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无需外源性孕激素给药的微剂量人绒毛膜促性腺激素作为黄体期支持:循环中人绒毛膜促性腺激素浓度的数学模型及初步临床经验

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

作者信息

Andersen C Yding, Fischer R, Giorgione V, Kelsey Thomas W

机构信息

Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children and Reproduction, Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Laboratory of Reproductive Biology, Section 5712, The Juliane Marie Centre for Women, Children and Reproduction, University Hospital of Copenhagen, University of Copenhagen, Blegdamsvej 9, Rigshospitalet, 2100, Copenhagen, Denmark.

出版信息

J Assist Reprod Genet. 2016 Oct;33(10):1311-1318. doi: 10.1007/s10815-016-0764-7. Epub 2016 Jul 22.

Abstract

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

摘要

在过去二十年中,外源性孕激素给药一直被用作黄体期支持(LPS),与控制性卵巢刺激相结合,并使用人绒毛膜促性腺激素(hCG)触发卵泡最终成熟。引入促性腺激素释放激素激动剂(GnRHa)触发排卵表明,在不补充hCG的情况下给予外源性孕激素不足以获得令人满意的妊娠率。这促使人们开发替代的黄体期支持策略。通过多个黄体增加局部内源性孕激素的产生一直是一个重点,一方面强调避免卵巢过度刺激综合征的发生,另一方面提供足够水平的孕激素以维持着床。本研究评估了微剂量hCG用于黄体期支持的情况,并探讨了其潜在的优缺点。基于hCG的药代动力学特征,结合几种不同的hCG给药方式作为黄体期支持,对黄体期hCG浓度曲线的数学模型进行了评估。研究表明,目前与GnRHa触发联合使用的黄体期支持剂量(即1500 IU)过强,而每日微剂量hCG给药可能会利用现有药物提供优化的黄体期支持。文中展示了微剂量hCG方法的初步临床结果。

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