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低反应患者行未刺激周期的卵泡激素谱:是否为低雄激素血症?

The follicular hormonal profile in low-responder patients undergoing unstimulated cycles: Is it hypoandrogenic?

机构信息

Clinical Embryology Laboratory, IVI Valencia, Institut Universitari IVI, Plaza de la Policía Local, 346016 Valencia, Spain.

出版信息

Hum Reprod. 2013 Jan;28(1):224-9. doi: 10.1093/humrep/des349. Epub 2012 Sep 27.

DOI:10.1093/humrep/des349
PMID:23019297
Abstract

STUDY QUESTION

What is the final hormonal milieu of pre-ovulatory follicles of low-responder (LR) patients undergoing unstimulated cycles?

SUMMARY ANSWER

Neither androgen secretion nor LH was impaired in pre-ovulatory follicles of LR women.

WHAT IS KNOWN ALREADY

Therapies currently used to improve ovarian response in LR women have an impact on the final hormonal follicular milieu, and these changes are believed to be partially responsible for determining the success rate in these women. Surprisingly, as far as we know, there is no report of the final hormonal profile of LR women undergoing unstimulated cycles or evidence that follicular androgen secretion in LR women is impaired.

STUDY DESIGN, SIZE AND DURATION: A prospective case-control study including 94 women, 36 normal controls and 58 LR patients (19 Young ≤ 35 years LR and 39 Aged >35 years LR) from 2009 to 2011.

PARTICIPANTS/MATERIALS, SETTING AND METHODS: Fifty-eight LR women were divided into two groups: Young LR (age ≤ 35; n = 19) and Aged LR (ALR; age >35; n = 39). The control group (group C) comprised 36 egg donors undergoing an unstimulated cycle in our IVF unit. Serum and follicular fluid hormonal concentrations for estradiol (E₂), progesterone, testosterone and androstendione were measured. The spindle parameters of metaphase II oocytes generated from these groups were also analysed.

MAIN RESULTS AND THE ROLE OF CHANCE

Pre-ovulatory follicles from LR patients had similar androgenic and LH concentrations to those observed in the control group. However, higher intrafollicular concentrations of FSH and progesterone were observed in ALR. Moreover, no differences were found for the spindle evaluation of oocytes between groups by the Oosight technology.

LIMITATIONS, REASONS FOR CAUTION: The controls were younger and had a lower BMI than the LR women. The sample size available restricted statistical power.

WIDER IMPLICATIONS OF THE FINDINGS

This study suggests that the problem with LR women is not the final pre-ovulatory follicular androgen concentration since this is similar to normal responders, but in the ability to respond to controlled ovarian stimulation protocols. Therefore, efforts should be focused on long-interval androgen priming to potentially increase the recruitment of small antral follicles rather than increasing the intraovarian androgen levels within the current cycle.

STUDY FUNDING/COMPETING INTEREST: The present project has been supported by the R+D programme from the Generalitat Valenciana (Regional Valencian Government) IMPIVA MIDTF/2010/95. The authors have no conflict of interest to declare.

摘要

研究问题

在接受非刺激性周期的低反应(LR)患者的排卵前卵泡中,最终的激素环境是什么?

总结答案

LR 女性的排卵前卵泡中既没有雄激素分泌也没有 LH 受损。

已知事实

目前用于改善 LR 女性卵巢反应的治疗方法会影响最终的卵泡激素环境,据信这些变化部分决定了这些女性的成功率。令人惊讶的是,据我们所知,目前还没有关于接受非刺激性周期的 LR 女性的最终激素谱的报告,也没有证据表明 LR 女性的卵泡雄激素分泌受损。

研究设计、规模和持续时间:一项前瞻性病例对照研究,纳入了 2009 年至 2011 年间的 94 名女性,36 名正常对照组和 58 名 LR 患者(19 名年轻≤35 岁 LR 和 39 名年龄>35 岁 LR)。

参与者/材料、设置和方法:58 名 LR 患者分为两组:年轻 LR(年龄≤35 岁;n=19)和老年 LR(ALR;年龄>35 岁;n=39)。对照组(C 组)由在我们的 IVF 单位接受非刺激性周期的 36 名卵子供体组成。测量血清和卵泡液中雌二醇(E₂)、孕酮、睾酮和雄烯二酮的激素浓度。还分析了来自这些组的中期 II 期卵母细胞的纺锤体参数。

主要结果和机会的作用

LR 患者的排卵前卵泡雄激素和 LH 浓度与对照组观察到的相似。然而,ALR 中观察到更高的卵泡内 FSH 和孕酮浓度。此外,通过 Oosight 技术对各组卵母细胞的纺锤体评估未发现差异。

局限性、谨慎的原因:对照组比 LR 女性更年轻,BMI 更低。可用的样本量限制了统计能力。

研究结果的更广泛影响

这项研究表明,LR 女性的问题不是排卵前卵泡雄激素浓度的最终问题,因为这与正常反应者相似,而是对控制性卵巢刺激方案的反应能力。因此,应集中精力进行长间隔雄激素预处理,以潜在增加小窦卵泡的募集,而不是增加当前周期内卵巢内雄激素水平。

研究资金/利益冲突:本项目得到了 Generalitat Valenciana(瓦伦西亚地区政府)R+D 计划的支持(IMPIVA MIDTF/2010/95)。作者没有利益冲突需要声明。

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