Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization
Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization
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DOI：
10.1172/jci75730
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发表时间：
2014-08-01
影响因子：
15.9
通讯作者：
Dhillo, Waljit S.
中科院分区：
文献类型：
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作者：
Jayasena, Channa N.;Abbara, Ali;Dhillo, Waljit S.
背景。具有使kisspeptin信号失活的突变的患者是不育的。kisspeptin -54是kisspeptin在人体内主要的循环异构体，能有效刺激人体内生殖激素的分泌。动物研究表明kisspeptin参与促黄体激素的产生，这是排卵所必需的；因此，我们假设kisspeptin-54可以用来触发接受体外受精治疗的女性的卵子成熟。在使用重组促卵泡激素和促性腺激素释放激素拮抗剂预防早泄后，53名妇女接受单次皮下注射kisspeptin-54 (1.6 nmol/kg, n = 2; 3.2 nmol/kg, n = 3; 6.4 nmol/kg, n = 24; 12.8 nmol/kg, n = 24)，以诱导黄体生成素增加和卵子成熟。注射kisspeptin后36小时经阴道取出卵子，评估成熟情况（主要结局），并通过卵胞浆内单精子注射受精，随后移植一个或两个胚胎。在kisspeptin-54的每个测试剂量下，观察到卵子成熟，并且每个患者成熟卵子的平均数量通常以剂量依赖的方式增加。92%（49/53）的kisspeptin-54治疗患者的卵子受精和胚胎移植到子宫。生化和临床妊娠率分别为40%（21/53）和23%（12/53）。本研究表明，单次注射kisspeptin-54可以诱导接受体外受精治疗的低生育能力妇女的卵子成熟。kisspeptin-54给药后成熟卵子的后续受精和由此产生的胚胎的移植可导致成功的人类妊娠。
BACKGROUND. Patients with mutations that inactivate kisspeptin signaling are infertile. Kisspeptin-54, the major circulating isoform of kisspeptin in humans, potently stimulates reproductive hormone secretion in humans. Animal studies suggest that kisspeptin is involved in generation of the luteinizing hormone surge, which is required for ovulation; therefore, we hypothesized that kisspeptin-54 could be used to trigger egg maturation in women undergoing in vitro fertilization therapy.METHODS. Following superovulation with recombinant follicle-stimulating hormone and administration of gonadotropin-releasing hormone antagonist to prevent premature ovulation, 53 women were administered a single subcutaneous injection of kisspeptin-54 (1.6 nmol/kg, n = 2; 3.2 nmol/kg, n = 3; 6.4 nmol/kg, n = 24; 12.8 nmol/kg, n = 24) to induce a luteinizing hormone surge and egg maturation. Eggs were retrieved transvaginally 36 hours after kisspeptin injection, assessed for maturation (primary outcome), and fertilized by intracytoplasmic sperm injection with subsequent transfer of one or two embryos.RESULTS. Egg maturation was observed in response to each tested dose of kisspeptin-54, and the mean number of mature eggs per patient generally increased in a dose-dependent manner. Fertilization of eggs and transfer of embryos to the uterus occurred in 92% (49/53) of kisspeptin-54-treated patients. Biochemical and clinical pregnancy rates were 40% (21/53) and 23% (12/53), respectively.CONCLUSION. This study demonstrates that a single injection of kisspeptin-54 can induce egg maturation in women with subfertility undergoing in vitro fertilization therapy. Subsequent fertilization of eggs matured following kisspeptin-54 administration and transfer of resulting embryos can lead to successful human pregnancy.