意义。
在30小时的IVM方案中加入1-10μM FF-MAS是安全的。
