Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH:: a pharmacogenetic approach to controlled ovarian hyperstimulation
Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH:: a pharmacogenetic approach to controlled ovarian hyperstimulation
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DOI：
10.1097/01.fpc.0000167330.92786.5e
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发表时间：
2005-07-01
影响因子：
2.6
通讯作者：
Simoni, M
中科院分区：
文献类型：
--
作者：
Behre, HM;Greb, RR;Simoni, M
卵泡刺激素（FSH）受体基因的p.N680S序列变异先前已被证明会影响正常排卵女性接受控制性卵巢过度刺激时卵巢对FSH的反应。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是否会导致p.N680S序列变异纯合子女性的雌二醇水平降低，以及是否可以通过更高的FSH剂量来克服这种差异。接受体外受精或卵浆内单精子注射控制卵巢过度刺激且纯合子为野生型或p.N680S FSH受体的妇女被随机分配到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）， FSH剂量为150u /d。各组年龄和基础FSH水平无显著差异。促排卵时，I组（1631 96 U）和111组（1640 57 U）的FSH总剂量相当，但II组（2421 +/- 112 U）的FSH总剂量显著高于I组（P < 0.001）。注射人绒毛膜促性腺激素（hCG）当天雌二醇峰值（5680 +/- 675 pmol/1）明显低于对照组（8679 +/- 804 pmol/l） （P=0.028）。将FSH剂量从150至225 U/天增加，克服了Ser/Ser组（II组，7804 +/- 983 pmol/l）女性较低的雌二醇反应。在接受控制性卵巢过度刺激的女性中，pn680s序列变异导致FSH刺激后雌二醇水平降低。这种较低的促卵泡刺激素受体敏感性可以通过增加促卵泡刺激素剂量来克服。药物遗传学和基因组学
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 111 (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/1) 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. Pharmacogenetics and Genomics