Article: Ovulation induction for anovulatory patients

出自文章：口服促排卵药

Author: Evert J. P. van Sanbrink and Bart C. J. M. Fauser

Book: Ovarian Stimulation

书籍： 卵巢促排（2011年第一版）

Editors: Mohamed Aboulghar and Botros Rizk

主编：Mohamed Aboulghar 和 Botros Rizk

In hypogonadotropic hypoestrogenic patients anovulation results from a hypothalamic or pituitary problem.

在低促性腺激素低雌激素患者中，无排卵是由下丘脑或垂体问题引起的。

A gonadotropin-releasing hormone (GnRH) stimulation test may help to distinguish between the origin of the problem; administration of GnRH agonist will cause only an increase in serum gonadotropins if the pituitary gland is functional. In case the anovulation is caused by extreme weight loss, the primary goal will be to restore the normal weight that will likely result in the return of a regular ovulatory cycle (1).

促性腺激素释放激素（GnRH）刺激试验可能有助于区分问题的根源。如果垂体功能正常，使用GnRH激动剂只会增加血清促性腺激素水平。如果无排卵是由严重性体重减轻引起的，则主要调整目标是恢复正常体重，这可能有助于恢复正常排卵周期（1）。

Alternatively, ovulation induction in patients who are in hypogonadotropic and hypoestrogenic status with a functional pituitary gland may be achieved using a pulsatile GnRH-agonist pump. It is remarkable that continuous GnRH agonist administration results in pituitary “down-regulation” as used in IVF procedures to prevent a premature LH rise (2), while pulsatile GnRH agonist administration may restore an ovulatory cycle leaving the physiologic feedback loop intact.

对于有正常垂体腺但有低促性激素和低雌激素症的患者，可以通过GnRH激动剂脉冲治疗来诱导排卵。不过需要注意的是，连续使用GnRH激动剂会导致垂体出现“降调”的作用，类似于试管周期中为了避免出现黄体过早升高而进行的控制（2），而脉冲式GnRH激动剂给药能在保持生理反馈回路完整的情况下恢复排卵周期。

If the pituitary gland is functionally absent, or in case of treatment failure with the GnRH-agonist pump, direct stimulation of the ovaries with exogenous gonadotropins (FSH and LH) may result in ongoing follicle growth and ovulation. In this patient group, administration of FSH should be performed with extra caution while, in contrast with patients who are in normogonadotropic and normoestrogenic status, there will not be any inhibition of the endogenous FSH release during follicle development. Moreover, the only FSH around will be exogenously administered and accumulation due to the long half-life could result in serious ovarian hyperstimulation.

如果垂体功能缺失，或者在GnRH激动剂脉冲治疗失败的情况下，用外源性促性腺激素（促卵泡素和促黄体生成素）直接刺激卵巢可能会产生持续的卵泡生长和排卵。给上面提到的患者用促卵泡素刺激卵巢应当格外谨慎。对于有正常促性腺激素和正常雌激素水平的患者，在卵泡发育过程中使用外源性性性腺激素不会出现抑制内源性促卵泡素释放的情况。而对于低促性腺激素和低刺激患者，身体内的促卵泡素来源于外源性给药，并且由于其半衰期长而积累可能导致严重的卵巢过度刺激。

Furthermore, it should be noted that a corpus luteum insufficiency may occur in absence of a functional LH pulse generator (hypothalamic dysfunction), resulting in an insufficient luteal phase and low implantation chances. This may be prevented by administration of “luteal support”. Support of the luteal phase may be achieved by administration of human chorionic gonadotropin or progesterone from the day of ovulation until sufficient chorionic gonadotropin production is provided by the trophoblast cells to rescue the corpus luteum (3).

应当注意的是，在没有功能性促黄体素脉冲式刺激（下丘脑功能障碍）的情况下，可能会发生黄体功能不足，导致黄体期时间短和植入机会低。这可以通过“黄体支持”给药来避免，即通过从排卵日起开始服用人绒毛膜促性腺激素或黄体酮来支持黄体期，直到滋养层细胞产生足够的绒毛膜促性腺激素以挽救黄体（3）。

References

参考文献

1. Wiksten-Almstromer M, Hirschberg AL, Hagenfeldt K. Prospective follow-up of menstrual disorders in adolescence and prognostic factors. Acta Obstet Gynecol Scand 2008;87: 1162-1168.

2. Filicori M. Gonadotrophin-releasing hormone agonists. A guide to use and selection. Drugs 1994;48:41-58.

3. Beckers NG, Platteau P, Eijkemans MJ, et al. The early luteal phase administration of estrogen and progesterone does not induce premature luteolysis in normo-ovulatory women. Eur J Endocrinol 2006;155:355-363.

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