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特发性早发性卵巢功能不全:对 ART 反应不良的年轻女性中,是否存在与绝经前加速生物学衰老有关?

Idiopathic early ovarian aging: is there a relation with premenopausal accelerated biological aging in young women with diminished response to ART?

机构信息

Fertility Clinic, Department of Obstetrics and Gynecology, Horsens Regional Hospital, Horsens, Denmark.

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

出版信息

J Assist Reprod Genet. 2021 Nov;38(11):3027-3038. doi: 10.1007/s10815-021-02326-7. Epub 2021 Oct 1.

Abstract

PURPOSE

To evaluate whether young women with idiopathic early ovarian aging, as defined by producing fewer oocytes than expected for a given age over multiple in vitro fertilization (IVF) cycles, have changes in telomere length and epigenetic age indicating accelerated biological aging (i.e., increased risk of morbidity and mortality).

METHODS

A prospective cohort study was conducted at two Danish public fertility clinics. A total of 55 young women (≤ 37 years) with at least two IVF cycles with ≤ 5 harvested oocytes despite sufficient stimulation with follicle-stimulating hormone (FSH) were included in the early ovarian aging group. As controls, 52 young women (≤ 37 years) with normal ovarian function, defined by at least eight harvested oocytes, were included. Relative telomere length (rTL) and epigenetic age acceleration (AgeAccel) were measured in white blood cells as markers of premenopausal accelerated biological aging.

RESULTS

rTL was comparable with a mean of 0.46 (± SD 0.12) in the early ovarian aging group and 0.47 (0.14) in the normal ovarian aging group. The AgeAccel of the early ovarian aging group was, insignificantly, 0.5 years older, but this difference disappeared when adjusting for chronological age. Sub-analysis using Anti-Müllerian hormone (AMH) as selection criterion for the two groups did not change the results.

CONCLUSION

We did not find any indications of accelerated aging in whole blood from young women with idiopathic early ovarian aging. Further investigations in a similar cohort of premenopausal women or other tissues are needed to fully elucidate the potential relationship between premenopausal accelerated biological aging and early ovarian aging.

摘要

目的

评估在多个体外受精(IVF)周期中,由于卵巢储备功能降低导致年轻女性(≤37 岁)产生的卵母细胞数量少于预期,这些女性是否存在端粒长度和表观遗传年龄的变化,表明其存在加速的生物学衰老(即,发病率和死亡率增加的风险)。

方法

本研究为前瞻性队列研究,在丹麦两家公立生育诊所进行。共纳入 55 名年轻女性(≤37 岁),她们至少进行了两次 IVF 周期,尽管使用卵泡刺激素(FSH)进行了充分的刺激,但每个周期仅获得≤5 个可采集的卵母细胞,被诊断为卵巢储备功能降低。作为对照组,纳入了 52 名年轻女性(≤37 岁),她们的卵巢功能正常,定义为至少获得 8 个可采集的卵母细胞。通过测量白细胞中的相对端粒长度(rTL)和表观遗传年龄加速(AgeAccel)作为绝经前加速生物学衰老的标志物。

结果

rTL 在卵巢储备功能降低组中的平均值为 0.46(±0.12),与卵巢功能正常组(0.47±0.14)相当。卵巢储备功能降低组的 AgeAccel 平均年长 0.5 岁,但当按实际年龄调整后,这种差异消失。使用抗苗勒管激素(AMH)作为两组的选择标准进行亚组分析,结果没有改变。

结论

我们没有发现卵巢储备功能降低的年轻女性全血中存在加速衰老的迹象。需要进一步在类似的绝经前女性队列或其他组织中进行研究,以充分阐明绝经前加速的生物学衰老与卵巢储备功能降低之间的潜在关系。

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