低剂量阿司匹林

　　Low-dose aspirin was first reported to increase ovarian and uterine blood flow and IVF pregnancy rate in a large, well-designed trial using 100 mg daily starting with mid-luteal agonist and continuing uninterrupted into early pregnancy [1]. ASA increases blood flow by increasing the amount of vasodilating prostacycline relative to thromboxane. Because stress has been associated with reduced IVF outcomes [2], a logical mechanism of the benefit of ASA is to counter the effect of stress in reducing pelvic blood flow. It may be necessary to begin ASA well before OS is begun and to continue it without interruption until oocyte retrieval to have a maximal effect on ovarian blood flow, ovarian response, and health of the oocyte, and the period between hCG and retrieval may be particularly important when chromosome segregation is taking place.

　　在一项精心设计的大型试验中，研究人员发现低剂量阿司匹林可增加卵巢和子宫血流量和试管妊娠率，该试验从黄体中期开始使用激动剂，每天服用100毫克的阿司匹林，并持续至妊娠早期 [1]。低剂量阿司匹林通过增加有血管舒张作用的前列环素的数量来增加血流量。因为压力也会导致试管婴儿成功率降低[2]，使用低剂量阿司匹林的一个逻辑机制是抵消压力增加导致的盆腔血流减少的影响。也许有必要在促排周期开始前服用低剂量阿司匹林，直到取卵，以对卵巢血流、卵巢反应和卵母细胞的健康产生最大影响。当染色体分离时，即使用hCG 和取卵之间的时间段，使用阿司匹林可能变得尤为重要。

　　Unfortunately, subsequent studies did not reproduce the parameters of the original study, including the fact that it took place in a busy and stressful environment. Meta-analyses have been published collating highly heterogeneous study designs, resulting in a conclusion that ASA is of no benefit[3，4] . In two trials the ASA was begun on the day that OS was begun, and in another trial the ASA was stopped at the time of hCG. Two studies were in frozen embryo cycles and one was in oocyte donation recipients where an effect on ovarian response and oocyte quality would not be seen. One trial was in poor responders and one was in women refractory to usual doses of estrogen. The patient populations varied from a small town in Scandanavia to environments closer to that of the original trial. However, in spite of such remarkable heterogeneity, a subsequent reanalysis of these studies by the Division of Epidemiology of the National Institutes of Health [5] concluded that the clinical pregnancy rate was increased and“there is no reason to change clinical management and discontinue the use of aspirin. ”In a large randomized clinical trials that is available online but not yet in print, ASA resulted in a highly significant reduction of the incidence of severe OHSS, which would itself be a sufficient reason to continue use of this simple adjunct [6]. In addition, ASA may reduce the chance of a thromboembolic episode. The sole concern has been whether its use could increase the chance of bleeding following oocyte retrieval, but there have been no indications of such an effect.

　　然而，随后的研究并没有得到同样的结果，尽管该研究是在繁忙和紧张的环境中进行的。已发表的荟萃分析整理了高度异质性的研究设计，得出的结论是低剂量的阿司匹林没有益处[3，4]。在两项试验中，低剂量阿司匹林是在开始促排周期的当天服用，在另一项试验中，低剂量阿司匹林在开始hCG 时停止。两项研究是在冷冻胚胎周期中进行的，一项是在卵母细胞受赠者中进行的，在这些受赠者中，卵巢反应和卵母细胞质量不会受到影响。一项试验针对反应不佳者，另一项针对对常规剂量的雌激素无反应的女性。患者人群也不一样，从来自斯堪的纳维亚的一个小镇到更接近原始试验的环境。然而，尽管存在如此显著的异质性，美国国立卫生研究院流行病学部 [5] 随后对这些研究重新分析得出结论，临床妊娠率增加，“没有理由改变临床管理并停止阿司匹林的使用。“在一项可在线获取但尚未出版的大型随机临床试验中，低剂量阿司匹林显著降低了严重卵巢过度刺激综合症的发生率，这本身就是继续使用这种简单辅助手段的充分理由 [6]。此外，低剂量阿司匹林可能会减少血栓栓塞的机率。 唯一的担忧是它的使用是否会导致取卵后出血的概率增加，但没有迹象表明存在这种影响。

　　Reference数据参考

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　　2. Ebbesen SM,Zachariae R, Mehlsen MY, et al.Stressful life events are associated with a poor in-vitro fertilization (IVF) outcome: a prospective study. Hum Reprod. 2009; 24: 2173-2182.

　　3. Khairy M, Banerjee K, El-Toukhy T, Coomarasamy A, Khalaf Y. Aspirin in women undergoing in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril.2007;88:822-831.

　　4. Gelbaya TA,Kyrgiou M, Li TC, Stern C,Nardo LG. Low-dose aspirin for in vitro fertilization: a systematic review and meta-analysis. Hum Reprod Update2007; 13: 357-364.

　　5. Ruopp MD, Collins TC, Whitcomb BW, Schisterman EF. Evidence of absence or absence of evidence? Are analysis of the effects of low-dose aspirin in in vitro fertilization. Fertil Steril 2008; 90: 71-76.

　　6. Várnagy A, Bódis J, Mánfai Z,et al. Low-dose aspirin therapy to prevent ovarian hyperstimulation syndrome. Fertil Steril 2010;93:2281-2284.