Behre Hermann M, Greb Robert R, Mempel Andrea, Sonntag Barbara, Kiesel Ludwig, Kaltwasser Petra, Seliger Ewald, Röpke Friedrich, Gromoll Jörg, Nieschlag Eberhard, Simoni Manuela
Andrology Unit, Department of Urology, University Hospital, Halle, University Hospital, Münster, Germany.
Pharmacogenet Genomics. 2005 Jul;15(7):451-6. doi: 10.1097/01.fpc.0000167330.92786.5e.
The p.N680S sequence variation of the follicle-stimulating hormone (FSH) receptor gene was previously shown to influence the ovarian response to FSH in normo-ovulatory women undergoing controlled ovarian hyperstimulation. In this prospective, randomized, controlled study, we tested whether the same daily dose of FSH results in lower levels of oestradiol in women homozygous for the p.N680S sequence variation, and whether the difference can be overcome by higher FSH doses. Women undergoing controlled ovarian hyperstimulation for in vitro fertilization or intracytoplasmic sperm injection and homozygous for the wild-type or for the p.N680S FSH receptor were randomly assigned to group I (Ser/Ser, n=24), receiving an FSH dose of 150 U/day, or group II (Ser/Ser, n=25), receiving an FSH dose of 225 U/day. In group III (Asn/Asn, n=44), the FSH dose was 150 U/day. Age and basal FSH levels were not different between groups. At ovulation induction, total FSH doses were comparable in group I (1631+/-96 U) and group III (1640+/-57 U) but significantly higher in group II (2421+/-112 U) (P<0.001). Peak oestradiol levels on the day of human chorionic gonadotrophin (hCG) administration were significantly lower in group I (5680+/-675 pmol/l) compared to group III (8679+/-804 pmol/l) (P=0.028). Increasing the FSH dose from 150 to 225 U/day overcame the lower oestradiol response in women with Ser/Ser (group II, 7804+/-983 pmol/l). In women undergoing controlled ovarian hyperstimulation, the p.N680S sequence variation results in lower oestradiol levels following FSH stimulation. This lower FSH receptor sensitivity can be overcome by higher FSH doses.
促卵泡激素（FSH）受体基因的p.N680S序列变异先前已表明会影响接受控制性卵巢过度刺激的正常排卵女性对FSH的卵巢反应。在这项前瞻性、随机、对照研究中，我们测试了相同每日剂量的FSH是否会使p.N680S序列变异纯合子女性的雌二醇水平更低，以及更高剂量的FSH是否能克服这种差异。接受体外受精或卵胞浆内单精子注射控制性卵巢过度刺激且为野生型或p.N680S FSH受体纯合子的女性被随机分配到I组（Ser/Ser，n = 24），接受150 U/天的FSH剂量，或II组（Ser/Ser，n = 25），接受225 U/天的FSH剂量。III组（Asn/Asn，n = 44）的FSH剂量为150 U/天。各组之间年龄和基础FSH水平无差异。在排卵诱导时，I组（1631±96 U）和III组（1640±57 U）的总FSH剂量相当，但II组（2421±112 U）显著更高（P<0.001）。与III组（8679±804 pmol/l）相比，I组在人绒毛膜促性腺激素（hCG）给药当天的雌二醇峰值水平显著更低（5680±675 pmol/l）（P = 0.028）。将FSH剂量从150 U/天增加到225 U/天可克服Ser/Ser女性（II组，7804±98 pmol/l）较低的雌二醇反应。在接受控制性卵巢过度刺激的女性中，p.N680S序列变异导致FSH刺激后雌二醇水平更低。这种较低的FSH受体敏感性可通过更高剂量的FSH克服。
