Trapa bispinosa Roxb. extract lowers advanced glycation end-products and increases live births in older patients with assisted reproductive technology: a randomized controlled trial.

Trapa bispinosa Roxb. extract lowers advanced glycation end-products and increases live births in older patients with assisted reproductive technology: a randomized controlled trial.
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DOI:
10.1186/s12958-021-00832-y
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发表时间:
2021-09-27
期刊:
Reproductive biology and endocrinology : RB&E
影响因子:
--
通讯作者:
Jinno Y
Jinno Y
中科院分区:
其他
文献类型:
--
作者:
Jinno M;Nagai R;Takeuchi M;Watanabe A;Teruya K;Sugawa H;Hatakeyama N;Jinno Y

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晚期糖基化终末产物 (AGE) 会随着胰岛素抵抗和衰老而积累,损害卵泡生成,并可能降低子宫内膜容受性。菱(Trapa bispinosa Roxb.)提取物是一种安全的草药,在体外强烈抑制 AGE 形成。我们确定了 Hishi 是否可以降低老年辅助生殖技术 (ART) 患者的 AGE 并增加活产率。这项前瞻性随机开放标签对照试验纳入了 64 名 38 岁至 42 岁的患者,他们在 2015 年 6 月 11 日至 2019 年 7 月 12 日期间接受了有或没有菱提取物的 ART。没有人出现超过 2 次 ART 失败、糖尿病、子宫异常或卵巢储备衰竭的情况。分配后,菱组接受菱提取物(100 毫克/天)直至妊娠晚期或失败。对照组不接受提取物。两组均接受1周期常规不孕不育治疗; 1个长方案周期的卵巢刺激、卵母细胞取出、体外受精/胞浆内单精子注射和新鲜胚胎移植(ET);如果需要,冷冻保存 ET 直至活产或胚胎耗尽。在 ART 之前和期间测量血清 AGE,以及卵泡液 (FF) 中的 AGE。 32 名 Hishi 患者的累积活产率为 47%,显着高于 31 名对照者的 16%(p<0.01;RR,4.6;95% CI,1.4 – 15.0;1 名对照者退出)。使用 Hishi 后,每次 ET 的活产率(包括新鲜和冷冻保存)显着更高(47 个 ET 中为 28%,49 个 ET 中为 10%;p<0.05;RR,3.4;95% CI,1.1-10.4)。在年龄、第 3 天 FSH、抗苗勒氏管激素和 Hishi 等变量中,逻辑回归发现只有 Hishi 与累积活产增加显着相关(p<0.05;OR,5.1;95% CI,1.4 - 18.3)。 Hishi 显着增强了卵母细胞的发育潜力,改善了自然周期中的子宫内膜容受性,并降低了血清和 FF 中的 AGE。使用 Hishi 后血清 AGE 降低幅度更大,与更多卵母细胞成为第 2 天胚胎有关。 Hishi 降低了血清和 FF 中的 AGE,改善了卵母细胞的发育潜力和子宫内膜容受性,从而增加了老年患者的活产率。通过降低 AGE 来治疗不孕症是不孕症治疗的新补充。可以考虑对 Hishi 治疗其他 AGE 相关疾病进行治疗试验。 UMIN 于 2015 年 6 月 1 日在日本注册 (UMIN000017758)。 https://www.umin.ac.jp/ctr/index.htm
Advanced glycation end-products (AGE), which accumulate with insulin resistance and aging, impair folliculogenesis and may decrease endometrial receptivity. Hishi (Trapa bispinosa Roxb.) extract, a safe herbal medicine, strongly inhibits AGE formation in vitro. We determined whether Hishi lowers AGE and increases live births in older assisted reproductive technology (ART) patients. This prospective randomized open-label controlled trial included 64 patients 38 to 42 years old undergoing ART with or without Hishi extract between June 11, 2015 and July 12, 2019. None had over 2 ART failures, diabetes, uterine anomalies, or exhausted ovarian reserve. After allocation, the Hishi group received Hishi extract (100 mg/day) until late pregnancy or failure. The control group received no extract. Both groups underwent 1 cycle of conventional infertility treatment; 1 long-protocol cycle of ovarian stimulation, oocyte retrieval, in vitro fertilization/intracytoplasmic sperm injection, and fresh embryo transfer (ET); and, if needed, cryopreserved ET until live birth or embryo depletion. Serum AGE were measured before and during ART, as were AGE in follicular fluid (FF). Cumulative live birth rate among 32 Hishi patients was 47%, significantly higher than 16% among 31 controls (p<0.01; RR, 4.6; 95% CI, 1.4 – 15.0; 1 control dropped out). Live birth rate per ET, including fresh and cryopreserved, was significantly higher with Hishi (28% in 47 ET vs. 10% in 49 ET; p<0.05; RR, 3.4; 95% CI, 1.1-10.4). Among variables including age, day-3 FSH, anti-Müllerian hormone, and Hishi, logistic regression identified only Hishi as significantly associated with increased cumulative live birth (p<0.05; OR, 5.1; 95% CI, 1.4 - 18.3). Hishi significantly enhanced oocyte developmental potential, improved endometrial receptivity in natural cycles, and decreased AGE in serum and FF. Larger serum AGE decreases with Hishi were associated with more oocytes becoming day-2 embryos. Hishi decreased AGE in serum and FF and improved oocyte developmental potential and endometrial receptivity, increasing live births in older patients. Treatment of infertility by AGE reduction represents a new addition to infertility treatment. Therapeutic trials of Hishi for other AGE-associated diseases might be considered. UMIN registration in Japan (UMIN000017758) on June 1, 2015. https://www.umin.ac.jp/ctr/index.htm
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