Arce Joan-Carles, Andersen Anders Nyboe, Fernández-Sánchez Manuel, Visnova Hana, Bosch Ernesto, García-Velasco Juan Antonio, Barri Pedro, de Sutter Petra, Klein Bjarke M, Fauser Bart C J M
Reproductive Health, Ferring Pharmaceuticals, Copenhagen, Denmark.
Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Fertil Steril. 2014 Dec;102(6):1633-40.e5. doi: 10.1016/j.fertnstert.2014.08.013. Epub 2014 Sep 23.
To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrations.
Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0-14.9 pmol/L [0.7-<2.1 ng/mL]; high: 15.0-44.9 pmol/L [2.1-6.3 ng/mL]) trial.
Seven infertility centers in four countries.
PATIENT(S): Two hundred sixty-five women aged ≤37 years.
INTERVENTION(S): Controlled ovarian stimulation with either 5.2, 6.9, 8.6, 10.3, or 12.1 μg of rhFSH, or 11 μg (150 IU) of follitropin alfa in a GnRH antagonist cycle.
MAIN OUTCOME MEASURE(S): Number of oocytes retrieved.
RESULT(S): The number of oocytes retrieved increased in an rhFSH dose-dependent manner, from 5.2 ± 3.3 oocytes with 5.2 μg/d to 12.2 ± 5.9 with 12.1 μg/d. The slopes of the rhFSH dose-response curves differed significantly between the two AMH strata, demonstrating that a 10% increase in dose resulted in 0.5 (95% confidence interval 0.2-0.7) and 1.0 (95% confidence interval 0.7-1.3) more oocytes in the low and high AMH stratum, respectively. Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata. No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata. Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum.
CONCLUSION(S): Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner. The availability of blastocysts is less influenced by the rhFSH dose and AMH level.
NCT01426386.
评估新型重组人促卵泡激素（rhFSH；FE 999049）在接受体外受精/卵胞浆内单精子注射治疗患者中与卵巢反应的剂量-反应关系；并前瞻性研究初始抗苗勒管激素（AMH）浓度的影响。
随机、对照、评估者盲法、AMH分层（低：5.0 - 14.9 pmol/L [0.7 - <2.1 ng/mL]；高：15.0 - 44.9 pmol/L [2.1 - 6.3 ng/mL]）试验。
四个国家的七个不孕不育中心。
265名年龄≤37岁的女性。
在GnRH拮抗剂周期中，分别用5.2、6.9、8.6、10.3或12.1 μg的rhFSH或11 μg（150 IU）的重组促卵泡素α进行控制性卵巢刺激。
获取的卵母细胞数量。
获取的卵母细胞数量呈rhFSH剂量依赖性增加，从每天5.2 μg时的5.2±3.3个卵母细胞增加到每天12.1 μg时的12.2±5.9个。rhFSH剂量-反应曲线的斜率在两个AMH分层之间有显著差异，表明剂量增加10%时，低AMH分层和高AMH分层分别多获得0.5（95%置信区间0.2 - 0.7）和1.0（95%置信区间0.7 - 1.3）个卵母细胞。在两个AMH分层中，随着rhFSH剂量增加，受精率和囊胚/卵母细胞比率均显著下降。未观察到rhFSH剂量与总体囊胚数量或按AMH分层的囊胚数量之间存在线性关系。报告了三个最高rhFSH剂量组和高AMH分层中有5例卵巢过度刺激综合征病例。
rhFSH剂量增加会导致获取的卵母细胞数量以AMH依赖的方式呈线性增加。囊胚的可得性受rhFSH剂量和AMH水平的影响较小。
NCT01426386。
