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不同剂量芳香化酶抑制剂来曲唑治疗异位妊娠及其对绒毛滋养层组织的影响的评价。

Evaluation of Different Doses of the Aromatase Inhibitor Letrozole for the Treatment of Ectopic Pregnancy and Its Effect on Villous Trophoblastic Tissue.

机构信息

Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, 44519, Egypt.

Department of Pathology, Faculty of Medicine, Benghazi University, Benghazi, Libya.

出版信息

Reprod Sci. 2022 Oct;29(10):2983-2994. doi: 10.1007/s43032-022-00993-0. Epub 2022 Jun 14.

Abstract

Letrozole, an aromatase inhibitor, has recently been introduced as a favorable medical treatment for ectopic pregnancy. We aimed at evaluating the effects of different doses of letrozole for termination of ectopic pregnancy and study their effects on villous trophoblastic tissue. Sixty patients with undisturbed ectopic pregnancy were classified into three equal groups. Group I: the control group that contained women who underwent laparoscopic salpingectomy, Group II: patients who received letrozole (5 mg day) for 10 days, and Group III: patients who received letrozole (10 mg day) for 10 days. Subsequently, the β-hCG levels were determined on the first day and after 11 days of treatment. Group IV consisted of patients of GII and GIII; their β-hCG did not drop below 100 mIU/ml within 11 days, and underwent salpingectomy. Placental tissues from patients undergoing salpingectomy either from the control group or GIV were processed for the evaluation of estrogen (ER) and progesterone (PR) receptors, vascular endothelial growth factor (VEGF), and cleaved caspase 3 (CC-3) expression. Cases exposed to high dose letrozole 10 mg day resulted in a higher ectopic pregnancy resolution rate of 85% (17/20), while the resolution rate of the low dose letrozole-treated group (5 mg day) was 65% (13/20), and also showed a significant reduction in β-hCG levels on the 11th day, 25.63 ± 4.29 compared to the low dose letrozole group 37.91 ± 7.18 (P < 0.001), Meanwhile, the letrozole-treated group GIV showed markedly reduced expression of ER, PR, and VEGF and a significant increase in the apoptotic index cleaved caspase-3 compared to the control group (P < 0.001). The utilization of letrozole at a dose of 10 mg day for medical treatment of ectopic pregnancy results in a high-successful rate without any severe side effects. Letrozole depriving the placenta of estrogen that had vascular supporting signals resulted in destroying the vascular network with marked apoptosis.

摘要

来曲唑是一种芳香化酶抑制剂,最近被引入作为异位妊娠的一种有利的医学治疗方法。我们旨在评估不同剂量的来曲唑终止异位妊娠的效果,并研究它们对绒毛滋养层组织的影响。60 例未受干扰的异位妊娠患者被分为三组。I 组:对照组,包括接受腹腔镜输卵管切除术的妇女;II 组:接受来曲唑(5mg/天)治疗 10 天的患者;III 组:接受来曲唑(10mg/天)治疗 10 天的患者。随后,在治疗的第 1 天和第 11 天测定β-hCG 水平。IV 组由 GII 和 GIII 的患者组成;他们的β-hCG 在 11 天内没有降至 100mIU/ml 以下,接受了输卵管切除术。从对照组或 GIV 接受输卵管切除术的患者的胎盘组织被处理用于评估雌激素(ER)和孕激素(PR)受体、血管内皮生长因子(VEGF)和半胱氨酸天冬氨酸蛋白酶 3(CC-3)的表达。暴露于高剂量来曲唑 10mg/天的病例导致异位妊娠的缓解率为 85%(17/20),而低剂量来曲唑治疗组(5mg/天)的缓解率为 65%(13/20),并且第 11 天的β-hCG 水平也显著降低,25.63±4.29 与低剂量来曲唑组 37.91±7.18 相比(P<0.001)。同时,与对照组相比,来曲唑治疗组 GIV 的 ER、PR 和 VEGF 表达明显减少,凋亡指数半胱氨酸天冬氨酸蛋白酶-3 明显增加(P<0.001)。来曲唑剂量为 10mg/天用于异位妊娠的治疗具有很高的成功率,没有任何严重的副作用。来曲唑剥夺胎盘的血管支持信号的雌激素导致血管网络的破坏和明显的凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/321c/9537218/1b58c3ede101/43032_2022_993_Fig1_HTML.jpg

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