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在受孕时鉴定抑制素的来源,可为其在极早期妊娠中提供诊断作用。

Identification of the source of inhibins at the time of conception provides a diagnostic role for them in very early pregnancy.

作者信息

Lockwood G M, Ledger W L, Barlow D H, Groome N P, Muttukrishna S

机构信息

Nuffield Department of Obstetrics and Gynaecology, University of Oxford, United Kingdom.

出版信息

Am J Reprod Immunol. 1998 Nov;40(5):303-8. doi: 10.1111/j.1600-0897.1998.tb00058.x.

DOI:10.1111/j.1600-0897.1998.tb00058.x
PMID:9870072
Abstract

PROBLEM

Early diagnosis of a complicated or poor pregnancy outcome in patients undergoing assisted reproductive technique (ART) fertility treatment could aid their counseling and management. A possible role for the inhibin superfamily as markers of early pregnancy viability was investigated.

METHOD OF STUDY

To determine the source of the dimeric glycoproteins inhibin A (alpha-beta A) in early pregnancy, serial blood samples from women who became pregnant following in vitro fertilization (IVF) with fresh embryo transfer (n = 50), from women who achieved pregnancy with frozen-thawed embryos (n = 8), and from a control group of women with spontaneous conceptions (n = 7) were analyzed using a two-site enzyme-linked immunosorbent assay (ELISA). Gonadotropin-releasing hormone (GnRH) analogues are routinely used in ART treatment cycles and are recognized to be luteolytic, and hence, periconceptual administration may be deleterious to pregnancy outcome. Serum samples were obtained from 8 IVF patients who conceived during the cycle in which they had inadvertent luteal phase exposure to GnRH analogues.

RESULTS

Elevated serum levels of inhibin A were detected in ongoing pregnancies from 4 weeks' gestation and increased to an initial peak at 9-10 weeks' gestation. Significantly higher levels (P < 0.05) were found in the multiple pregnancies, and nonviable clinical pregnancies had very low levels of inhibin A. Inhibin pro-alpha C was detectable at levels above normal late luteal values in singleton and multiple pregnancies arising from IVF with fresh embryo transfer. In pregnancies established without corpus luteum activity, frozen-thaw embryo replacement, the levels of pro-alpha C containing inhibins were extremely low, suggesting that the corpus luteum is the major source of the alpha monomer. In pregnancies following inadvertent periconceptual exposure to GnRH analogue, the levels of pro-alpha C were statistically significantly higher in successful pregnancies than in early pregnancy failures.

CONCLUSIONS

The feto-placental unit is confirmed as the major source of inhibin A in early pregnancy, and the initially low levels and very rapid decline in inhibin A in pregnancies with embryonic failure suggest a role for this glycoprotein as a monitor of early pregnancy viability. The corpus luteum is demonstrated to be the major source of inhibin pro-alpha C in early pregnancy, and very low levels in patients with peri-implantational exposure are indicative of lytic damage and herald pregnancy failure despite luteal supplementation with progesterone.

摘要

问题

对接受辅助生殖技术(ART)生育治疗的患者,早期诊断复杂或不良的妊娠结局有助于对其进行咨询和管理。研究了抑制素超家族作为早期妊娠存活标志物的可能作用。

研究方法

为确定妊娠早期二聚体糖蛋白抑制素A(α-βA)的来源,对以下三组女性的系列血样进行分析:接受新鲜胚胎移植体外受精(IVF)后怀孕的女性(n = 50)、接受冻融胚胎移植后怀孕的女性(n = 8)以及自然受孕的女性对照组(n = 7),采用双位点酶联免疫吸附测定(ELISA)法。促性腺激素释放激素(GnRH)类似物常用于ART治疗周期,已知其具有溶黄体作用,因此,受孕前后给药可能对妊娠结局有害。从8例在周期中意外黄体期暴露于GnRH类似物期间受孕的IVF患者获取血清样本。

结果

在妊娠持续至4周的孕妇中检测到抑制素A血清水平升高,并在妊娠9 - 10周时升至初始峰值。多胎妊娠中抑制素A水平显著更高(P < 0.05),而不可行的临床妊娠中抑制素A水平非常低。在新鲜胚胎移植IVF后的单胎和多胎妊娠中,抑制素原αC在黄体晚期高于正常水平时可检测到。在无黄体活动的冻融胚胎移植建立的妊娠中,含αC的抑制素水平极低,表明黄体是α单体的主要来源。在受孕前后意外暴露于GnRH类似物后的妊娠中,成功妊娠的抑制素原αC水平在统计学上显著高于早期妊娠失败的情况。

结论

胎儿 - 胎盘单位被确认为妊娠早期抑制素A的主要来源,胚胎发育失败的妊娠中抑制素A最初水平低且迅速下降,提示该糖蛋白可作为早期妊娠存活的监测指标。黄体被证明是妊娠早期抑制素原αC的主要来源,植入前后暴露患者中抑制素原αC水平极低表明存在溶黄体损伤,预示着尽管补充了黄体酮仍会发生妊娠失败。

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