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来曲唑对行卵母细胞冷冻保存的癌症患者卵泡液甾体浓度的影响。

Effect of letrozole on follicular fluid steroids concentrations in cancer patients undergoing oocyte cryopreservation.

机构信息

Infertility Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Manfredo Fanti, 6 20122, Milan, Italy.

Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Milan, Italy.

出版信息

J Assist Reprod Genet. 2022 May;39(5):1169-1176. doi: 10.1007/s10815-022-02477-1. Epub 2022 Mar 29.

DOI:10.1007/s10815-022-02477-1
PMID:35348950
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9107531/
Abstract

PURPOSE

To investigate the impact of letrozole administration on follicular steroid hormones during controlled ovarian hyperstimulation for fertility preservation.

METHODS

One hundred and nineteen women with cancer undergoing oocytes retrieval for fertility preservation were recruited. All women underwent ovarian hyperstimulation according to a random start protocol. Those with hormone-sensitive tumors also received letrozole, an aromatase inhibitor aimed at keeping peripheral estrogen levels low. At the time of oocytes retrieval, a sample of follicular fluid was collected and frozen. All samples were assayed concomitantly after thawing, by liquid chromatography tandem mass spectrometry. The concentration of 15 steroid hormones was determined and results were compared between women who did and did not receive letrozole.

RESULTS

Fifty-two women were treated with letrozole, while 67 were not. Statistically significant differences emerged for 12 of the 15 tested steroids. They were the following: cortisol, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), estradiol, androstenedione, testosterone, dihydrotestosterone (DHT), 17-hydroxyprogesterone, progesterone and corticosterone. The most striking differences were observed for testosterone that showed a more than 200-time increase in women receiving letrozole. Estradiol was conversely reduced to a third.

CONCLUSIONS

The endocrine microenvironment surrounding oocytes is markedly perturbed by the concomitant assumption of letrozole. Robust clinical evaluation is pressingly needed to rule out any detrimental effect on the chance of live birth with the use of these oocytes.

摘要

目的

研究在进行控制性卵巢超刺激以保存生育力时,来曲唑给药对卵泡类固醇激素的影响。

方法

招募了 119 名正在接受卵母细胞采集以进行生育力保存的癌症患者。所有女性均根据随机起始方案进行卵巢超刺激。那些患有激素敏感型肿瘤的患者还接受了来曲唑治疗,这是一种旨在降低外周雌激素水平的芳香化酶抑制剂。在卵母细胞采集时,采集并冷冻了卵泡液样本。所有样本解冻后同时通过液相色谱串联质谱法进行检测。测定了 15 种类固醇激素的浓度,并比较了接受和未接受来曲唑治疗的女性之间的结果。

结果

52 名女性接受了来曲唑治疗,而 67 名女性未接受。在 15 种测试类固醇中,有 12 种出现了统计学上的显著差异。它们分别是:皮质醇、11-脱氧皮质醇、21-脱氧皮质醇、硫酸脱氢表雄酮 (DHEAS)、脱氢表雄酮 (DHEA)、雌二醇、雄烯二酮、睾酮、二氢睾酮 (DHT)、17-羟孕酮、孕酮和皮质酮。最显著的差异出现在接受来曲唑治疗的女性中,其睾酮水平增加了 200 多倍。相反,雌二醇降低到三分之一。

结论

来曲唑的同时使用显著改变了卵母细胞周围的内分泌微环境。迫切需要进行严格的临床评估,以排除使用这些卵母细胞对活产机会的任何不利影响。

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本文引用的文献

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Hyperandrogenism by Liquid Chromatography Tandem Mass Spectrometry in PCOS: Focus on Testosterone and Androstenedione.采用液相色谱串联质谱法检测多囊卵巢综合征中的高雄激素血症:聚焦睾酮和雄烯二酮
J Clin Med. 2020 Dec 31;10(1):119. doi: 10.3390/jcm10010119.
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Predictors and outcomes in breast cancer patients who did or did not pursue fertility preservation.是否进行生育力保存的乳腺癌患者的预测因素和结局。
Breast Cancer Res Treat. 2021 Apr;186(2):429-437. doi: 10.1007/s10549-020-06031-4. Epub 2021 Jan 4.
3
Efficacy and safety of controlled ovarian stimulation using GnRH antagonist protocols for emergency fertility preservation in young women with breast cancer-a prospective nationwide Swedish multicenter study.采用 GnRH 拮抗剂方案控制性卵巢刺激在年轻乳腺癌女性中进行紧急生育力保存的疗效和安全性:一项前瞻性全国性瑞典多中心研究。
Hum Reprod. 2020 Apr 28;35(4):929-938. doi: 10.1093/humrep/deaa029.
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Adjuvant treatment strategies in ovarian stimulation for poor responders undergoing IVF: a systematic review and network meta-analysis.辅助治疗策略在 IVF 中对卵巢刺激反应不良者的应用:系统评价和网络荟萃分析。
Hum Reprod Update. 2020 Feb 28;26(2):247-263. doi: 10.1093/humupd/dmz046.
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Letrozole supplementation during controlled ovarian stimulation in expected high responders: a pilot randomized controlled study.在预期的高反应者中进行控制性卵巢刺激时添加来曲唑补充:一项随机对照试验。
Reprod Biol Endocrinol. 2019 May 10;17(1):43. doi: 10.1186/s12958-019-0483-x.
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